Memorable

Psychiatry
 
 
Jonathan Heldt, M.D.

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Also available from the same author: Memorable Psychopharmacology Memorable Neurology
 

e content of this book is not intended to be a replacement for proper medical training, nor is it
intended to substitute for professional medical advice, diagnosis, or treatment. Always seek the
advice of your physician or other quali ed health provider with any questions you may have
regarding a medical condition.
 

Editing and behavioral consultation provided by Juliane Heldt, BCBA (Board Certi ed
Behavior Analyst).
Copyright © 2018 Jonathan Heldt.
All rights reserved.
Revision 1.3. Last revised October 22, 2019.
ISBN: 1543093205
ISBN-13: 978-1543093209

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DEDICATION
 
 
To my grandparents Steve and Young-cha Pai who crossed more oceans, worked longer
hours, and endured greater hardships than anyone should have to so they could provide for
their family. ank you for giving us the life we have today.

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CONTENTS

     

     

     

Acknowledgments i
 

1 1
Introduction
2 Diagnosis 3
3 Evaluation 17
4 Psychiatric Emergencies 33
5 Depression 55
6 Mania 77
7 Psychosis 97
8 Addiction 125
9 Anxiety 151
10 Obsessions and Compulsions 171
11 Trauma 193
12 Personality 211

     

     

     

     

     

13 233

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 Borderline
14 Dissociation 253
15 Somatization 269
16 Eating Disorders 287
17 Development 301
18 Autism 323
19 Inattention and Hyperactivity 339
20 Externalization 355
21 Psychopathy 371
22 Dementia 383
23 Sleep 407
24 Final Review 423

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ACKNOWLEDGMENTS
 
 
A world of thanks to Juliane Heldt, BCBA (Board Certi ed Behavior Analyst) for
putting my books into the hands of so many people who would not otherwise have seen
them. ank you for being the best editor, publicist, supporter,
interdisciplinary consultant, and sister I could ask for. 

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1 INTRODUCTION

Welcome to the most fascinating eld in medicine. Psychiatry

deals with the most complex organ in the human body—the brain—and the way in which
it interfaces not only with the other parts of the body but also with other people and society
as a whole. More than any other discipline of medicine, psychiatry requires a meaningful
understanding of the world and its complexities. However, too often psychiatry is
experienced not as fascinating but as bewildering, mystifying, or illogical. e central
tension of psychiatry—how little we know about the brain and its inner workings—is
viewed not as a target for curiosity but instead as a barrier to entry. Attempts to make sense
of the mind’s workings (such as the algorithmic diagnoses that form the basis for most
textbooks on psychiatry) often risk going too far in the opposite direction, trading in the
dynamic intricacies of the human mind for a simpli ed “cookbook” of what can go wrong
with the brain. is makes psychiatry less bewildering, but it also risks turning it into
something boring, tedious, and rote.
ere is a middle ground. is book aims to make the disorders we treat
understandable through the use of clear explanations, analogies, and mnemonics. A good
understanding of these disorders is essential for allowing clarity in diagnosis and avoiding
the pitfalls of overdiagnosis, including use of ineffective or even harmful treatments. In
addition, this book also aims to provide practical clinical tools that you can use when
working with patients in the real world.
By design, some of the mnemonics and analogies included may be silly, shocking, or
amusing. is is done in service of making the information more accessible, as provoking an
emotional response is one of the best ways of getting information to stick. Nothing in this
book is intended to stigmatize, trivialize, or humiliate anyone struggling with any of the
disorders mentioned.
We’ll begin our study of mental disorders with an overview of the line between normalcy
and illness. From there, we will learn how to perform a clinical evaluation of someone with
a psychiatric problem as well as how to respond to psychiatric emergencies. After that, the
diagnostic portion of the book begins in earnest as we begin to learn about the major
syndromes in psychiatry, including depression, mania, psychosis, anxiety, addiction,
personality disorders, and more.
rough each chapter, we will not only learn about each disorder in isolation but also
discover out how to differentiate between different psychiatric disorders, many of which
have similar or overlapping symptoms. Unfortunately, this means that the going will be a

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little rough at the beginning, as there is no way to compare diagnoses across categories
without bringing up disorders that we have not covered yet. However, rest assured that it
will get easier as time goes on! In addition, don’t be afraid to skip ahead if you need more
background information on any given subject. Frequent references between chapters will
also be made to facilitate understanding. A general understanding of physiology (including
the autonomic nervous system) and pathology will be helpful for understanding all of the
concepts, but it is not required.
Concepts in boxes are particularly high-yield!
An easy way to remember them will be in italics below.
Now, let’s begin…
 

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2 DIAGNOSIS

In medicine, diagnosis is the process of determining what

condition best explains someone’s illness. Accurate diagnosis is the basis on which clinicians
make decisions about how best to relieve suffering, and without a diagnosis, appropriate
treatment remains out of reach. Diagnosis is accomplished through a careful evaluation of a
patient’s signs (objective ndings that you can observe directly, such as redness of the eyes)
and symptoms (subjective concerns that the patient tells you about, such as a headache).
Signs and symptoms in psychiatry are collectively referred to as phenomenology.
Within psychiatry, many of the conditions we treat are syndromes rather than speci c
disease processes. A syndrome is a set of signs and symptoms that tend to occur together.
For example, when someone says that they have a “cold,” they are saying that they have a set
of signs and symptoms (such as cough, runny nose, sore throat, fatigue, muscle aches, and
loss of appetite) that tend to signify something when they cluster together.
Diagnosing a syndrome is not the same as identifying the underlying cause (just
saying you have a cold is not the same as identifying a rhinoviral infection). However, even
if it doesn’t identify the exact cause of the problem, diagnosing a syndrome is still helpful
because it suggests a certain prognosis and treatment response. For example, identifying
that someone has a cold suggests that the signs and symptoms will probably go away on
their own in a few days or weeks (its prognosis) and that antibiotics are unlikely to help (its
treatment response).
e process of diagnosing a syndrome applies to the majority of conditions that are
seen in psychiatry. By saying that someone has depression, we are not saying that we have
identi ed the speci c anatomic, physiologic, or cellular processes associated with that
disorder. Rather, we are saying that we have recognized a consistent set of signs and
symptoms (in the case of depression, things like sadness, fatigue, insomnia, psychomotor
slowing, and an inability to enjoy activities) that tend to occur together and predict a certain
prognosis (6 to 12 months before recovery in most cases) and treatment response (a
bene cial effect from serotonin-boosting medications and psychotherapy). It is possible
that, with future research, we will eventually discover more of the mechanisms underlying
these syndromes. However, at least at this time, the precise pathology of most mental
disorders remains out of our grasp.
Because of this, psychiatric syndromes are referred to as disorders rather than
diseases. is is because the biological, psychological, and social impairment that they create
in peoples’ lives (the “disorder”) can often be observed objectively, even if there is less

9
agreement on why the impairment is happening (the “disease”). However, the lack of clear
objective ndings that de nitively rule in or out a certain disease process makes psychiatric
diagnosis an inherently subjective process.
Most psychiatric disorders are syndromes and not
speci c pathologies, making psychiatric diagnosis an
inherently subjective process.
Syndromes are subjective, pathologies are provable.
As with any subjective process, not everyone is going to agree. is is made especially
difficult because a diagnosis implies a distinction between what is normal and abnormal.
For example, a boy who is worried about a test at school may believe that having a sore
throat is “abnormal enough” to be able to stay home from school. For his mother, however,
the lack of a fever suggests that his condition is “normal enough” that he still needs to go to
school. e mother may ask a doctor to come by to provide a more formal evaluation.
However, even a doctor’s professional opinion remains a subjective determination as long as
objective markers of a speci c disease process are missing.

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NORMAL VERSUS ABNORMAL
A central tenet of psychiatry is the notion that, at any given time, there are people whose
ability to function has been compromised by emotional, cognitive, and/or behavioral
problems. ese individuals are said to be suffering from mental disorders that are distinct
enough from “normal” life to warrant medical attention. ere is general agreement in the
medical community that mental disorders exist. However, there is much less agreement on
where to draw the line between normalcy and illness.
At the center of this disagreement is the idea that words like “normal” and “abnormal” are
binary descriptions of dimensional concepts. Most psychiatric syndromes are not binary
“yes-or-no” conditions that are either there or not. Rather, the majority of psychiatric
disorders occur on a spectrum where some people are severely impaired, others have only
mild symptoms, and still others have no symptoms at all. However, the act of diagnosis is a
binary “yes-or-no” decision where you either say that someone has the diagnosis or they
don’t. is attempt to shoehorn non-binary disorders into a binary diagnostic system is
inherently problematic, and disagreements are bound to arise.

To understand this better, imagine that you have been given an

assignment to de ne what “abnormally tall” is. On the surface, this seems like a simple task.
You initially think, “6 foot 5 inches seems pretty tall.” However, you realize that most
people will have their own equally arbitrary de nition of the height over which someone
becomes “too tall,” so you decide to be scienti c about it. Given that height falls on a
normal distribution, you decide that everyone above the 95th percentile should be
considered “abnormally tall.” You nd that in the United States this corresponds to
approximately 6’2” for men and 5’8” for women. Upon further re ection, you realize that
this distribution varies widely from country to country, making it feel less standardized than
you rst thought. You then decide to normalize this by only comparing someone’s height to
their own personal growth trajectory. However, this wouldn’t capture someone who has
always been abnormally tall even from a young age, so you throw out this idea.
You then decide to go the other way and de ne “abnormally tall” as being whenever
someone feels that they are too tall? No, wait, that’s too loose and open to various
interpretations. Let’s try to be scienti c again but take a different approach. Maybe there
are some biological traits associated with height that you can use to de ne it rather than
everyone having their own arbitrary de nitions? For example, certain brain tumors cause an
excess of growth hormone which can result in people being really tall. However, you realize
that these speci c abnormalities won’t account for everyone, as there are some really tall

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people who don’t have pituitary tumors and other people with pituitary tumors who are
average height.
Instead, you consider de ning “abnormally tall” in terms of how functionally
impairing it is, such as needing to special-order clothing that will t or frequently stooping
down to avoid hitting one’s head on doorways. However, that also seems very culturally
dependent. Getting frustrated, you begin to wonder: why even have a de nition of
“abnormally tall” in the rst place? ese are all just extremes of normalcy, and it’s not good
to hold people to any particular standard. Maybe we should be focusing on challenging the
obsession that we as a society have with height and appearance rather than making people
feel bad for thinking they are too tall or too short. However, then you realize that—like it or
not—everyone still has an idea of what “abnormally tall” looks like, even if they don’t agree.
Increasingly tired of this assignment, you decide to combine several approaches by saying
that if someone is over 95th percentile for height given their country of origin or there is a
known biological abnormality, then you will say that they are “abnormally tall” provided that
this is associated with functional difficulties, personal distress, or medical problems.

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ADVANTAGES AND DISADVANTAGES OF DIAGNOSIS
e preceding story serves to illustrate the challenges of trying to de ne the line between
normal and abnormal, even for a concept as simple, objective, and easily measured as
height. When you make the concepts involved more abstract (such as the “invisible”
concepts in mental health), reaching consensus becomes even more difficult. Indeed, this
complexity underlies the reasons why agreeing on diagnostic schemes for mental disorders
has been (and will likely remain) such a contentious process. Everyone has their own
internal sense of what “abnormal” is, which makes consensus difficult to achieve. Given the
trouble of coming up with a diagnostic scheme for even one “disorder,” you might be
tempted to conclude that there is no point in even having diagnoses at all. However, there
are several reasons why diagnosis remains important:
It predicts prognosis and treatment response. As mentioned before, diagnosis predicts
prognosis and treatment response, even for conditions that are syndromes rather than
clearly de ned pathological processes.
 

It facilitates communication. Diagnosis provides an efficient shorthand for people to

communicate quickly with others. For example, rather than saying, “ is young lady has
grandiose thoughts that she is going to colonize the moon, is displaying erratic behavior, is
talking incredibly fast, and hasn’t felt the need to sleep for over 2 weeks,” someone could
simply say, “She is likely experiencing a manic episode” (although in some cases this may
have the undesirable effect of obscuring important differences between cases even when the
same diagnosis may be appropriate).

It allows research to be coordinated. By standardizing de nitions of what exactly

constitutes a speci c condition, researchers in different places are able to work together to
study the causes and potential treatments of these disorders. Without this standardization,
one group could not be sure that they are attempting to study the same condition as another
group, and research efforts would likely become uncoordinated and slow.
 

It validates distress. Diagnosis by a quali ed professional provides validation of, and some
level of explanation for, the distress that people with mental disorders experience. is does
more than merely offer emotional support. Professional validation of distress carries weight
in many areas of life, including rallying the support of family and friends, satisfying
employers (as in a doctor’s off-work letter), explaining behavior to authorities, and justifying
reimbursement from health insurance companies, among many other things.
 

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It supports community building. A diagnosis can serve as a rallying point for groups of
people affected by similar conditions to support one another and work towards positive
changes.
 

Nevertheless, there are also some signi cant downsides associated with diagnosis that
cannot be ignored. Despite the bene ts of diagnosis, it is not an entirely benign process.
Always keep the following drawbacks of diagnosis in mind when evaluating patients:
 

It can lead to overdiagnosis and overtreatment. By making a set of signs and symptoms
into a recognizable “disorder,” providers are encouraged to actively look for these patterns.
is can lead to the overdiagnosis and overtreatment of things that are not necessarily
pathological. For example, someone who feels emotions strongly but remains functional still
risks being diagnosed with a mood disorder by an overzealous clinician.
 

It can be stigmatizing. Especially in the realm of mental health, diagnosis can

be a highly stigmatizing experience. People often feel “labeled” with a diagnosis and may be
treated differently by others as a result. Stigma against mental disorders is real (for a quick
example, consider whether you would feel comfortable having someone diagnosed with a
mental illness babysitting your children). Receiving a diagnosis may also change someone’s
self-image, leading to decreased self-esteem or lack of belief in their own abilities. Like
labels, psychiatric diagnoses can be hard to peel off, and people often nd that the negative
effects of diagnosis persist even after the initial problem has gone away.
 

It can lead to a sense of premature closure. Providing a psychiatric diagnosis can

“medicalize” normal problems in living and give both the patient and their provider a sense
of premature closure. is is especially problematic in psychiatry, as all mental disorders
have not only a biological component but psychological and environmental dimensions as
well. For example, someone who has been diagnosed with depression may start believing
that they have found the explanation for their distress (“I have a chemical imbalance”) and
then stop looking for other things they can do to potentially improve their mood, such as
strengthening the relationships in their life or doing more activities that they enjoy. A
doctor may similarly be convinced that they have gured the situation out and neglect to

14
look for other possible explanations, such as thyroid abnormalities, that could account for
changes in mood.

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PRINCIPLES OF PSYCHODIAGNOSTICS
Despite the signi cant disadvantages to diagnosis, the bene ts that diagnosis provides are
important enough that it is worthwhile to look for a middle ground. e following
Principles of Psychodiagnostics can serve as guidelines for how to maximize the bene ts of
diagnosis while minimizing the drawbacks.
 

1. Normalcy is always on the differential. Normalcy should always be considered as a

possible explanation for any patient presenting with a psychiatric complaint. Many mental
disorders resemble normal aspects of everyday life (such as depression resembling sadness),
making it essential to consider normalcy as an explanation before applying a diagnosis.
Occasionally the line between normalcy and illness is clear, but most of the time it is not. In
these cases, carefully considering both the advantages and disadvantages of diagnosis can
help in making an informed decision.
 

2. Process over content. e eld of psychiatry is lled

with bizarre and exotic sounding symptoms, including hallucinations, impostors,
government conspiracies, and multiple personalities. Because of this, it is easy to get swept
up in the content of what you’re hearing. However, the content of a patient’s presentation is
far less important than the process of how these symptoms have come about. As one
example, when most people hear the term “auditory hallucinations,” they immediately think
of schizophrenia. After all, hearing voices has to be pathological, right? However, research
has revealed that around 5% of people hear voices and are not in any way troubled or
impaired by them. If you focused solely on the content of the case, it would be easy to jump
to a diagnosis of schizophrenia. However, by focusing on the process, you would notice that
these people still lead lives free of distress and remain functional both at home and in the
community. In contrast, you should be more inclined to diagnose someone with
schizophrenia when they are presenting with auditory hallucinations in the context of
worsening performance at work, difficulty communicating with others, and a sudden lack of
self-care. is is just one of many examples, and we will return to the idea of prioritizing
process over content many times throughout this book.
 

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3. At extremes, the quantitative becomes qualitative. As mentioned earlier, the process of
diagnosis is inherently problematic because it involves shoehorning quantitative (non-
binary) concepts into qualitative (binary) diagnoses. Using the same example from earlier,
someone’s height is a quantitative measure that can be counted in inches or centimeters.
However, we also have qualitative terms like “short” and “tall.” For those in the middle (say,
someone of around average height), there is generally poor agreement for who quali es for
these terms. However, at extremes (say, someone who is 7 feet tall), there is no
disagreement: this person is tall by any standard you would use. In this way, you can see that
at extremes, a quantitative measure (being 7 feet tall) becomes a qualitative measure (this
person is “tall”). Mental disorders are the same way. Milder presentations of certain
conditions can result in disagreement between different providers, but for severe cases there
is often little doubt that a particular patient is suffering from a mental disorder. erefore, it
seems reasonable to reserve use of diagnosis for those cases that are impairing enough to be
considered severely disruptive to someone’s life.
 

4. It’s never just one thing. Be incredibly skeptical of anyone who offers a singular
explanation for a mental disorder. Instead, the majority of psychiatric syndromes can be
conceptualized as the result of a complex interaction between each individual’s inherent
vulnerability to that syndrome (known as a diathesis) and the speci c environmental
in uences that are present (known as stress). is interaction is known as the diathesis-
stress model of illness, which states that both a stress and a biological, psychological, and/or
social vulnerability to that stress are needed for dysfunction to occur.

For example, let’s say that someone is slicing

bread for dinner and accidentally makes a deep cut into their nger. is person will likely
begin bleeding and require immediate medical attention. However, is this bleeding a
disorder? No. Cuts and scrapes happen all the time, and bleeding is a normal and
physiologic response to this form of injury. is person’s bleeding is more accurately
conceptualized as a medical condition: a state that is not necessarily pathological but may
still need medical attention. (Pregnancy is another example of a medical condition.)
However, let’s say that this person also had hemophilia, a genetic de ciency in one of their
clotting factors. In this case, even an accidental cut from a kitchen knife can be a potentially
deadly event if the bleeding is not be controlled. In this way, when an environmental stress
(an accidental cut from a knife) meets a pre-existing diathesis (a de ciency in clotting
factors), a disorder is formed.
Like the concept of a disorder itself, the concepts of stress and diathesis are not binary
but instead occur on a spectrum. ere are big stressors and little stressors, just as there are
severe diatheses and minor diatheses. It is the combination of the stressor and the diathesis
that ultimately determines the severity of a disorder. Continuing the same example from
earlier, someone with hemophilia (a severe diathesis) may live their entire lives without ever

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having a problem as long as they never run into an injury of any kind (no stressors).
However, if they run into even a small cut (a little stressor), that may still create a major
disorder. On the other hand, someone with an intact clotting system (no diathesis) is not
likely to have too many problems from just a small cut (a little stressor) but may end up
bleeding to death if they experience a severe injury (a big stressor).
e diathesis-stress model explains much of what we see in psychiatry. Post-traumatic stress
disorder (PTSD) is an excellent example. Not everyone who experiences trauma (a stressor)
will go on to develop symptoms of PTSD. In fact, the majority of those who exposed to
trauma do not go on to develop PTSD. However, people with a particular set of
vulnerabilities (including certain genes, personality traits, coping styles, and social supports)
can experience PTSD even after what most would consider to be a minor trauma (large
diathesis + small stressor = disorder). In addition, someone with only a minor diathesis for
PTSD may still develop symptoms if they experience a severe enough trauma (small diathesis +
large stressor = disorder). Someone with a signi cant vulnerability to trauma who
experiences a major trauma may end up with an incredibly severe disorder (large diathesis
+ large stressor = severe disorder). e concept of both diatheses and stressors
contributing to mental disorders is well validated, con rming the idea that it’s never just one
thing.
 

5. Taking someone seriously does not mean always taking them literally. Finally, it’s
important to keep in mind that the language of medicine is not always used in the same way
by different people. For example, a patient may tell their therapist that they are “very
depressed” after having a single stressful day at work. To take this statement at its literal
face value and diagnose clinical depression would be an example of gross overdiagnosis.
However, to ignore the distress at the heart of what the patient is saying would also not be
the right thing to do. e middle ground is to always take what your patient tells you
seriously, even if you do not always take it literally.
is distinction is necessary because the language of medicine and psychiatry is often
used as an idiom of distress. Idioms of distress are a culturally understood way of expressing
that you are suffering and require assistance. For example, you can probably think of at least
one movie where a character on-screen immediately downs an entire glass of wine in
response to an awkward or stressful situation. In our culture, drinking an entire glass of
wine at once is a culturally-accepted expression of distress. In the medical eld, similar
idioms of distress can include saying you have a particular mental or physical disorder
(“Work’s been really stressful, I’ve been having panic attacks all week”), using medical
terminology to demonstrate the seriousness of your situation (“I’m a danger to myself, a
danger to others, and I’m gravely disabled”), or asking for diagnostic tests (“I need to get my
brain scanned”).
Complicating the matter further is the complex relationship between distress and
disease. Too often, someone coming into a doctor’s office saying that they are in distress is
immediately treated as though they have a disease. is is reasonable, as distress is often
caused by disease, so the presence of distress should prompt a search for an underlying
cause. However, it is wrong to assume that distress is itself a disease, as there are many cases
where someone can be in distress in the absence of any biological disease process (such as
difficult situations at work or in the home). e simplest way to capture the relationship

18
between distress and disease is to remember that distress is not disease but can be caused
by a lot of things, including disease.
Making a distinction between taking someone seriously and taking them literally
should not be seen as an encouragement to never take someone literally. e majority of the
time, taking someone’s statements at face value is the best approach, both for diagnostic
accuracy and for preserving the provider-patient relationship (after all, who likes having
everything they say doubted all the time?). But you also should not completely ignore the
downsides of overliteralizing expressions of distress, and the best way to do this is to always
take your patient seriously, even if your clinical intuition and expertise tells you that what
they’re saying shouldn’t be taken literally at this moment.
 

Psychiatric diagnosis is a powerful tool with many

advantages and disadvantages that must be taken
into account.
 

Remember the Principles of Psychodiagnostics: 1.

Normalcy is always on the differential.
2. Process over content.
3. At extremes, the quantitative becomes qualitative.
4. It’s never just one thing.
5. Taking someone seriously does not mean always taking
them literally.

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THE DSM
With these principles of psychodiagnostics under our belt, we can begin talking about the
process by which we diagnose certain conditions. As we discuss each of the major types of
psychiatric disorders, we will make occasional reference to the Diagnostic and Statistical
Manual of Mental Disorders (often abbreviated as DSM). e fth edition (or DSM-5)
was published by the American Psychiatric Association in 2013. Within its pages are
speci c diagnostic criteria for hundreds of mental disorders. e DSM uses an algorithmic
approach to diagnosis, meaning that each disorder is presented as a set of criteria which are
either met or not, resulting in a qualitative diagnosis. If we return to the example from
earlier of the concept of “abnormally tall,” the algorithmic criteria would be presented as:
Excessive Height Disorder:
A. e patient meets criteria for either or both of the following:
a. Height above the 95th percentile adjusted for country of origin
b. Evidence of an underlying biological abnormality (e.g., elevated
levels of insulin-like growth factor-1)
B. e person has functional difficulties, personal distress, and/or medical
problems as a result of Criterion A
 

Using this algorithmic approach, we can say that

someone de nitely does or does not qualify for a diagnosis of “Excessive Height Disorder.”
is decreases ambiguity and ensures that two people who use the same term are in fact
talking about the same diagnosis. While use of algorithmic criteria has greatly increased the
reliability of psychiatric diagnoses, this may have come at the expense of their validity (or
the extent to which the diagnostic criteria actually correspond to the real-life syndrome that
they are trying to describe). To use an analogy, someone trying to come up with diagnostic
criteria for a mental disorder is akin to an archer trying to hit a target. A reliable archer
would have all of their arrows hit at approximately the same place. However, this does not
mean that they are on target. A valid archer would hit the target but would not necessarily
do this consistently. Only an archer who is both reliable and valid would consistently hit the
target.
 

20
 Neither reliable nor valid Reliable but not valid Valid but not reliable Both reliable and valid

In the same way, using the DSM criteria makes it so that speci c terms are more
reliable (two different clinicians evaluating the same patient are likely to arrive at the same
diagnosis), but it is no guarantee of the validity of this diagnosis (it does not necessarily
capture the real-life clinical syndrome that they are referring to).

e distinction between reliability and

validity is a valuable reminder that the diagnostic criteria in the DSM are not the disorders
themselves. Instead, they are representations of disorders. is distinction is frequently
confused In psychiatry, and it’s not uncommon to hear a clinician say something like, “He
seems really depressed, but he technically doesn’t meet DSM criteria for major depressive
disorder.” is is absolutely the wrong way to use the DSM, as it confuses a representation of
a disorder with the disorder itself. To use an example, imagine a family living in a small
town about a mile from the Mississippi River. One day, a massive rainstorm hits the area
and causes the boundaries of the river to swell, ooding the town in waist deep water.
While gathering their belongings to evacuate, the young girl says to her father, “It’s crazy
that the Mississippi River is right outside our front door.” e father, looking at a map of
the area, replies, “No sweetie, don’t be absurd, the Mississippi River is over a mile away.”
In this story, the father has let a representation of the area (a map) get in the way of
understanding what the map is trying to represent (the river itself ). While maps of rivers
are static and unchanging, rivers are dynamic and evolve in response to current weather
conditions. In the same way, the diagnostic criteria outlined in the DSM act like a map of
mental disorders: they provide guidelines and boundaries, but ultimately they should be
seen as a standin for the disorders rather than being the disorders themselves. rough this,
we see that the DSM is not “the Bible of psychiatry” as it is often described. It is more like
a dictionary: it makes sure that we are all speaking the same language when we use these
terms.
roughout this book, the DSM criteria for a particular disorder may be referenced
from time to time. is is done when the diagnostic criteria have proven helpful for

21
understanding a disorder (such as the SIGECAPS symptoms seen in depression). However,
you should always take them with a grain of salt and remember that these are proxies for the
disorder, not the disorder itself. In addition, we will make reference to the “official” names
for each disorder as listed by the DSM but will not use them exclusively. For example,
Alzheimer’s disease will be discussed as a form of “dementia” rather than a subtype of
“major neurocognitive disorder.” is is done to help prepare you for actual clinical
experiences where these non-technical terms continue to be used frequently by both
professionals and patients. However, keep in mind that the names of disorders found in the
DSM are often carefully chosen with the goal of decreasing stigma and increasing scienti c
accuracy, so in your own practice you should consider what the most appropriate term
should be.

22
PUTTING IT ALL TOGETHER
Diagnosis is one of the most powerful tools that psychiatrists and other healthcare providers
use in their daily practice. Like any tool, diagnosis is not inherently good or bad. Rather,
whether the process of psychiatric diagnosis is used in a constructive or destructive way
depends largely on the skills and intentions of the person using it.
To maximize your chances of making a helpful diagnosis, use the mnemonic LEAD to
remember the types of information you should be looking for. Diagnosis should be
Longitudinal and encompass information from across the patient’s lifespan (rather than
cross-sectional or based on a single moment in time). In addition, accurate diagnosis
requires someone with Expertise and experience in the eld (rather than being something
that is easily performed by any random person on the street). Finally, accurate diagnosis
relies on the use of All Data that is available (including not only what the patient tells you
but also reports from collateral contacts, review of previous records, and reports from other
healthcare providers who have previously cared for the patient).
 

Diagnostic accuracy is improved when relying on

information that is longitudinal, involves expert
assessment, and is based on all available data.
 

LEAD: Longitudinal Expert All Data

e information in this chapter is not high-yield in the sense that you will suddenly
be able to answer more test questions because of it. Rather, the concepts in this chapter will
allow a deeper understanding of each of the psychiatric syndromes we will discuss in later
chapters, and we will refer back to these concepts frequently throughout the book.
 

23
REVIEW QUESTIONS
1. A 23 y/o M is referred for psychiatric evaluation for evaluation of obsessive-
compulsive disorder. He reports repetitive thoughts that he is unclean and is
covered in bugs. In order to relieve the distress caused by these thoughts, he has
taken to picking at his skin to the extent that he breaks the skin and causes
bleeding. Physical examination of the patient is shown below:

How would this patient’s visible physical injuries best be classi ed?
A. Symptom
B. Sign
C. Behavior
D. Disorder
E. Syndrome
2. A research team is developing a set of 3 screening questions for heroin addiction
that takes only one minute to complete. Answering “Yes” to at least 2 of these
questions is considered a positive screen for heroin use. To make sure that these
questions are helpful, they compare patients’ responses to these questions to the
results of their urine toxicology tests. e team nds that 100% of patients who
answered “Yes” to at least 2 of the questions have use of heroin con rmed on urine
testing. However, 52% of patients who have a positive urine test do not screen
positive using the questions. What is the best description of this screening test?
A. It is reliable but not valid
B. It is valid but not reliable
C. It is both reliable and valid
D. It is neither reliable nor valid
E. None of the above

24
1. e best answer is B. Physical ndings that can be observed objectively are considered
signs. His subjectively reported feelings (such as a sensation of distress that precedes
skin picking) would be considered symptoms (answer A), while his skin picking itself
would be the behavior (answer C). Finally, it is the combination of his reported
symptoms, signs, and behaviors that would comprise a disorder or syndrome (answers
D and E).
2. e best answer is B. Because the screening questions accurately capture what they are
hoping to (with use of heroin being con rmed by urine testing in 100% of cases), it
would be considered a highly valid test (ruling out answers D and E). However,
because it only identi es patients with disordered use of heroin less than half of the
time, it would not be considered a reliable test (answers A and C).
 

25
3 EVALUATION

A psychiatric evaluation is the process by which

clinicians gather information about a patient with the goal of establishing an accurate
diagnosis. e primary tools used by psychiatrists, doctors, therapists, and other clinicians
for evaluating and diagnosing mental disorders are the psychiatric interview and the
mental status exam. e importance of learning to correctly perform these two assessments
cannot be overstated. Unlike in other elds of medicine (where physical exam ndings, lab
tests, and imaging can help to diagnose a disease even in the absence of a well-taken
history), in psychiatry the clinical interview will almost always be your primary source of
diagnostic data, so learn how to do it well.
Being able to evaluate a patient with a psychiatric concern is a critical skill for all
healthcare providers regardless of their specialty, as mental disorders are often comorbid
with physical ailments. In fact, it is estimated that up to a quarter of all primary care
patients have a psychiatric condition. In addition, many psychiatric syndromes can interact
with or closely mimic diseases in nearly every other eld of medicine (whether it’s body
dysmorphic disorder in plastic surgery, panic attacks in emergency medicine, post-partum
depression in obstetrics and gynecology, conversion disorder in neurology, or Munchausen
syndrome by proxy in pediatrics, all of which we will discuss in more detail in later
chapters). Despite a high prevalence of psychiatric conditions in nearly all elds of
medicine, less than half of patients actually end up receiving adequate mental health care.
Much of this has to do with clinicians feeling ill-informed or unprepared about what to do
when presented with a psychiatric concern. To help yourself feel more comfortable in these
situations, spend some time learning how to do a good psychiatric interview and mental
status exam.

26
THE PSYCHIATRIC INTERVIEW
e psychiatric interview is a structured clinical assessment that focuses on matters related
to mental health. It is similar to the history and physical performed when seeing a patient in
any medical setting but includes a greater focus on psychological and social aspects of
health. e primary goal of conducting a psychiatric interview is to obtain information that
will lead to an accurate diagnosis and a reasonable treatment plan. However, a psychiatric
interview should also be used as an opportunity to build rapport and create a therapeutic
alliance with your patient.
ere are many elements of the psychiatric interview to remember, but you can use
the mnemonic CHAMPION FISH CALLER to keep them in your head. By mentally
running through this mnemonic during your interview, you can make sure that you’re not
forgetting any major topics before you leave the room. We’ll now go over each of these
elements one by one:
 

Chief Complaint
How Can We Collateral
Help? Family Abuse
Allergies Income Legal
Medications Social Leaving
Past History Support Examination
Ideation Housing Review of
Orientation   Systems
Narcotics and  
Substances

27
 

28
CHIEF COMPLAINT

After introducing yourself, begin the interview by asking about the

patient’s reason for coming to medical attention. Try to keep the conversation open-ended
by asking questions that cannot be answered with a simple yes or no (such as asking, “Tell
me about where you live” rather than saying, “Do you have a home?”). Providing at least a
few minutes of “free” speech at the beginning of the interview can help to focus the rest of
the conversation, as the patient will often bring up whatever is concerning them the most at
this time.
 

HOW CAN WE HELP?

After framing the nature of the problem, ask the patient how they think that you can be of
help. After all, the patient came to medical attention for a speci c reason, and it can be
helpful to make their desires known from the beginning of the interview. Common reasons
for coming to psychiatric attention include speci c symptoms for which they would like a
diagnosis (or a reassurance of normalcy), wanting a prescription for medication, or desiring
to begin therapy. In emergency settings, patients may ask to be admitted to the hospital (or,
in cases where they were brought involuntarily, may want to leave). By knowing the
patient’s preferences from the very beginning of the interview, you can focus the rest of the
interview on gathering the information necessary to determine whether their request is
appropriate or not.

ALLERGIES AND MEDICATIONS

It is crucial to know the names, dosages, schedules, and indications of all medications that a
patient is taking. Remember to ask about over-the-counter medications and supplements as
well. For patients you will be treating, asking about past psychiatric medication trials can
help to direct future treatment. Try to outline exactly when each of these trials occurred as
well as the outcome (was the medicine stopped due to the side effects or was it simply
ineffective?). Asking about past allergic reactions is important as well, especially in acute
situations where emergency medications may be needed.

PAST PSYCHIATRIC AND MEDICAL HISTORY

29
Asking about a patient’s past psychiatric history (including both inpatient and outpatient
treatment) can help clue you into the nature and severity of their problem. Even for two
people with the same diagnosis, there’s a large difference between someone who has “seen a
therapist once or twice” and someone who has been hospitalized over a dozen times and has
been on “every medication known to man.” Make sure to inquire about non-psychiatric
medical conditions as well. is will help you screen for current threats to health as well as
determine which psychiatric treatments would be appropriate given their conditions (for
example, you wouldn’t prescribe lithium to a patient with chronic kidney disease).

IDEATION
ere are two types of ideation that you will often be asked about in psychiatry: suicidal
ideation (sometimes abbreviated SI) and homicidal ideation (HI). Because nearly all
psychiatric conditions increase the risk of suicide, screening for suicidal ideation should be
done for every patient presenting with a mental health concern. In contrast, assessment of
homicidal ideation can be done only in cases where it is relevant. Because suicide and
violence are two of the most tragic outcomes of mental disorders, we’ll spend more time
going over these in greater detail in Chapter 4.

ORIENTATION
A patient’s current level of orientation can be assessed by asking about person (“What is
your name?”), place (“Where are we at this moment?”), time (“Do you know what the date
is?”), and situation (“Why are you here right now?”). If your patient has been answering all
other questions coherently, it can be disruptive (and even a bit insulting) to ask the
orientation questions. However, for anyone who appears confused or has had recent changes
in cognition, assessing orientation can provide valuable insights into their current mental
status. Decreased levels of orientation are most often related to delirium or dementia
(discussed in Chapters 4 and 22, respectively).

NARCOTICS AND SUBSTANCES

Substance use and mental health are intricately linked. Not only can speci c drugs produce
clinical signs and symptoms that mimic a variety of mental disorders, but many mental
disorders can also be triggered or exacerbated by use of substances. At a minimum, ask
patients if they drink alcohol, smoke cigarettes, or use any recreational drugs. In cases where
substance use appears to play a large role, consider taking a full substance history, including
speci c substances used, age of rst use, amount and frequency of use, time of last use,
positive or negative effects of use, and any history of treatment efforts.

FAMILY HISTORY
Nearly all psychiatric syndromes are heritable to a certain degree, and knowing how mental
disorders have affected other people in the patient’s family can inform current diagnosis and

30
treatment decisions. For example, certain forms of dementia are strongly heritable, so
knowing that multiple rst-degree relatives have been affected by early-onset Alzheimer’s
disease increases the probability of this diagnosis signi cantly in someone presenting with
memory loss.

INCOME

At this point, the psychiatric interview starts to diverge from the

standard history taken in most medical settings towards a greater focus on social aspects of
health. First, knowing about income can help to provide important insights into the
patient’s functional status and overall level of support (including whether the patient is
working or if they are supported by family or disability payments). Financial topics can be
sensitive, so avoid asking speci cally how much money the patient makes. Instead, ask how
they support themselves on a day-to-day basis.

SOCIAL SUPPORT
Friends and family play a key role in supporting mental health, so knowing your patient’s
level of support can often directly impact management. For example, you should be much
more hesitant to discharge a suicidal patient who is socially isolated and lives alone
compared to someone who will return home to a large supportive family who has
volunteered to keep a close eye on them over the next few days.

HOUSING

Never assume that your patient has a home to go to. Many of

your patients won’t live in traditional houses but rather in group homes, nursing facilities,
rehabilitation programs, or out on the street. is can be important diagnostically (as
certain disorders, such as addiction or schizophrenia, are more likely to result in chronic
homeless than others). However, it can and should factor into your clinical decision making
as well, such as providing referrals to social resources as appropriate.

31
COLLATERAL
e term “collateral” refers to obtaining information from people other than the patient.
Collateral information can be sought from the people who know the patient best, such as
family members, roommates, friends, or other healthcare providers. Collateral contacts can
be crucial in determining the diagnosis and making a treatment plan, as they can provide an
outside perspective that the patient is not always willing or able to give. For example, when
evaluating someone who was brought to the hospital after threatening suicide, reports from
collateral can help to swing your decision-making one way or another. Whether the
patient’s mother tells you, “Oh, he says this all the time but he has never gone through with
it” versus something like, “ e last time he said that, he went out and tried to jump off of a
building” should carry signi cant implications for your treatment plan. In addition,
collateral can help you to determine how culturally normative certain beliefs or behaviors
are. If someone comes in talking about how demons are controlling their thoughts, talking
with someone from their church can help you determine whether these beliefs are shared by
others in the congregation or if they are unique to the patient (in which case they are more
likely to represent a delusion).

ABUSE

Asking about abuse, neglect, and exposure to violence is

important for all patients but becomes particularly crucial when working with dependents
(people who rely on others for their safety and survival, including children, the elderly, and
the disabled). Inquiring about abuse may give your patients an opportunity to speak with
someone about their experience and take steps to either manage or remove themselves from
a dangerous situation. In most places, healthcare providers are mandated reporters who are
required to report cases of suspected abuse to local agencies. Be familiar with the laws in
your area of practice.

LEGAL
Legal issues are another frequently forgotten part of the interview. However, knowing about
your patient’s past and present intersections with the legal system may reveal important
information. For example, a past arrest for driving under the in uence of alcohol may
suggest a substance use disorder, impulsivity due to mania, or reckless disregard for the
rights of others related to antisocial personality disorder. However, it should never be
assumed that any interaction with the legal system is automatically re ective of psychiatric
pathology, as by de nition legal situations often involve more than one side to the story.

32
LEAVING
Especially in emergency settings, knowing where a patient will go after nishing the
evaluation can helpful in coming up with a treatment strategy. Try to think through their
stated plan and determine if it is reasonable given the circumstances. For example, when
working with a patient who would like to return home but was brought in by ambulance,
ask yourself, “How would they get there? Do they have a family member willing to pick
them up? If not, are they too impaired to take a cab or a bus?”

EXAMINATION
While diagnosis in psychiatry is highly reliant upon subjective symptoms rather than
objective signs, the physical exam remains a core part of evaluation. Certain psychiatric
conditions have physical signs (such as swollen salivary glands from recurrent vomiting in
someone with bulimia nervosa). In addition, you may pick up on speci c side effects related
to psychiatric medications (such as a tremor suggesting lithium toxicity). e exam may also
reveal signs of other medical conditions such as diabetes that need to be taken into
consideration when deciding upon treatment.

REVIEW OF SYSTEMS
Finally, a thorough medical review of systems can help to identify other conditions that
deserve attention. e review of systems can be as comprehensive or brief as the situation
allows. Young, otherwise healthy adults may not need a full review, but you may decide to
be more thorough when working with elderly patients or those with multiple medical
conditions.
 

A psychiatric interview is a structured evaluation

of the patient’s present circumstances and past
history.
 

CHAMPION FISH CALLER:

Chief Complaint
How Can We
Help? Collateral
Family
Allergies Abuse Legal
Income
Medications Past Leaving
Social
Psychiatric History Examination
Support
Ideation Review of
Housing
Orientation Systems
Narcotics and
Substances

33
 

34
THE MENTAL STATUS EXAM
e mental status exam (abbreviated MSE) is psychiatry’s equivalent of the physical exam.
Just as you would use ndings from the physical exam to argue for or against the presence of
a speci c disease (such as a heart murmur suggesting a valve problem), you can use ndings
from the mental status exam to rule speci c diagnoses in or out. Unlike a physical exam,
however, a mental status exam does not need to be performed separately, as conducting a
full psychiatric interview will often allow you to comment on all aspects of the mental status
exam.
When reviewing ndings from the mental status exam, it’s important to keep in mind
that a single nding rarely, if ever, proves de nitive for diagnosing a speci c mental
disorder. For example, speaking very rapidly can be a sign of a manic episode. However,
much often than not, differences in rates of speech are entirely within the realm of
normalcy, as some people simply talk faster than others. In contrast, for someone who not
only speaks rapidly but also wears excessive make-up, cannot complete a single sentence
without changing their train of thought, and plans to save the world by reuniting the
members of the Beatles, it is more likely to be a sign of a speci c mental process. As always,
focus on process over content, and avoid reading too much into any single nding without
rst putting the overall picture together.

e mental status exam is classically broken down into the

following domains: Appearance, Behavior, Speech, Mood, Affect, Thought content,
Thought process, Perception, Cognition, Insight, and Judgment. You can remember these
using the phrase “ABS! MATT Please, Can I Judge?” To remember this, think of a young
girl who is at a body building competition with her friend Matt who is a judge for the
competition. She is obsessed with nice six-packs, so when it comes time to judge the
competitors on their abdominal muscles, she says, “ABS! MATT Please, Can I Judge? ”
Use this phrase (and the admittedly somewhat stupid story that accompanied it) to
remember each component of the mental status exam.
 
APPEARANCE
For better or worse, appearance is the rst thing that most people notice when meeting
someone new, and accordingly it is the rst domain of the mental status exam. Someone’s
appearance can contain important diagnostic clues. Someone’s apparent age can increase
the likelihood of certain diagnoses (such as attention de cit hyperactivity disorder in young

35
children or dementia in elderly adults). Speci c facial features can suggest certain diagnoses
as well (such as a masked facies suggesting Parkinson’s disease or certain physical features
being associated with particular types of intellectual disability). Someone’s level of
grooming can also be telling: for example, if the patient appears disheveled and unkempt,
this may re ect a lack of self-care (which can be found in a variety of psychiatric syndromes,
including schizophrenia and severe depression). Weight can provide diagnostic clues as
well, as someone with an eating disorder who is underweight is likely to have anorexia
nervosa (compared to bulimia, where weight is normal or slightly overweight).
BEHAVIOR

e domain of behavior encompasses many aspects. First, you

can the patient’s level of alertness (ranging from awake and alert to drowsy, stuporous, or
comatose). Next, cooperativeness, rapport, and eye contact all provide information about
the quality of the relationship you have with the patient. One’s overall level of activity can
also provide important clues. Decreased activity can occur in severe states of depression
(known as psychomotor retardation), while increased activity can be a sign of anxiety or mania
(psychomotor agitation). While cooperativeness, rapport, eye contact, and level of activity can
be observed spontaneously, some aspects of behavior need to be speci cally elicited,
including aspects of the motor examination. A variety of abnormalities of movement and
gait can be observed which can either be related to speci c conditions (such as motor tics in
Tourette syndrome or waxy exibility in catatonia) or represent a side effect of the
medications used to treat them (such as extrapyramidal symptoms caused by antipsychotic
drugs).
 
SPEECH
When evaluating speech, taking note of how words are being said can be just as informative
as the words themselves. Is the patient talking much more than normal (hyperverbal), or are
they barely talking at all (hypoverbal)? Are they talking unusually quickly or slowly (rate of
speech)? Does their speech contain the melodic quality that normal speech has (known as
prosody)? Does their speech feel pressured, like they can barely contain the words they have
inside of them, or are they having difficulty getting words out (halting speech)? Are their
words slurred or hard to understand (articulation), or are they completely unable to speak
(aphasia)? Abnormalities in speech can be a sign of a variety of mental conditions (such as
absent prosody suggesting depression or poor articulation suggesting alcohol intoxication).
 
MOOD AND AFFECT

36
 A patient’s mood re ects their internal emotional experience. As
such, mood is assessed primarily by asking, “How are you feeling right now?” You can
report the patient’s response verbatim (such as “good,” “okay,” “frustrated,” “angry,” and so
on). In contrast, affect is the patient’s external emotional expression which can be evaluated
semi-objectively by the interviewer. Affect is most often described by the words euthymic (a
normal, well-balanced mood), dysthymic (a sullen mood), and euphoric (an intensely elated
mood). However, there are other affective states as well (including irritable, angry, playful,
or suspicious). You can also note the range of affect. Someone with a full range of affect will
show a variety of facial expressions throughout the interview, whereas someone with a
restricted range would show only a narrow range of emotion. A labile affect involves rapid
shifts from extremes of emotions (such as going from laughing to crying in a matter of
seconds) and can be seen in certain syndromes such as borderline personality disorder,
whereas a blunted or at affect refers to a lack of emotional expression and can be suggestive
of schizophrenia or advanced dementia. Finally, you can comment on the appropriateness of
one’s affect. For example, someone in a manic state may appear ecstatic even when talking
about the recent death of a family member while someone who is depressed may seem sad
even when talking about a joyous occasional, both of which would be examples of an
inappropriate affect.
 

THOUGHT CONTENT
ought content involves the speci c ideas and beliefs that a patient has in mind. Speci c
areas of thought content which are relevant to psychiatry include suicidal ideation, homicidal
ideation, preoccupations (thoughts that command the entirety of the person’s attention to the
point where they cannot focus on anything else), and delusions (false beliefs that are
inconsistent with the patient’s background and cannot be corrected by reasoning). Given
that no one has the ability to read minds, thought content can only be assessed through
what the patient tells you directly.
 
THOUGHT PROCESS
ought process refers to the nature and quality of the connections between thoughts and,
in contrast to thought content, can be analyzed more objectively. e majority of people
have a linear and logical thought process, meaning that they proceed from one topic to
another in a natural and straightforward way that is easy for a listener to follow. is is not
always the case in psychiatry, however, as some mental disorders involve a degree of thought
disorganization that makes it difficult to follow someone’s train of thought. When asked a
question, a patient may veer off into unrelated topics before eventually answering the

37
question (circumstantiality) or may never answer the original question at all (tangentiality).
e rate and amount of thoughts matters as well: someone in a manic state may have so
many thoughts that they cannot keep track of them ( ight of ideas), whereas someone who is
depressed or psychotic may appear to have a complete lack of spontaneous thinking (poverty
of thought). At other times, thoughts can become so disorganized that the words coming out
of someone’s mouth make absolutely no sense (word salad). We will discuss this and other
ways in which thought process can become derailed more fully in later chapters.
 
PERCEPTION

Perception refers to one’s ability to accurately take in

information about the world. Common impairments in perceptions include illusions
(misperceptions of genuine stimuli, such as seeing a drape moving in a dark room and
assuming it is a person) and hallucinations (false perceptions in the absence of any external
stimuli, such as hearing someone’s voice saying mean things about you even when no one
else is in the room). e speci c form of the hallucination matters, with auditory
hallucinations (hearing voices) being common in psychiatric syndromes like schizophrenia
and visual hallucinations (seeing things) being more often related to non-psychiatric medical
conditions.
COGNITION
Cognition refers to the patient’s general level of intellectual ability. A variety of
standardized questions can be used to assess these domains, including memory (“I’m going
to tell you 5 words then ask you to repeat them to me in 10 minutes”), attention (“Can you
spell the word ‘world’ backwards?”), general knowledge (“Who is the current president?”)
and executive functioning (“Can you draw a clock for me?”). ere are also standardized
cognitive tests, such as the Montreal Cognitive Assessment (MoCA) or Mini–Mental State
Examination (MMSE), that can provide an even greater level of detail on the patient’s
current cognitive level. Impairments in cognition can be either temporary (as in delirium) or
chronic (as in dementia or intellectual disability). In addition, certain disorders will have
certain patterns of impairment (such as attention de cit hyperactivity disorder showing
impaired attention but preserved memory, knowledge, and executive functioning).
 
INSIGHT AND JUDGMENT
Insight and judgment are related domains that involve the patient’s ability to accurately
understand their situation (insight) as well as to know how to act appropriately within it
(judgment). Insight and judgment are closely linked, as it can be difficult to make
appropriate decisions if your understanding of the situation is lacking. For example,
someone who is delirious and does not know who or where they are (poor insight) is
unlikely to have a sufficient understanding of their situation to make informed decisions

38
about their medical treatment (poor judgment). As another example, a drunk person who
decides to drive is doing so as a result of alcohol impairing not only their insight but also
their judgment (“I’m th ne to drife!”). Certain mental disorders can directly impair insight,
most often in thought disorders like schizophrenia where delusions and hallucinations can
lead one to believe things that are not consistent with reality.
It’s important to realize that evaluations of insight and judgment are inherently
subjective. A multitude of factors, including culture, religion, and worldview, in uence
every patient’s experience of illness and may make them disagree with your diagnosis or
with what you believe to be the best course of action. Be very mindful not to use “poor
insight and judgment” as a synonym for “the patient disagrees with me.” Instead, keep in
mind the subjectivity inherent to any patient-provider interaction.
 

A mental status exam consists of a structured

evaluation of multiple domains and is the
psychiatric equivalent of a physical exam.
 

ABS! MATT Please, Can I Judge?:

Mood Affect Perception
Appearance
Thought Cognition
Behavior Speech
Content Insight
!
Thought Process Judgment
 

39
A STATISTICAL FRAMEWORK FOR EVALUATION
e psychiatric interview and mental status exam are both intended to help guide the
interviewer towards or away from particular diagnoses. In this way, every step of the
interview can be seen as a medical test, the result of which either increases or decreases the
likelihood of a particular diagnosis. For example, asking someone, “Over the past 2 weeks,
have you had little interest or pleasure in doing things that you normally enjoy?” will help to
rule in or out a diagnosis of major depressive disorder, with a response of “Yes” suggesting
depression and “No” arguing against it. During a mental status exam, speci c signs can
similarly help to support or argue against a speci c diagnosis. When assessing an adult
patient, for example, a complete lack of any eye contact argues for a diagnosis of autism
while sustained eye contact strongly argues against it.
It can be strange to think of the psychiatric interview and mental status exam as essentially
a series of dozens (if not hundreds) of consecutive medical tests, but viewing them within
that framework opens up a deeper understanding of the process. As with any medical test,
steps within the psychiatric interview and mental status exam are prone to error. e two
types of error are false positives (also known as type I errors) and false negatives (or errors).
A false positive occurs when a test suggests the presence of a diagnosis that is not actually
there, while a false negative occurs when a test suggests the absence of something that is

actually there, as seen in the following example:

False negative Type II error

False positive Type I error

No test is perfect 100% of the time, and there will always be false positives and false
negatives associated with any medical examination. e concept of sensitivity and

40
speci city can help us to better understand exactly what each step of the evaluation process
is telling us. Sensitivity and speci city both describe the ways in which you can trust (or not
trust) what a test is telling you.
e sensitivity of a test tells you how good it is at avoiding false negatives. If a highly
sensitive test is negative, then you can be relatively certain that that diagnosis is ruled out.
Using the same example as earlier, if someone answers “No” to the question of “Over the
past 2 weeks, have you had little interest or pleasure in doing things that you normally
enjoy?” you can be almost certain that this person is not currently suffering from a major
depressive episode, as this question is highly sensitive. For this reason, highly sensitive tests
are often used for screening as they can rapidly and efficiently rule out a diagnosis. Use the
mnemonic Sn-N-out to remember that if a Sensitive test is Negative then the diagnosis is
Out.

Sensitivity is a statistical measure of the true

positive rate and is helpful for ruling out a
diagnosis.
 

Sn-N-out = If a Sensitive test is Negative then the

diagnosis is Out.

Conversely, speci city tells you how good a test is at

avoiding false positives. If a highly speci c test is positive, then you can be relatively certain
that that diagnosis is ruled in. For example, the presence of certain types of delusions (such
as believing that one’s thoughts are somehow being broadcasted to the world or that one’s
movements are under someone else’s control) are highly speci c for schizophrenia and can
reliably be used to differentiate schizophrenia from other syndromes that also involve
psychotic experiences. For this reason, if someone says that they have these beliefs, you can
be relatively certain that they are suffering from schizophrenia. Use the word Sp-P-in to
remember that if a Speci c test is Positive then the diagnosis is In. Tests with perfect

41
speci city (meaning that if they are positive then the diagnosis can be ruled in 100% of the
time) are called pathognomonic signs. For example, someone with an asymmetric pill-
rolling resting tremor is almost certain to have Parkinson’s disease. While pathognomonic
signs are incredibly helpful, they are basically non-existent in psychiatry due to the
complexities of the nervous system and human behavior.
 

Speci city is a statistical measure of the true

negative rate and
is helpful for ruling in a diagnosis.
 

Sp-P-in = If a Speci c test is Positive then the diagnosis

is In.

It is worthwhile to keep in mind that Sp-P-In and Sn-N-Out are rules of thumb, and the
actual reality is not as simple as these mnemonics make them out to be. Very few tests are
both 100% sensitive and 100% speci c, and any improvements in a test’s sensitivity often
lowers its speci city (and vice versa). Because of the limitations of sensitivity and speci city,
it may be more helpful to consider using likelihood ratios which combine sensitivity and
speci city into a single metric. Likelihood ratios tell us, in very practical terms, how much
more certain we can be after doing a test. Likelihood ratios are highly dependent upon the
pre-test probability. In the absence of any information about a particular patient, the pre-
test probability is equivalent to the base rate of a given condition in the general population.
For example, the base rate of Alzheimer’s disease in the general population is less than 1%.
However, in particular circumstances, the pre-test probability can be either higher or lower.
Let’s say that we are evaluating a 75-year-old for Alzheimer’s disease. Using the general
base rate of Alzheimer’s disease (less than 1%) would be ridiculous, as age is a major risk
factor for this form of dementia, with the base rate for a 75-year-old being roughly 10%.
However, if this same patient has also had recent onset of memory loss and confusion while
driving, the pre-test probability of him having Alzheimer’s disease goes up even further (say,
to 50%). To help gain further diagnostic clarity, we order brain imaging. e MRI has a
positive likelihood ratio of 19 for diagnosing Alzheimer’s disease, meaning that if the scan is
positive (if there are signs of brain degeneration) then we can be 19 times more certain that
this patient has Alzheimer’s disease (equivalent to a post-test probability of over 95%). In
contrast, if this same test were positive for a 75-year-old with no memory difficulties, the
post-test probability would only be 70% (still signi cant, but not nearly as de nitive). In
this way, likelihood ratios help to guide the clinician towards or away from particular
diagnoses provided that they are based on an accurate pre-test probability.
 
EFFECT SIZES
While this book will be primarily focused on diagnosis, we will also discuss treatment
strategies for most of the disorders we will talk about. When discussing treatment, a
different set of biostatistics will be used. In this book, we will primarily use effect size to
describe the effectiveness of a treatment. Effect sizes are superior to other statistics about

42
treatment (such as p-values, which measure statistical signi cance) because they answer not
only the question, “Is this treatment effective for this condition?” but also the arguably more
important question, “How effective is it?”

To understand the bene ts of using effect sizes, consider the

question, “Is food effective at treating hunger?” On the surface, it seems that we can answer
that question with a de nitive yes. However, the answer depends largely on the amount and
type of food, as a sandwich is going to be signi cantly more satiating than a stick of celery.
To answer the question, "How effective is each type of food at treating hunger?” we would
need to use effect size. In statistical terms, the effect size of a sandwich is going to be larger
than the effect size of a celery stick even though we would say that both are effective “anti-
hunger treatments.”
To use a more clinically relevant example, consider the question, “Are antidepressants
effective at treating depression?” e majority of studies show that approximately 60% of all
patients get better after starting an antidepressant. is would seem to suggest that
antidepressants are, in fact, effective. However, these same studies also show that around
40% of people taking placebos also get better. is 20% difference cannot be ignored
(meaning that antidepressants are likely effective). However, we can get a much clearer
picture by asking, “How effective are they?” ere are many different ways to calculate effect
size, but one of the most common is known as Cohen's d. e signi cance of this number
is arbitrarily de ned, but generally a score of 0.2 shows a small effect size, 0.5 shows a
medium effect size, and 0.8 and above is a large effect size. So where do antidepressants fall
on this scale? Published studies show that antidepressants have an effect size of between 0.2
to 0.4, which is considered a small effect size. is may seem like a damning indictment of
antidepressants. However, a small effect size does not mean no effect size, and many other
medications commonly used in modern medicine also have a small effect size, including
treatments for osteoporosis, high cholesterol, and stroke prevention. (For what it’s worth,
the use of mnemonics in teaching new material has an effect size of 1.6, which is considered
between “very large” and “huge.”)
 

43
PUTTING IT ALL TOGETHER
Accurate diagnosis is the foundation upon which we are able to provide effective treatments
for people suffering from psychiatric disorders. However, we cannot formulate accurate
diagnoses without a rm foundation in the process of psychiatric evaluation. is chapter
has hopefully given you the tools necessary to do so (the psychiatric interview and the
mental status exam) as well as provided a statistical framework for interpreting speci c
ndings from these exams. is framework will set the stage not only for understanding
information in subsequent chapters but also for evaluating patients in clinical settings.

As a nal note, when approaching the differential

diagnosis for a patient presenting with psychiatric concerns, it can be helpful to have a list
of all major categories of mental disorders prepared. Use the mnemonic DAMP DESPOT
DADS (which stands for Depression, Anxiety, Mania, Psychosis, Dissociation, Eating,
Somatization, Personality, Obsessive, Traumatic, Dementia, Addiction, Developmental,
and Sleep) to keep these handy for rapid recall. You can use this mnemonic to make sure
you are not forgetting any potential explanations for the signs and symptoms you are seeing.
 

Keeping a framework of the major categories of

psychiatric disorders in mind while evaluating a
patient can help to structure your clinical decision
making.
 

DAMP DESPOT DADS:

Dissociation
Eating Dementia
Depression
Somatization Addiction
Anxiety Mania
Personality Developmental
Psychosis
Obsessive Sleep
Traumatic
 

44
REVIEW QUESTIONS
1. A 46 y/o F is brought into the emergency department by her wife who is
concerned because the patient has stopped eating or responding to questions for
the past week. On exam, the patient’s facial expression shows a furrowed brow. She
rocks continuously back and forth in her chair while wringing her hands. When
interviewed, she looks up in response to questions but does not answer them
verbally, instead looking down at the oor. Which of the following aspects of the
mental status exam cannot be evaluated at this time?
A. Appearance
B. Behavior
C. Alertness
D. Mood
E. Affect
2. A nurse practitioner is about to see a new patient in her clinic. She reviews the
patient’s packet of information prior to the visit and sees that the PHQ-9 (a self-
report questionnaire for depression) is positive, with the patient scoring 12 points.
Scores of 10 or greater on the PHQ-9 have a sensitivity of 88%, a speci city of
88%, and a positive likelihood ratio of 7.1 for major depressive disorder. Which of
the following conclusions can the doctor make with certainty?
A. is patient has major depressive disorder
B. is patient does not have major depressive disorder
C. is patient is more likely than not to have major depressive disorder
D. is patient is more likely than not to not have major depressive
disorder
E. None of the above
3. A 26 y/o F who recently gave birth is discussing the risks and bene ts of starting
an antidepressant with her doctor. e doctor knows that this particular
antidepressant has an effect size of 0.3 for post-partum depression. Which of the
following statements can be made to the patient?
A. “ is medication has a 30% chance of working.”
B. “You are likely to feel around 30% better after starting this
medication.”
C. “It is more likely than not that this medication will be effective.”
D. “It is more likely than not that this medication will be ineffective.”
E. None of the above

45
1. e best answer is D. Because mood is a self-reported item that re ects a patient’s
subjective experience of their internal emotions, it cannot be evaluated in a patient
who is non-verbal. One could try to infer this patient’s mood by their behaviors
and facial expressions (such as her hand wringing), but this would be classi ed as
their affect rather than their mood (answer E). e other aspects of the mental
status exam can be evaluated by an observer even for patients who do not respond
to questions.
2. e best answer is E. While sensitivity and speci city are very helpful measures of
a medical test’s performance, they rarely tell us anything with certainty. Only in
cases of 100% sensitivity or speci city can a diagnosis be ruled in or out with
certainty (answers A and B). In addition, while it may be tempting to conclude
that a positive screen on a test with 88% speci city can make us certain that a
diagnosis of major depressive disorder is at least more likely than not, this is not
the case either. Instead, we would need to know the pre-test probability (that is,
what percentage of people coming into the clinic are likely to have major
depressive disorder) and then use that to calculate the chance that this patient has
major depressive disorder based on the positive likelihood ratio. Without knowing
the pre-test probability, we cannot make any of these conclusions with certainty.
3. e best answer is C. In medicine, effect sizes tell us the strength of an association
between two items. In this case, an effect size of 0.3 between antidepressants and
post-partum depression tells us that there is likely to be an effect (as the effect size
is greater than 0), which rules out answer D. Effect sizes do not tell us the chance
of a medication working (answer A) or the precise amount that a medication will
work (answer B). Instead, interpreting effect sizes is largely based on arbitrarily
de ned cut-offs (such as above 0.2 being a small effect size, above 0.5 being a
medium effect size, and above 0.80 being a large effect size).

46
4 PSYCHIATRIC EMERGENCIES

e term “psychiatric emergency” refers to any dangerous or

life-threatening situation that occurs as a consequence of a mental disorder, including
suicide, violence, abuse, delirium, and catatonia. Each of these states must be recognized
and addressed independently of the diagnosis. For example, someone coming to the
emergency room with a plan to commit suicide should be triaged and evaluated
immediately regardless of whether their suicidal thoughts are coming from an underlying
diagnosis of depression, bipolar disorder, schizophrenia, borderline personality disorder, or
any other condition. at’s not to say that nding the underlying diagnosis is not
important! However, in an emergency situation, coming up with the “correct” diagnosis is a
secondary priority to making sure that the patient and others are safe.
Psychiatric emergencies can be difficult to recognize. When most people think of
emergencies, they tend to picture medical conditions like heart attacks, strokes, or car
accidents. In contrast, when most people think of psychiatry, they tend to think of chronic
conditions such as depression or anxiety that are usually seen in less acute settings.
Nevertheless, certain circumstances related to mental disorders absolutely require rapid
evaluation and treatment, as they can result in immediate and signi cant harm if left
unaddressed.
Unlike the conditions we will cover for the rest of the book, psychiatric emergencies
are not disorders in and of themselves (there is no “suicide disorder,” for example). Because
of this, recognizing the presence of a psychiatric emergency is merely the starting point for
a full evaluation in search of an underlying cause.

47
SUICIDE
Suicide is by far the most common psychiatric emergency, with over 50% of all urgent
psychiatric consults being related to suicidal thoughts or attempts. Suicide is a major public

health concern and is the tenth most common cause of death wo

rldwide. While adults between the age of 45 and 65 are at the highest risk, suicide is a
leading cause of death among teenagers and young adults due to the fact that most people
in this group are otherwise healthy. For every death by suicide, there are as many as 25
suicide attempts. Women attempt suicide more often, while men die by suicide more often
due to use of more lethal methods such as rearms. With the exception of dementia and
intellectual disability, all mental disorders increase the lifetime risk of suicide. Because of
this, screening for suicidal ideation should be done on every patient presenting with a
mental health concern.
People with suicidal ideation may recognize the dangerousness of their situation and
bring themselves in for medical attention, or they may be brought in by others. As with any
psychiatric emergency, rst make sure that the patient is safe. ere are several steps to take
when assessing a patient with thoughts of suicide. is involves doing the same things that
you would for any patient presenting with any psychiatric complaint, including conducting
an interview, performing an exam, and ordering labs and imaging if appropriate. However,
for a patient with thoughts of suicide or a high likelihood of future attempts, a few
additional considerations must be taken. You can remember these steps using the mnemonic
DIOS MIO:
D is for Detainment. All states allow involuntary detainment of people who are determined
to be a danger to themselves as a consequence of a mental disorder. You should consider
detaining a patient at high risk for suicide to prevent them from leaving the hospital and
carrying out their plans to harm themselves.
 

I is for Inpatient. For suicidal patients who have a mental disorder that could bene t from
treatment, inpatient hospitalization may be an appropriate option for intensive monitoring
and treatment.
 

O is for Observation. You should consider what level of observation is needed, including
arranging for a one-to-one “sitter” if necessary to ensure safety.

48
  

S is for Sharps. You should be careful that patients thinking of suicide do not have access to
any means by which to harm themselves while in the hospital such as access to glass or
other potentially sharp items.
 

M is for Medical clearance. Patients with suicidal ideation can have medical problems as
well, which should be assessed to determine whether the patient would be best served by
medical or psychiatric hospitalization.
 

I is for Injuries. is involves conducting a careful and thorough physical exam for signs
that a patient has already tried to harm themselves, such as cuts from a knife or injuries
from jumping off a building.
 

O is for Occult overdoses. People coming into the hospital with thoughts of suicide may
have already ingested certain drugs in an attempt to overdose. While the effects of some
drugs are immediately noticeable, for others the signs and symptoms of an overdose are not
apparent for several hours. Because of this, you should consider ordering labs (like an
acetaminophen and acetylsalicylic acid level) for patients with suicidal ideation.
 

When evaluating a patient with suicidal ideation,

consider what steps you need to take to assure their
safety.
 

DIOS MIO: Detainment Inpatient Observation

Sharps Medical clearance Injuries Occult overdoses

While there are many considerations to make, the ultimate question often comes
down to whether someone having thoughts of suicide is safe to go home or whether they
will need inpatient hospitalization (the I in DIOS MIO). is is a complicated question, as
not every patient with suicidal ideation will require hospitalization. In the majority of cases,
the decision is based on whether or not this person will try to commit suicide in the near
future, in which case the 24/7 monitoring and treatment offered by a hospital should be
sought. However, it is necessary to keep in mind that hospitalization does not inherently
prevent suicide. People can and do commit suicide while hospitalized, even with the closest
observation. At best, being in the hospital can delay suicide, but it does not inherently
prevent it. Why then do we consider hospitalizing someone presenting with suicidal
ideation? e key is that hospitalization can be helpful in treating the underlying mental
disorder that is contributing to the risk of suicide. For example, for someone in a severe

49
episode of depression, treatment in the hospital can help to rapidly reduce the feelings of
hopelessness and isolation that make them feel that suicide is the only option.

When assessing someone’s immediate risk for suicide,

consider factors with high likelihood ratios for suicide attempts in the near future,
including access to guns, Recent suicide attempts in the past few weeks, Ongoing thoughts
of suicide, recent Self-harm, and use of Ethanol or other disinhibiting Substances that may
increase impulsivity. You can remember these factors using the mnemonic Guns &
ROSES.
A number of factors raise the likelihood of a suicide
attempt in the near future.
 
Guns & ROSES: Guns
Recent attempts Ongoing thoughts Self-harm Ethanol
Other Substances

However, even considering these factors, accurate prediction of suicide remains out of
our grasp. is is because suicide has an overall low base rate in the general population
(around 0.01%). is means that, even if likelihood ratios predicted that someone was 100
times more likely to attempt suicide, their chance of doing so would still only be around 1%,
leaving a 99% chance of a false positive. erefore, at the end of the day, your clinical
judgment and intuition remain the best tools available for predicting which patients are at
the highest risk and most in need of inpatient hospitalization.
Just as important as knowing which factors increase the foreseeability of suicide is
knowing what has not been found to reduce the risk. One of these factors is the idea of
“contracting for safety,” or the notion that if a patient promises a clinician that they will
not harm themselves then they are at lower risk of suicide. However, there is no evidence
that safety contracts are protective against suicide or accurately identify patients at a lower
risk of suicide, so don’t use them for this purpose. In addition, there is a tendency to see
“passive” suicidal ideation (where someone expresses a wish to end their life but has not
developed a speci c plan to do so) as being lower risk compared to “active” suicidal ideation
(where they have developed a plan). However, this idea is not supported by data. It can still
be helpful clinically to stratify suicidality as “active” or “passive,” but do not let this sway you
too much. If the foreseeability of someone committing suicide is high, you should still
consider admitting them even if they have “only” passive suicidal ideation.
Once safety is assured, the task then becomes determining what is contributing to the
desire to commit suicide. In the United States, the vast majority of people who die by
suicide (up to 98% by some estimates) show evidence of having had a mental disorder.
Mood disorders like depression and bipolar disorder are most frequently found, with

50
around one-third of all fatal suicide attempts involving a mood disorder. However, they are
not the only causes, with addiction, schizophrenia, and personality disorders each
accounting for around 15% of the total.
Consistent with the idea that it’s never just one thing, suicide is rarely the result of any
single cause or stressor. Rather, suicide often stems from a combination of a desire to end
one’s own life as well as the means to do so. A desire to commit suicide is related to a
number of different factors, including life experiences, personality traits, cultural in uences,
and religious beliefs. Two thought patterns are frequently reported by people planning a
suicide attempt: a feeling that one is a burden on others as well as a lack of any sense of
belonging to a group. Once these thought patterns are present, the risk of suicide increases
signi cantly.
While thinking of suicide can represent a psychiatric emergency in and of itself, it is
not until one has acquired the means to lethally self-harm that the possibility of committing
suicide becomes imminent. e means of committing suicide has a large impact on the
dangerousness of the situation, with certain suicide methods being signi cantly more lethal
than others (for example, rearms are associated with a mortality rate of over 90%, while
the mortality rate from overdosing on medications is less than 5%). In most cases, suicides
are planned and involve preparatory thoughts and actions for several weeks or months
leading up to the attempt (such as acquiring a rearm or storing up medications for an
overdose). However, up to a quarter of all suicides appear to be impulsive in response to a
speci c situation or circumstance.
While there are moral and philosophical issues surrounding suicide (such as whether
someone has the right to take their own life and whether it is ethical to involuntarily
commit someone), the fact remains that only around 20% of people who survive a suicide
attempt report feeling that they wish the attempt had succeeded. is suggest that taking
steps to prevent suicide, including hospitalization, may be warranted to help someone get
through a particularly difficult time of their lives and survive until the underlying mental
disorder or environmental stressor is addressed.
 
NON-SUICIDAL SELF-HARM

Some people actively hurt or harm themselves without any

intention of dying. Most often, this involves making non-lethal cuts on their body
(although other methods such as burning are used as well). is behavior is not uncommon,
with around 10% of adults having self-harmed at some point in their life. ere is some
overlap between non-suicidal self-injurious behavior and suicide, as people who self-harm
often have thoughts of suicide. However, as a general rule, most people who self-harm are
not necessarily suicidal. In fact, only 5% of patients who self-harm commit suicide within

51
10 years of the self-harm incident. For this reason, self-harm differs enough from suicide
that it warrants separate discussion.
e question that most people have when learning about self-harm is: why? For the
majority of people, the idea of self-harm (and the pain that this would naturally involve)
makes little sense. Yet people who engage in self-harm report that, paradoxically, self-harm
helps them to feel better. It is believed that many people who self-harm have a profoundly
unbalanced emotional state that turns an act which causes most people pain into one that
actually brings relief from an inner sense of emotional turmoil. ( ere are other reasons why
people self-harm as well, which we will talk about in subsequent chapters.) While self-harm
is associated with a number of mental disorders, it is most associated with borderline
personality disorder, with over 90% of people with this condition having engaged in self-
harm. In addition, a diagnosis of borderline personality disorder increases the risk of self-
harm by over 5 times, and dialectical behavior therapy (a treatment for this disorder) is one
of the few interventions that appears to reliably reduce this behavior. While self-harm is not
a perfectly sensitive or speci c marker of this disorder, it is correlated enough that the
presence of self-harm should at least put borderline personality disorder on your differential.

52
VIOLENCE

Violence or threats against others can be a psychiatric emergency.

However, in contrast to suicide (which is related to a mental disorder in the vast majority of
cases), violence should not automatically be assumed to be psychiatric in origin. In fact, the
idea that people with mental disorders are more likely to be violent is a myth, as individuals
with a mental disorder are much more often the victims of violence rather than its
perpetrators. Nevertheless, in some cases, certain mental disorders can increase the risk of
violence, and mental health providers must be ready to evaluate violence and respond to the
situation. When discussing violence, it can be helpful to make a distinction between
agitation and aggression. Both agitation and aggression can result in violence, but the
underlying causes are distinct and require a different treatment approach.
 
AGGRESSION
When most people think of violence, they tend to think of aggression, which is more
common in non-medical settings. Aggression is often organized and involves a speci c
target. It can be premeditated (such as someone who has been planning to attack someone
else for weeks) or impulsive (such as someone suddenly striking another person during an
argument). While aggressive acts can sometimes have their roots in a mental disorder, it is
more often the result of con ict between ordinary people. is is not to say that it never
occurs as a consequence of a mental disorder. For example, someone with schizophrenia
may develop a delusional belief that the Catholic church is trying to kill them and may
spend months planning an attack on a neighbor who wears a cruci x around their neck. In
addition, several categories of mental disorders are de ned by the presence of aggressive acts
(including externalizing disorders which will be discussed in more detail in Chapter 20).
However, aggression originating from a psychiatric condition in this way is the exception
rather than the rule, and most cases of aggression do not involve mental disorders.

53
 Because aggression is not always psychiatric in origin, you need to
make a distinction between threats requiring legal intervention (such as calling the police)
and those stemming from a mental disorder (in which case psychiatric treatment and
hospitalization would be more appropriate). Use the psychiatric interview to screen for signs
of a mental illness that could be underlying threats of violence. Using the earlier example of
someone with schizophrenia who has a delusional belief revolving around the Catholic
church, this sort of delusional belief is likely psychiatric in origin, making inpatient
hospitalization a good option in this case. In contrast, someone who was brought in after
stabbing their partner during a ght is more likely to require legal, rather than psychiatric,
attention. In addition, unless there is a primary psychiatric disorder driving the risk of
violence, use of medications like antipsychotics or mood stabilizers do little to alter the risk
of violence.

Psychiatrists and other health care providers have a

duty to protect potential victims of violence in most states. is means that, if a patient
expresses a desire to in ict violence upon an identi able target, you have a legal duty to
make a reasonable attempt at protecting the identi ed victim. is often involves notifying
the victim and/or law enforcement. e duty to protect was based upon cases when a
potential victim was not warned of the threat on their life and ended up being killed. ( e
details vary by state, so be familiar with the laws governing your local area of practice.)
AGITATION
In contrast to the purposeful and organized violence seen in aggression, agitation is a state
of psychological and physiologic tension, excitement, or restlessness that can result in
purposeless and disorganized acts of violence. Unlike aggression, agitation is associated
with medical or psychiatric conditions more often than not. In particular, any psychiatric
conditions that present with confusion or fear (including psychosis, mania, anxiety,

54
delirium, dementia, and substance intoxication) should be on the differential for someone in
a state of agitation.
When working with an agitated patient, the primary goal is rapid de-escalation.
Verbal de-escalation should always be attempted rst provided it is safe to do so and
involves establishing rapport with the patient and setting rm limits on behavior (“You will
not harm or attack yourself or anyone else”). In addition, because agitation results from a
sense of confusion, using simple and concrete statements can help to provide a sense of
orientation (“My name is Dr. Gómez. I’m a doctor here in the hospital. It is 11:00 on
Saturday night. Your family brought you here because they are concerned about you.”)
which can be quite calming. If verbal de-escalation is not working, medications (including
benzodiazepines and/or antipsychotics) can be offered. ese medications can help to
rapidly reduce the inner tension driving the state of agitation.
When both verbal and pharmacologic de-escalation have failed to make the situation
safe, physical restraints (such as arm or leg straps) may be needed. Restraints are not
treatment, but they may be needed to prevent further harm from being in icted by the
patient (either to themselves or those around them). Restraints are associated with both
physical and mental harm, including a high risk of physical injury, organ damage,
psychological trauma, and even death from strangulation. Because of this, restraints should
be avoided whenever possible. However, for highly agitated patients, it is not always
possible to avoid use of restraints. erefore, try to nd a balance by minimizing the use of
restraints whenever possible while still allowing for their use in extreme circumstances when
someone’s safety is at risk.
 
VIOLENCE RISK ASSESSMENT
Psychiatrists are often asked to assess the risk of violence in a given situation, as many states
allow for people who are a danger to others to be detained against their will provided that
this danger stems directly from a mental disorder that could potentially be treated during
psychiatric hospitalization. As with suicide, there is no way to accurately predict who will go
on commit a violent act. erefore, foreseeability (rather than predictability) remains the
standard to which you will be held. To aid you in determining the foreseeability of a violent
act, you can use the mnemonic PV’d MALES, which stands for Previous Violence, Male,
Adult (as opposed to children or the elderly), Low intelligence, Estranged from others, and
Substance use. Of these, previous violence is by far the most important risk factor, as it is
associated with the highest likelihood ratio.
 

A number of factors signi cantly raise the likelihood

of violence in the near future.
 

PV’d MALES: Previous Violence Male Adult Low

intelligence Estranged Substance use

55
 While substance use is listed as a risk factor for violence, this
does not necessarily apply to all drugs. e speci c substances that have been associated
with an increased risk of violence include Phencyclidine (PCP), Inhalants, Steroids,
Stimulants such as methamphetamine or cocaine, and Ethanol. You can remember these
speci c substances using the mnemonic PISS-E.
 

Several substances increase the likelihood of

violence during intoxication.
 

PISS-E: Phencyclidine (PCP) Inhalants Steroids

Stimulants Ethanol

Once the risk of violence has been determined, attention can then turn to diagnosing
and treating the underlying mental disorder (if any) that is driving this risk. Whether it
involves agitation or aggression, in cases where there is a treatable psychiatric condition
(such as the example of someone with psychosis-related delusions described earlier),
inpatient hospitalization may be needed for close monitoring and immediate treatment. In
some cases, violent acts may have already been committed, in which case the patient may
instead be seen in legal (rather than medical) settings. ese intersections between mental
health and the legal system form the basis for the eld of forensic psychiatry.

56
ABUSE AND NEGLECT

Abuse is a form of violence that involves physical, sexual, verbal,

emotional, or other forms of cruelty in icted upon others. Unlike agitation or aggression
(states that are diagnosed in perpetrators of violence), abuse is more often diagnosed in
victims of violence, making it necessary to have a separate discussion of how to evaluate
these patients. While all forms of abuse can constitute an emergency, recognizing the
presence of abuse is particularly urgent when it involves vulnerable groups who are not able
to defend themselves such as infants or children (although other dependents, such as the
elderly or disabled, can often be victims of abuse as well). Child abuse is unfortunately
common, with around 25% of people reporting a history of verbal abuse, 15% reporting
physical abuse, and 10% reporting sexual abuse during childhood. Child abuse is associated
with both immediate harms to the child (including a risk of permanent injury or death) as
well as increasing the risk of a multitude of mental and physical disorders later in life. For
this reason, quick and accurate recognition of the signs of child abuse is crucial.
Diagnosing abuse is based on unusual details from the patient’s history as well as
certain objectively observable signs. Use the phrase Fuzzy DETAIL to remember aspects
of a reported history that are suggestive of abuse:
Fuzzy is for Fuzzy or vague. Parents or other caregivers who are abusing their child may try
to provide an alternative explanation for any observed injuries in an attempt to de ect
attention. ese fabricated histories are often vague so as to provider fewer opportunities for
doctors and other healthcare providers to nd inconsistencies.
 

D is for Denied. In some cases, parents or other caregivers will outright deny injuries that
are objectively observable. is is highly suggestive of abuse.
 

E is for Evolving. Be wary of stories that are constantly evolving and changing, especially if
these changes seem to conveniently t any new details that emerge.
 

T and A are for Tardy or Absent. For serious injuries, parents and other caregivers have a
responsibility to bring their child to medical attention as soon as possible. Any delay in
seeking treatment (or a complete failure to bring their child to medical attention) should be
looked into.
 

57
I is for Inconsistent. Any form of inconsistency should be a red ag for abuse (for example,
if the caregiver’s explanation of the injuries is inconsistent with the observed physical exam
or if different caregivers provide differing explanations).
 

L is for Lacking. Sometimes, caregivers will try to provide no explanation or give an

explanation that is clearly insufficient (such as saying that widespread bruises are the result
of the child bumping their knee during sports).
Explanations for injuries that are inconsistent or
lacking should raise a red ag for child abuse.
 

Fuzzy DETAIL: Fuzzy or vague Denied Evolving

Tardy Absent Inconsistent Lacking

In addition to the presence of fuzzy details while taking a history, speci c objective ndings
on physical examination can also suggest intentional injury. Use the mnemonic TEN-4
Over & OUT to remember these features:
TEN is for Torso, Ears, or Neck. e vast majority of “normal” injuries during childhood
(those that are unrelated to abuse) occur on the knees, shins, forehead, and other parts of
the body that sit over bony prominences. In contrast, bruises on other areas of the body
should warrant investigation, with the torso, ears, and neck being among the most common
sites of intentional injury to children.
 

4 is for Four months. Infants below the age of four months are largely sedentary, as they
cannot yet move around. Because of this, any injuries in infants younger than 4 months or
who cannot yet move around are highly suggestive of abuse (“those who cannot cruise
cannot bruise”).
 

Over is for Over the body. A pattern of injuries occurring in multiple areas of the body or
involving multiple organ systems is incredibly unusual and suggests abuse.
 

O is for Obvious patterns. Sometimes, abuse-related injuries will follow an obvious

pattern, such as an elliptical pattern signaling a bite wound or multiple punctate scars being
related to cigarette burns (seen below).
 

58
 Multiple punctate scars suggestive of intentional injury.
U is for Unexposed. Any cuts, bruises, or other injuries to areas that are not commonly
exposed (such as the genitals or anus) are essentially pathognomonic for sexual abuse. e
presence of sexually transmitted infections in children is also suggestive of sexual abuse,
although this is not necessarily pathognomonic depending on the speci c infections
involved (for example, gonorrhea and syphilis are almost always associated with abuse while
human papillomavirus and chlamydia can be passed from mother to child during childbirth
and may have long incubation periods before overt symptoms appear).
 

T is for Timing. Injuries that appear to be in different stages of healing suggest that they
were incurred at various times, raising the possibility of abuse.
 

Speci c patterns seen on physical exam, including

injuries to unusual or unexposed parts of the body,
are strongly suggestive of abuse.
 

TEN-4 Over & OUT: Torso, Ears, and Neck Less than
4 months or pre-mobile Over the body Obvious patterns
Unexposed body parts Timing

Not all abuse is physical. Psychological abuse can include shaming, ridiculing,
terrorizing, threatening, isolating, or exploiting a child (or someone that the child loves) for
various reasons and can be equally damaging. Psychological abuse can be incredibly difficult
to diagnose, as it does not always leave objective evidence in the same way that physical and
sexual abuse can (although abnormal weight loss or failure to meet milestones can
sometimes occur).

59
 While abuse speci cally refers to acts of commission (meaning
that a violent act was done), neglect involves the omission of speci c acts that are necessary
to provide for a child’s basic needs, resulting in actual or potential harm. While neglect is
often more subtle than abuse, it can be equally damaging both physically and mentally.
Indeed, neglect is actually more common than abuse yet remains underrecognized and
underreported. Neglect can take various forms, including physical neglect (failure to
provide basic food, clothing, hygiene, and shelter), medical neglect (failure to provide access
to health care), educational neglect (failure to provide access to school or other educational
opportunities), social neglect (failure to provide social opportunities), and emotional
neglect (lack of affection, nurturing, and positive interactions). Neglect is not always
intentional, as some families are unable to meet the needs of their dependents due to
poverty or other factors. However, that does not necessarily mean that the damaging effects
of neglect are any less, and a variety of disorders related to antisocial behavior appear to
have direct links to a history of childhood neglect. For this reason, rapid recognition of
neglect is essential, even though the lack of objective signs in many cases can make this
challenging.
While none of these features on their own are diagnostic of abuse or neglect with any
degree of certainty, the more that are present the more troubling the picture becomes. In
some cases, hospitalization of the child may be necessary to treat injuries and/or to protect
them from further harm. In cases of sexual assault, additional measures (such as preventing
pregnancy, providing prophylaxis against sexually transmitted infections, and collecting
forensic evidence) must be taken as well. If abuse is suspected, examining siblings or other
dependents in the home may reveal additional injuries. As a reminder from the previous
chapter, healthcare providers across the United States are mandated reporters of child
abuse, meaning that all cases of suspected child abuse must be reported to appropriate
government agencies.

60
DELIRIUM
Delirium is an acute state of confusion that is caused by a medical illness. People in a state
of delirium display pronounced de cits in their mental abilities such as attention, memory,
and concentration. While the diseases which cause delirium are not necessarily psychiatric
in origin, psychiatrists are often consulted on delirium given their specialty in evaluating
mental status.
Delirium is common in hospitalized patients, with anywhere from 10 to 30% of all
hospitalized patients experiencing some form of delirium. It is even more common in those
parts of the hospital with the sickest patients, such as the intensive care unit where rates of
delirium approach 50 to 75%. Delirium has been found to be an independent predictor of
multiple negative outcomes, including worse recovery from illness and a higher rate of
death. Because of this, assessing and treating delirium promptly is crucial.
e psychiatric interview and the mental status exam are the primary tools used to
recognize the presence of delirium. In particular, asking questions to determine the patient’s
current level of orientation (including person, place, time, and situation) can provide a
rapid assessment of their mental state. As someone becomes more delirious, their ability to
answer orientation questions will be lost in reverse order: rst they won’t be able to say why
they are in the hospital, then they won’t be able to say what the month or year, then they
won’t know where they are, and nally their knowledge of their own name will vanish. In
addition, delirium can have varying effects on behavior. Some people react to their state of
confusion by becoming hyperactive or agitated, while others become hypoactive and shut
down behaviorally. Delirium can also cause major disruptions in one’s perception, with
hallucinations being common. ese hallucinations are much more likely to be visual (as
opposed to auditory hallucinations, which are more likely to be psychiatric as we will
discover in Chapter 7).

Visual hallucinations are more likely medical than

psychiatric in origin.
 

Visual hallucinations come from diseases of the viscera.

All of these symptoms tend to uctuate, with symptoms waxing and waning over a matter
of hours or days. For example, someone may be fully oriented and lucid at lunch, then be
actively hallucinating and unable to remember their own name by dinnertime.

61
 Like all psychiatric emergencies, delirium is not
a disease in and of itself but rather is a syndrome that is caused by a disease. erefore, the
presence of delirium should initiate an immediate work-up to determine the primary cause.
e possible causes of delirium are vast, but the major categories can be summed up in the
mnemonic DIM TOP (as in someone’s whose head is not too bright at the moment). is
stands for Drugs (including both prescription medications and recreational substances),
Infections, Metabolic derangements (such as hyperglycemia or hyponatremia), Trauma
(especially involving the head or spine), Oxygen de cits (such as severe blood loss), and
Psychiatric conditions (when no other medical cause can be found).
 

Common causes of delirium include substances,

infections, metabolic abnormalities, trauma, and
blood loss.
 

DIM TOP: Drugs Infections Metabolic derangements

Trauma (physical) Oxygen de cits Psychiatric conditions

Once a cause is found, immediate treatment should be rendered (such as using

antibiotics to treat an underlying infection). However, it is also possible to treat the state of
delirium itself. Treatment involves use of antipsychotics to prevent or reduce the duration of
delirium, which has a small effect size of around 0.4. In addition, non-pharmacologic
strategies can be used, including placing pictures of family and friends in the room, turning
off the lights at night, and asking every visitor to introduce themselves by name. In the
majority of cases, delirium is transient and reversible, though in cases of prolonged injury,
neuronal injury can result in persistent cognitive de cits.

CAPACITY
In cases of delirium or other causes of altered mental status, you may be asked to perform a
capacity evaluation (also known as a competency evaluation). Capacity is the question of
whether a patient has the cognitive ability to make medical decisions for themselves. Most
patients at a baseline mental state should be able to thoughtfully consider whether they

62
want speci c medical or surgical interventions. However, someone who is delirious or
confused may not be able to make this decision. Psychiatrists are often asked to evaluate
capacity in difficult cases. However, all medical providers should be able to perform a
capacity evaluation, and this process should be part of the consent process for any medical
treatment (especially for invasive or non-reversible interventions such as surgery). You can
use the mnemonic CURBSIDe to remember the elements of a capacity evaluation. If a
patient meets all of these criteria, they are deemed to have capacity; if they are missing even
one of these elements, they do not have capacity for that decision.
 

C is for Communicate. Is the patient able to communicate meaningfully with others? If

this basic criterion is not met, then assessment of capacity is impossible to perform. For
example, if someone is comatose or unresponsive to questions, then by de nition they do
not have capacity.
 

URB is for Understanding Risks and Bene ts. Is the patient able to understand both the
risks and bene ts of the decision they are making? For example, a patient with gas gangrene
(a severe infection that is uniformly fatal without treatment) may be told that limb
amputation is necessary. is procedure obviously carries risks, including lifelong deformity
and disability, yet given the 100% mortality rate without treatment, the bene ts outweigh
the risks in nearly all cases. A patient with capacity must be able to understand and compare
these risks and bene ts when making a decision.
 

S is for Situation. Is the patient able to fully appreciate the situation that they are in, or
does it seem like they are minimizing or exaggerating the gravity of their condition?
Continuing the same example, the patient with gas gangrene must be able to comprehend
that their life is at risk if they decline treatment.
 

I is for Impact. Does the patient appreciate the likely impact that their decision will have
on their situation? For example, if the patient with gas gangrene wants to decline treatment
and leave the hospital, they need to be able to state that they will likely continue to become
sick and potentially die.
 

De is for Decision. Is the patient able to clearly express a preference for a particular choice
given their situation? e patient must be able to synthesize their understanding of their
situation, the risks and bene ts of the proposed intervention, and the impact of their choice
into a coherent decision.

63
 A capacity evaluation involves a structured
evaluation of a patient’s ability to make medical
decisions in a reasonable way.
 

CURBSIDe: Communicate Understand Risks and

Bene ts Situation Impact Decision

Capacity provides a clear legal standard for allowing patients to have autonomy over
treatment decisions without putting severely ill patients at risk of not receiving appropriate
treatment. It’s important to be clear that making bad decisions is not the same as lacking
capacity! For example, if the patient with gas gangrene is able to communicate an
understanding of the risks and bene ts of amputation, the situation they are in, the impact
of their decision, and an ultimate decision to discontinue care, they are protected in doing
so even if the majority of doctors would think that they are “crazy” for making this decision.
It’s also important to note that capacity applies to a speci c decision, not to a speci c patient.
Someone may have the capacity to make one decision (such as disagreeing with the speci c
antibiotic being proposed) while lacking the capacity to make another (such as wanting to
leave the hospital) at the same time. For this reason, capacity should be evaluated on an
ongoing basis with each new major decision rather than being applied as a blanket “label” to
the patient.
In situations where a patient has capacity, their decision on the matter should be
respected, even if it is in disagreement with what the treatment team would like to do. In
cases where a patient lacks capacity, a surrogate decision maker should be sought (often a
spouse, family member, or close friend). e surrogate decision maker should be encouraged
to make decisions as the patient would have to the best of their knowledge, rather than
basing the decision on the surrogate’s own values and beliefs. In cases where the patient
lacks capacity but a surrogate decision maker cannot be found, the treating team may elect
to make decisions on the patient’s behalf. In emergency situations, this may mean
immediate treatment.
 

64
65
CATATONIA

Catatonia is an abnormal mental and behavioral state

characterized by stupor, or a low level of consciousness where the patient acts in a way that
appears purposeless or senseless to an outside observer (up to and including being entirely
non-responsive). An easy way of remembering catatonia is to think that it turns man into
mannequin. People in a state of catatonia are often silent, robbed of their ability to
communicate. ey may be completely silent (mutism) or, like certain dolls, may re exively
repeat what someone else just said (echolalia). Physically, they may exhibit severe muscular
rigidity (catalepsy) that causes them to stand in the same position for hours on end, even
holding the position against gravity (pictured on the opposite page). ey may even allow
someone else to move them into different positions and then hold those positions for hours
(waxy exibility). ey may only respond by copying others’ movements (echopraxia). is
motionlessness may persist even in situations where most people would involuntarily react,
such as when a ball is thrown at them (negativism). In this and other ways, catatonia turns
man into mannequin.
 

Catatonia is de ned by a state of purposeless stupor.

 

Catatonia turns man into mannequin.

Like the other psychiatric emergencies we have discussed so far, catatonia is not a
disorder in and of itself but rather can be thought of as a manifestation of a variety of
mental disorders. In the modern day, catatonia most often occurs with mood disorders,
with over half of all cases being related to bipolar disorder and an additional third being
related to depression. However, it can be seen in schizophrenia as well, with 10 to 15% of
cases being associated with psychotic conditions.
Catatonia must be recognized and treated promptly, as the condition tends to worsen
without treatment. e mainstay of treatment is benzodiazepines such as lorazepam, which

66
often produce dramatic improvements in mental state within minutes of administration.
Benzodiazepines are effective in up to 80% of cases. In cases of severe or treatment-
refractory catatonia, electroconvulsive therapy (ECT) should be considered, which produces
roughly equivalent treatment response rates.
A particularly severe form of catatonia known as malignant catatonia involves not
only the core features of catatonia (stupor and rigidity) but also signi cant autonomic
nervous system instability, including fever. e presence of fever in catatonia must be
recognized promptly, as malignant catatonia is a potentially deadly illness with over half of
patients dying without treatment. e presence of malignant catatonia generally warrants
immediate use of ECT.
 

67
  
Patients displaying various signs associated with catatonia such as catalepsy.

68
PUTTING IT ALL TOGETHER
Psychiatric emergencies are not disorders in and of themselves but represent some of the
most tragic outcomes of mental illness. Suicide, violence, abuse, delirium, and catatonia do
not represent a comprehensive list of psychiatric problems you may encounter in emergency
settings but instead are conditions that warrant separate consideration over and above their
associated disorders. For example, your approach to the evaluation and treatment of a
patient with depression will necessarily change if they are also reporting suicidal ideation or
if they appear to have signs of catatonia. Because of the need for rapid recognition of these
conditions, it is worthwhile to review what we have learned.
When evaluating a patient with suicidal ideation, rst make sure to ensure the
patient’s safety using the DIOS MIO mnemonic. When it comes time to decide whether
this patient needs inpatient hospitalization, acknowledge that it is impossible to predict
immediate risk of suicide and instead focus on whether a suicide attempt is foreseeable by
considering the factors in the Guns & ROSES mnemonic. Finally, remember that
hospitalization does not inherently prevent suicide but rather provides an opportunity to
treat any underlying mental disorders that may be increasing the patient’s risk of suicide.
For violence, it is crucial to make a distinction between aggression (purposeful actions
which can either be impulsive or premeditated in nature) and agitation (a state of
purposeless or disorganized restlessness and irritability), as only the latter is reliably related
to the presence of a medical or psychiatric condition. Management of violence or threats
may involve inpatient hospitalization when there is evidence of a psychiatric condition,
especially in cases where the PV’d MALES and PISS-E mnemonics predict a higher risk of
violence. When a speci c target has been identi ed, healthcare providers often have a duty
to warn and/or protect the target.
Cases of physical and sexual abuse can be recognized using the Fuzzy DETAIL and TEN-
4 Over & OUT mnemonics. On the other hand, neglect and psychological abuse don’t
often leave objective signs in the same way and can be much more difficult to recognize.
Management of abuse and neglect involves taking immediate steps to make sure that the
victims are safe, treating injuries or de ciencies that may be present, and involving law
enforcement as necessary.
Delirium is a state of confusion that can be recognized by changes in cognition that follow a
waxing and waning course. Prompt investigation for potential causes as captured in the
DIM TOP mnemonic is essential, as de nitive treatment involves addressing the
underlying condition. However, adjunctive treatment can include antipsychotics and taking
steps to re-orient the patient. Patients with altered mental status may need to undergo a
capacity evaluation to determine their ability to make medical decisions; this can be done
using the CURBSIDe mnemonic.
Finally, catatonia is a state of stupor that turns man into mannequin by causing speci c
abnormalities in thought, speech, and behavior. Speci c ndings on the mental status exam
(including mutism, echolalia, catalepsy, negativism, echopraxia, and waxy exibility) can
clue you into the presence of catatonia. Benzodiazepines should be used for immediate
treatment, with additional steps taken to address the underlying condition (most often
bipolar disorder, depression, and schizophrenia).

69
REVIEW QUESTIONS
1. A 51 y/o M calls a suicide hotline saying that he is having thoughts of shooting
himself with a handgun. He says that he is out of his medications and has not seen
his psychiatrist in over 10 months. What is the most appropriate next question for
the counselor to ask?
A. “What medications do you take?”
B. “Who is your psychiatrist?”
C. “Where are you right now?”
D. “Have you ever had a manic episode?”
E. “Do you have a history of non-suicidal self-harm like cutting?”
2. A 22 y/o M is brought into the Emergency Department by police who found him
running in a busy city square waving a gun around and yelling nonsensically. e
gun has been con scated. In the hospital, he is uncooperative with a psychiatric
interview and instead yells and swings his sts wildly, nearly hitting a nearby staff
member. What is the best next step?
A. Determine any potential targets of violence and contact them
B. Speak to the patient loudly and rmly
C. Determine whether the gun was loaded or not
D. Obtain a urine sample for a toxicology test
E. Administer medications
3. (Continued from previous question.) Serum and urine samples are collected.
Toxicology testing shows the presence of a single substance. Which of these
substances is least likely to have been identi ed?
A. Alcohol
B. Steroids
C. Heroin
D. Phencyclidine
E. Methamphetamine
4. An 81 y/o F is admitted to the hospital for intravenous antibiotic treatment of a
urinary tract infection. During the second night of hospitalization, she awakens at
2:30 in the morning and attempts to climb out of bed, pulling an IV out of her
arm in the process. She continues to repeat, “I’m going home, I’m going home, I’m
going home.” On interview, she knows her name but not where she is or why she
is in the hospital. What is the best next step?
A. Restrain the patient
B. Initiate an immediate work-up for causes of delirium
C. Administer antipsychotic medications
D. Arrange for a sitter
E. Increase the dose of antibiotics
 

5. (Continued from previous question.) After several minutes, the patient calms and
agrees to return to her hospital bed. However, when the nurse attempts to replace
the IV, the patient begins yelling, “I don’t want it! I don’t want it!” What is the best
next step?
A. Perform a capacity evaluation

70
 B. Attempt to nd a surrogate decision maker
C. Consult psychiatry
D. Consult ethics
E. Restrain the patient and place the IV
6. A 19 y/o M is brought to the hospital by his mother who says that the patient has
been acting “like a zombie” for the past three days. He has a history of a single
manic episode one year ago which was successfully treated. Due to the patient’s
stability, his medications were discontinued one month ago. Initial vital signs are
HR 126, BP 142/90, RR 10, and T 101.1°F. e patient is unable to participate in
an interview and does not respond to any questions asked, instead staring
motionlessly at the ground throughout the entire interview. Neurologic exam is
notable for muscular rigidity. e doctor accidentally drops her pen on the ground
which makes a sharp noise, but the patient does not inch or even move at all in
response to this. An attempt to conduct a neurologic exam shows that the patient
will leave his arms in any position that they are put in, even against gravity. Which
of the following aspects of the patient’s presentation predicts the worst prognosis?
A. Mutism
B. Negativism
C. Waxy exibility
D. Catalepsy
E. Hyperthermia
7. (Continued from previous question.) Which of the following is the best next step?
A. Admitting to the hospital for observation
B. Administering lorazepam
C. Arranging for electroconvulsive therapy
D. Restarting previous medications for bipolar disorder
E. Starting an antipsychotic

71
1. e best answer is C. e most important rst step in responding to a psychiatric
emergency like suicidal ideation is to immediately assess for the patient’s safety.
Asking the patient’s location will permit the hotline counselor to intervene by
calling emergency medical services. Other questions may be helpful in eshing out
the patient’s history or determining a diagnosis but ultimately are less important
than securing the patient’s safety.
2. e best answer is B. is patient is exhibiting signs of severe agitation. In these
cases, the best approach is to attempt rapid behavioral de-escalation. Verbal de-
escalation should be attempted rst, with other measures such as restraints and/or
medications (answer E) being performed only after verbal de-escalation has failed.
Other steps to obtain additional history (answers C and D) or ful lling one’s duty
to protect (answer B) are important but take secondary priority after managing the
acute behavioral emergency.
3. e best answer is C. All of the substances listed are associated with an increased
risk of violence except for opioids, which tend to cause sedation rather than
agitation.
4. e best answer is D. is patient is suffering from delirium, a psychiatric
emergency that requires prompt assessment and intervention. In the majority of
cases, the presence of delirium should initiate an immediate work-up for causes;
however, in this case the presence of a urinary tract infection provides a reasonable
explanation for delirium, and a further work-up may not be necessary and is, at the
very least, not an immediate priority (answer B). Antipsychotic medications are
helpful at reducing the duration of delirium, so using them in this patient is not
unreasonable (answer C); however, arranging for a sitter who can provide verbal
reassurance is more likely to result in immediate behavioral de-escalation.
Restraining the patient (answer A) may be necessary in cases of severe delirium
where verbal de-escalation and administration of antipsychotics have not been
effective, but they should be used as rarely as possible owing to the signi cant
medical and psychological risks associated with restraint. Finally, changing the
dose of antibiotics should only be done as clinically necessary for treatment of her
infection and is irrelevant to the discussion of treatment of delirium (answer E).

72
5. e best answer is B. As mentioned in the previous question, this patient lacks an
understanding of where she is or why she is in the hospital. Because of this, it is
already clear that she lacks capacity to make this decision as she is unable to
appreciate her situation (answer A). In cases where the patient lacks capacity, a
surrogate decision maker should be sought. Consulting psychiatry (answer C) may
help to provide clarity on cases where the presence or absence of capacity is not
clear cut, but would not provide much helpful information in cases like these
where the lack of capacity is immediately evident. Ethics consultation (answer D)
may be required in the future if a surrogate decision maker is unable to be found,
but this must be con rmed rst. Finally, administering non-voluntary treatment
should not be done unless if the situation is immediately life-threatening. In this
case, an infection is unlikely to be immediately life-threatening, giving the
provider time to search for a surrogate decision maker.
6. e best answer is E. is patient is exhibiting clear signs of catatonia, including
mutism (not speaking), negativism (not reacting to loud sounds), waxy exibility
(maintaining his arms in any position they are placed in), and catalepsy (muscular
rigidity) (answers A, B, C, and D, respectively). However, only hyperthermia (the
presence of a fever) is suggestive of malignant catatonia, a life-threatening form of
catatonia with a high mortality rate.
7. e best answer is C. While administering a benzodiazepine such as lorazepam
(answer B) is indicated as a rst-line treatment for most cases of catatonia, for
cases of malignant catatonia electroconvulsive therapy is the rst-line treatment, as
evidence suggests that early use of ECT for malignant catatonia results in better
outcomes and lowered mortality rates. Observation (answer A) is inappropriate for
a potentially life-threatening condition. Using medications to treat the underlying
bipolar disorder (answers D and E) may be helpful for long-term treatment but
would not be expected to result in immediate treatment of catatonia.
 

73
5 DEPRESSION

Let’s begin our whirlwind tour of the major categories of

psychiatric conditions with depression. Depression has the highest lifetime prevalence of
any single psychiatric disorder, with 20% of all people experiencing a depressive episode
during their lifetime. Because of this, depression has been called the “common cold” of
psychiatry. However, in spite of how common it is, depression is not easy to diagnose. Like
cancer, depression is an illness with many faces, and it is likely that the various disorders
that we currently lump together under the term “depression” are in fact many separate
conditions, each with their own unique causes and treatment considerations. It is this mix
of ubiquity and heterogeneity that makes diagnosing depression such a challenge: its
ubiquity makes it so that everyone who walks through your door will come with a
preconceived notion of what “depression” means, while its heterogeneity ensures that this
notion will differ drastically from one person to the next.
To help you make sense of this, we will learn about depression rst as the core
syndrome that psychiatry has classically referred to as “depression”: speci cally, episodic
unipolar major depressive disorder and its various subtypes. From there, we’ll go over all
the misdiagnoses and missed diagnoses that patients and medical professionals alike often
lump together under the term “depression.” Because the approach to treatment varies so
widely for different clinical entities that are often called “depression,” it is imperative to
accurately diagnose the situation as soon as possible. In contrast, if you were to treat every
person who walks through your door complaining of “depression” as if they have episodic
unipolar major depressive disorder, you are likely to enter your patients into a cycle of failed
treatments and dashed expectations. For this reason, knowing the phenomenology and
appearance of depression across the lifespan is essential.

74
SIGNS AND SYMPTOMS OF DEPRESSION
First, we will learn about the signs and symptoms of episodic unipolar major depressive
disorder (also known as “clinical depression”) that can be seen at a single moment in time.
As with any syndrome, when these signs and symptoms occur together they suggest a
certain prognosis and treatment response. e speci c signs and symptoms of depression are
captured in the mnemonic SIGECAPS. (Legend has it that SIGECAPS refers to an old
practice where a doctor making a prescription would write “SIG” for directions and then
“E-CAPS” for energy capsules, an old term for antidepressants.)
S is for Sleep. Disturbances in sleep are a core symptom of depression and are experienced
by more than 90% of people during an episode. Depression causes not only difficulty in
falling asleep but also early morning awakenings, disrupting both the amount and quality
of sleep that people are able to get. Research shows that depression is even able to alter
someone’s circadian rhythm, making them feel perpetually jetlagged. Due to this, people
with depression classically complain of severe symptoms of depression in the mornings
which partially lift by the afternoon.

I is for Interest or enjoyment. A hallmark symptom of depression is

an inability to feel pleasure, known as anhedonia. Anhedonia is evidenced by decreased
interest in activities that are normally pleasurable such as participating in hobbies or
socializing with others. Anhedonia is what makes depression a non-reactive state, meaning
that someone’s mood will remain the same no matter what is going on around them. For
example, someone in a state of depression would feel no joy even in situations that would
normally inspire mirth, such as celebrating a birthday, getting a promotion at work, being
with family and friends, or riding a giant chicken. Out of all the symptoms of depression,
anhedonia is the most sensitive marker, and the absence of anhedonia reliably rules out
major depressive disorder.
 

G is for Guilt or hopelessness. People in a state of depression often nd that their thoughts
become narrowed and, after a while, they are only able to focus on negative thoughts. e
thought content in depression often revolves around feelings of guilt (“I deserve this”),
worthlessness (“All I am is a burden on people”), or hopelessness (“ ere’s no way out of

75
this hole I am in”). ought patterns of depression are often ruminative, as certain
thoughts are “chewed over” repeatedly.
 

E is for Energy. Levels of energy and activity are often severely decreased in depression,
sometimes to the point where even getting out of bed in the morning is a major challenge.
e low energy found in this state even exceeds what would be expected merely from the
sleep disturbances present in depression, suggesting that fatigue is a core feature of the
disorder (rather than merely an effect of other related symptoms).
 

C is for Concentration. e rumination, poor sleep, and low energy experienced during a
depressive episode often make it difficult to concentrate, leading to impairments in work,
school, and relationships. In contrast to syndromes like attention de cit hyperactivity
disorder where concentration de cits are chronic, in depression the ability to concentrate
improves when the mood episode ends.
 

A is for Appetite. e majority of people with depression nd that their appetite and food
intake are signi cantly decreased, which can result in noticeable weight loss or even
malnutrition over time. People in a state of depression often describe food as unappetizing
or avorless (“It’s like I’m eating cardboard”).
 

P is for Psychomotor retardation. While many features of depression are symptoms that
can only be subjectively reported, in some cases depression involves signs that can be
objectively observed by others. Psychomotor retardation refers to a general slowing of
speech and physical movements which together suggest an inner slowing of cognition as
well. It is generally considered to be a sign of severe depression.
 

S is for Suicide. For people in the depths of depression who are unable to nd any pleasure
in life and are constantly haunted by feelings of guilt, worthlessness, and hopelessness,
suicide can seem like the only way out. While suicide is never the result of just one thing,
the fact remains that over half of all people who die by suicide were in a depressive episode
at the time of their death, making the link between depression and suicide incredibly
robust.
 

A major depressive episode involves depressed

mood, anhedonia, and a variety of other signs and
symptoms.
 

76
 Depressed mood + SIGECAPS: Sleep disturbance
Interest or enjoyment (decreased) Guilt or hopelessness
Energy (decreased) Concentration (impaired) Appetite
(decreased) Psychomotor retardation Suicidal thoughts

Having at least 5 of these 9 symptoms for 2 or more weeks is diagnostic of a major

depressive episode per DSM-5 criteria. However, it’s important to note that the DSM
criteria do not capture the entirety of depression. ere are a variety of additional signs and
symptoms that are clinically seen in depression, including a slouched posture, monotone
speech that lacks prosody, severe anxiety, a high rate of unexplained medical symptoms like
headaches and stomach pain, feelings of depersonalization and derealization (“It’s like I’m
seeing the world through a fog”), and a general lack of motivation. While not officially
recognized in the diagnostic criteria, these signs and symptoms can be helpful for
diagnosing depression as well.
Per the DSM-5, patients must have 5 out of 9
symptoms for a period of
2 weeks or more to qualify for major depressive
episode.
 

e timeframe for depression is two blue weeks.

77
DEPRESSION ACROSS THE LIFESPAN
e signs and symptoms of depression are important to understand, but ultimately they are
only the rst step in being able to diagnose depression. is is because evaluating signs and
symptoms can only give you a cross-sectional snapshot of a patient at a single moment in
time. However, as we learned in Chapter 2 with the LEAD mnemonic, diagnosis should be
based on longitudinal information as much as possible and take into account the patient’s
history across the entire lifespan. Because of this, we will spend some time discussing the
epidemiology, prognosis, and treatment response associated with depression to provide you
with additional tools for getting the diagnosis right.
As mentioned previously, depression is the single most common psychiatric disorder,
with over 20% of all people experiencing at least one depressive episode during their
lifetime. is gives depression a high base rate in the population, putting it high on your
differential for all patients presenting with any psychiatric concern (even if you know
nothing else about them). For patients speci cally presenting with any kind of mood-
related concerns, it should be at or near the top of your differential.
Depression can develop at any age, although it begins most often in early adulthood
with a median age of 32. However, up to a quarter of people with depression do not have
their rst episode until after the age of 50, so a lack of prior episodes (even in an elderly
patient) does not automatically rule out a major depressive episode. Women are diagnosed
with depression twice as often as men.
 
PROGNOSIS
Evaluated longitudinally, the signs and symptoms of major depressive disorder tend to occur
in discrete episodes. Untreated, an episode of depression usually lasts between 6 to 12
months. After this time, most patients will spontaneously recover and enter a period of
normal reactive mood known as euthymia (although many will have some residual
depressive symptoms even between episodes). Functioning is often signi cantly impaired
during an episode of depression but preserved between episodes. ( is is in contrast to
other disorders, such as schizophrenia or personality disorders, where functioning is
continuously impaired.) After a single episode of depression, the risk for developing another
episode is approximately 50%. is means that as many as half of all people diagnosed with
depression will only have a single (or isolated) episode during their lifetime. For the other
half, depression becomes a recurrent disorder, with the risk of recurrence increasing to 80%
after a second lifetime episode and getting even higher with each additional episode after
that.
 

e relationship between depression and life events is complex. Although exact numbers are
hard to come by, depressive episodes are sometimes but not always precipitated by stressful life
events. Generally, these life events involve some form of a major disruption to one’s social
circumstances, with the most common being con ict with one’s spouse, moving
geographically, being forced to change jobs, receiving a diagnosis of a major medical illness,
having a family member leave home, or experiencing the death of a relative or close friend.
Interestingly, the relationship between major life events is most clearly established for one’s
rst lifetime episode of depression. After that, depression seems to take on “a life of its
own,” with episodes happening more and more often without a clear link to life events.

78
 Depression carries a signi cant mortality rate. Mood disorders are found in the
majority of people who die by suicide, and up to 5% of people with depression will
eventually take their own lives. Depression also worsens outcomes for a variety of medical
illnesses including cancer, heart disease, and stroke, leading to decreases in life expectancy
of up to 10 years even after removing suicide from the equation.
 
TREATMENT
Treatment for depression consists of psychotherapy, medications, or a combination of the
two. With treatment, the average length of a major depressive episode can be reduced to
less than 3 months.
Several types of psychotherapy have been shown to be helpful. e most well-studied
by far is cognitive behavioral therapy (CBT) which focuses on the connections between
thoughts, feelings, and behavior and teaches speci c skills for breaking out of the cycle of
depression. CBT is associated with a moderate effect size (around 0.6) for treating
depression. Other types of therapy, including behavioral activation, acceptance and
commitment therapy (ACT), interpersonal therapy (IPT), and psychoanalytic therapy, have
evidence as well.
Most medications used to treat depression (known as antidepressants, although this
is a marketing term more than a scienti c one) alter transmission of the neurotransmitter
serotonin in the brain. Serotonin reuptake inhibitors (SRIs), which increase the amount of
serotonin that is active and available in the brain, are the most popular class of
antidepressants. Not all antidepressants work by increasing serotonin, however, with some
working on other neurotransmitters (such as norepinephrine and dopamine) as well.
Antidepressants are helpful for treating depression, but their effect size is less than for CBT
(around 0.3, or a small effect size). Antidepressants also take some time to work, with a full
effect often not being seen for up to 2 months after beginning the medication.
Treatment response in depression appears to follow a “Rule of irds,” as about one-third of
patients who receive treatment experience complete recovery from their symptoms (known
as remission), one-third notice the improvement of some but not all symptoms (known as
response), and one-third do not get any better with the rst treatment tried (known as
treatment resistance). Patients who have not received any bene t even after multiple trials
of therapy and medications are considered to have treatment-resistant depression. In these
cases, treatments such as electro-convulsive therapy (ECT) may be considered. While ECT
is an invasive and complicated procedure, it is highly effective, with a large effect size
around 0.8 even for people who have not received any bene t from other treatments tried.

79
MECHANISMS OF DEPRESSION
roughout this book, we will explore what is known about the underlying pathophysiology
of the disorders that we are studying with the goal of using this information both to
improve diagnostic accuracy as well as to identify those people who are most likely to
bene t from speci c treatments. However, it is worth keeping in mind that the brain is a
complicated organ, and given how little we know about it, these mechanisms should be seen
as likely hypotheses rather than established facts.
Looking at the pathophysiology of this condition, it is worth stating right off the bat
that there is no evidence that depression results from an inherent “chemical imbalance”
of any kind. While medications that increase serotonin are effective at reducing the
symptoms of depression in the majority of people who take them, that does not mean that
depressed people lack serotonin, and decades of research have yet to provide much evidence
for the “chemical imbalance theory” of depression.
Instead, depression appears to involve speci c changes in the way that people process
information. To put it simply, depressed people see the world differently. Depression
involves a tendency to focus on negative, rather than positive, stimuli. When presented with
a list of words, for example, people with depression are more likely to focus on words like
“hate” or “pain” rather than “love” or “comfort.” When shown a variety of faces, a depressed
person will xate on people with negative facial expressions (like anger or disgust) while
blocking out those with positive expressions (like smiling or laughter). Like an invisible
magnet, depression draws one’s mind preferentially towards negative stimuli, not only in
terms of what occupies attention in the current moment but also what information is
remembered weeks or months down the line.

Perspective of a non-depressed Perspective of a depressed person

person

80
 On a neurobiological level, these differences in emotional processing are re ected in
the amygdala and other parts of the limbic system. In someone who is depressed, these
brain regions are hyperactive when shown a sad or angry face and hypoactive when shown
happy or smiling faces. is phenomenon is referred to as a negative affective bias: negative
for sad or pessimistic, affective for one’s current emotional state, and bias for being drawn to
certain stimuli over others. Negative affective biases tend to accumulate, trapping people in
a vicious cycle where the negative thought patterns of depression are constantly reinforced.
Negative affective biases explain much of what is seen in the phenomenology of
depression. For one, each person at their baseline has an intrinsic tendency to focus on
either positive or negative stimuli and, like many things in psychiatry, this occurs on a
spectrum. Research has found that people who have a greater tendency towards negative
emotional processing (even when not in an episode of depression) are at higher risk for
developing depression compared to people with a greater tendency towards positive stimuli,
suggesting that this represents an inherent vulnerability towards depression regardless of
current mood state. In addition, negative affective biases tend to accumulate in a snowball-
like effect, explaining the “slide” into depression that people experience (rather than
depression being a state that comes on all at once like a u). Finally, negative affective biases
lead people with depression to consistently underestimate their chances of success at
various activities, leading to the speci c cognitive and behavioral patterns seen in depression
such as feelings of hopelessness (“I never do anything right”), isolating oneself socially (“I’m
not going to see people, they will all just laugh at me”), and a lack of desire to engage in
pleasurable or rewarding activities (“Maybe it works for other people, but it won’t work for
me”). ( is tendency towards underestimation of success will form the basis of a crucial
distinction between depression and mania in the next chapter.) e involvement of negative
affective biases also explains much of what we see during treatment of depression. In
particular, negative affective biases provides a mechanism for why antidepressants take so
long to work. As mentioned previously, antidepressants often take up to 2 months to have a
full effect, which makes them different from other drugs (like stimulants or alcohol) that
exert psychological effects almost immediately after taking them. However, studies have
demonstrated that antidepressants do in fact have immediate effects—just not the ones you
might expect. Within minutes of taking an antidepressant, a signi cant lessening of
negative affective biases is observed, with people more able to focus on positive stimuli,
less reactive to negative facial expressions, and more accurate at estimating their chances of
success at various activities. It is believed that this change in emotional processing sets the
stage for a gradual unlearning of depressive thought patterns and behaviors. In fact, studies
have found that the extent to which an antidepressant will ultimately improve mood for a
particular person can be predicted by how much it changes their affective processing within
the rst few days of treatment. Negative affective biases also explain why antidepressants do
not elevate mood in non-depressed people (they are not “happy pills”), as they won’t work if
there are no negative affective biases to lift. ey also explain why drugs and CBT are both
effective in treating depression and in roughly the same amount of time, as both types of
treatments reduce negative affective biases and allow someone with depression to establish
new thoughts patterns and different ways of interpreting the world.
No one theory is going to explain a condition as complex as depression, and additional
mechanisms are likely at work (including prominent dysregulation of the hypothalamic–
pituitary–adrenal axis, discussed further in Chapter 9). Nevertheless, negative affective

81
biases serve a practical purpose by helping to con rm a diagnosis of depression and to
provide a speci c neurobiological target for treatment.
 

e presence of negative affective bias can help to

identify a speci c treatment target in patients with
major depressive disorder.
 

Use Negative Affective Biases to NAB some certainty

when diagnosing depression.

82
DIAGNOSING DEPRESSIVE DISORDERS
Like most mental disorders, a diagnosis of depression is determined primarily using the
psychiatric interview and the mental status exam. Speci c symptoms of depression, as well
as their timing across the lifespan, should be directly assessed. Certain ndings on the
mental status exam (including slowed movements, absent prosody, dysthymic affect, a
ruminative thought process, and suicidal ideation) may also argue for the diagnosis.
Even once you have diagnosed major depressive disorder, however, your job is not yet
done. ere are various subtypes of major depressive disorder that should be considered as
well, all of which t the phenomenology and life course of “textbook” depression to some
extent. e presence of any of these subtypes can carry implications for treatment, so make
sure to keep them on your differential. Unlike the misdiagnoses and missed diagnoses we
will talk about in the next section, all of these entities would accurately be considered to be
unipolar major depressive disorder.
 
MAJOR DEPRESSIVE DISORDER
Major depressive disorder is the prototypical depressive disorder and is characterized by
episodes of depression without accompanying episodes of mania (making it a unipolar,
rather than a bipolar, disorder). Even a single major depressive episode is sufficient to
diagnose major depressive disorder per DSM-5 standards despite the fact that only 50% of
people will go on to have another episode. For clarity, people with multiple episodes of
depression are said to have recurrent major depressive disorder.
 
ATYPICAL DEPRESSION

Atypical depression has some unique features compared to “textbook”

depression. Most notably, mood remains reactive in atypical depression, and people with
atypical depression will often experience a lifting of depressive symptoms during happy life
events. However, the ip side of the coin is that they can be even more deeply affected by
negative events. In particular, patients with atypical depression display a long-standing
pattern of interpersonal rejection sensitivity, even when not in an episode of depression.
Other unique features of atypical depression are an increase in appetite (rather than a
decrease) which can result in weight gain, sleeping too much (rather than too little), and a
sensation that one’s limbs feel too heavy to lift (known as leaden paralysis). ese are often
referred to as reversed neurovegetative symptoms to differentiate them from those found

83
in typical or melancholic depression (discussed next). Compared to standard
antidepressants, a speci c class of medications known as monoamine oxidase inhibitors
(MAOIs) are particularly effective for atypical depression.
You can remember atypical depression by thinking of it as ate-typical depression. A
depressed person who had mood reactivity and became happy when they ate food would
probably start to gain weight, causing their limbs to feel heavy. ey may then become
sensitive to people rejecting them because of their weight.
 

Atypical depression involves increased appetite,

hypersomnia, leaden paralysis, and interpersonal
rejection sensitivity.
 

Ate-typical depression involves eating, leading to

heaviness and rejection sensitivity.
 
MELANCHOLIC DEPRESSION
Historically, the “melancholic” speci er was used to describe particularly severe cases of
depression that appeared to come “out of the blue” (as opposed to being brought on by life
events) and, in comparison to atypical depression, were completely non-reactive to external
stimuli. Often, biological features of depression such as psychomotor retardation, severe loss
of appetite, weight loss, fatigue, inattention, and disrupted sleep are particularly pronounced
(these are collectively referred to as neurovegetative symptoms). It is unclear if melancholic
depression represents a distinct subtype of major depressive disorder as opposed to simply a
very severe form. In any case, treatment is largely the same as for severe forms of depression
and often involves earlier consideration of ECT.
 

POSTPARTUM DEPRESSION
In around 15% of births, the mother develops clinical depression within a few weeks of
delivery. It is unclear why the postnatal state increases the risk of depression, but many
factors (including hormonal changes, sleep deprivation, and childcare stress) are believed to
play a role. Postpartum depression is not considered to be a separate syndrome from major
depressive disorder and is treated like “textbook” depression with the exception of taking
some additional considerations into account when choosing medications if the mother is
breastfeeding.

84
 Postpartum depression should be differentiated from “baby
blues,” a transient state of mild depressive symptoms that resolves within a few weeks. Baby
blues occur in 80% of mothers following delivery and are considered to be a normal part of
the human experience. Severe symptoms lasting more than a few weeks should raise the
consideration for a diagnosis of postpartum depression (remember “two blue weeks”).
Postpartum depression should also be carefully separated from postpartum psychosis,
another psychiatric syndrome that occurs in the period following childbirth. In contrast to
baby blues or postpartum depression, postpartum psychosis is characterized by symptoms of
psychosis or mania, including rapid swings in mood, hallucinations, bizarre beliefs, and
paranoia. Postpartum psychosis is one of the leading causes of infanticide and is considered
to be a medical emergency necessitating immediate psychiatric hospitalization and
treatment.
 
PSYCHOTIC DEPRESSION
Psychotic depression is characterized by the presence of paranoia, delusions, or
hallucinations in addition to all of the usual symptoms of major depressive disorder.
Psychotic symptoms do not occur in all cases of severe depression, but nearly all cases of
psychotic depression involve severe depressive symptoms. Treatment involves a combination
of both antidepressants and antipsychotics. In many cases, hospitalization and/or ECT
should be considered. (Differentiating psychotic depression from other disorders where
mood and psychotic symptoms co-occur, including bipolar disorder with psychotic features,
schizoaffective disorder, and even schizophrenia itself, can be challenging. We will defer
discussion of this until Chapter 7, as it requires a greater understanding of both mania and
psychosis.)
CATATONIC DEPRESSION
Catatonia can occur in severe cases of major depressive disorder. It manifests in the speci c
signs and symptoms described in Chapter 4 and often requires intensive treatment in a
hospital setting. As with all forms of catatonia, benzodiazepines should be used liberally, as
they are often very effective at rapidly reversing the state of catatonia. If medications are not
effective or if there are signs suggestive of malignant catatonia, ECT should be considered.
 
SEASONAL DEPRESSION

85
 Seasonal depression (also known as seasonal
affective disorder) is a subtype of major depressive disorder where depressive episodes have a
clearly established link with the changing of the seasons. Most often, depression develops
during the winter months. is is likely related to lower levels of sunlight during the
winter, as the rate of seasonal depression increases the farther away from the equator you go.
Treatment for seasonal depression involves bright light therapy for at least 30 minutes each
day to help offset the loss of sunlight. Most houselights do not produce the full spectrum of
light (as sunlight does), so specialized “light boxes” should be used. Standard treatments for
major depressive disorder, including conventional antidepressants and psychotherapy, can be
used as well and are equally effective.

86
DIFFERENTIAL DIAGNOSIS OF DEPRESSIVE DISORDERS
Now that we have a good understanding of depression and its various subtypes, let’s explore
what actually happens when patients walk into the door complaining of “depression.” Even
the most well-read students can have difficulty adjusting to real-world clinical settings
where cases of “textbook” depression are the exception rather than the rule. Even in cases
where someone technically meets diagnostic criteria for major depressive disorder, a
different diagnosis (such as bipolar disorder or borderline personality disorder) may do a
much better job of explaining the patient’s distress and pointing towards a helpful treatment
strategy. is re ects a major shortcoming of the DSM and other algorithmic approaches to
diagnosis: they have increased the reliability of diagnosis at the expense of sacri cing the
validity of what the diagnostic criteria are supposed to represent.
 

For this reason, when evaluating a patient complaining of depression, it can be helpful
to approach the psychiatric evaluation with an eye towards misdiagnoses and missed
diagnoses. Misdiagnoses are fundamentally incorrect diagnoses. For example, if someone
with a history of both depression and mania was diagnosed with unipolar (rather than
bipolar) depression, this would simply be a wrong diagnosis. In contrast, missed diagnoses
are those that are frequently encountered with depression (such as anxiety or substance
abuse) and can interact with or mimic many of its symptoms. Understanding the most
common misdiagnoses and missed diagnoses of depression can be exceptionally challenging,
even for experienced clinicians. It will be even more challenging early in this book, as we
will not have discussed many of the conditions we will be comparing with depression. Rest
assured that it will get easier as you progress in knowledge. In the meantime, feel free to
jump ahead to other chapters of the book to gain additional insight into these disorders.
Both when answering test questions as well as when evaluating patients in clinical
settings, having a framework for evaluating mood concerns can give you a structured process
for picking up on clinically important features. You can use the mnemonic Reactive
PLANETS to remember the speci c high-yield factors that commonly differentiate
depression from alternative diagnoses:
R is for Reactivity. e presence or absence of mood reactivity is an important diagnostic
clue. Non-reactivity suggests a mood disorder such as unipolar or bipolar depression, while
a reactive mood may suggest atypical depression, borderline personality disorder, or even
just plain old normalcy.
 

P is for Polarity. A history of both depression and mania is the diagnostic hallmark of
bipolar disorder. Make sure to inquire about any history of manic or hypomanic episodes, as
bipolar depression requires a fundamentally different treatment approach compared to
unipolar depression.
 

L is for Lability. Mood symptoms can either be stable or labile. Mood symptoms from
major depressive disorder or bipolar disorder are often quite stable and endure for weeks,

87
months, or years at a time. In contrast, a labile affect (changing within minutes or hours) is
often more characteristic of personality disorders or substance use.
 

A is for Attributability. In some cases, depression can be attributable to speci c causative

factors, including medical conditions (like hypothyroidism), substances (alcohol), external
circumstances (postpartum depression), and timing (seasonal depression or premenstrual
dysphoric disorder) among many others.
 

N is for Normality. Normalcy is always on the differential. You should take time to consider
whether the patient’s reported symptoms are within the realm of normal human emotion.
When the boundary between normal and abnormal is unclear, considering the level of
functional impairment or gathering collateral information from a friend or family member
can help to decide.
 

E is for Episodicity. Depressive symptoms can often occur in discrete and long-lasting
episodes, which is characteristic of both unipolar major depressive disorder as well as bipolar
disorder. Chronic non-episodic depression should raise your suspicion for other diagnoses,
including dysthymia and personality disorders.
 

T is for Treatment responsivity. How well a person has responded to treatments for
depression can offer a helpful clue as well. A history of failing multiple trials of conventional
antidepressants should have you searching for alternate explanations, including
misdiagnoses (bipolar disorder), missed diagnoses (anxiety disorders), or other attributable
factors (alcohol-induced depression). However, poor treatment response in and of itself is
not sufficient to rule out major depressive disorder (they may just have treatment-resistant
depression). e best way of conceptualizing the effect of treatment response is to think that
poor treatment response can be but is not always a marker of a misdiagnosis or missed
diagnosis.
 

S is for Severity. Finally, the severity of depressive symptoms can help to differentiate
between “full blown” and subsyndromal symptoms of depression as well as to differentiate
between normalcy and pathology.
 

Diagnosing depression is more than just using

SIGECAPS! Try to focus on the patient’s pattern of
symptoms across the lifespan.
 

88
 Use Reactive PLANETS to systematically assess mood
complaints: Reactivity Polarity Lability Attributability
Normality Episodicity Treatment responsivity Severity

89
NORMALCY
Sadness, grief, misery, distress, and heartache are painful, and it’s not uncommon for people
to seek psychiatric care when they experience these emotions. However, to label these
experiences as a mental disorder risks unnecessarily pathologizing normal human emotion.
When deciding where to draw the line between illness and pathology, consider both
reactivity and severity. For example, someone who recently lost a spouse after a long battle
with cancer is likely to experience grief. e symptoms of grief overlap signi cantly with
those of depression, including an intense and protracted state of poor mood, difficulty
enjoying activities, trouble concentrating, poor appetite, and difficulty sleeping. However,
most people agree that grief should ultimately be considered a normal part of the human
experience and not be diagnosed as a mental disorder. Focusing on reactivity and severity
can help to identify those cases where distress and dysfunction are clearly in excess of what
most people would experience during grief. While many people experience intense sadness
while grieving, it is a minority of people who have a completely non-reactive mood, who are
unable to focus on any positive stimuli, who feel completely hopeless about the future, who
begin to feel worthless or lack self-esteem, or who begin having persistent thoughts of
suicide following bereavement. In these cases, the line between normalcy and pathology has
been crossed, and a discussion of treatment options may be helpful. While bereavement is
only one example, it provides a good case study for demonstrating the challenges of
separating normalcy from depression.
It’s also not uncommon for people to use the language of depression as an idiom of
distress. For example, someone who is upset because they did not get a promotion at work
may tell others “I’m depressed” as a way of communicating and seeking validation for their
emotions. Distress is not inherently pathological, so always make sure to ask further
questions before giving a clinical diagnosis.

ADJUSTMENT DISORDER

Adjustment disorder is de ned as depressive and/or anxious

symptoms that occur soon after a major life stressor such as going through a divorce or
losing a job. Given that we have already established that depressive episodes can also occur
after major life events, how can we differentiate between depressive episodes and
adjustment disorder? e key here is that the symptoms are not so severe that the patient

90
would meet criteria for clinical depression. In effect, adjustment disorder is a “diagnosis of
normalcy” that recognizes that some degree of distress is normal and expected following a
major life change. e continued existence of adjustment disorder as a diagnosable “mental
disorder” likely re ects the fact that it ultimately serves a practical purpose by allowing
clinicians to provide treatment for grieving or suffering patients in a way that is
normalizing, non-stigmatizing, and permits reimbursement for medical services. Treatment
for adjustment disorder involves a speci c type of psychotherapy known as supportive
therapy that allows the patient to discuss their psychological reactions in a setting that is
empathic and compassionate.

DYSTHYMIA
Dysthymia (referred to as “persistent depressive disorder” in the DSM-5) is on the
spectrum of depression but differs from major depressive disorder in two crucial ways. First,
it is chronic rather than episodic, with symptoms being present most of the time without a
break for at least two years. Second, it is subsyndromal in that the patient does not quite
meet full criteria for a major depressive episode but still suffers from depressed mood. Mood
symptoms in dysthymia tend to avoid those symptoms of depression that are generally
found more often in severe cases of depression (such as psychomotor retardation or
thoughts of suicide). is suggests that dysthymia can be conceptualized as a milder but
more chronic form of major depressive disorder, and this idea is supported by the fact that
treatment for dysthymia is largely the same as for “textbook” depression. You can remember
the common symptoms and time course of dysthymia using the mnemonic “HE’S 2 SAD.”
 

Dysthymia (also known as persistent depressive

disorder) is a state of chronic depressive symptoms
that are less severe than “textbook” depression.
 

HE’S 2 SAD: Hopelessness Energy (decreased) Self-

esteem (decreased) 2 years minimum Sleep (abnormal)
Appetite (abnormal) Decision-making (impaired)

Up to a quarter of all patients with depression have both dysthymia and major depressive
disorder, a clinical situation commonly called “double depression.” In these cases, the
patient spends most of their life in a chronic subsyndromal state of depression punctuated
with discrete episodes of more severe depression. People with double depression also tend to
relapse much more quickly than those with “textbook” major depressive disorder. Double
depression is notoriously difficult to treat, but the approach to treatment remains the same:
therapy and/or medications.

BIPOLAR DEPRESSION

91
Depression that occurs in someone with a history of mania or hypomania should be
diagnosed as bipolar (rather than unipolar) depression. Clinically, bipolar depression is often
indistinguishable from unipolar depression. However, major differences in prognosis and
treatment response between unipolar and bipolar depression suggest that these two
conditions should be conceptualized as entirely separate disorders despite the signi cant
overlap in symptoms. A patient presenting with current depressive symptoms can be
diagnosed with bipolar I disorder if there is a clear history of even a single manic episode,
while a history of even a single hypomanic episode is sufficient to diagnose bipolar II
disorder. (Both mania and hypomania will be discussed further in Chapter 6.)
What complicates the process signi cantly is the fact that patients who have bipolar
disorder will often have several depressive episodes before their rst manic episode. How can
we be certain that a patient having their rst major depressive episode is not, in fact,
presenting with bipolar depression? After all, around 15% of all people seeking treatment
for depression will ultimately be diagnosed as having bipolar disorder, and 40 to 70% of
people with bipolar disorder are initially diagnosed with unipolar depression. ere are
some clues that can point us in the right direction. Compared to people with unipolar
depression, people with bipolar depression tend to have their rst episode earlier in life, to
spend more of their time impaired by mood symptoms, to have more psychomotor
retardation, to display melancholic, atypical, or psychotic features, and to have a family
history of mania. Treatment response can be helpful as well, as conventional antidepressants
are likely to be ineffective and may actually increase the rate at which the patient alternates
between mania and depression (known as “rapid cycling”). Pay close attention to the
presence of any of these during the initial evaluation as well as subsequent treatment.
However, at the end of the day, none of these clues are sufficient to de nitively diagnose
bipolar depression, and you can never be certain that a patient has bipolar disorder until
they have “declared themselves” by having their rst manic or hypomanic episode. While
operating within this kind of ambiguity can be frustrating, it is worthwhile to be cautious
before diagnosing bipolar depression, especially considering that the treatments for bipolar
disorder (including mood stabilizers and antipsychotics) are signi cantly more harmful than
those for unipolar depression.

CYCLOTHYMIA
Just as dysthymia can be conceptualized as a milder but more chronic form of depression, so
too cyclothymia can be seen as a milder but more chronic form of bipolar disorder.
Cyclothymia can be differentiated from unipolar depression by its lower severity and
bipolarity. In cyclothymia, someone has periods of mild depression (that never quite meet
criteria for a major depressive episode) alternating with episodes of hypomania (that never
quite meet criteria for a manic episode). While conceptually cyclothymia makes sense, in
practice it is rarely diagnosed as most people who have either manic or hypomanic episodes
tend to have “full blown” major depressive episodes at some point during their lives.

SUBSTANCE INDUCED MOOD DISORDER

e relationship between depression and substance use is often a two-way street. e effects
of certain drugs (such as alcohol or benzodiazepines) can resemble depression during

92
intoxication, while others (including stimulants like methamphetamine) can resemble
depression during withdrawal. Other substances may induce depression to the extent that
someone may be depressed even when they are not actively intoxicated. e most common
substance associated with depression is alcohol, but even prescription drugs (such as
benzodiazepines or steroids) can impact mood. e key for diagnosing a substance-induced
mood disorder is attributability and timing, as use of the substance will often correlate
with increases in depressive symptoms while abstaining from the substance will tend to
resolve the symptoms. In cases where symptoms persist even after substance use is stopped
for some period of time, a diagnosis of a primary depressive disorder should be considered.
MOOD DISORDER DUE TO A GENERAL MEDICAL CONDITION
Certain medical conditions can “masquerade” as depression and remain undiagnosed for
long periods of time. A classic example is hypothyroidism, a condition whose symptoms
(such as fatigue and poor appetite) overlap signi cantly with and are often mistaken for
clinical depression. Other examples include cardiac disease, chronic hypotension, infections,
certain forms of cancer, and neurologic disorders such as multiple sclerosis. e key is for
the clinician to have a high index of suspicion for any physical signs or symptoms that may
suggest a medical etiology. Additional clues can be found in the attributability and timing
of symptom onset. As a word of caution, be mindful to not confuse a normal grief reaction
to being diagnosed with an illness like cancer (which would be considered in the realm of
normalcy or adjustment disorder) with the severe and non-reactive symptoms of major
depressive disorder.

PREMENSTRUAL DYSPHORIC DISORDER

Premenstrual dysphoric disorder (sometimes abbreviated PMDD) is a cluster of
physiological and psychological symptoms, including low mood, irritability, anxiety, fatigue,
and various somatic symptoms, that occurs in some women. e symptoms of premenstrual
dysphoric disorder overlap with those of clinical depression quite a bit, but the diagnostic
key is the menstrual pattern to symptoms. Speci cally, mood symptoms often begin in the
luteal phase and end soon after menstruation begins. On average, symptoms last six days
but can last up to two weeks. Premenstrual dysphoric disorder is not mutually exclusive with
depression, as some people will have both discrete episodes of depression in addition to
premenstrual dysphoria (in which case the existing symptoms of depression often get
signi cantly worse prior to menses). Asking your patients to complete a mood chart for at
least a month can help to con rm the diagnosis (although often patients will know on their
own that their symptoms have a clear relationship with their menstrual cycle). Once the
diagnosis is reached, treatment options can include antidepressant medications and/or
psychotherapies like CBT, which have both been found to be effective.

BORDERLINE PERSONALITY DISORDER

Borderline personality disorder is a complex syndrome de ned by unstable emotions, a poor
sense of self, and volatile interpersonal relationships. It is the most commonly encountered
personality disorder in clinical settings, and we will discuss it at length in Chapter 13.
Despite how common it is, borderline personality disorder is frequently overlooked as an
explanation for mood symptoms.

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 Mood symptoms in borderline personality disorder are characterized primarily by two
features: affective lability and chronic dysphoria. Affective lability refers to rapid changes
in emotional expression. In contrast to the mood episodes seen in clinical depression or
bipolar disorder which often last for weeks or months, affective instability results in
emotional changes within a matter of minutes or hours. For example, someone with
borderline personality disorder may switch from joyous laughing to furious screaming
within the span of 60 seconds. ese changes in affect are often precipitated by external
events (such as threats of abandonment), making mood notably reactive (rather than non-
reactive as in major depressive disorder).
In addition to affective instability, people with borderline personality disorder often
experience chronic dysphoria that can be mistaken for depression. e key difference is that
clinical depression occurs in discrete episodes lasting months or even up to a year, whereas
chronic dysphoria often persists for years or decades. Chronic dysphoria also needs to be
distinguished from the chronic low-level depressive symptoms seen in dysthymia, which are
similarly non-episodic in nature. e key lies in the difference between dysthymia and
dysphoria. Dysthymia is a low-grade depression, whereas dysphoria is a state of profound
dissatisfaction and disappointment with one’s self and one’s life. is is admittedly a difficult
distinction to make, and many people diagnosed with dysthymia likely have chronic
dysphoria (and vice versa). For help in making the diagnosis, look for other aspects of the
patient’s history (such as self-harm, impulsivity, a disturbed sense of identity, and a history
of abuse) that may help to suggest borderline personality disorder.
Recognizing the presence of borderline personality disorder when assessing a patient
with depression is of crucial importance, as it drastically changes the approach required for
successful treatment options. Attempting to treat depression in a patient with borderline
personality disorder is an exercise in futility, as traditional antidepressant medications do
little to help in these cases. Instead, treatment of borderline personality disorder itself must
take rst priority. Treatment involves speci c forms of therapy such as dialectical behavior
therapy (DBT) that speci cally address the unique symptom patterns of the disorder.
Because of this, poor treatment responsivity can be diagnostically helpful (as can lability
and lack of episodicity).

SCHIZOPHRENIA
Schizophrenia is a disorder characterized by a mixture of dramatic positive symptoms
(including paranoid delusions, auditory hallucinations, and thought disorganization) as well
as more subtle negative symptoms (such as lack of motivation, at affect, poor energy, social
isolation, and poverty of thought). At rst, the bizarre symptoms of psychosis can seem a
world away from the more recognizable syndrome of depression. However, it’s not
uncommon for schizophrenia to be mistakenly diagnosed as depression, as the negative
symptoms of schizophrenia can strongly resemble the neurovegetative symptoms found in
depression (especially in early stages of the disorder before the more dramatic positive
symptoms emerge).
e relationship between depression and psychosis is complicated further by the fact
that depression, bipolar disorder, schizophrenia, schizoaffective disorder, and even
borderline personality disorder can all feature a mixture of mood and psychotic symptoms,
yet each is a distinct clinical entity with separate treatment considerations. We will discuss

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the relationship between mood and psychotic disorders at some length in Chapter 7, but in
the meantime, try to focus on process over content when trying to differentiate depression
from schizophrenia. People with psychotic depression often have relatively preserved
functioning between mood episodes, whereas people with schizophrenia often have
progressive deterioration of functioning even during periods when symptoms are not
active.

ATTENTION DEFICIT HYPERACTIVITY

DISORDER
Attention de cit hyperactivity disorder (ADHD) is a neurodevelopmental disorder
characterized by chronic inattention and hyperactivity. It often begins in childhood, but for
some it persists into adult life as well. For some, the social difficulties and low occupational
attainment that often occur in untreated ADHD can lead to a sense of frustration,
dissatisfaction, and helplessness which can often be misdiagnosed as depression. In these
cases, the mood symptoms should improve with adequate treatment of ADHD. In cases
where it does not, consideration of a separate diagnosis of depression may be warranted (as
it is absolutely possible to have both depression and ADHD at the same time).
In other cases, the inattention seen in depression can be misdiagnosed as ADHD,
although the episodic nature of depression should help to separate it from the chronic
inattention seen in ADHD. In these cases, treatment of depression should naturally
improve concentration.

POST-TRAUMATIC STRESS DISORDER

Post-traumatic stress disorder (PTSD) is a complex syndrome of cognitive and behavioral
symptoms that begins following exposure to a life-threatening or violent event. ere is
signi cant overlap in symptoms between depression and PTSD, as both feature anhedonia,
sleep disturbance, and difficulty concentrating. However, despite this overlap, depression
and PTSD should be conceptualized as two distinct conditions. Depression is not a “natural
effect” of experiencing trauma, and people who meet criteria for both PTSD and depression
experience more distress and have worse functional outcomes than people with either
diagnosis alone. In addition, there are distinct biological pro les associated with each,
suggesting two separate processes (even if they do overlap in some ways). While
psychotherapy and/or antidepressants can be helpful for both depression and PTSD, a more
trauma-focused therapy is often necessary for successful treatment of PTSD.

ANXIETY DISORDERS
Anxiety disorders are characterized by frequent and excessive worrying. ey are frequently
comorbid with depression, with as many as 60% of people with depression also having an
anxiety disorder. Ignoring the presence of anxiety in a person with depression is more of a
missed diagnosis than a misdiagnosis. Luckily, the same types of treatments are helpful in
both disorders, including antidepressant medications and psychotherapies like CBT.

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DEMENTIA
e term “dementia” refers to a group of neurocognitive disorders that all involve a
progressive decline in cognitive abilities such as memory and complex thinking. In the
elderly, severe depression can be mistaken for dementia, and people with depression may
even score poorly on objective tests used to diagnose dementia. e term “pseudodementia”
has been coined to describe patients who appear to have dementia. A prior history of
depressive episodes, the presence of other symptoms of depression, and a lack of effort on
cognitive tests (as opposed to an inability to engage) can all point towards a diagnosis of
pseudodementia. In addition, patients with pseudodementia often have insight into their
cognitive problems (“I’m losing my memory”) while those with dementia do not.
Identi cation of pseudodementia is critical, as depression is a highly treatable condition
(dementia much less so).

DISSOCIATION
As mentioned previously, feelings of depersonalization and/or derealization are seen
commonly in depression even though they aren’t formally included in the DSM criteria for
diagnosis. Dissociative disorders and depression are highly comorbid, and it is possible to
have both at the same time. When dissociative symptoms are present, they tend to predict a
worse response to conventional treatments. However, dissociative symptoms that occur only
in the context of a depressive episode should not necessarily warrant a separate diagnosis of
a dissociative disorder.

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PUTTING IT ALL TOGETHER

If depression is an illness with many faces, you will need to be

able to recognize each one to be able to arrive at the correct diagnosis. e differences in
signs and symptoms between the various syndromes that can all present as “depression” can
be slight, yet the prognosis and treatment response associated with each can be worlds
apart. Because of this, a diagnosis of depression should be given cautiously and only after
careful consideration of alternative explanations. Use the mnemonic SIGECAPS to
remember the core signs and symptoms of depression at a single moment in time. e
phrase “two blue weeks” can help you to recall the diagnostic timeframe. Major depressive
disorder is notably a non-reactive and episodic disorder, with episodes typically lasting 6-
12 months without treatment and 3-6 months with treatment. Treatment consists of
therapy and/or antidepressant medications, either alone or in combination.
A variety of distinct clinical entities, including atypical, melancholic, postpartum, psychotic,
catatonic, and seasonal depression, all should be considered various subtypes of depression
but must still be recognized due to the implications they carry for treatment. In contrast,
there are many misdiagnoses and missed diagnoses that may present with similar symptoms
but ultimately should not be considered as a form of major depressive disorder. Use the
Reactive PLANETS framework to guide your clinical judgment whenever you encounter
someone presenting with problems related to mood. ese questions can help you to spot
when the patient’s presentation differs signi cantly enough from “textbook” depression for
consideration of an alternative explanation.
 

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REVIEW QUESTIONS
1. A 23 y/o F comes to a psychiatrist’s office for evaluation of performance anxiety.
She is a graduate student in piano performance and has heard that propranolol can
be a helpful medication for this. Wanting to be thorough, her psychiatrist conducts
a psychiatric review of systems. To rule out depression, the psychiatrist asks about
her mood, which she describes as “normal.” What is the best next question to rule
out a diagnosis of a current major depressive episode?
A. “How is your sleep?”
B. “Were you abused as a child?”
C. “Do you enjoy things like you normally do?”
D. “How is your appetite?”
E. “Do you have thoughts that you would be better off dead?”
2. A 36 y/o M is seen for an initial psychiatric evaluation. He reports that since he
was red from his job 6 months ago, he has been spending all day in bed due to an
inability to sleep at night and severe fatigue during the day. He has two children
under the age of 3, and nances are becoming tight. He says, “I know I need to be
looking for a job to take care of my wife and kids, but I just can’t.” His wife
recently has taken to calling him “worthless,” and he says, “After hearing it enough
times, I nd it hard to disagree.” He is worried that his wife will divorce him and
that his friends will leave him, saying, “Everyone just looks angry or disappointed
at me all the time.” When asked about his food intake, he reports that he has been
eating only a bowl of cereal each day. He denies use of alcohol or any other
substances. He has feelings of hopelessness but no thoughts of suicide. On exam,
he moves and talks noticeably slower. Without treatment, how much longer would
these symptoms be expected to continue?
A. Less than 1 month
B. Between 1 and 6 months
C. Between 6 and 12 months
D. More than 1 year
E. ese symptoms will likely continue until treatment is started
3. (Continued from previous question.) e psychiatrist recommends starting the
antidepressant sertraline along with CBT. at night, the patient takes his rst
dose of the medication. Which of the following symptoms is likely to resolve rst?
A. Finding it hard to disagree when his wife calls him “worthless”
B. Spending all day in bed
C. Eating only a single bowl of cereal each day
D. Moving and talking noticeably slower
E. Feeling that everyone looks angry or disappointed at him
F. All of these symptoms are equally likely to respond rst
4. (Continued from previous question.) e patient returns to see his psychiatrist
several times over the next few months. By the fourth month, he reports that his
mood is entirely back to normal. e decision is made to continue both CBT and
sertraline for another year. One year later, he is successfully tapered off of
medication with no return of depressive symptoms. e patient says, “ at was the
worst few months of my life, but I’m glad it’s over. I hope nothing like this ever

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 happens again.” What is this patient’s risk of experiencing another episode in the
future?
A. 100% (it is certain that he will have another episode)
B. Between 50 and 100% (it is more likely than not)
C. 50% (it is equally likely and unlikely)
D. Between 0 and 50% (it is less likely than not)
E. 0% (it is completely unlikely)
5. A 47 y/o F who works as a business executive presents to a psychiatrist reporting
worsening mood symptoms over the past four weeks, including depressed mood,
irritability, feeling cold all of the time, difficulty sleeping, lack of energy, poor
appetite, and constipation. She normally enjoys trail running but has not been able
to exercise for more than a few minutes at a time for the past two months. Despite
eating very little, she says that she has gained more than 15 lbs. over this same
time period. She says, “My sister has suffered with depression as well and says that
uoxetine works really well for her. I was wondering if I could go on that too.”
Which of the following is the next best step?
A. Prescribe uoxetine
B. Refer for CBT
C. Prescribe uoxetine along with a referral for CBT
D. Order laboratory testing
E. Reassure the patient that her symptoms are normal
6. A 72 y/o F sees her primary care doctor for the rst time in over a decade. She says
that her husband of over 50 years suffered a stroke two months ago that left him
“basically like a vegetable.” e patient now spends most of her time caring for her
husband, which leaves her feeling exhausted and depressed. She thinks constantly
about what it would mean if her husband were to die, although she also admits
that “sometimes I think it would be good for him to go, which makes me feel like a
horrible person.” She denies feeling hopeless or having thoughts of suicide. Her
appetite and concentration are intact. Which of the following is the next best step?
A. Refer for therapy
B. Reassure the patient that her symptoms are normal
C. Discuss risks and bene ts of medications
D. Provide referrals to social resources such as caregiver support
E. All of the above
 

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1. e best answer is C. Apart from a subjective sense of depressed mood, asking
about anhedonia is a highly sensitive marker for ruling out depression. Someone
who denies both a depressed mood and anhedonia is exceedingly unlikely to be
currently in a major depressive episode. e other questions may be important to
ask to get a better sense of the patient’s current mental state (especially suicide,
answer E) but are not as sensitive for ruling out a major depressive episode.
2. e best answer is B. is patient is likely suffering from major depressive disorder
(although other causes cannot be entirely ruled out at this time). e average
length of an untreated depressive episode is between 6 and 12 months. Given that
he has already had symptoms for 6 months, it is most likely that his symptoms will
last up to another 6 months, ruling out answers A, C, and D. As an episodic
disorder, the symptoms of depression are unlikely to continue inde nitely even if
treatment is not started (answer E).
3. e best answer is E. e core symptoms of depression, including feelings of
worthlessness (answer A), fatigue (answer B), poor appetite (answer C), and
psychomotor retardation (answer D) are all unlikely to respond to antidepressant
treatment within a single day. In contrast, antidepressants have been shown to
reduce negative affective biases even within the rst day of treatment, suggesting
that this patient’s feelings that others look angry or disappointed will resolve rst.
4. e best answer is C. Around 50% of people with a rst episode of depression will
have an isolated episode, while the other 50% will develop recurrent major
depressive disorder.
5. e best answer is D. While the patient reports symptoms consistent with
depression, there are also other symptoms that suggest a medical etiology,
including cold intolerance, constipation, an inability to exercise, and signi cant
weight gain in the absence of food intake. e most likely explanation is untreated
hypothyroidism, which would need to be con rmed with laboratory testing.
Treating her symptoms with antidepressants or CBT (answers A, B, and C) would
not be appropriate until hypothyroidism has been ruled out. She should not be
reassured that her symptoms are normal when there is evidence of likely medical
pathology (answer E).
6. e best answer is E. is patient is likely suffering from adjustment disorder
given the recent major life change and resulting symptoms of depression that do
not meet criteria for a full disorder. Adjustment disorder is a “diagnosis of
normalcy,” so reassurance should be given (answer B). Treatment for adjustment
disorder includes supportive therapy (answer A), with referrals to social support
when indicated (answer D). It is reasonable to have a discussion about the risks
and bene ts of medications even if the risks likely outweigh the bene ts in this
case (answer C).
 

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6 MANIA

Mania is an abnormal mental state characterized by excessive

elevations in mood and energy. In many ways, mania can be thought of as the opposite of
depression. While both are episodic and non-reactive mood states that result in
dysfunction, with mania the culprit is too high of a mood rather than too low. With
depression, people have trouble even getting out of bed in the morning; with mania, they
haven’t felt the need to sleep for days. With depression, people think of themselves as so
worthless that they don’t deserve to live; with mania, they see themselves as the greatest
person to have ever walked the face of the earth. With depression, people are so xated on
hopeless thoughts that they can think about nothing else; with mania, they may have so
many thoughts going on at once that others can’t keep up. People in a manic state speak
quickly, think quickly, move quickly, and act quickly. While it is de nitely an
oversimpli cation to say that mania is simply the opposite of depression, this rule of thumb
will work most of the time.
Mania is the hallmark state of bipolar disorder, a psychiatric condition that involves
both manic highs and depressive lows. In contrast to depression, bipolar disorder is
signi cantly more rare, with only 1% of the population experiencing a manic episode during
their lifetimes. Despite this rarity, bipolar disorder can be a difficult and disabling condition
due to its severity, chronicity, and onset early in life. Because of this, prompt diagnosis and
treatment of bipolar disorder is essential. With this in mind, we will rst learn about
“textbook” mania so that you can easily recognize this syndrome when it occurs. From there,
we will discuss how to diagnose bipolar disorder and its various subtypes before learning
about all the misdiagnoses and missed diagnoses that frequently accompany a diagnosis of
bipolar disorder.

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SIGNS AND SYMPTOMS OF MANIA
While elevated (or irritable) mood and increased energy are the hallmarks of mania, they
are frequently accompanied by other clinical features as well. e signs and symptoms of
mania that can be seen at a particular moment in time are summarized in the mnemonic

DIG FAST: D is for Distractibility. People in a state of mania

often describe their thoughts as “racing” and have trouble staying on any one subject. ey
may have difficulty nishing a conversation or even a single sentence, as their attention is
quickly pulled in different directions.
I is for Impulsivity. Impulsivity, indiscretion, and irresponsibility characterize most cases of
mania. e increase in goal-directed behavior is often accompanied by a lack of having fully
considered the possible consequences. Accordingly, people in a state of mania are known to
engage in risky behaviors, including drug use, reckless driving, unprotected sex, and
spending thousands of dollars at a time on unnecessary purchases.
G is for Grandiosity. ought content in mania often involves a degree of grandiosity that
can border on the psychotic. People in a manic state can come to believe that they are a
special or exalted gure (such as a king, president, prophet, messiah, leader, or CEO) and
make plans accordingly. Often, these plans lack a clear connection to reality (“I’m going to
save the world by selling microgreens right back to farmers!”) and aren’t very durable,
changing drastically from one minute to the next.
F is for Flight of ideas. While grandiosity describes the thought content in mania, ight of
ideas describes the thought process. In mania, ideas “ y” through the mind so rapidly that it
is difficult for anyone to keep track of the conversation (“I have the most beautiful cat in the
world. I need to pick up a dozen gallons of orange juice from the store. What is congress
thinking? Is this microphone even on?”). Difficulty keeping up with a patient that you are
interviewing is highly suggestive of a manic episode.
A is for Activity. More than any other sign or symptom, an increase in energy and goal-
directed activity (sometimes referred to as psychomotor acceleration) is a key hallmark of
mania. e “increased busyness” of people in a manic state has been noted since the early
days of psychiatric diagnosis, and it appears to be a highly sensitive marker of mania
(analogous to anhedonia in depression). In fact, the DSM-5 changed its diagnostic criteria
so that the absence of increased activity absolutely rules out a diagnosis of mania. When
this goal-directed activity is blocked (such as by a well-meaning spouse or friend who is
concerned about how erratically they are behaving), someone in a manic state is liable to

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become quite irritable, yelling or lashing out at the person who is getting in the way of
their world-changing aspirations.
S is for Sleep. Decreased sleep is another key symptom of mania. In contrast to depression
which is most often characterized by a perceived inability to sleep, sleep disturbance in
mania is experienced as a decreased need for sleep (generally due to the increase in goal-
directed activity). It’s not uncommon for people in a manic state to keep going for days or
even weeks on only a few hours of sleep per night.

T is for Talkativeness. Finally, people in a manic state

are often hypersocial and exceptionally talkative, which is described on a mental status exam
as pressured speech. ey may walk around a room repeatedly shaking the hand of every
single person present. Some studies have even found that speci c aspects of speech, such as
uctuating pitch and high rate of speech, are highly sensitive markers of mania.
A manic episode involves an increase in
psychomotor energy and activity accompanied by
other signs and symptoms.
Elevated or irritable mood + DIG FAST:
Distractibility Impulsivity Grandiosity Flight of ideas
Activity (increased) Sleep (decreased need for)
Talkativeness
Per DSM standards, having at least 3 of these 7 symptoms for 1 week or more
quali es the patient for a manic episode (think “one fun week” versus “two blue weeks” in
depression). At least one of these symptoms must be increased activity. Like with
depression, the DSM criteria do not capture the entirety of mania, and some additional
signs and symptoms can often be seen. Many people in a manic state describe a feeling of
mental and physical robustness (“I’ve never felt better in my life!”). Friends and family will
often say that there is a change in moral standards that accompanies mania (such as a
trustworthy banker who suddenly begins to write bad checks). People in a state of mania are
noted to be very quick witted and genuinely humorous in a way that is infectious. A variety
of delusions are often seen in mania as well; they tend to be grandiose and even playful in
nature and are much less stable and systematized than the complex belief systems seen in
schizophrenia.
Per the DSM-5, patients must have 3 out of 7
symptoms for a period of 1 week or more to qualify
for an acute manic episode.
e timeframe for mania is one fun week.
Some may wonder what exactly is pathological about mania. It makes sense that “too
much sadness” would be a disorder; “too much happiness” less so. e key with mania lies
not in the content of the disorder but in the process. Just like depression, in mania a patient’s
mood is notably non-reactive, rendering someone incapable of experiencing emotions other
than happiness. To use an analogy, it’s not a problem if a car can go fast as long as it is

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capable of slowing down when it needs to. However, if the car is always moving at top
speed and cannot slow down for any reason, then this becomes a dangerous situation not
only for the driver but also for everyone else on the road. To put it simply, mania is life with
the brakes off. To push the car analogy even further, driving without brakes is likely to end
in a crash. is is exactly what we see with mania, as manic episodes are frequently followed
by depressive episodes. Indeed, the relationship between mania and depression is so well
characterized that we don’t refer to people as only having one or the other (there is no
“manic disorder”). Instead, we refer to people who have manic episodes as having bipolar
disorder (formerly, and perhaps more accurately, known as “manic-depressive disorder”).
 

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BIPOLAR DISORDER ACROSS THE LIFESPAN

Mania is not difficult to diagnose in person. As

any experienced clinician can tell you, once you have seen someone in a state of “full blown”
mania, you never forget it. is would make diagnosing bipolar disorder, of which mania is
the hallmark state, a seemingly easy matter. However, in reality bipolar disorder is often
quite challenging to diagnose. e challenge comes from the fact that, despite being the
de ning state of bipolar disorder, mania is not the most frequent state. In fact, studies show
that people with bipolar disorder spend as little as 1% of their time in a manic state, with
the rest being divided between euthymia (about 50%), depression (35%), a state of milder
manic symptoms known as hypomania (10%), and cycling between episodes (5%). So
unless you happen to catch someone in the part of their lifetime that they spend manic, you
must instead rely upon subjective reports from the patient or collateral. As with anything
subjective, these reports are highly variable, as someone else’s de nition of “manic,”
“bipolar,” or “hyperactive” cannot be assumed to align with clinical standards of diagnosis.
Because of this, take any past reports of “manic” symptoms with a grain of salt, and ask
patients and their families to avoid using jargon in favor of objective descriptions of
behavior that are more likely to capture the increased goal-directed activity that de nes
mania.
e challenge in diagnosing bipolar disorder is compounded further by the fact that
bipolar disorder is a relatively rare syndrome. Bipolar I disorder is found at a rate of around
1% of the population (compared to 20% for unipolar depression and up to 30% for anxiety
disorders as a whole). e combination of a rare hallmark state and a low base rate virtually
ensures that bipolar disorder will be overdiagnosed.
 

Looking across the lifespan, bipolar disorder tends to begin earlier in life than
depression, with onset in the late teens and early adulthood (with an average age of 21
years for a rst episode). Men and women are affected equally often, although men with
bipolar disorder have manic episodes more often than women with the disorder.
 
PROGNOSIS
Like major depressive disorder, functioning is often signi cantly impaired during a mood
episode but preserved between episodes. However, people with bipolar disorder tend to
spend more of their lives in a mood episode compared to people with unipolar depression.
In contrast with depression, bipolar disorder is a highly recurrent syndrome. Whereas the
risk of recurrence after a single depressive episode is only 50%, the risk of having another
mood episode after even a single manic episode is over 90%! is has important
implications, both for educating patients and families about the nature of their illness as
well as deciding on how long to continue with treatments.

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 Bipolar disorder shares with depression a signi cant mortality rate, including a high
risk of suicide during depressive episodes. Up to 1% of all people with bipolar disorder will
attempt suicide within a one-year span, a rate 60 times higher than the general population.
In addition, people with bipolar disorder tend to use highly lethal means such as rearms
more often, with one death for every 3 suicide attempts (as opposed to one for every 25
attempts in the general population).
While suicide tends to happen in depressive or mixed episodes, mania can also be a
highly destructive state. It is not uncommon for patients to engage in high-risk behavior
such as reckless driving or drug abuse which may cause both immediate and delayed harm
to themselves, others, and their livelihood. Because of this, mania and depression should
both be considered high-risk states that warrant immediate diagnosis and treatment.
 
TREATMENT
Untreated, an episode of mania typically lasts around 3 to 6 months, but with treatment a
manic episode can be stopped within a matter of days or weeks. Like unipolar depression,
an episode of bipolar depression can last up to a year without treatment, but this can be
reduced down to 2-3 months with treatment. Given the risks involved with both bipolar
mania and depression, hospitalization is often necessary for acute stabilization and initiation
of treatment. Given that mania is often experienced as an enjoyable state, patients may be
hesitant or unwilling to consider treatment (“What do you mean you think I should be in
the hospital? You must not know how amazing my fruit smoothies are!”). Involving family
and friends to help encourage treatment can be highly effective. In cases where insight is
severely impaired, a court order for involuntary treatment may be sought.
Treatment of bipolar disorder is signi cantly more complicated compared to unipolar
depression. is is because there are not one but two distinct mood states, each of which
requires separate treatment considerations. In addition, because of the highly recurrent
nature of bipolar disorder, treatment must be focused not only on treating the current
symptoms but also on preventing future episodes of both kinds. Unlike depression (where
treatment generally includes either therapy, medications, or both), for bipolar disorder the
standard of care is to almost always use both medications and psychotherapy, with therapy
alone not considered sufficient for treating bipolar disorder in the majority of cases.
Medications used to treat bipolar disorder are known as mood stabilizers. e oldest
known mood stabilizer is lithium, which has been shown to be effective at both treating
and preventing manic and depressive episodes (with a moderate effect size above 0.5).
Interestingly, lithium appears to be most effective for patients who match “classic” mania
symptomatology, with less effect noted with increasing atypical features (such as mixed
features or rapid cycling, discussed in the next section). Lithium is also one of the few
medications that has been proven to lower suicide risk. In fact, patients taking lithium are
over 80% less likely to commit suicide while taking lithium than when not.
Certain anticonvulsant medications can also act as mood stabilizers but tend to only
treat one phase of the illness or another. For example, valproate and carbamazepine are
helpful for treating mania (with a small effect size around 0.3) but do not treat depression,
while lamotrigine prevents depression (with an effect size around 0.4) without having any
antimanic effects. Antipsychotics are also effective at treating bipolar disorder with an
effect size around 0.5. In fact, antipsychotics are actually faster at reversing a state of mania
than conventional mood stabilizers like lithium, valproate, and carbamazepine and should
be used as a rst-line treatment in situations when urgent treatment is needed. While any

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antipsychotic can treat mania, only a select few can treat bipolar depression (speci cally
quetiapine, lurasidone, and olanzapine which each have effect sizes in the range of 0.2 to
0.5). While one might be tempted to use antidepressants like SRIs to treat bipolar
depression, this would be a grave error, as conventional antidepressants are generally
considered to be ineffective for treating bipolar depression and may actually be harmful by
inducing a state of mania, a mixed state, or rapid cycling. Finally, electroconvulsive
therapy may be considered for patients who have not responded to less invasive treatments.
ECT is effective at treating both mania and bipolar depression, with over two-thirds of
patients responding well to this form of treatment.
Psychotherapy can be an incredibly helpful adjunct to medications for treating
bipolar disorder. Patients receiving psychotherapy in addition to medications have less
severe symptoms and a lower risk of relapse compared to people just on medications alone.
In particular, CBT has been shown to have a small to medium effect size on a variety of
outcomes including symptoms, treatment adherence, quality of life, and relapse prevention.
Other types of therapy that also have evidence to support their use in bipolar disorder are
psychoeducation, interpersonal and social rhythm therapy, family focused therapy, and
integrated care management. erapy can be delivered either individually or in groups, with
similar efficacy for both.

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MECHANISMS OF MANIA
One theory suggests that bipolar disorder develops as a consequence of individual
differences in processing reward-related stimuli. In particular, people with bipolar disorder
tend to show an emotional hypersensitivity to rewards, even when not in a manic state. (In
fact, reward hypersensitivity is highly predictive of developing mania even for someone who
has never had a manic episode.) Someone with reward hypersensitivity shows greater
behavioral, emotional, and cognitive responses to rewards, leading them to set overly
ambitious goals (particularly in the area of fame, achievement, and nances) and regularly
overestimate their chances of success.

To illustrate this, let’s say that there is a card game that

costs $20 to play. You get to ip over a single card from a full deck. If that card is an ace,
you win $100; otherwise, you lose. With 4 aces in a deck of 52 cards, the odds of drawing
an ace are less than 8%, making this an objectively bad deal. Someone with an average level
of sensitivity to reward-related stimuli might nd this interesting and decide to play.
However, after losing a game or two, they would likely recognize that the odds are against
them and stop playing. In contrast, someone with reward hypersensitivity might see this
game and think, “If I play at least a few times, I’m sure to win! And if I win once, I can
keep playing and eventually build up $1000. With this money, I can nally begin
developing that smartphone app I’ve been thinking about.” Even after losing ve, ten, or
twenty times, this person is likely to continue believing that they will make money off of
this venture due to persistent overestimation of their likelihood of reward.
is hypersensitivity to reward-related stimuli explains why increased goal-directed
activity is such a sensitive marker for mania, as many of the other symptoms of mania
(including grandiosity, ight of ideas, decreased need for sleep, and talkativeness) are
secondary manifestations of this core abnormality. Indeed, increased goal-directed activity is
a clearly identi ed prodrome of mania and often precedes other manic symptoms by days
or even weeks. is intense focus on goal-directed behavior also explains the tendency to
engage in extremely pleasurable or rewarding activities such as sex, shopping, and drug use
(known as hyperhedonia).
Reward hypersensitivity is correlated with overactivation of neural circuits in the left
lateral orbitofrontal cortex, a region of the brain that governs the relationship between
emotions and decisions. Interestingly, bipolar depression and unipolar depression are both
associated with decreased reward sensitivity in the left lateral orbitofrontal cortex which in
turn reduces motivation and the ability to gain pleasure from normally enjoyable activities.
(Recall from the previous chapter that negative affective biases involve persistent
underestimation of chances of success.) In this way, the left lateral orbitofrontal cortex may
hold the key to both depression and mania, as it explains both the increased goal-directed
activity seen in mania as well as the anhedonia that is the most sensitive marker of

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depression. You can remember the association of the Left lateral orbitofrontal cortex by
thinking of it as the part of the brain that says “Let’s live outrageously! Forget
consequences.”
e left lateral orbitofrontal cortex is overactivated
in bipolar disorder.
Left lateral orbitofrontal cortex = “Let’s live
outrageously! Forget consequences.”

Knowing about reward hypersensitivity and increased goal-directed activity serves a

practical clinical purpose by delivering a highly sensitive marker for diagnosis. Because of
this, it may be more helpful to think of mania as a period of increased goal-directed activity
than simply a period of “feeling happier than normal,” as this is neither a sensitive nor
speci c marker of a manic episode.
Mania involves increased goal-directed activity
more often than elevated mood.
MANIA = More Activity, Not Inherently Affective

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DIAGNOSING BIPOLAR DISORDERS
us far, we have limited our discussion to the state of “textbook” mania and its associated
condition known as bipolar disorder. However, there are a variety of ways that mania and
bipolar disorder can manifest that carry important implications for prognosis and treatment.
BIPOLAR I DISORDER
Bipolar I disorder (also known as bipolar disorder type 1) is characterized by episodes of
mania alternating with episodes of depression. e presence of even a single manic episode
quali es the patient for a diagnosis of bipolar I disorder regardless of how many depressive
episodes they have had. ( ere may be rare cases of people who have only manic episodes
with no episodes of depression, but the vast majority of people who have even a single
manic episode will also have a major depressive episode at some point in their lifetime.
erefore, anyone presenting with mania but no history of depressive episodes may simply
have not experienced a depressive episode yet.) Recognition of manic and depressive
episodes is done on a clinical basis. You can use the mnemonic DIG FAST to remember
the symptoms of mania. As discussed in Chapter 5, depressive episodes in bipolar
depression are often indistinguishable from unipolar depression, and you can use the
SIGECAPS mnemonic to remember the signs and symptoms of a depressive episode.
BIPOLAR II DISORDER
Just as mania is the hallmark state of bipolar I disorder, hypomania is the hallmark state of
bipolar II disorder (also known as bipolar disorder type 2). Hypomania is a state of elevated
mood and heightened activity that is similar to, but not quite as severe as, mania. People in
a hypomanic state are productive, ecstatic, and indefatigable. ese symptoms might even
be noticeable by others, but by de nition they never reach a level of intensity that they cause
dysfunction in life. Compared to mania, the timeframe for diagnosing an episode of
hypomania is shorter, requiring only 4 days of sustained hypomanic symptoms to be
present.
Unlike mania, hypomania is not inherently pathological, and many people with bipolar II
disorder describe being at their peak level of functioning during an episode of hypomania.
So why is bipolar II disorder a problem? e problem with hypomania is that it is often, if
not always, associated with episodes of severe depression, which is when most people with
bipolar II will come to clinical attention. Indeed, despite the absence of “full-blown” manic
episodes, bipolar II disorder should not be seen as a milder disorder compared to bipolar I.
While their manic states are less pronounced, people with bipolar II disorder have more
frequent and severe depressive episodes, leading to greater overall levels of functional
impairment. In addition, people with bipolar II have higher rates of suicidal thoughts and
attempts than either bipolar I disorder or unipolar depression. You can remember the
predominant state of depression in bipolar II compared to I by thinking of the II as two
lower-case l’s in a row standing for lower lows (and lower highs as well).
Bipolar II disorder is characterized by both
hypomanic and depressive episodes, the latter of
which are often more frequent and severe compared
to bipolar I.
Bipolar ll disorder involves lower lows than bipolar I
disorder.

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 Treatment of bipolar II disorder has not been studied as extensively as bipolar I
disorder, but it largely resembles bipolar I in that mood stabilizers and antipsychotics appear
to be useful, while antidepressants are often ineffective or even harmful.

CYCLOTHYMIA In theory, cyclothymia is a mild form of

bipolar disorder where the patient has both hypomanic episodes (that do not meet criteria
for a manic episode) and periods of subsyndromal depression (that do not meet criteria for
a major depressive episode). It is similar in many ways to dysthymia by representing a more
persistent but less severe version of the prototype disorder. As with dysthymia, patients
must have the characteristic pattern of this disorder for 2 years prior to receiving the
diagnosis. In clinical practice, a diagnosis of cyclothymia is incredibly rare. A large part of
this is due to the fact that it is ultimately not that hard to meet criteria for a major
depressive episode (in which case they would be diagnosed with bipolar II disorder). In
addition, it is likely that someone who remains at a subsyndromal level of symptoms may
never actually reach the point where they present for clinical attention. Evidence on
treatment of cyclothymia is scarce, but existing data suggests that it should be treated
similarly to bipolar II disorder.
To aid your understanding of the relationship between unipolar depression, dysthymia,
bipolar I disorder, bipolar II disorder, and cyclothymia, a visual summary of these
conditions is found on the next page.
 

Major depressive disorder Dysthymia

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 Dysthymia and depression Bipolar I disorder

Bipolar II disorder Cyclothymia

Schematic diagrams of various mood disorders. e x-axis shows time in years (with individual years marked by a dotted line),
while the y-axis shows the patient’s mood state (with euthymia set at the x-axis, manic symptoms above the x-axis, and depressive
symptoms below the x-axis).
MIXED STATE
While classically depression and mania were considered to be mutually exclusive states,
decades of clinical research have demonstrated that it is possible for someone to have both
depressive and manic symptoms at the same time. is is known as a mixed state or mixed
manic episode. While it may seem paradoxical to be both manic and depressed at the same
time, recall that the predominant feature of mania is more activity and that it is not
inherently affective. erefore, a mixed state isn’t someone who feels both happy and sad at
the same time—rather, it is a combination of low mood (including thoughts of guilt,
hopelessness, despair, and suicide) and increased psychomotor activity which is often
expressed as severe irritability or even agitation.
As you might expect, the combination of profound depression and increased energy
makes mixed states a high-risk time, with a higher chance of reckless activity or suicide
compared to either depression or mania alone. Mixed states are considered to be in the
realm of bipolar disorder, and even for someone who has never experienced a full manic or
hypomanic episode, the presence of mixed features in a depressive episode is strongly
suggestive of a bipolar (rather than unipolar) mood disorder. As with most bipolar

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conditions, treatment of a mixed state involves mood stabilizers and/or antipsychotics, with
conventional antidepressants to be avoided.
BIPOLAR DISORDER WITH PSYCHOTIC FEATURES
Just as depression can present with psychotic features, so too can bipolar disorder co-occur
with symptoms resembling psychosis. is can occur during mania, depression, or a mixed
state. e frequency of psychotic symptoms in bipolar disorder is even more pronounced
than in unipolar depression, with more than half of all patients with bipolar disorder
experiencing some degree of psychotic symptoms during their lifetime. Treatment often
involves antipsychotics, sometimes on their own (as they often have mood stabilizing
properties) but more often combined with a mood stabilizer like lithium or an
anticonvulsant.
BIPOLAR DISORDER WITH CATATONIA While catatonia can occur in a variety of
severe psychiatric syndromes, in the modern day bipolar disorder is the most common
cause of catatonia with more than half of all patients with catatonia meeting criteria for
bipolar disorder. Like psychosis, it can occur during mania, depression, or a mixed state.
Catatonia is treated the same regardless of its etiology (using benzodiazepines or, if these
are ineffective, ECT).
RAPID CYCLING BIPOLAR DISORDER
Given that most depressive episodes last 6 to 12 months and manic episodes last 3 to 6
months, the majority of people with bipolar disorder have less than one major mood
episode per year. However, a small subset of patients with bipolar disorder are considered to
have a rapid cycling variant de ned as having 4 or more distinct mood episodes within a 1
year period. Rapid cycling bipolar disorder has been associated with use of antidepressants,
which may induce rapid cycling (another reason to avoid using them in any form of bipolar
disorder).
It’s important to note that rapid cycling does not refer to alternations in mood
episodes that happen over the course of minutes, hours, or days. As will be discussed in
Chapter 13, changes in mood and affect occurring within a short period of time are more
likely re ective of affective instability and should raise diagnostic consideration of borderline
personality disorder.
POSTPARTUM PSYCHOSIS
Postpartum psychosis is a state of disorganized restlessness and inability to distinguish
reality from fantasy that occurs in the rst few weeks after childbirth in around 0.1% of all
deliveries. Postpartum psychosis is considered to be a psychiatric emergency due to the
risks to both the baby and the mother, and immediate hospitalization is often required.
Medication treatment generally involves mood stabilizers and antipsychotics. Despite the
name postpartum “psychosis,” this condition is much more strongly associated with mania,
and women with bipolar I disorder have over a 35% chance of postpartum psychosis
following delivery.
 

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DIFFERENTIAL DIAGNOSIS OF BIPOLAR DISORDERS
Given how bipolar disorder is associated with both highs and lows, it is appropriate that the
disorder itself would be affected by both overdiagnosis and underdiagnosis. e low base
rate of the disorder in the general population ensures that overdiagnosis will remain a
problem, while the rarity of mania means that underdiagnoses and misdiagnoses will
continue. Nevertheless, studying the interface between bipolar disorder and many of the
misdiagnoses and missed diagnoses that frequently accompany the disorder can provide
clarity when approaching patients with mood symptoms. As with depression, the
mnemonic Reactive PLANETS (for Reactivity, Polarity, Lability, Attributability,
Normality, Episodicity, Treatment responsivity, and Severity) can provide a clinical
framework for assessing any patient presenting with extremes of mood.
 

 
NORMALCY
ere is nothing inherently pathological about emotions or moods. However, anyone who
experiences emotions strongly is at risk of being overdiagnosed as having bipolar disorder,
largely due to misconceptions about what the term “bipolar” means. More than just being
stigmatizing, overdiagnosis of bipolar disorder can lead to use of medications like mood
stabilizers and antipsychotics that are often harmful in the long-term. e “cure” for
overdiagnosis is for clinicians to understand the patterns and phenomenology of bipolar
disorder well enough to consistently arrive at an accurate diagnosis. As with unipolar
depression, the pathological mood states of bipolar disorder are distinguished from normal
everyday swings of emotion in that they are severe, sustained, and non-reactive to external
events. It is this non-reactivity that most reliably separates mood disorders from normalcy
(remember that it’s only a problem for a car to go fast if it is unable to brake when it needs
to).
 
UNIPOLAR DEPRESSION

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 Up to two-thirds of people with bipolar disorder are initially
diagnosed as having unipolar depression. While there are certain aspects of a patient’s
history that can suggest a possible bipolar etiology (including an earlier onset in life, a family
history of mania, pronounced psychomotor retardation, or the presence of melancholic,
atypical, or psychotic features), until someone has “declared” themselves by having their rst
manic, hypomanic, or mixed episode it is impossible to accurately distinguish between
unipolar and bipolar depression on the basis of clinical presentation alone. Because of
this, clinicians tend to fall into two camps: overcallers and undercallers. Overcallers cite the
dangers of undertreatment and mistreatment (including a risk of inducing rapid cycling by
using antidepressants) to justify a higher rate of false positives and more liberal use of mood
stabilizers and antipsychotics. In contrast, undercallers are wary of the stigma of
overdiagnosis as well as signi cant long-term toxicities associated with use of mood
stabilizers and antipsychotics and prefer to err towards the side of false negatives. Given
that there are risks associated with both undercalling and overcalling, try to use your best
clinical judgment on the initial diagnosis while always being mindful that your diagnosis
must remain exible as new information (such as the emergence of new symptoms or a
patient’s response to treatment) comes to light.
 
BORDERLINE PERSONALITY DISORDER
After unipolar depression, borderline personality disorder is the disorder that is most
commonly confused with bipolar disorder, with as many as half of all patients with
borderline personality disorder receiving a misdiagnosis of bipolar disorder at some time in
their lives. is is especially common when the diagnosis is based on reported history rather
personally witnessed symptoms. e reasons for this confusion stem from the fact that, at
least on a super cial level, many features are shared between the two disorders. Both are
characterized by extreme swings of emotion as well as a tendency towards recklessness and
impulsivity. In addition, irritability can be a sign of a manic episode as easily as it can be a
manifestation of the chronic anger and hostility seen in cases of borderline personality
disorder.
Making the distinction between bipolar disorder and borderline personality disorder is
highly dependent upon the timing of speci c symptoms. A core feature of borderline
personality disorder is affective instability resulting in rapid changes in emotional
expression. However, these swings occur within the span of seconds or minutes in contrast
to the mood episodes lasting weeks or months that are characteristic of bipolar disorder.

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(Even rapid cycling bipolar disorder is characterized by 4 mood shifts per year, suggesting
an average of 3 months between transitions.) In addition, the affective instability and
impulsivity found in borderline personality disorder tend to be chronic whereas the
recklessness seen in manic episodes only exists as long as the mood state is present.
Additional features of borderline personality disorder, including non-suicidal self-harm,
dissociative experiences, and chronic feelings of emptiness, may help to further the
distinction. Don’t use treatment response to distinguish between bipolar disorder and
borderline personality disorder, as antidepressants are ineffective in both conditions while
mood stabilizers and antipsychotics can each provide some bene t in either disorder.
 
OTHER PERSONALITY DISORDERS
Certain symptoms of mania can easily be mistaken for evidence of speci c personality
disorders. In particular, grandiosity can be confused for narcissistic personality disorder,
excessive emotionality can be confused for histrionic personality disorder, and irritability
can be confused for antisocial personality disorder. As with borderline personality disorder,
be careful not to confuse these state-dependent characteristics (which will come and go with
the mood episode) with the chronic and enduring traits found in personality disorders.
 

SUBSTANCE-INDUCED MANIA e behavioral effects of speci c drugs can often

resemble mania either during intoxication or withdrawal. For example, someone taking a
stimulant like cocaine or methamphetamine can develop high levels of energy, activity, and
sleeplessness that can closely mimic a manic episode, while withdrawal from depressants
like alcohol or benzodiazepines can induce a state of anxiety, restlessness, and insomnia that
can similarly be mistaken for a manic or mixed episode. Pay attention to the timing and
attributability of symptom onset to differentiate bipolar mania from substance-induced
mania. In addition, be mindful that even some prescription drugs (such as steroids) can
induce a prolonged state of mania.
 

ANTIDEPRESSANT-INDUCED MANIA While it is technically a form of substance-

induced mania, antidepressant-induced mania deserves special mention. For a long time, it
was believed that antidepressants, when given to someone with bipolar disorder, could
“switch” them into mania. e evidence on this is inconclusive, with some studies showing
a link between antidepressants and mania and others showing none. e current standard is
to avoid diagnosing bipolar disorder if the manic symptoms only developed in the context of
antidepressant use and go away soon after the medication is stopped. Only in cases where
mania persists for an extended period of time following antidepressant discontinuation
should a primary diagnosis of bipolar disorder be considered.
 

ADDICTION
Bipolar disorder and addiction are frequently comorbid, with up to 70% of patients with
bipolar disorder meeting criteria for a substance use disorder at some time in their lives. It is
likely that the two disorders feed into each other, with the recklessness and impulsivity of
mania predisposing towards use of addictive substances which can later bloom into an

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addiction. Conversely, continued overuse of drugs can exacerbate the depression and
irritability found in bipolar disorder, leading to a vicious cycle.
Because of this overlap, overdiagnosis and underdiagnosis of bipolar disorder in substance
abusing populations are equally problematic. As many as two-thirds of people who have
been diagnosed as having both bipolar disorder and a substance use disorder do not meet
criteria for bipolar disorder when structured interviews are used, suggesting high rates of
overdiagnosis in this population. Yet clinicians need to be mindful to screen for addiction in
patients with bipolar disorder to avoid missing an important part of the picture. In nearly all
cases, conducting a careful substance use history and requesting a urine toxicology screen
can be helpful. Finally, be sure to carefully assess the timing and attributability of the
relationship between mood symptoms and substance use (for example, if irritability and
sleeplessness only appeared when someone stopped drinking).
 
MANIA DUE TO A MEDICAL CONDITION
A state resembling mania can be induced by a variety of medical conditions, including
hyperthyroidism, Cushing’s disease, and various intracranial conditions including tumors
and infections. Consider the possibility of mania due to another medical condition in
patients who do not have a personal or family history of bipolar disorder (especially if they
are older and have not yet had a mania episode), where there is anything atypical about the
clinical presentation, or when mania presents with unexplained neurologic or physical
ndings such as vital sign abnormalities.
 
ANXIETY DISORDERS
Anxiety is common in bipolar disorder but is generally more of a missed diagnosis than a
misdiagnosis. However, in some cases the racing thoughts, irritability, and difficulty
concentrating found in anxiety disorders can be mistaken for similar symptoms in bipolar
disorder. e episodicity of bipolar disorder should help to distinguish these symptoms
from the more chronic course associated with anxiety disorders.
 
ATTENTION DEFICIT HYPERACTIVITY DISORDER
Certain symptoms of ADHD, including racing thoughts and impulsivity, can resemble
mania. However, in ADHD these symptoms will have been continually present since
childhood, whereas in mania they will come and go in an episodic pattern.
 
SCHIZOPHRENIA AND SCHIZOAFFECTIVE DISORDER
e relationships between mood and psychotic disorders will be explored more fully in the
next chapter. For now, just know that bipolar disorder can present with psychotic
symptoms, so the presence of psychosis does not necessarily rule in schizophrenia, nor does
it rule out bipolar disorder.
 

THE “MANIAS”
Several recognized mental disorders have the word “mania” in their name, including
kleptomania (excessive stealing), pyromania ( re starting), and trichotillomania
(compulsive hair pulling). Don’t let the suffix confuse you: these conditions are not in any
way related to bipolar disorder.

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PUTTING IT ALL TOGETHER
In many ways, bipolar disorder is a paradox. It is characterized by opposite extremes of
mood that can somehow happen at the same time. Its hallmark state is exceptionally easy to
recognize clinically, yet diagnosing the disorder as a whole is incredibly challenging. It is
somehow both overdiagnosed and underdiagnosed as well as both overtreated and
undertreated, leading to perpetuation of stigma, pathologizing of normal emotions, and use
of ineffective and harmful treatments.
Appropriate use of the bipolar diagnosis requires a rm understanding of the
phenomenology of the disorder as well as its epidemiologic, prognostic, mechanistic, and
treatment considerations. Use the DIG FAST and SIGECAPS mnemonics to recognize
the speci c signs and symptoms of bipolar mania and bipolar depression, respectively, while
remembering that MANIA is associated with More Activity and is Not Inherently
Affective. Consider that it is not always possible to differentiate bipolar depression from
unipolar depression until someone has had their rst manic or hypomanic episode.
However, making this distinction is crucial as the prognosis differs signi cantly between the
two conditions (with a much higher rate of recurrence after a rst episode in bipolar
disorder) and requires different treatment considerations. Both mania and depression are
high-risk states and can often require immediate and intensive treatment. Treatment for
bipolar disorder involves both medications and therapy, with mood stabilizers and
antipsychotics being used for treatment and prevention of both mania and depression
(although the speci c medications used within these classes will differ depending on the
mood state). Finally, use the Reactive PLANETS mnemonic to evaluate mood states in a
structured way that allows for identi cation of potential misdiagnoses and missed
diagnoses.
 

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REVIEW QUESTIONS
1. A 22 y/o F is brought into the emergency department by police after she was
involved in a physical altercation at a local supermarket. According to the police
report, the patient hit another person in the head with a nutcracker while dancing
in the aisles. Upon entering the room, the psychiatrist on-call sees that she is only
wearing her underwear. She stands up and says, “You need to let me go! I have to
get back to the store so that I can make my ‘world’s greatest pecan pie’!” She
proceeds to detail her plans to bake the “the biggest, baddest pecan pie that man
has ever seen” so she can qualify for a baking show competition on television. She
speaks of these plans very rapidly but is easily distracted, saying, “Oh you’re a
doctor? Where did you go to school? Did you go to Harvard? I’ve been to
Harvard, I taught there before. I taught them everything they know!” Her husband
arrives who reports that the patient has no prior psychiatric history and takes no
medications outside of oral contraceptives. While the psychiatrist is talking with
her husband, she begins banging on the door and yelling, “ at’s the jerk who
threw away my pie! I’m gonna kill him!” What is the most appropriate next step?

A. Start lithium

B. Start an anticonvulsant mood stabilizer

C. Start an antipsychotic

D. Start an antidepressant

E. Defer medications until the results of a urine drug screen are available

2. (Continued from previous question.) e patient is admitted to the hospital for

further management. She consistently denies that there is any problem and
declines any medication that is offered to her. e urine drug screen returns
negative. For the rst two days of hospitalization, the patient is seen walking
around the unit shaking hands with other patients and inviting them on trips with
her to Bermuda and Hawaii. While talking with one of the male nurses, she
attempts to reach her hand down his pants and is escorted back to her room.
During a family meeting that day, her husband breaks down in tears and says,
“ is isn’t her. I don’t know what happened to my wife. Is she going to be like this
forever?” What is the most appropriate response?

A. “Yes, this is likely a permanent change in her personality.”

B. “No, but it is very likely that she will have times like this in the
future.”

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 C. “No, but there is a 50-50 chance that she will have times like this in
the future.”

D. “No, and it is unlikely that she will have times like this in the future.”

E. “No, this is likely the rst and last time this will ever happen.”

3. An 18 y/o M comes to a psychiatric clinic for an initial evaluation. He reports that

over the past 5 weeks he has lost all interest in interacting with other people,
saying that socializing “tires me out and I can’t afford that right now.” He has not
been participating in soccer intramurals despite being team captain. His mood is
“terrible,” and he admits that he has been thinking of ways to kill himself over the
past several days. When asked about his appetite, he responds by saying, “It is
impossible for me to eat when I have spiders living in my throat.” He denies that
this is a metaphor and voices his belief that spiders have taken up residence in his
vocal cords. He believes that the spiders sometimes “vibrate my vocal cords” to
communicate with him while he is falling asleep at night. Further history taking
reveals that his father and paternal grandmother have both been hospitalized for
manic episodes. He has no personal psychiatric history and has never taken
medications. Physical examination reveals no abnormalities other than slowed
movements and speech. Which of the following features argues for a higher
likelihood of bipolar rather than unipolar depression?

A. Onset during adolescence

B. Presence of psychomotor retardation

C. Presence of psychotic features

D. Family history of mania

E. All of the above predict a higher chance of bipolar depression

F. None of the above predict a higher chance of bipolar depression

4. (Continued from previous question.) Which of the following is the most

appropriate statement to make at this time?

A. “You have bipolar disorder. We should start a mood stabilizer.”

B. “You probably have bipolar disorder. We should avoid

antidepressants.”

C. “It’s possible you have bipolar disorder. Let’s monitor closely and not
prescribe any medications.”

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 D. “It’s unlikely but not impossible that you have bipolar disorder. Let’s
start an antidepressant with an antipsychotic.”

E. None of the above

5. A 45 y/o F comes into the psychiatrist’s office. She is being considered for
promotion to an executive office at her company on Wall Street and has been asked
to undergo a comprehensive mental health evaluation. On interview, she denies
feeling depressed either now or in the past. She does endorse having times in her
life when she is able to function at a higher level than usual, “writing reports and
lling out spreadsheets like a madwoman.” ese episodes usually last for several
weeks at a time. During these episodes, she often is able to function on “only a few
hours, maybe 3 or 4 hours” of sleep per night but does not feel signi cantly
fatigued during the day. She denies use of caffeine, nicotine, alcohol, or other
substances. She denies auditory hallucinations, delusions, or paranoia other than
saying “sometimes I think other people at work are jealous of me and would want
nothing more than to see me dead, but that’s Wall Street for you” with a laugh.
She is married to her husband of 3 years and has a 5-year-old son at home. She
has never taken psychiatric medications and is not aware of any medication
allergies. What is the most likely diagnosis?

A. Bipolar I disorder

B. Bipolar II disorder

C. Schizoaffective disorder, bipolar type

D. Schizoaffective disorder, depressive type

E. Major depressive disorder

F. None of the above

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1. e best answer is C. is patient is likely suffering from a manic episode,
although due to a lack of history other causes like a substance-induced mood
disorder cannot be ruled out. However, given the patient’s high level of agitation
and risk of violent behavior, it is appropriate to initiate treatment even before
diagnostic clarity is achieved (ruling out answer E). Out of the options available,
antipsychotic medications are the most effective at rapidly reducing a state of
mania and should be started rst. Lithium or an anticonvulsant mood stabilizer
can be started concurrently but should not be the only medication prescribed in an
emergent situation like this (answers A and B). An antidepressant runs the risk of
exacerbating manic symptoms or inducing rapid cycling and should be absolutely
avoided in this situation (answer D).
2. e best answer is B. Mania is associated with a high chance (over 90%) of future
mood episodes, even with treatment. For this reason, patients and their families
should be counseled on the risk of recurrence and be advised on how to prepare for
them, such as coming up with a safety plan and knowing who to contact in case of
an emergency. Mania is an episodic condition, not a permanent change to
someone’s personality (answer A).
3. e best answer is E. All of these clinical features predict a higher chance of
bipolar depression compared to unipolar depression.
4. e best answer is D. Despite a high number of risk factors that increase the
likelihood of bipolar depression in this patient, rst episodes of depression should
be considered to be unipolar in origin until proven otherwise. erefore, it is not
appropriate to tell the patient that he has bipolar disorder with any degree of
certainty (answers A and B). Considering that bipolar depression is signi cantly
less common than unipolar depression, it is reasonable to say that it is unlikely that
he has bipolar depression, in which case he would likely qualify for a diagnosis of
major depressive disorder with psychotic features which is treated with a
combination of an antidepressant and an antipsychotic (answer D). Given the
severity of his current symptoms, it would not be appropriate to monitor without
recommending treatment (answer C).
5. e best answer is F. is patient shows no evidence of distress or dysfunction in
her life, precluding a diagnosis of a mental disorder. It is questionable whether she
experiences hypomanic episodes, as her self-reported description of her behavior is
at least consistent with hypomania. However, as there is no evidence of
impairment from these episodes and no associated depressive episodes, they would
not be diagnosed as being a disorder. It is possible that, in the future, she will
develop depressive episodes, at which time a diagnosis of bipolar II disorder could
be considered. Until that time, however, there is no justi cation for any psychiatric
diagnosis for this patient (answers A through E).
 

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7 PSYCHOSIS

Psychosis is an abnormal mental state where one is

unable to distinguish reality from falsehoods. While the nature of reality can be debated,
when used in a clinical sense it often refers to a shared or consensus reality (what most people
would agree upon as being real or true). Psychosis is an incredibly broad term that can
encompass many possible symptoms and causes. For example, you could say that someone
with delirium is psychotic, and under this de nition you would be right. Within the eld of
psychiatry, however, the word often has a much more speci c meaning, referring to a state
of primary psychosis that is not attributable to any other medical or psychiatric condition.
Primary psychosis is the hallmark state seen in thoughts disorders like schizophrenia.
In this chapter, we’ll review the phenomenology of schizophrenia including the speci c
forms of hallucinations, delusions, thought disorganization, and negative symptoms that are
seen. From there, we will learn about the progression of schizophrenia across the lifespan,
including its onset, prognosis, and characteristic course as well as the possible mechanisms
underlying the disorder. Finally, we will cast our eye on the misdiagnoses and missed
diagnoses that must be considered when evaluating anyone with psychotic symptoms.
Schizophrenia is among the most challenging mental disorders to diagnose, as many other
conditions have signs and symptoms that can mimic those of primary psychosis. Despite
this challenge, understanding schizophrenia is crucial, as people with this disorder are often
among the most vulnerable and stigmatized in all of medicine. By taking the time to
understand the phenomenology of schizophrenia on a deeper level, you can make sure that
the diagnostic “label” is only applied when it would be both accurate and bene cial to the
patient.

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SIGNS AND SYMPTOMS OF PSYCHOSIS
Symptoms in schizophrenia are classically split into two groups known as positive
symptoms and negative symptoms. Positive symptoms are those that are present in
schizophrenia but aren’t for most people, whereas negative symptoms are those that are not
present in schizophrenia but are for most people. When most people think of
schizophrenia, it is the dramatic positive symptoms such as hallucinations and bizarre
delusions that come most rapidly to mind. However, the dysfunction caused by
schizophrenia owes as much to the presence of these positive symptoms as it does to the
absence of normal abilities caused by negative symptoms, including major de cits in
emotional, social, and cognitive functioning.
Positive symptoms include delusions (often paranoid and bizarre in nature),
hallucinations (typically auditory rather than visual), disorganized speech, and
disorganized behavior. Negative symptoms include blunted affect, decisional
ambivalence, and social withdrawal. You can remember these core symptoms by thinking
that patients with schizophrenia have BeN 2 HaDeS and back. Per DSM-5 criteria, at
least 2 of these symptoms must be present for a period of at least 6 months to qualify for
the diagnosis of schizophrenia. We’ll go over each major symptom type individually.
 

A state of primary psychosis involves delusions,

hallucinations,
disorganized speech, disorganized behavior, and
negative symptoms.
 

BeN 2 HaDeS: Behavior (disorganized) Negative

symptoms 2 or more of these symptoms for at least 6
months Hallucinations Delusions Speech (disorganized)
 
DELUSIONS

Delusions are a form of positive symptom found

frequently in schizophrenia and are among the most speci c symptoms seen in this
disorder. A delusion is de ned as a xed false belief: xed because they are unchangeable
even in the face of clear evidence to the contrary, false because the they are clearly incorrect
or incompatible with reality, and belief because they are an idea that a person holds.
Delusions must also be clearly outside the norms of one’s cultural or religious background.
For example, followers of certain religions have beliefs that would be considered xed and

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false by people who are not in that belief system (such as a belief in reincarnation in
Hinduism or the virgin birth in Christianity). However, these would not be considered
delusions because they are shared by others in the same belief system.

Delusions in schizophrenia often take speci c and

recognizable forms. In particular, schizophrenic delusions tend to be paranoid and
persecutory in nature, such as someone believing that they are the target of a complex
conspiracy (“Someone’s watching me, I just know it. ey mean to do me harm.”).
Delusions can be classi ed as bizarre (beliefs that are so outlandish as to be strictly
impossible, such as someone who believes that aliens from a nearby galaxy have sent
detached eyeballs to watch their every move) or non-bizarre (beliefs that are highly unlikely
to be true but are technically possible, such as someone who believes that the government
has hacked their internet router and is broadcasting their internet history to all of their
neighbors). ese delusions often involve ideas of reference where random or everyday
events are connected in a way that has some great or cosmic signi cance. For example,
someone watching the news on television may believe that the anchors are blinking in
Morse code in order to communicate a special coded message that only they can
understand.
In addition to ideas of reference, delusions in schizophrenia also frequently involve
beliefs that one’s thoughts or actions are being manipulated by outside forces. ese
delusional forms include thought broadcasting (the idea that one’s thoughts are being
transmitted externally to be heard by others), thought withdrawal (the idea that one’s
thoughts are being taken out of their mind), thought insertion (the idea that thoughts are
being inserted into one’s head by others), and delusions of control (the idea that one’s
movements are not their own and that they are being controlled by someone else like a
puppet). It is unclear why people in a state of psychosis begin to believe that their thoughts
and actions are suddenly outside their conscious control. Some research suggests that people
with schizophrenia have speci c neurologic abnormalities that impair their ability to
recognize that their own thoughts and actions are actually self-generated. Evidence for this
comes from the fact that many people with schizophrenia are able to tickle themselves. For
most people, trying to tickle yourself is futile because your brain generates a signal that the
sensory input it is receiving has originated from your own body. However, in schizophrenia
this “self ” signal is dampened, leading to difficulties in recognizing when thoughts and
behaviors are internally generated. is likely accounts for the distinct sensation of outside

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forces being in control. e ability to self-tickle also correlates highly with unusual
perceptual experiences like hallucinations, suggesting a shared mechanism.
 
HALLUCINATIONS
In contrast to the visual hallucinations found in delirium (which are typically visceral in
origin), hallucinations associated with schizophrenia are primarily auditory (or odd-itory)
in nature, re ecting the oddness of psychosis.
 

Hallucinations related to schizophrenia are

generally auditory, not visual.
 

Odd-itory hallucinations are linked to odd behavior,

speech, and thoughts.
People with schizophrenia “hear voices” in a characteristic and recognizable way. e voices
typically take the form of a running commentary between several

speakers (often a mix of male and female voices) who

talk about the person in a critical or demeaning way. e voices are intermittent (rather
than continuous) and are clearly perceived as coming from outside one’s head (so you
should take a few moments to consider diagnostic possibilities other than schizophrenia in
someone who complains of “voices inside my head”). ese voices are not vague or
nebulous; instead, people with schizophrenia hear what the voices say in a clear and vivid
fashion. People with auditory hallucinations related to schizophrenia often experience them
as distressing and will generally try to nd speci c reducing behaviors (such as smoking a
cigarette or watching television) that can decrease the intensity of the voices. People will
also generally try to hide or minimize the fact that they experience auditory hallucinations,
so be cautious in diagnosing schizophrenia in anyone who eagerly volunteers that they hear
voices. People experiencing auditory hallucinations related to primary psychosis may be seen
verbally or physically reacting to what the voices are telling them (“Shut up! You don’t know
what you’re talking about!”), which is described on the mental status exam as responding to
internal stimuli. Auditory hallucinations also almost never occur in the absence of other
positive symptoms, with delusions being reported concurrently with auditory hallucinations
nearly 90% of the time.
To aid your memory, the typical characteristics of auditory hallucinations in primary
psychosis can be recalled using the mnemonic “It’s clear he’s too AWD to hide outside,”
which reminds you that the voices are clear (rather than vague), Associated With Delusions

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(rather than occurring as an isolated symptom), hidden (rather than being enthusiastically
volunteered during the interview), and perceived as coming from outside the head (rather
than inside). e derogatory nature of this statement should help remind you of the “critical
running commentary” nature of auditory hallucinations in schizophrenia as well.
 

e auditory hallucinations in schizophrenia are

generally clear, associated with delusions, hidden,
and perceived as coming from outside the head.
 

“It’s clear he’s too AWD (Associated With Delusions) to

hide outside.”
 
DISORGANIZATION
e nal category of positive symptoms is thought disorganization. People with
schizophrenia often have profound difficulty with maintaining a clear and coherent train of
thought. While thought disorganization can be trickier to evaluate than either
hallucinations or delusions (as it relies on thought process more than thought content), it is
even more important for diagnosing schizophrenia as it is quite speci c for primary
psychosis (compared to auditory hallucinations and delusions which can also be found in
other conditions such as delirium, depression, or mania).

Because psychiatrists cannot read minds, thought

disorganization must be inferred from disorganization in more objectively observed domains
such as speech and behavior. Speech and behavior both follow rules that are so ingrained
that most people don’t even realize them until they are broken. For example, during a
conversation most people go from one concept to another based on a linear train of thought
involving logical associations between words and ideas. If you were to ask someone in a
non-psychotic state what the relationship is between an orange and a banana, the answer
will likely be, “ ey’re both fruit.” However, if you were to ask the same question to
someone in a state of primary psychosis, the answer is almost never going to be, “ ey’re
both fruit.” ( ey may instead say something like, “A banana is a cog and an orange is its
place in the machine just like you and me!”) In schizophrenia, the normal connections from
one thought to the next are replaced by a general loosening of associations in which words
and thoughts are connected by less meaningful processes.
Disorganized speech is often quite noticeable when it is present. For example,
someone in a psychotic state who is asked a question may answer based on the sounds of
words rather than their actual meanings, known as a clang association (“What do you do at
the beach?” “Beach? at’s no leech, preach, let me teach.”). In this case, the important part

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of the word (its meaning) is replaced by an irrelevant characteristic (its phonetic sound).
Other ways in which thought disorganization can become apparent is when people simply
make up words (neologisms), repeat what the other person said without any understanding of
its meaning (echolalia), or say the same word repeatedly without any purpose (perseveration).
In severe cases, thought disorganization can go so far that the words coming out of their
mouth are complete non-sense (often called a word salad) or they are unable to produce any
speech at all (thought blocking). In all of these cases, it is as if the train of thought has been
hijacked and forced to take irrelevant connections.
In addition to speech, thought disorganization can manifest in disorganized behavior.
Whereas most people behave in a way that is dictated by clear motivations, disorganized
behavior in schizophrenia is notable for its purposelessness. People with schizophrenia may
act bizarrely or unpredictably such as walking around endlessly from one corner of the room
to the next, repeating the same motions over and over (motor perseveration), or copying a
movement that someone else just did (echopraxia). e behavioral symptoms of catatonia,
including negativism, catalepsy, and waxy exibility, can also be seen in severe cases of
schizophrenia.
 
NEGATIVE SYMPTOMS
In contrast to positive symptoms (things that should not be present but are), negative
symptoms are things that should be present but aren’t, including de cits in the emotional,
social, and cognitive skills that most people have.
Emotionally, people in a state of primary psychosis often have a blunted affect as if
their facial expressions are being constrained by an unseen force. Because of this, their affect
is often completely incongruent to what they say they are saying. For example, you might
think that someone who believed that their every thought was

being transmitted to a secret society intent on

destroying the world would appear quite distraught when talking about this. However, due
to the blunting of affect seen in schizophrenia, they may instead talk about it passively
without any change in their facial expressions. Affective de cits often begin prior to the
onset of any positive symptoms of psychosis, and family members will often describe that a
person looks “off ” even months before an official diagnosis. Affective de cits also tend to be
progressive, and older people with long-standing psychotic conditions may develop a
completely at affect with zero trace of emotional expression.
Another negative symptom in schizophrenia is ambivalence or extreme difficulty in making
decisions. A certain amount of uncertainty in decision making is completely normal.
However, in schizophrenia this ambivalence is severe and extends into many areas of life,
preventing most meaningful or goal-directed behavior. Even when asked about things that
should be relatively uncontroversial (“It’s particularly cold tonight. Do you want a

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blanket?”), someone with schizophrenia-related ambivalence may still have trouble deciding
(“Hmm… I’m not sure.”).
A state of anhedonia can be associated with schizophrenia as well. (Recall that while
anhedonia is quite sensitive for depression, it is not necessarily speci c and can be seen in
other disorders as well.) People with schizophrenia often lack the ability to feel pleasure or
engage in activities that they previously found enjoyable. Instead, someone with
schizophrenia may simply sit and stare at a wall for hours on end or lay motionless in bed.
Anhedonia sometimes leads to a state of amotivation where people stop trying to pursue
any form of goal-directed behavior. Despite going by the same name, anhedonia in
schizophrenia likely differs from depressive anhedonia on a mechanistic level and probably
represents a downstream effect of affective de cits.
Finally, people with schizophrenia often develop severe difficulties relating to other people
and instead are preoccupied with their own internal experiences. (While this phenomenon
was classically known as “autism,” in modern psychiatry the term autism generally refers to
autism spectrum disorder, so for the sake of clarity we will not use the term in this way.)
People with schizophrenia often appear completely disinterested in what is going on around
them, even during major life events that would normally provoke strong emotions such as
death, birth, and marriage. Many end up withdrawing socially and “live in their own
world,” leading to isolation and loneliness. ese social difficulties may be due, at least in
part, to the presence of positive symptoms, which can be disturbing or off-putting to others.
However, the social de cits in schizophrenia often extend far beyond what would be
expected from the effects of positive symptoms alone.

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SCHIZOPHRENIA ACROSS THE LIFESPAN
Learning about schizophrenia is a step more challenging than learning about mood
disorders like depression or bipolar disorder. is is because mood disorders occur in
discrete episodes, so you only have to learn what the clinical picture looks like during an
episode. In contrast, schizophrenia is not strictly speaking an episodic disorder. While there
are times when symptoms are more pronounced than others, on the whole schizophrenia is
best conceptualized as a chronic and progressive disorder with occasional exacerbations.
For some people, there may be periods of lucidity as well, although this is not always the
case.
Schizophrenia is diagnosed in 0.5 to 1% of the population, giving it a very low base rate
and increasing the risk of overdiagnosis. Men are affected more frequently than women,
with 3 men diagnosed for every 2 women. Interestingly, people born in cities and those with
immigrant status appear to be at higher risk.
Like bipolar disorder, schizophrenia is typically diagnosed in early adulthood. e
age of onset is earlier in men (between 18 and 25) than it is for women (between 25 and
35). However, as many as 15% of people with schizophrenia do not develop symptoms until
after the age of 40, with 5% doing so after the age of 60. For this reason, late-life onset of
symptoms generally argues against a diagnosis of schizophrenia but does not de nitively rule
it out.
While the characteristic symptoms of schizophrenia generally do not begin until early
adulthood, many people who are diagnosed with schizophrenia showed signs even in
childhood, including odd beliefs, social withdrawal, physical clumsiness, and poor
performance in school. is pre-syndromal state is known as a prodrome. Although these
symptoms are common in people who go on to develop schizophrenia, they are
unfortunately not speci c enough to allow for early diagnosis as only around one-third of
patients diagnosed as having a prodrome actually go on to have a rst break where active
symptoms of psychosis emerge. As the other two-thirds do not develop schizophrenia, the
risk of false positives from diagnosing and treating based only on prodromal symptoms is
too high.
 
PROGNOSIS
Schizophrenia involves a lifelong pattern of acute symptomatic exacerbations on top of
progressive functional deterioration. ( e progressive nature of schizophrenia is
underscored by the fact that it was originally called dementia praecox or “early dementia,”
referencing another condition characterized by continuous decline.) As a progressive illness,
social and occupational functioning are often signi cantly impaired even when there are
no active symptoms of psychosis. ( is is in contrast to mood disorders, where functioning
is generally preserved between episodes.) Once a rst break has occurred, the chance of
future symptom recurrence is high, with 80-90% of people having another exacerbation in
their lifetime (a recurrence rate as high as bipolar disorder). is has important implications
both for educating patients and families about the nature of the illness as well as deciding
on how long to continue with treatments. An earlier age of onset tends to predict a more
severe course of illness.
Psychotic symptoms do not have a “natural expiration date” in the same way that
manic or depressive episodes do. Studies have found that, without treatment, symptoms of

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psychosis can continue unabated for years at a time, although for some people symptoms
naturally take on a more waxing and waning course.

People with schizophrenia often lead difficult lives. Less than 20% of
people with schizophrenia are able to nd employment, leaving them dependent upon
others for support. Without any support, outcomes are even worse, and people with
schizophrenia are over 10 times more likely to be incarcerated or chronically homeless. On
average, people with schizophrenia live 10 to 20 years less than their peers. A variety of
explanations exist for this discrepancy, including the effects of chronic homelessness, a lack
of interest in following up with medical care, and a higher propensity for developing
medical illness (either due to the disorder itself or from common side effects of
medications). Some of this gap in life expectancy may be attributed to suicide as well.
While not as common as in mood disorders, suicide still occurs in schizophrenia, with the
diagnosis being found in around 15% of all fatal suicides. When suicide does occur, it tends
to happen in an early stage of the illness when someone’s insight is sufficiently preserved
that they know that they are unwell and that they will likely not be able to live the life that
they would have wanted to.
 
TREATMENT
Treatment of schizophrenia consists of medications and psychotherapy. Like bipolar
disorder, the standard of care almost always involves medications, as psychotherapy alone is
not considered sufficient for treating schizophrenia in most cases. With treatment,
psychotic symptoms can be reduced in a matter of days or weeks.
Medications used to treat schizophrenia are known as antipsychotics. e majority of
antipsychotics act as dopamine receptor blockers and lead to rapid reductions in positive
symptoms with a medium effect size (around 0.5). While antipsychotics are effective at
treating the positive symptoms of schizophrenia, they are much less effective at treating
negative symptoms and may even worsen them by blocking the sense of motivation and
drive that dopamine normally provides. Because of this, antipsychotics are much more
effective at improving symptomatic outcomes than functional ones.
Antipsychotics are associated with some signi cant side effects that must be taken
into account. Older (or “typical”) antipsychotics are known for causing speci c motor side

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effects known as extrapyramidal symptoms, including sudden uncontrollable muscle
contractions (acute dystonia), motor restlessness (akathisia), slowed movement (bradykinesia),
and uncontrollable movements (tardive dyskinesia). Newer (or “atypical”) antipsychotics
tend to have fewer extrapyramidal symptoms but can cause severe metabolic effects
including obesity, diabetes, and hyperlipidemia. Typical and atypical antipsychotics are
equally effective, so the decision to use one antipsychotic over another is generally based on
the side effect pro le.
In cases of treatment-refractory schizophrenia, a particular antipsychotic known as
clozapine is signi cantly more effective, with a large effect size around 0.9. However,
clozapine is associated with a small but signi cant risk of agranulocytosis, a rare but
potentially deadly side effect that depletes the immune system and makes someone unable
to ght off even small infections. Because of this, regular laboratory monitoring of blood
cells is required for anyone on clozapine. While the risk of agranulocytosis makes clozapine
impractical as a rst-line treatment, in particularly severe or refractory cases it can be a life-
saving treatment (as can ECT which has a large effect size even for those already taking
medications).
Hospitalization may be required for severe symptoms in schizophrenia. Even in cases
where someone with psychosis is not actively dangerous to themselves or others, many
states allow for involuntarily detainment of individuals who are gravely disabled to the
extent that they are unable to secure basic provisions such as food, clothing, and shelter due
to their condition. In cases where insight is severely impaired, a court order for involuntary
treatment may need to be sought.
In addition to medications, psychotherapy can be an incredibly helpful adjunctive
treatment. e best studied form of therapy in schizophrenia is CBT for psychosis which
has been shown to reduce both positive and negative symptoms while improving the overall
level of functioning with a small effect size (around 0.4).
e outcomes of schizophrenia treatment vary across the world. Paradoxically,
countries with less access to mental health care have been found to have better functional
outcomes for schizophrenia than those with more well-developed healthcare systems. e
reasons for this are unclear, but it may have to do with the superior ability of communities
to care for patients with psychotic illnesses in more family-oriented cultures compared to
industrialized societies that tend to place a strong emphasis on independence and
individuality. In addition, more frequent use of antipsychotics in developed nations may be
partially to blame, as they may actually worsen functional outcomes (despite being effective
for positive symptoms). However, this must be weighed against other evidence showing that
the duration of untreated psychosis is itself predictive of poor long-term functioning, so it
remains unclear what the optimal treatment strategy for maximizing long-term functional
outcomes should be.

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MECHANISMS OF PSYCHOSIS
e experience of psychosis is not one that most people will easily understand. Unlike other
psychiatric syndromes like depression where most of the symptoms (like fatigue or sadness)
will be familiar to most people, in schizophrenia the most prominent symptoms of the
disorder (like delusions or hallucinations) don’t have any direct parallels in most people’s
lives. Because of this, schizophrenia can be an incredibly difficult disorder to comprehend,
leading to misinformation, misconceptions, and misdiagnoses. However, by focusing on the
underlying mechanisms of the disorder, we can avoid these pitfalls and improve our
diagnostic skills.
At its core, a state of primary psychosis appears to involve abnormalities in the process of
assigning salience. Salience is the “interestingness” of information and re ects how relevant
we perceive that information to be. While reading a textbook, for example, you might
highlight passages that you perceive to be particularly salient (maybe you’re even doing it in
this textbook). By highlighting certain words and not others, you are saying in effect that

some words are more important or salient than the words around
them. We use salience to lter information, giving salient items more attention and being
more likely to act upon them. For example, if you were given ten random numbers (say, 15
58 37 82 90) but not told anything about them, you probably wouldn’t nd them to be
particularly salient and, without that salience, they would drop from your attention and
quickly be forgotten. However, if you were told that these same ten numbers are from
tomorrow's winning million dollar lottery ticket and that there’s still time to enter, then
suddenly the numbers become very interesting indeed. By being given this context, the
salience of the information has increased even though the numbers themselves have not
changed at all. is illustrates that salience is not an inherent property of the information
itself; rather, it is assigned based on the context of the situation. On a biological level, the
neurotransmitter dopamine appears to be involved in the process of salience. When
information is found to be salient, your brain releases dopamine which makes you more
likely to pay attention to the information and act upon it.

Going back to schizophrenia, people with this

condition are believed to be in a pro-salient state characterized by a tendency to assign
salience indiscriminately without regard to context, leading to connections and patterns
being perceived in things that are not actually connected. To help you understand what it
is like to be in a pro-salient state, imagine that one morning as you’re leaving your house

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you notice a black car parked across the street. As soon as you see it, the car starts and drives
off quickly. You nd this a little odd but ultimately don’t think too much of it. However, the
next day the exact same thing happens. It’s enough to bother you slightly, but you are still
able to put it out of your mind. When it happens for a third day in a row (and then a fourth
and a fth), however, it begins to get under your skin. After a week of seeing this black car
drive off every day as soon as you walk out of your house, you are absolutely convinced that
this is no mere coincidence—there must be some signi cance to what you are noticing.
Maybe someone is spying on you. But why? You’re just a regular person. Why would
someone go through all this trouble? Unless… maybe you know more than you think you
do? As you go throughout your day, you begin to notice things that you never noticed
before. Your boss seems a little bit colder towards you than normal. Is she in on this too?
While going home at night, you see four different police cars. Are there normally that many?
Am I a part of some vast international conspiracy? Do I have some kind of superpower that I am
unaware of ? What is going on?!?
Take the way you are feeling right now and save it in a bottle labeled “pro-salient state.”
is feeling is exactly what people in initial stages of schizophrenia experience. When we
perceive patterns in things, it causes us to assign salience to information more easily. In this
way, pro-salient states can be adaptive by enabling us to make mental connections we
otherwise would not have (like a detective putting together seemingly disparate clues to
solve a murder case). However, when this process goes too far, confusion and dysfunction
can result.
People with schizophrenia are believed to be in a state of aberrant salience where
importance is assigned to every bit of new information without any clear connection to
whether it is relevant. Returning to the lottery numbers from earlier, the sudden increase in
the salience of those ten numbers upon revealing their signi cance was likely noticeable, but
at least we knew why the salience had increased. However, having schizophrenia is like
suddenly entering a world in which every bit of information had the potential to make you a
million dollars in the same way as tomorrow’s winning lottery ticket. is makes life
initially quite vivid and dramatic for someone in a state of aberrant salience, and people in
early stages of schizophrenia often report a distinct sense that everything, everywhere feels
like a potential clue to solving some vast puzzle, saying things like:
“My senses were sharpened. I developed a greater awareness of the world and became fascinated by
the little insigni cant things around me.”
 

“My senses seemed alive… ings seemed clear-cut, I noticed things I had never noticed before.”
 

“I felt that there was some overwhelming signi cance in this.”

 

“I felt like I was putting a piece of the puzzle together.”

 

While this can initially be quite thrilling, a state of aberrant salience rapidly becomes
a confusing and unbearable way to live. In a pro-salient state, your mind is particularly likely

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to make connections even between unrelated or disparate events, setting the stage for the
development of new (and often delusional) beliefs. If someone watches the news in a state
of aberrant salience, they might come to believe that the president is using their State of the
Union address to communicate a special coded message meant only for them. When
listening to music, they may get the feeling that there must be a reason why that particular
song (say, “Every Breath You Take”) came on the radio at that exact moment. On the
internet, any random stimulus—maybe a pop-up ad about a new brand of lotion—may
seem so special and compelling that it must somehow be the key to saving the world. To
everyone else, these ideas sound, frankly, psychotic. For someone in a state of aberrant
salience, however, these delusions help them to make sense out of a senseless mental
environment where everything is suddenly imbued with a sense of world-changing
importance.
Aberrant salience also explains the profound thought disorganization that occurs in
schizophrenia. Our brains use salience to lter incoming information by focusing on what
seems most important and giving less attention to the rest (like highlighting words in a
book). A state of aberrant salience, however, is like reading a book where every single word is
highlighted. Normally highlighting helps to organize information and allows you to focus
on what is most important. When every word is highlighted, however, this system of
organization breaks down, and you can no longer rely on a sense of salience to guide your
attention. is is exactly what is seen in schizophrenia, with aberrant salience appearing to
leave people in a state of perpetual information overload. When the lter of salience
breaks, people become constantly bombarded by new information every second of the day
with no way of making sense of it all. It would be like trying to watch dozens of TV screens
all at the same time or listening to ten different conversations at once. In this state of
confusion, it is no wonder that people with schizophrenia appear to have such profound
difficulty following even a simple train of thought.
e concept of aberrant salience can inform not only our understanding of
schizophrenia but also how we treat it. If aberrant salience is associated with excess
dopamine, then using medications to block dopamine should reduce the symptoms of
schizophrenia. is appears to be true, as all of the drugs prescribed for schizophrenia block
dopamine receptors to some degree. is creates a state of dampened salience where
information lacks the power to capture attention that it once had, leading to dramatic
reductions in positive symptoms. However, this comes at a cost, as antipsychotics cause a
global dampening of salience for all information that the brain processes (not just aberrantly
salient information). is shows both the power and the limitations of using antipsychotics
to treat schizophrenia: these drugs reverse the excess of dopamine driving a state of aberrant
salience, but in doing so they can interfere with the normal ability of salience to guide
attention, motivation, and goal-directed behavior as well.

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 Ultimately, no single theory is going to explain a
disease as complex as schizophrenia. For example, while aberrant salience explains the
delusions of reference and thought disorganization that are found in schizophrenia, other
symptoms (such as auditory hallucinations or delusions of control) appear to be related to a
profound inability to differentiate between self-generated stimuli and those coming from
the external environment (the “self-tickling” hypothesis mentioned earlier). In addition,
neither of these hypotheses account for the profound negative symptoms that are often
found in advanced stages of the illness. While there are clearly multiple mechanisms to be
uncovered, the concept of aberrant salience can still provide a helpful framework for
understanding the phenomenology of schizophrenia as well as the bene ts and drawbacks
to using dopamine-blocking medications to treat it.
Primary psychosis involves a process of aberrant
salience or the attribution of signi cance and
meaning without any logical connections.
 

If someone is convinced they’ve been abducted by aliens,

there might be a problem with their salience.

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DIAGNOSING PSYCHOTIC DISORDERS
While a state of primary psychosis often implies a diagnosis of schizophrenia, there are a
variety of related disorders that should be considered as well, including delusional disorder,
schizoaffective disorder, and psychotic disorders related to mood, substance use, or medical
conditions. We’ll cover the most common types of psychosis-related disorders in this
section.
 

SCHIZOPHRENIA Diagnosing schizophrenia is based on the presence of certain signs

and symptoms in combination with a characteristic course of illness across the lifespan.
Speci c ndings on the mental status exam that argue for a diagnosis of schizophrenia can
include a disheveled appearance (due to inability to engage in purpose-driven behavior),
disorganized speech and behavior, blunted or at affect, and the presence of delusions,
paranoia, and/or auditory hallucinations. Insight and judgment are often impaired due to
the inability to tell reality from fantasy (as people with schizophrenia genuinely believe their
delusions and are convinced that the voices they hear are real).
Research has shown that many of the positive symptoms in psychosis are highly
speci c for schizophrenia. ese rst-rank symptoms include auditory hallucinations in the
characteristic “critical running commentary,” delusions of thought manipulation (including
thought withdrawal, insertion, interruption, and broadcasting), and delusions of control
(including a sense that one’s actions are being manipulated by outside forces). While rst-
rank symptoms are highly speci c for schizophrenia, they are not particularly sensitive. In
contrast, the negative symptoms of schizophrenia are quite sensitive, and a lack of negative
symptoms can help to rule out the diagnosis (particularly for someone who has had the
diagnosis for several years, as the ratio of negative symptoms to positive symptoms tends to
increase over time). However, negative symptoms are not very speci c, as anhedonia,
ambivalence, and lack of motivation can be found in non-psychotic illnesses such as severe
depression as well.
 

Positive symptoms are those that are present in

schizophrenia and are quite speci c for the disorder,
while negative symptoms are functions that are
absent in schizophrenia and are quite sensitive for
the disorder.
 

Positive symptoms = Symptoms that are Present but

shouldn’t be = Speci c Negative symptoms = Skills that
are Not present but should be = Sensitive

Historically, the DSM differentiated between several subtypes of schizophrenia,

including paranoid, disorganized, catatonic, undifferentiated, and residual forms. However,

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in the DSM-5 these subtypes were removed as there did not appear to be any diagnostic or
prognostic bene ts to differentiating between the subtypes, and schizophrenia is now
considered a single diagnosis.
 

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BRIEF PSYCHOTIC DISORDER AND SCHIZOPHRENIFORM DISORDER
e primary distinction when making a diagnosis of a primary psychotic disorder is in
regards to timeframe. Because a diagnosis of schizophrenia prognostically “commits”
someone to a lifetime of symptoms, it is wise to be cautious when assigning the diagnosis.
For this reason, schizophrenia should only be diagnosed when psychotic symptoms are
sustained for at least 6 months. Psychotic symptoms lasting less than one month should be
diagnosed as brief psychotic disorder, while those lasting between 1 and 6 months should
be diagnosed as schizophreniform disorder. e distinction between brief psychotic
disorder, schizophreniform disorder, and schizophrenia appears to have prognostic value, as
only a third of patients with brief psychotic disorder progress to having “full blown”
schizophrenia while two-thirds of patients with schizophreniform disorder progress to
schizophrenia. While the 6 month cut off is ultimately arbitrary, it underscores the point
that the duration of psychotic symptoms matters signi cantly in the prognosis of primary
psychosis.

DELUSIONAL DISORDER
Delusional disorder is a condition in which people develop delusions that are similar to
those found in schizophrenia. However, in delusional disorder the other signs and
symptoms of schizophrenia (including disorganized thoughts, auditory hallucinations, and
negative symptoms) are notably absent. In addition, the life course of individuals with
delusional disorder does not mirror that of schizophrenia, as these people are often
employed, married, and lack other features suggestive of a mental disorder. On interview,
they are often coherent, sensible, and reasonable—until they begin talking about their
particular delusions.
If all the other parts of schizophrenia are missing, then why is delusional disorder a
disorder at all? After all, delusions may be entirely normal. However, for some people, their
belief in these delusions is rm enough that it can cause signi cant problems in their lives
even in the absence of any other symptoms. For example, if your spouse of 30 years suddenly
started believing that they had been abducted by aliens working for the CIA and refused to
stop talking about it, it may begin to strain the marriage (not to mention their ability to
hold a job or maintain other friendships).
Pharmacologic treatments for delusional disorder do not appear to be very effective,
with very limited evidence for use of antipsychotics (although they could be tried in severe
cases). Cognitive behavioral therapy or other psychotherapies do not appear to reduce the
intensity of the delusion itself, but they can nevertheless be helpful for mitigating the social
or occupational dysfunction resulting from the delusions (such as teaching people the
situations in which it is or is not appropriate to talk about the delusions).

SCHIZOAFFECTIVE DISORDER
Traditionally, the eld of psychiatry made a distinction between psychotic disorders like
schizophrenia and mood disorders like depression or mania, as these were thought to be
entirely separate and distinct processes with different prognostic and treatment
considerations. As time went on, however, this split between psychotic and affective

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disorders became harder to justify, as people with depression and mania often developed
psychotic symptoms while those with schizophrenia sometimes had mood changes. In
addition, there seemed to be people who clearly had mood episodes while also having
discrete periods of psychotic symptoms.
To address this reality, the diagnosis of schizoaffective disorder was created to describe
people who, by all appearances, genuinely experienced both psychotic and affective
symptoms. e key with schizoaffective disorder is that both processes need to have been
present in the absence of the other for at least some period of time. Someone who has only
ever had psychotic symptoms during a mood episode would be diagnosed with a mood
disorder with psychotic features. Only when there is a clear history of psychosis in the
absence of an abnormal mood state and an additional history of mood episodes should the
diagnosis of schizoaffective disorder be applied. Mood symptoms must be in excess of what
would be expected from the psychotic disorder alone (such as anhedonia or lack of
motivation).
Schizoaffective disorder is intended to be a rare diagnosis, and people who truly
qualify for the diagnosis are few and far between. Because of its rarity, schizoaffective
disorder is liable to rampant overdiagnosis, and studies have found that the majority of
people diagnosed with schizoaffective disorder appear to have never met the criteria for the
disorder at any point in their lives. It is also a highly unstable diagnosis, with only one-
third of people diagnosed with schizoaffective disorder during a rst hospitalization still
having that diagnosis 6 months later (compared to over 90% for schizophrenia, over 80%
for bipolar disorder, and over 70% for depression). ese incorrect diagnoses often stem
from improper history taking and a knee-jerk tendency to assume that any patient with
both psychotic and mood symptoms has schizoaffective disorder (rather than more common
disorders like a mood disorder with psychotic features). is is important enough that it
bears repeating:
Mood + Psychosis ≠ Schizoaffective Disorder
While there are some cases of genuine schizoaffective disorder, for most clinicians the
diagnosis should be considered rare and only given after careful consideration of every other
disorder that involves a combination of mood and psychotic symptoms. In cases of
“genuine” schizoaffective disorder, the prognosis lies at a sort of “halfway point” between
schizophrenia and the mood disorders, and we see this re ected in the fact that people with
schizoaffective disorder appear to have better functioning between episodes compared to
people with “pure” psychotic disorders but worse inter-episode functioning compared to
people with “pure” mood disorders. Treatment almost always involves medications,
including both antipsychotics and mood stabilizers. As with bipolar disorder,
antidepressants should generally be avoided due to a risk of inducing rapid cycling. Recent
revisions to the diagnostic criteria for schizoaffective disorder bring it closer to the mood
disorders than the psychotic disorders, as it now requires that mood episodes be present for
“the majority of the total active and residual course of illness from the onset of psychotic
symptoms up until the current diagnosis.” However, only time will tell what effect this has
on the reliability and validity of schizoaffective disorder.

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 Schizophrenia Major depressive disorder with
psychotic features

Bipolar I disorder Bipolar I disorder

with psychotic features with psychotic features

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 Schizoaffective disorder, Schizoaffective disorder,
depressive type bipolar type

 
Schematic diagrams of various disorders featuring both mood and psychotic symptoms. e x-axis shows time in years (with
individual years marked by a dotted line), the y-axis shows the patient’s mood state (with euthymia set at the x-axis, manic
symptoms above the x-axis, and depressive symptoms below the x-axis), and a jagged line indicates the presence of psychotic
symptoms.

MOOD DISORDERS WITH PSYCHOTIC

FEATURES
People in depressive or manic episodes can develop psychotic symptoms, especially when
mood symptoms are severe. However, the presence of psychotic symptoms does not
automatically imply a diagnosis of schizophrenia or schizoaffective disorder. Rather, a
diagnosis of depression or bipolar disorder with psychotic features should be considered.
is is more than just semantics: the prognosis and treatment considerations between mood
disorders with psychotic symptoms and primary psychotic disorders differ so drastically that
getting the diagnosis wrong could enter the patient into a futile cycle of misinformation and
incorrect treatments. As with schizoaffective disorder, the key is to look at the relationship
of psychotic symptoms to mood episodes. Provided that psychotic symptoms have only
occurred during mood episodes, a diagnosis of a mood disorder with psychotic features is
appropriate.
Spend some time studying the schematics on the opposite page, as they will help to
clarify the relationships between mood and psychotic disorders. If there is a history of
psychosis but no mood episodes, a diagnosis of schizophrenia should be given (top-left). If
psychotic symptoms occur only during depressive episodes and there is no history of mania,
a diagnosis of major depressive disorder with psychotic features is appropriate (top-right). If
there is a history of manic episodes as well as psychosis but the psychotic symptoms have
only occurred during a mood episode (either depression, mania, or both), the diagnosis
would be bipolar disorder with psychotic symptoms (middle row). Only if psychotic
symptoms have occurred even in the absence of a mood episode should a diagnosis of
schizoaffective disorder be considered (bottom row). Schizoaffective disorder can be
depressive type or bipolar type depending on the type of mood episodes present. (As a
nal note, there is no such thing as dysthymia or cyclothymia with psychotic features as, by
de nition, the presence of psychotic features implies a severe mood episode.)
 

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DIFFERENTIAL DIAGNOSIS OF PSYCHOTIC DISORDERS
As a rare condition, schizophrenia is subject to overdiagnosis more often than
underdiagnosis (especially considering that the positive symptoms of schizophrenia are
often quite dramatic and bizarre, making them hard to miss). Overdiagnosis of
schizophrenia can almost always be attributed to a focus on content over process. A
diagnosis of schizophrenia should never be given on the basis of a single symptom (even
“classic” symptoms like auditory hallucinations and bizarre delusions). Instead, the process by
which those symptoms have come about, including the patient’s level of functioning across
their lifespan and the presence of aberrantly salient thought processes, are much more
helpful in con rming a diagnosis. With this in mind, we will explore the most common
misdiagnoses and missed diagnoses that frequently accompany psychosis.
 
NORMALCY
Most of the symptoms of schizophrenia are not inherently pathological. For example, up to
10% of the population hears voices under normal circumstances but are not signi cantly
impaired by this experience. In addition, many cultures and subcultures have speci c beliefs
that would likely be considered delusional by people coming from another worldview, which
is why it’s so important to consider the cultural context of a belief before calling it a
delusion. Even people who have beliefs that are genuinely outside the norms of their society
are not necessarily ill. For example, as many as 5% of Americans believe that they have been
abducted by aliens, yet studies on these individuals have shown that the vast majority show
no signs of psychiatric pathology. erefore, it is imperative to avoid diagnosing
schizophrenia in someone who reports auditory hallucinations or delusions unless there are
additional features (such as thought disorganization or negative symptoms) to indicate a
certain level of actual dysfunction.
In some cases, psychotic symptoms can represent a culturally accepted idiom of distress.
For example, someone might tell their doctor that they are hearing voices as a way of
bringing attention to an unpleasant life circumstance such as bereavement or abuse. As
before, look for evidence of actual dysfunction across the lifespan to avoid overliteralizing
and overmedicalizing these concerns.
 
DEPRESSION
Schizophrenia can sometimes be misdiagnosed as depression, as a number of symptoms
overlap between the two conditions (including apathy, anhedonia, and lack of motivation).
is is especially true during the prodromal state before the characteristic rst-rank
symptoms of schizophrenia have emerged. In these cases, it is not always possible to “call”
the diagnosis correctly from the get-go. Similar to cases of bipolar depression that present
initially as depression, there may be times when you have to wait for schizophrenic
symptoms to “declare themselves” before being certain about your diagnosis (although the
presence of certain symptoms, such as odd or eccentric beliefs that do not quite reach the
level of a delusion, may keep schizophrenia higher on your differential).
 
MANIA
Even in the absence of psychotic symptoms, mania can sometimes be misdiagnosed as
schizophrenia. e source of confusion is often related to the presence of delusions in both
disorders. People in a manic state may have delusions, but this does not automatically mean

143
that they have schizophrenia or delusional disorder. Instead, the nature of delusions matters.
In mania, delusions tend to be grandiose and reward-oriented while in primary psychosis
they are more likely to involve classic rst-rank delusions including conspiratorial thinking,
paranoia, thought manipulation, or delusions of control by outside forces. e line between
manic and psychotic delusions is not always clear, but the presence of other distinguishing
symptoms (such as distractibility and ight of ideas in mania or thought disorganization
and negative symptoms in schizophrenia) as well as careful consideration of the pattern of
illness across the lifespan (whether it is episodic or progressive) can help as well.
 
FACTITIOUS DISORDER AND MALINGERING
Factitious disorder and malingering (discussed further in Chapter 15) both involve the
intentional production of symptoms for speci c gains such as wanting to be in the sick role
or to gain disability bene ts. It is not uncommon for psychosis to be the condition feigned
by people with factitious disorder or malingering, as schizophrenia only requires the
production of subjective psychiatric symptoms (rather than physical signs, which are harder
to fake). A key diagnostic feature of people who are producing or exaggerating psychotic
symptoms is that they will often be quite willing to volunteer these symptoms during an
interview whereas most people with schizophrenia will attempt to hide their symptoms and
only talk about them when asked. In addition, people who are producing symptoms tend to
focus on the symptoms of schizophrenia that are more easily fabricated (such as auditory
hallucinations or delusions) while avoiding symptoms like thought disorganization that are
more difficult to fake. (To get a sense of this, put down the book and record yourself trying
to make neologisms, clang associations, or a world salad—it’s not easy to do.) e “It’s clear
he’s too AWD to hide outside” mnemonic from earlier is extremely helpful in
differentiating genuine from produced symptoms, as people who report vague continuous
“voices inside my head” without any sort of associated delusions are much less likely to
qualify for a diagnosis of schizophrenia.
 
CLUSTER A PERSONALITY DISORDERS
Schizophrenia and personality disorders can be difficult to disentangle, as both are chronic
and life-long conditions (as opposed to episodic disorders like depression and bipolar
disorder). In particular, the cluster A personality disorders have symptoms that overlap
signi cantly with schizophrenia, including paranoia (paranoid personality disorder), social
isolation (schizoid personality disorder), and strange beliefs (schizotypal personality
disorder). Of these, only schizotypal personality disorder appears to be actually related to
schizophrenia, with strong genetic links between the two disorders. In addition, some
people with schizotypal personality disorder will go on to develop “full-blown”
schizophrenia (although the majority do not). e other cluster A personality disorders
(paranoid and schizoid) may super cially resemble schizophrenia but ultimately should not
seen as related conditions.
 

Schizotypal personality disorder is genetically and

phenomenologically related to schizophrenia.
 

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 Schiz-o-typal is a type-o-schizo.
 
CLUSTER B PERSONALITY DISORDERS
Cluster B personality disorders and in particular borderline personality disorder are
frequently missed on the differential for psychosis. However, it is not at all uncommon for
people with borderline personality disorder to report psychotic symptoms (including
auditory hallucinations and paranoia) that can resemble schizophrenia. In fact, in primary
care settings, up to 20% of patients presenting with psychotic symptoms meet criteria for
borderline personality disorder rather than schizophrenia.
We’ll go over borderline personality disorder in more detail in Chapter 13, but for
now just know that it differs from schizophrenia in a few key ways. First, people with
schizophrenia tend to experience a progressive decline over time whereas those with
borderline personality disorder tend to have a stable (or even improving) level of
dysfunction after early adulthood. Borderline personality disorder also tends to lack the
thought disorganization or negative symptoms that characterize schizophrenia. Self-
reported psychotic symptoms in borderline personality disorder are often more in line with
idioms of distress than they are with the classic phenomenology of auditory hallucinations
and paranoid delusions related to schizophrenia. ese so-called “micropsychotic”
symptoms are often experienced during times of extreme stress and are sometimes
accompanied by dissociative symptoms, discussed next.
 
DISSOCIATIVE DISORDERS
We’ll discuss dissociation more in Chapter 14, but brie y this term refers to a transient state
of feeling detached from reality. Any condition involving the words “feeling detached from
reality” is naturally going to invite comparisons to (and confusion with) schizophrenia and
other psychotic disorders. However, dissociation and psychosis are ultimately very different
states. e key is that someone in a state of dissociation will say that their experience feels
unreal but will still be able to distinguish between their own internal experiences and the
objective reality of the outside world. In contrast, someone in a state of psychosis is
genuinely unable to tell that their subjective experiences do not represent a shared reality. e
concept of “reality testing” (or the ability to tell what is real from what is fake) is used to
distinguish between these two experiences, as this ability is impaired in psychosis but intact
in dissociation.
 
DEMENTIA
On the surface, one may think that dementia and schizophrenia would rarely be confused,
especially since dementia tends to begin much later in life compared to schizophrenia.
However, there are overlapping features of the disorders that can cause confusion. For one,
dementia can often present with psychotic symptoms (including hallucinations and
delusions), especially in advanced stages of illness. In addition, schizophrenia itself is
associated with cognitive de cits that may resemble dementia (keep in mind that the
original name for schizophrenia was “premature dementia”).
If you focused only on content, it may be tempting to diagnose new-onset psychotic
symptoms as signs of a late-onset schizophrenia (which, while rare, does occur). However,
looking at the process, a late-life onset and a lack of prior psychiatric history both point
towards dementia. People with late-life schizophrenia also tend to be socially isolated and
unmarried, whereas those with dementia would match the average population in this regard.

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Further, hallucinations in dementia are primarily visual rather than the classic “running
commentary” auditory hallucinations reported in schizophrenia, while delusions tend to
take speci c forms in dementia (including delusional misidenti cations such as someone
believing that their son is trying to kill them even though he is only coming over to help
with gardening).
For particularly unsure cases, cognitive testing such as the MoCA or MMSE
(discussed more in Chapter 22) can be performed. While patients with schizophrenia do
have some cognitive de cits, they have relatively intact recall of learned information and
visuospatial ability (two things that patients with dementia frequently struggle with).
Assessing one’s level of orientation can be helpful as well, as patients with schizophrenia
often still know their name, location, and time (although their understanding of the
situation may be impaired due to poor insight).

DELIRIUM AND PSYCHOSIS DUE TO A GENERAL MEDICAL CONDITION

Broadly speaking, schizophrenia and delirium are both “psychosis” in that they share an
inability to distinguish fantasy from reality. However, delirium would be considered a case
of secondary psychosis as opposed to primary psychosis. It is generally not too difficult to
distinguish delirium from schizophrenia, as the mental changes in delirium are often of an
acute onset (as opposed to a slow onset in schizophrenia), represent a dramatic change
from baseline, and are accompanied by other signs and symptoms of a medical illness such
as fever, vital sign abnormalities, and/or focal neurologic de cits. In addition, the mental
state in delirium tends to be highly uctuant (waxing and waning from one hour to the
next), while it is more stable across days or weeks in schizophrenia. e hallucinations in
delirium also tend to be visual rather than auditory (recall that visual hallucinations are
typically visceral in origin). Finally, keep in mind that a history of schizophrenia does not
preclude someone from developing delirium: it is absolutely possible for someone with
schizophrenia to develop delirium as the result of a medical illness!
A variety of medical conditions can also cause a state of secondary psychosis, including
malignancies (such as brain tumors), infections (tertiary syphilis), genetic disorders
(Wilson’s disease), neurologic conditions (multiple sclerosis), endocrine diseases
(hyperthyroidism), and many others. As with delirium, it is exceedingly rare for a medical
condition to cause psychosis as de ned in terms of schizophrenia (including the classic
“running commentary” auditory hallucinations, paranoid delusions, and thought
disorganization), and the same features of the history (including sudden onset, decreased
levels of orientation, and lack of prior psychiatric history) can prove illuminating as well. In
cases where a medical etiology is suspected, a complete work-up should be considered.
Brain imaging may be helpful in cases where there is reason to suspect central nervous
system involvement such as patients who report a headache, have a history of recent head
trauma, or exhibit focal neurologic de cits on exam.
 

146
 ANTI-NMDA RECEPTOR ENCEPHALITIS
Anti-NMDA receptor encephalitis is technically a form of secondary psychosis due to a
general medical condition, but it deserves special mention because (unlike most other
medical conditions) it can and does present with psychotic symptoms that are highly
reminiscent of “textbook” psychosis as seen in schizophrenia, including delusions, auditory
hallucinations, and even catatonia. In addition, psychiatric symptoms may be present for
several weeks before any focal neurologic signs like memory loss or seizures occur, making it
possible that a psychiatrist may evaluate someone with this condition before any other
medical specialty.
Anti-NMDA receptor encephalitis is caused when someone’s immune system generates
autoantibodies that target a speci c type of glutamate receptor in the brain. Often, this is
caused by microstructural similarities between NMDA receptors and teratomas, or tumors
made up of multiple types of tissues. Anti-NMDA receptor encephalitis is most often
associated with ovarian teratomas, making it much more common in women compared to
men. While anti-NMDA receptor encephalitis is rare, consider the diagnosis in cases of
new-onset psychosis with any focal neurologic de cits, alterations in sensorium, or vital sign
instability, especially if there is no prior psychiatric history. Treatment involves
immunotherapy and surgical removal of a teratoma, if present.
 
ADDICTION AND SUBSTANCE-INDUCED PSYCHOTIC DISORDER
People with schizophrenia use substances at a rate that far exceeds that of the general
population. Because of this, an assessment of current and past substance use should be done
for every patient diagnosed with schizophrenia. Similar to mood disorders, the relationship
between substance use and schizophrenia is a two-way street. e stress of having
schizophrenia likely increases the chances of using drugs, but use of drugs can also increase
the chance of developing psychosis. ree classes of drugs in particular deserve special
mention: stimulants, hallucinogens, and cannabis. Stimulants like methamphetamine can
create a mental state that strongly resembles psychosis, including paranoia and
hallucinations (likely due to the increased release of dopamine). A state resembling
psychosis can also occur with certain types of hallucinogens, particularly dissociative
hallucinogens such as phencyclidine. In the majority of cases, this substance-induced
psychosis tends to be self-limiting and lasts only as long as the drug is in one’s system.
However, in cases of prolonged use (especially of methamphetamine), there may be
permanent symptoms and functional impairment even during periods of sustained sobriety.
In contrast, the acute mental state changes produced by cannabis are rarely confused for
psychosis even though some degree of paranoia can occur. ( is does not hold true for high
potency forms of cannabis, including synthetic cannabinoids, which may be associated with
an acute psychotic state.) However, prolonged use of cannabis has been found to be a risk
factor for developing a state of chronic psychosis that can be nearly indistinguishable from
“ordinary” cases of schizophrenia. It appears that in certain individuals who are biologically
vulnerable to developing schizophrenia, exposure to cannabis can “unmask” the disorder and

147
cause it to develop earlier than it might have otherwise. While this does not apply across
the board, individuals with a strong genetic predisposition towards schizophrenia should be
counseled about the risk of developing psychosis with cannabis use, especially during
adolescence.
Finally, a variety of prescription medications, including steroids, prescription stimulants,
immunomodulators, anticholinergics, and drugs that increase dopamine transmission in the
brain (such as L-dopa and amantadine) can cause psychotic symptoms in some individuals.
 
OBSESSIVE-COMPULSIVE DISORDER
Obsessive-compulsive disorder (OCD) is a condition characterized by obsessive thoughts
and beliefs that are often not consistent with reality. e beliefs seen in obsessive-
compulsive disorder may be occasionally confused for the delusions seen in schizophrenia as
both involve thoughts that persist even when presented with clear and convincing evidence
to the contrary. However, the key differentiating factor is that the obsessions in obsessive-
compulsive disorder are ego-dystonic (meaning that the person recognizes that they are
excessive or unreasonable) whereas the delusions in schizophrenia are ego-syntonic (as the
person truly believes them). We will discuss this distinction further in Chapter 10.
POST-TRAUMATIC STRESS DISORDER
Post-traumatic stress disorder (PTSD) can be confused with schizophrenia for a number of
reasons. Combat veterans returning from active duty are often in the same age range as the
average onset of schizophrenia in men. In addition, some symptoms including paranoia and
affective blunting (the characteristic “thousand yard stare” in returning combat veterans) are
seen in both schizophrenia and PTSD. Flashbacks and re-experiencing episodes related to
PTSD can sometimes take on an intensity that resembles a psychotic state, although one’s
reality testing ability remains intact during these periods. As with nearly all of the disorders
that are confused for schizophrenia, the key to differentiating between the two lies in the
process of the disorder rather than its content. A traumatic event is required for a diagnosis
of PTSD (although this does not necessarily rule out schizophrenia, as trauma appears to
increase one’s risk for developing schizophrenia). When paranoia occurs in PTSD, it is
often related to the traumatic event rather than being bizarre or hypersalient in nature. In
addition, disorganization and negative symptoms are often lacking in PTSD but present in
schizophrenia.
 
ANXIETY DISORDERS
Anxiety disorders are rarely confused for schizophrenia, likely because in anxiety disorders
there is a heightening of affect compared to the blunted affect seen in schizophrenia. Given
this, an anxiety disorder is more of a missed diagnosis than a misdiagnosis, as comorbidity
between psychosis and anxiety disorders (including panic disorder and generalized anxiety
disorder) is not uncommon.
 
AUTISM
Autism is a condition characterized by difficulties in social communication combined with
restricted interests and behaviors. Individuals with autism begin exhibiting signs in early
childhood, including poor eye contact, social withdrawal, and at or inappropriate affect.
Given that these exact same symptoms are found during the prodrome of schizophrenia
(and at the same time of life), it is perhaps not surprising that there is some diagnostic
confusion between autism and schizophrenia. However, some factors can point more

148
towards one or the other. It is rare for schizophrenia to have “full blown” psychotic
symptoms beginning before the age of 13, so onset of clinically signi cant symptoms during
early childhood suggests autism (though does not rule out schizophrenia entirely). In
addition, there is nothing that suggests that someone cannot have both autism and
schizophrenia, and indeed some studies have found that autism may be an independent
predictor of later development of a psychotic disorder, suggesting shared genetic and
environmental contributors to both. In general, though, be cautious about diagnosing
schizophrenia in someone with autism unless it is clear that the signs and symptoms
observed exceed what would be expected from autism alone and are directly in line with
what is known about the phenomenology of a primary psychotic disorder.

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PUTTING IT ALL TOGETHER
Schizophrenia is an incredibly disabling, stigmatizing, and tragic condition. Despite new
cases being relatively rare compared to other disorders like depression and anxiety,
schizophrenia still takes a large toll on society due to its early age of onset and progressive,
unremitting course. Because of this, a diagnosis of schizophrenia should be considered only
when there is a high degree of diagnostic certainty. e DSM has built in at least one
safeguard (the 6 month requirement) to prevent against overdiagnosis. However, the best
defense against misdiagnosis is to develop a rm knowledge of the clinical features that
suggest schizophrenia rather than other forms of psychosis, including an understanding of
the key role that salience plays in schizophrenia. Diagnostic criteria (as captured in the BeN
2 HaDeS mnemonic) are tools to help remember major symptom domains, but they should
be used with caution. Indeed, the presence of any of these symptoms should be the starting
point for further investigation rather than the end process. For example, if someone says that
they hear voices, you should not place a checkmark next to “Auditory Hallucinations” and
move on. Instead, the presence of this symptom requires further characterization. Are the
voices inside or outside the head? Are they associated with delusions? Are they hidden or
eagerly volunteered during the interview? What evidence is there that these voices are
causing any sort of distress or impairment? More than most psychiatric disorders,
schizophrenia requires a deep understanding of what exactly is meant by each of these
symptoms.
When psychotic symptoms overlap with mood disturbances, a high degree of care should be
taken to characterize the exact relationship of these symptoms to each other to avoid
overdiagnosing schizophrenia or schizoaffective disorder. Review the diagrams in the
section on schizoaffective disorder to solidify your understanding of these relationships.

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REVIEW QUESTIONS
1. A 21 y/o M is brought into the hospital by his roommates who are concerned that
he has been “acting crazy” since last night. ey say that he has been “talking
endlessly” about how the government has sent spies to poison him because he is
“an agent of impending destruction.” On exam, the patient appears highly
suspicious and gives very short answers to any questions asked. He is noted to be
perseverative on thoughts related to the government and often returns to this topic
no matter what kinds of questions he is asked. He denies visual or auditory
hallucinations. His roommates, one of whom has known the patient since he was a
child, said that he has never acted like this before. He works as a salesman at a
local shoe store and has a girlfriend. Which of the following aspects of the history
argues most strongly against a diagnosis of a primary psychosis for this patient?
A. Non-bizarre nature of delusions
B. Presence of paranoia
C. Sudden onset of symptoms
D. Age of the patient
E. Absence of auditory hallucinations
2. A 37 y/o F is brought into the emergency department after she was detained for
walking into oncoming traffic. On interview, the patient asks the psychiatrist if he
is a surgeon. When the psychiatrist responds no, the patient asks for someone who
can remove the “reverse hearing aids” in her ears. When asked about this further,
the patient says that she has been tted with “reverse hearing aids” by a television
news anchor who is attempting to extract her innermost thoughts on how to create
a vaccine for HIV. Otological exam is unremarkable. What term best describes
this patient’s belief ?
A. ought broadcasting
B. ought withdrawal
C. ought insertion
D. Delusions of control
E. Not a delusion
3. (Continued from previous question.) e patient’s sister arrives at the hospital. She
says that the patient has never had symptoms like this before and was “completely
normal” 3 months ago. However, she started to behave oddly after losing her job as
a clerk at a local grocery store 2 months ago. e sister then asks, “I work as a
nurse at another hospital and have seen people come in with schizophrenia. Do
you think that’s what my sister has?” Assuming that the patient meets criteria for
an episode of primary psychosis, what is the best response?
A. “Your sister almost certainly will develop schizophrenia.”
B. “Your sister is more likely than not to develop schizophrenia.”
C. “Your sister has about a 50% chance of developing schizophrenia.”
D. “It is possible but unlikely that your sister will develop
schizophrenia.”
E. “Your sister de nitely will not develop schizophrenia.”
4. (Continued from previous question.) e patient is admitted to the hospital and
started on an antipsychotic. She improves to the point where the patient’s family
feels comfortable with her discharging from the hospital to live with them at

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 home. Which of the following signs and symptoms that were present at the time
the patient was admitted to the hospital is most likely to still be present at the time
of discharge?
A. Having a facial expression that does not change
B. Appearing to engage in conversations when no one else is in the room
C. Believing that she has “reverse hearing aids” in her ears
D. Saying words like “ earing” or “teck neck”
E. Feeling that there is some “overwhelming signi cance” to events
5. A 26 y/o M with a history of schizophrenia since age 19 is brought to a clinic for
an intake evaluation after his family moved across the country. He has had a long
and unremitting course of the disorder with over 10 hospitalizations related to
aggressive behavior in the context of paranoid delusions. He is currently taking
two different antipsychotics, including risperidone 6 mg/day and quetiapine 400
mg/day. Despite this, he continues to have severe psychotic symptoms, including
bizarre delusions, auditory hallucinations, and thought disorganization. He lives at
home, and his mother (who was previously employed as a lawyer) is unable to work
due to his need for constant supervision. He has previously taken multiple other
antipsychotic medications, including olanzapine, ziprasidone, and haloperidol,
none of which resulted in sustained decreases in symptom severity or increases in
functional status. What is the next best step?
A. Increase the dose of risperidone
B. Increase the dose of quetiapine
C. Discontinue risperidone
D. Discontinue quetiapine
E. Replace the existing antipsychotics with a new medication
 

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1. e best answer is C. Symptoms related to a primary psychotic disorder such as
schizophrenia rarely have an acute onset. Instead, signs of symptom progression
are often apparent for several weeks or months before they become clinically
signi cant. In addition, there is often a prodromal state characterized by cognitive
and social de cits that result in social and occupational dysfunction (neither of
which appear to be present here). An acute onset of symptoms usually argues for a
substance-induced psychotic disorder. While the patient’s delusions are notably
non-bizarre, this does not rule out a diagnosis of primary psychosis as many
patients with schizophrenia have non-bizarre delusions (answer A). Paranoia is
common in primary psychosis and would argue for the diagnosis, not against it
(answer B). e patient’s age is within the normal window of developing
schizophrenia in men (answer D). Finally, the absence of auditory hallucinations
does not effectively rule out a diagnosis of primary psychosis, as this is not a
required symptom and is more speci c for the diagnosis than it is sensitive (answer
E).
2. e best answer is A. is describes a clear example of thought broadcasting
where someone in a state of primary psychosis believes that their thoughts are
being transmitted to others.
3. e best answer is B. Assuming that this patient meets criteria for primary
psychosis, she would likely be diagnosed as having schizophreniform disorder
given that her symptoms have been present for around 2 months. Around two-
thirds of cases of schizophreniform disorder progress to having schizophrenia,
making her chances “more likely than not.”
4. e best answer is A. Out of the answer choices, only a at affect is considered to
be a negative symptom. Negative symptoms are the least likely to respond to
treatment with antipsychotic medications. Auditory hallucinations (answer B),
delusional beliefs (answer C), disorganized speech (answer D), and a pro-salient
state (answer E) are all considered to be positive symptoms that would generally
respond to medications.
5. e best answer is E. is patient appears to be suffering from treatment-
refractory schizophrenia as evidenced by continued symptoms and dysfunction
despite treatment with two different antipsychotics at effective doses. Given this, a
trial of clozapine appears to be warranted, as this medication is the most effective
option for treating treatment-refractory cases of schizophrenia. Simply increasing
the dose of his existing medications (answers A and B) would be unlikely to result
in improvement, while discontinuing either medication (answers C and D) can
precipitate further psychotic symptoms.
 

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8 ADDICTION

Use of psychoactive substances is very common, with over

90% of people in the United States taking them on a regular basis. While many people are
able to use psychoactive substances without major negative effects on their physical or
mental health, a signi cant minority will develop ongoing problems as a direct result of
substance use. When trying to understand the relationship between mental health and
substance use, it is crucial to make a distinction between the states of intoxication,
withdrawal, and addiction. Intoxication is an acute state of being under the in uence of a
psychoactive substance, with the speci c constellation of signs and symptoms associated
with each substance being known as its toxidrome. Withdrawal is also an acute state
involving the physiological and psychological effects of sudden discontinuation of a
substance. In contrast, addiction is a chronic condition characterized by repeatedly engaging
in intrinsically rewarding behaviors despite suffering severe negative consequences as a
result. When this involves speci c drugs, it is known as a substance use disorder. However,
addiction can also involve speci c behaviors such as gambling that have similar effects in
the brain as addictive substances. Because not all addictions involve substances, the term
reinforcer will instead be used to refer to the various substances and behaviors that can be
the targets of addiction.
We will begin this chapter by exploring the speci c states of intoxication and withdrawal
associated with each of the most common types of psychoactive substances. From there, we
will turn our attention to understanding the phenomenon of addiction, including how it
presents on a clinical level, its trajectory across the lifespan, and how to approach treatment.

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INTOXICATION AND WITHDRAWAL

Psychoactive substances can be divided into a few

broad categories, including stimulants (those with a net activating effect on the central
nervous system), depressants (which have an inhibiting effect), opioids (pain-relieving
compounds), cannabinoids (which are found in marijuana and have a distinct set of
effects), hallucinogens (which cause perceptual disturbances), and inhalants (which cause a
characteristic “head rush”). It’s important to be able to recognize states of intoxication and
withdrawal related to each of these substances, especially considering that some (especially
alcohol and opioids) can be incredibly dangerous in both intoxication and/or withdrawal
and may require emergency treatment. For this reason, we will spend some time describing
the toxidromes and withdrawal states associated with each of the most common classes of
psychoactive substances.
A diagnosis of intoxication is based on the presence of particular signs and symptoms
as well as someone’s reported history of substance use (although this cannot always be
assumed to be accurate). Urine toxicology tests, which screen for common substances of
abuse, can provide objective evidence to aid the diagnosis. Intoxication exists on a
continuum with overdose in which so much of a particular substance is taken that it results
in disease, disability, or death. Overdoses can be intentional (as in a suicide attempt) or
accidental (as in someone who underestimated how much of the drug they were taking).
e problems caused by overdosing vary drastically from substance to substance, with some
(like opioids) being highly toxic in overdose while others (like cannabinoids) are quite safe.
Following intoxication, drugs are metabolized out of the body according to their half-
life. Abrupt discontinuation of a drug can lead to a state of withdrawal which, for many
substances, often produces the opposite effects of what is seen during intoxication. For
example, withdrawal from stimulants produces a state of fatigue and lethargy while
withdrawal from depressants leads to restlessness and anxiety. You can remember this by
thinking that what goes up must come down and what goes down must come back up. Not all
substances have clinically signi cant withdrawal states, and for those that do, the
dangerousness of withdrawal varies widely from being potentially lethal (like alcohol) to
being merely uncomfortable (like cocaine).
Because the intoxication and withdrawal states of certain substances can mimic
mental disorders so closely, differentiating between a primary psychiatric disorder and a
substance-induced condition can be a challenge. e key is to focus on the timing of
symptom onset and termination. For example, someone with a methamphetamine-induced
psychotic disorder may look and sound exactly like someone in an agitated psychotic or
manic state, yet within 24 hours their thought process and level of psychomotor activity are
largely back to normal. In contrast, symptoms of a primary psychiatric disorder will rarely

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resolve this quickly. Because of this, rapid onset or resolution of symptoms is highly
suspicious for a substance-induced syndrome.
 
STIMULANTS

Stimulants, also known as “uppers,” include a wide range of

substances ranging from mild stimulants such as caffeine and nicotine to moderate
stimulants including prescription drugs such as methylphenidate (Ritalin) and
amphetamine salts (Adderall) and nally up to incredibly powerful stimulants like the
illegal drugs cocaine (coke or crack), methamphetamine (speed or crystal), and MDMA
(ecstasy or molly). What these stimulants all share in common is that they increase the
amounts of the neurotransmitters dopamine and norepinephrine in the central nervous
system, leading to an overall activating effect.
People taking stimulants generally feel fantastic: they have increased energy, are better
able to focus, feel less inhibited around other people, and are able to perform tasks better (a
state that bears a striking resemblance to mania). Physiologically, the effects of stimulants
are largely mediated by the sympathetic nervous system and include increases in vital signs
(such as heart rate, blood pressure, breathing rate, and temperature) as well as mydriasis (or
dilation of the pupils). At high doses, increased psychomotor energy can turn into
restlessness, anxiety, paranoia, and aggression while overactivation of the sympathetic
nervous system can lead to hypertension, hyperthermia, cardiac arrhythmias, or seizures. A
state of substance-induced psychosis is commonly associated with high doses of stimulants
like methamphetamine and can be clinically indistinguishable from either mania or primary
psychosis.
In contrast to the activating effects seen during intoxication with stimulants,
stimulant withdrawal generally involves feelings of low energy, poor mood, and apathy
(remember that what goes up must come down). Despite being uncomfortable, stimulant
withdrawal is rarely life-threatening.
 
DEPRESSANTS
Depressants, also known as sedatives or “downers,” include alcohol and the prescription
drug classes benzodiazepines and barbiturates. ese drugs work by binding to the
GABA receptor which inhibits neuronal ring in the brain and causes a global decrease in
central nervous system activity.
Depressant intoxication is associated with sleepiness, low energy, difficulty focusing,
cognitive impairment, muscle relaxation, slowed motor activity, and poor muscle
coordination (all of which together can strongly resemble a state of depression—hence the
name “depressant”). Depressant overdoses present with severe sedation and slowed vital
signs. In contrast to stimulants, depressants are signi cantly more dangerous in overdose.
In the case of alcohol and barbiturates, overdose can even lead to coma or death. In fact,
alcohol remains one of the leading causes of substance-related death in the United States,
and barbiturates have even been used in lethal injections for many years. (Benzodiazepines

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are the exception here and are generally much safer in overdose.) Withdrawal from
depressants often involves feelings of restlessness, anxiety, and insomnia accompanied by
increases in vital signs (what goes down must come back up). In severe cases of withdrawal,
hallucinations, seizures, vital sign instability, or even death can occur. Alcohol withdrawal in
particular deserves special mention, as it can be a potentially deadly state especially for
people who have used alcohol regularly for long periods of time. Complicated alcohol
withdrawal often requires admission to the hospital for close monitoring of vital signs and
treatment with benzodiazepines to allow for a slow, steady return to baseline. e window
for complicated withdrawal is usually one week following the last drink.

ere are two clinical conditions related to alcohol

withdrawal that you must be able to recognize and differentiate between. e rst,
alcoholic hallucinosis, is a generally benign state in which people experience transient
visual, auditory, or tactile hallucinations within the rst 24 hours of their last drink. Aside
from monitoring for signs of complicated withdrawal, no speci c treatment is needed. In
contrast, the second condition, known as delirium tremens or DTs, is a potentially deadly
state associated with severe vital sign instability, confusion, and both visual and auditory
hallucinations (the classic “seeing pink elephants”) that occurs around 24 to 72 hours after
the last drink. In severe cases, seizures or death can occur. ere are often objective signs of
stress and organ damage as well, including markers of in ammation (such as elevated ESR
and white blood cell count) and liver damage. You can remember the syndrome using the
mnemonic DTS are HELL, which stands for Delirium, Tremor, Seizures, Hallucinations,
ESR, Leukocytosis, and Liver function tests.
 

Delirium tremens is a potentially fatal outcome of

alcohol withdrawal that must be differentiated from
alcoholic hallucinosis, which is more benign.
 

DTS are HELL: Delirium Tremor Seizures

Hallucinations ESR
Leukocytosis Liver function abnormalities
 
OPIOIDS

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 Opioids include both prescription painkillers like morphine and oxycodone
(OxyContin) as well as “street” drugs like heroin. (Despite differences in how they are
handled legally, on a biological level there is no difference between prescription and
recreational opioids.) Opioids are often lumped together with “downers” because they can
cause sedation, but their pharmacologic effects differ enough from depressants to warrant
separate consideration. Opioids bind to opioid receptors (rather than GABA receptors),
leading to a state of reduced pain perception, drowsiness, and euphoria. Physiologically, use
of opioids constricts the pupils (known as miosis), slows down the gastrointestinal tract
(leading to constipation), and depresses the respiratory drive. It is this latter effect that
makes opioids extremely dangerous in overdose, as the decrease in respiratory rate
combined with a general stupor can lead to hypoxemia and death. To remember the
functions of opioids, think of the 19th century disputes over British trade in China known
as the Opium Wars. is will help you connect opioids to the mental image of an ARMED
Colonialist, which stands for Analgesia, Respiratory depression, Miosis, Euphoria,
Drowsiness, and Constipation.
 

Drugs that bind to opioid receptors are clinically

useful as painkillers but can cause respiratory
depression, miosis, euphoria, drowsiness, and
constipation as well.
 

ARMED Colonialist: Analgesia Respiratory depression

Miosis Euphoria Drowsiness Constipation

As expected, opioid withdrawal produces the opposite signs and symptoms seen
during intoxication, with people experiencing increased pain perception, hyperventilation,
mydriasis, dysphoria, restlessness, and profuse diarrhea. In contrast to opioid intoxication
and overdose, withdrawal from opioids is rarely dangerous (although it can be very
uncomfortable).
 
CANNABINOIDS

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 Cannabinoids are the major psychoactive ingredients in cannabis or
marijuana. In particular, tetrahydrocannabinol (THC) is the molecule responsible for
producing the subjective “high” that is commonly associated with use of cannabis. However,
a variety of other psychological and physiologic effects are noticeable as well, including
increased hunger, impaired short-term memory, redness of the eyes, transient paranoia, and
a state of apathy or low motivation. Use the mnemonic PHARM to remind you of
Paranoia, Hunger, Apathy, Red eyes, and Memory loss.
 

Cannabinoids, which are the active ingredient in

marijuana, cause a subjective “high” as well as
paranoia, hunger, apathy, red eyes, and short-term
memory loss.
 

Cannabis is grown on a PHARM: Paranoia Hunger

Apathy Red eyes Memory loss (short-term)
Cannabinoids have long been considered to be relatively safe in overdose and to have
few, if any, negative effects in withdrawal. However, cannabinoids should also not be seen as
entirely benign drugs, as long-term use (especially beginning in adolescence) has been
linked not only to decreases in intelligence but also to an increased risk of developing a
permanent psychotic illness that can sometimes continue even after the drug has been
stopped. Increasing clinical attention to negative psychiatric effects of cannabinoids may be
due in part to increasing concentrations of THC in plants grown over the past few decades,
which may warrant reconsideration of cannabis’s status as a “benign” drug.
 
HALLUCINOGENS
Hallucinogens consist of two distinct classes of drugs: serotonergic hallucinogens, which
include LSD (acid), psilocybin (mushrooms or shrooms), and mescaline (peyote), as well as
dissociative hallucinogens, which include dextromethorphan, ketamine, and phencyclidine
(PCP). Both classes of hallucinogens share the ability to profoundly affect one’s senses, but
they are ultimately quite different in their effects and clinical signi cance.
Serotonergic hallucinogens tend to cause perceptual abnormalities such as visual
hallucinations and a feeling that different senses are merging together (such as being able to
“hear color” or “see music”). Serotonergic hallucinogens are not particularly dangerous in
either intoxication or withdrawal and are not considered to be addictive.
In contrast, dissociative hallucinogens distort perceptions of sight and sound and
produce feelings of detachment from one’s sense of reality and sense of self. ( e state of
dissociation will be discussed more fully in Chapter 14.) Often, people taking dissociative
hallucinogens report feeling that they are in a trance or dream-like state. Suppression of

160
pain signals is often noted as well (with ketamine in particular nding use in clinical
settings as an emergency anesthetic). Depending on the dose and the speci c drug involved,
other symptoms such as sedation, amnesia, and loss of coordination may be reported as
well. Dissociative hallucinogens are generally considered to be safe, and no consistent
withdrawal state has been described. However, phencyclidine has been associated with a
state of excited delirium that can resemble stimulant intoxication.
 
INHALANTS
Inhalants are a diverse class of substances that comprise everything from common
household products like paint and glue to anesthetics like nitrous oxide or diethyl ether.
Inhalants generally produce a transient “head rush” or “numbing” effect which lasts for only
a few seconds or minutes. Given the short duration of action, it is unlikely that you will ever
diagnose acute inhalant intoxication. In contrast, you may see people suffering the medical
consequences of chronic inhalant use. While the negative effects vary depending on the
speci c compounds used, they can be quite severe, including permanent damage to the nose
and lungs, increased risk of infection, and hypoxic brain damage. Due to their readily
available and generally inexpensive nature, inhalants are often used by children, teenagers,
and institutionalized or impoverished people who lack access to other psychoactive
substances.

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SIGNS AND SYMPTOMS OF ADDICTION
Now that we have an understanding of the states of intoxication and withdrawal associated
with each type of psychoactive substance, we can begin learning about the signs and
symptoms of addiction. Intoxication and addiction are closely related concepts, as addiction
typically involves repeated episodes of intoxication. However, from a diagnostic perspective
they should be considered separate diagnoses, as not everyone who is intoxicated with a
particular substance is necessarily addicted to it and not everyone who has an addiction is
currently intoxicated.
While the clinical presentation of addiction varies depending on the speci c
reinforcers involved, ultimately every case of addiction can be boiled down to a simple
three-part formula:
Repeated use of positive reinforcers despite negative repercussions
If those eight words describe the pattern of someone’s behavior, then in most cases
you can diagnose addiction. You can remember this by thinking that addiction is addicted
to Re’s (Repeated, Reinforcers, Repercussions). Let’s break this down into its three
components:
Repeated use. Addiction involves repeatedly doing something with an implied inability to
stop. is can involve use of substances such as a alcohol or speci c items or behaviors such
as gambling at slot machines.
 

Positive reinforcers. e speci c substances and behaviors in

addiction must be positively reinforcing. To understand what is meant by this, we will need
to discuss the psychological process of operant conditioning. Operant conditioning
describes how a behavior can be modi ed by the response it gets. Reinforcement is any
response that increases the frequency of the behavior, while punishment is any response that
decreases its frequency. As one example, picture a boy trying to sneak a cookie from the
cookie jar before dinner. If he is caught, he will get a swat on the hand (a punishment
meant to decrease that particular behavior). On the other hand, if he gets away with it, the
deliciousness of the cookie may act as a reinforcer of that behavior, and he is likely to try
and sneak more cookies in the future.
Reinforcements and punishments can be described as either positive or negative.
Positive and negative refer to whether something is introduced or taken away. In the cookie
example, both the reinforcer (the cookie) and the punishment (a slap on the hand) would be
considered positive because they both introduce something into the situation. However, you
can also get similar effects by taking things away. If the mother had taken away something
that the boy desired (such as access to the TV), this would be considered a negative
punishment as the behavior was made less frequent by taking something away. In contrast,

162
if the boy was incredibly hungry and the cookie’s primary effect was to remove hunger, this
would also be a negative reinforcement. A negative reinforcer can also act by preventing an
aversive experience. For example, someone who studies hard for a test may be negatively
reinforced by avoiding the upsetting experience of getting a bad grade, and they will likely
continue to study hard in the future.
 

Negative repercussions. Finally, negative repercussions are a key part of the equation for
addiction. If a behavior is repeated over and over again but never actually causes any
problems, then by de nition it cannot be a disorder.
 

Addiction involves repeated use of positive

reinforcers despite negative repercussions.
 

Addiction is addicted to Re’s (Repeated, Reinforcers,

Repercussions).

None of these components on their own are sufficient to diagnose addiction. Even
any two of them combined is not enough. It is only when all three components combine that
the speci c state of addiction emerges. Let’s see what happens when we remove any one of
these components from the de nition:
Repeated use of positive reinforcers (but no negative repercussions). Repeated use of
positive reinforcers is not a problem as long as there are no repercussions. Technically
speaking, things like eating an apple a day could fall under the banner of “repeated use of
positive reinforcers,” but because they cause no negative repercussions, they would not
satisfy any reasonable de nition of addiction.
 

Use of positive reinforcers with negative repercussions (but not repeated). is is slightly
more problematic, as even a one-time exposure to speci c substances can cause damage.
However, if it is not repeated—if the person is able to avoid the problematic reinforcer in
the future—then by de nition it cannot be an addiction. For example, someone with a
severe nut allergy who ate trail mix (a positive reinforcer) would likely end up in the hospital
(a negative repercussion). However, this person would likely do everything in their power to
avoid trail mix in the future and make sure this experience is not repeated, so it would not
make sense to call this an addiction.
 

Repeated use of items (that are not positively reinforcing) despite negative
consequences. is is the behavior that is most tempting to call an addiction, but it is more
accurately characterized as a compulsion (which we will talk about more in Chapter 10). To
understand what a compulsion is, picture someone who is perpetually worried about

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exposure to germs and frequently uses hand sanitizer throughout the day (repeated use).
Perhaps they use it so much that they begin to erode the skin on their hands, making them
more susceptible to infections (negative repercussions). However, this person is not using
hand sanitizer because it is inherently pleasurable in the same way that someone using
cocaine and heroin would be. Instead, they are using it as a negative reinforcer to calm an
internal sense of anxiety, making it a compulsive (rather than addictive) behavior. While
differentiating between compulsive and addictive behavior may seem like a minor
technicality, from a clinical standpoint they are associated with completely different
prognoses and treatment requirements, making such a distinction crucial.
On a clinical level, there are a variety of signs, symptoms, and behaviors that are commonly
seen in people struggling with addiction. Symptoms include intense cravings for the
reinforcer or thoughts about trying to cut down, while signs include objective evidence that
the patient has engaged in various forms of drug use (such as “track marks” on the arm of
someone who has repeatedly injected themselves with heroin or “meth mouth” related to
frequent use of methamphetamine).
However, the primary signs of addiction are behavioral, as someone who is addicted
tends to devote a signi cant amount of time and energy to obtaining the reinforcer. For
people with severe addictions, this soon becomes all-consuming to the point where up to
100% of their waking life is spent either using the reinforcer or going to great lengths to
obtain it. It is this monopoly of time and resources that directly leads to many of the
negative repercussions of use, including lost jobs, nancial ruin, and desertion by frustrated
family members.

is pattern of increasing time and energy spent on

obtaining the reinforcer is buoyed by a phenomenon known as tolerance in which the same
reinforcer feels less and less pleasurable each time it is used. Someone who tries heroin for
the rst time may experience “the most perfect feeling of bliss” that they have ever
experienced in their life—everything is wonderful, peaceful, perfect, and pleasantly numb.
However, several hours later this state begins to wear off. Wanting to return to this
wonderland, they take another hit. While some of the effect comes back, it’s de nitely not
as good as the rst time. Frustrated, they try taking a larger hit but still can’t quite get back
to where they were before. After a while, they are using heroin more often and via more
direct methods (such as injecting directly into their veins). ey have sold their possessions,
estranged all family and friends, and are living on the street. Still, that perfect dream world
that they experienced the rst time remains as elusive as ever. ( is is sometimes called
“chasing the dragon.”) Addictive behavior is often buoyed further by the process of
withdrawal, as the distressing and uncomfortable symptoms experienced during withdrawal
help to deter any attempts to quit using. For example, someone who is addicted to heroin

164
may experience a withdrawal state involving high levels of anxiety, restlessness, insomnia,
muscle aches, cramping, diarrhea, nausea, and vomiting. In someone who is highly tolerant
to the drug, they may continue using it largely to avoid a withdrawal state rather than for
any euphoric rush (which may have long since disappeared). is illustrates an important
point regarding addiction: while the object of an addiction is often positively reinforcing at
the beginning, in most cases the positive reinforcement wanes over time and is replaced by
primarily negative reinforcement.
Tolerance and withdrawal together help to explain why addictions are so powerful, as
they involve both positive and negative punishments for stopping as well as both positive and
negative reinforcements for using it again. Someone who attempts to quite heroin not only
loses the intensely pleasurable state of euphoria from the drug (a negative punishment) but
also experiences an incredibly uncomfortable withdrawal state (a positive punishment).
Using heroin again removes this withdrawal state (a negative reinforcement) and provides
that sense of euphoria which, while lesser than the rst time they used, remains intrinsically
rewarding (a positive reinforcement). is combination of all four kinds of reinforcement
is so potent that it can overwhelm the ability of other interventions to decrease the
behavior. is explains why many people who are addicted to speci c reinforcers often
continue to use them despite repeatedly being severely punished for their use and are
resistant to interventions (such as going to jail or being paid cash to not use drugs) that
involve only a single kind of reinforcement.

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ADDICTION ACROSS THE LIFESPAN

More than any of the conditions we have talked about so far,

addiction is a highly variable disorder that is dependent upon multiple factors. Most
important among these is the speci c reinforcer involved, as tobacco use disorder differs
from alcohol use disorder which differs from opioid use disorder which differs from
gambling disorder and so on. Nevertheless, despite this wide variation, a few consistent
themes emerge when looking at addiction across the lifespan. Taken as a whole, addiction is
one of the most common psychiatric conditions with a lifetime prevalence of around 10% of
people in the United States. is gives it a relatively high base rate in the population,
making it liable to underdiagnosis rather than overdiagnosis. e risk of underdiagnosis is
compounded further by the fact that many people will attempt to minimize or hide
addictive behaviors from their providers due to the stigma and prejudice that often occur.
Most addictions begin during adolescence or early adulthood, making prevention of
substance abuse largely a pediatric concern. However, in many cases, addictive behavior can
continue on into adulthood or older age as well. In systematic studies, men and women
appear to be equally vulnerable to addiction. However, in clinical settings, men are treated
for addictive disorders more than twice as often as women. is difference in gender ratio is
likely due to the fact that men tend to use illegal substances more often than women (who
may be more prone to addictions involving legal substances such as alcohol or
benzodiazepines that are less likely to come to clinical attention even if they can be equally
harmful).
Addiction is frequently comorbid with other mental disorders. In fact, up to half of all
people with a mental disorder will meet lifetime criteria for a substance use disorder and
vice versa. e presence of both an addiction and a separate mental disorder (known as dual
diagnosis) worsens the prognosis for both types of disorders considerably. is makes
screening for addictive behaviors important for every patient presenting with mental
health concerns. While the speci c reinforcer that is the target of the addiction carries
important implications for both prognosis and treatment, ultimately the diagnosis of
addiction is independent of the particular reinforcer involved, as the core features of the
disorder (including frequent use, cravings, tolerance, and severe consequences of use due to
the increasing time and effort spent on obtaining the reinforcer) are found across all
addictions.
 

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PROGNOSIS

Like other aspects of addiction, the prognosis for addictive

disorders is highly variable, with the strongest predictor of prognosis being the speci c
reinforcer involved. Reinforcers differ signi cantly in regards to how addictive they are, with
some being incredibly addictive and others having only minimal addictive properties. For
example, less than 10% of people who try cannabis become dependent upon it, but this
increases to 15% for cocaine, 25% for heroin, and more than 67% for nicotine. A couple of
factors, including the speed at which the drug reaches the brain and how strongly it
interacts with the dopamine receptor, are strongly correlated to how addictive a substance is.
ese variations lead to clinically signi cant differences in prognosis, with certain drugs
becoming more addictive when they are inhaled (consider that injected heroin is
signi cantly more addictive than orally ingested heroin). e inherent addictiveness of the
reinforcer also plays a large role in how easy it is to quit, with cannabis use disorder taking
on average 5 years to enter remission while tobacco use disorder takes 25 years.
Despite common misconceptions of “lifelong junkies,” the prognosis for addiction is
actually not as bad as previously thought. is is due in large part to the fact that most
studies on patients with addiction were conducted on people who were receiving treatment
for addiction within the health care system, where severe and treatment-resistant addictions
tend to be overrepresented. In reality, the majority of people who struggle with addiction
are able to enter remission without ever coming to medical attention. at is not to say that
there are not cases where the outcomes of addiction are very dire. In fact, the personal,
social, and societal harm caused by addiction places it up there with some of the biggest
killers in medicine, including diabetes and cancer. However, it’s important to remember that
a diagnosis of addiction does not make someone “an addict” or doom them to a life of
misery. For many people, it is entirely possible to overcome addiction with or without
treatment.
 

TREATMENT

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Like prognosis, treatment for addiction is also highly variable. For some people, quitting an
addiction is as simple as deciding to stop. For others, the initial desire to quit is followed by
decades of bouncing between abstinence and relapses. For still others, the desire to quit is
never there at all. Because of this variability, statistics on the efficacy of addiction treatment
are not very informative until they are broken down by the speci c reinforcers involved.
 

As a general process, treatment of addiction involves

facilitating the initial transition from frequent use of the reinforcer into sobriety (known as
detoxi cation or “detox”). is is followed by treatment focused on maintaining sobriety
(known as rehabilitation or “rehab”). For some reinforcers, detoxi cation is a simple
process. For others (like alcohol) where withdrawal can be potentially life-threatening,
detoxi cation may require admission to a medical facility for intensive monitoring.
Following detoxi cation, rehabilitation can be accomplished using a variety of treatment
modalities. Individual and group therapy can teach speci c skills to decrease cravings and
impulsivity, while interventions aimed at enhancing social support can strengthen ties with
family and friends in the hopes of improving one’s chances at success. For certain reinforcers
such as opioids and alcohol, medications can play a role by preventing withdrawal, reducing
cravings, and blocking the positive effects of the reinforcer. However, for other reinforcers
like methamphetamine or cocaine, no medications have yet proven to be helpful.
Of course, even beginning the process of detoxi cation and rehabilitation requires that the
patient is motivated for treatment. However, in many cases, the mere fact of being
dependent upon a reinforcer can signi cantly impair one’s insight that their use is
problematic, even in the face of signi cant evidence to the contrary (someone can go from
being a good father with a stable career to a homeless person living on the street in the span
of a year and still deny that there is any kind of problem). In fact, it is estimated that less
than 20% of people struggling with addiction will seek treatment on their own. To address
this, a speci c counseling technique known as motivational interviewing can be used to
increase a patient’s motivation to treat their addiction. Rather than approaching all patients
with addiction in the same way, motivational interviewing encourages providers to identify
the stage of change that the patient is in and use speci c techniques that are appropriate for
that stage. For example, when working with someone who doesn’t even think that their
alcohol use is a problem, doing something like setting a quit date is unlikely to be effective.
Instead, asking the patient to think of ways in which their drinking is harming them or
those around them is more likely to be effective. By matching the speci c interventions with
the stage of change, people with addiction are more likely to consider quitting. Motivational
interviewing is associated with a large effect size of 0.8 compared to treatment as usual.

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 Relapses are common in addiction treatment, and relapses should not be viewed as
failure either on the part of the patient, the provider, or the treatment itself. In fact, placing
too strong of an emphasis on sobriety as the only end-point of treatment can be
counterproductive. Instead of merely eliminating the addiction, it is more helpful to replace
it with other activities that the patient nds satisfying. For many people, engaging in
meaningful work, hobbies, or social activities can help to prevent the sense of boredom or
emptiness that often leads to relapses. Some evidence suggests that social support is one of
the most important, if not the most important, predictor of successful treatment. Because of
this, it is helpful to think that the opposite of addiction is not sobriety but connection and
community.

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MECHANISMS OF ADDICTION
While the concepts of operant conditioning can help us to understand the behavioral
processes at work in addiction, they don’t explain why some individuals develop an
addiction after even a single exposure to a reinforcer while others remain functional despite
decades of use. As with many parts of psychiatry, it’s never just one thing. While we have
already explored how different drugs vary in their addictiveness, different people also appear
to vary in their inherent vulnerability to addiction.
e precise reasons why some people are more prone to addiction than others are
unclear. Some evidence has suggested that people who are prone to addiction are more
likely to experience negative emotions at baseline. is makes use of substances both
positively and negatively reinforcing from the very rst use by not only inducing a pleasurable
feeling but also relieving the state of chronic dysphoria in which the person lives. (Compare
this to someone who is generally happy with their life and would therefore only receive

positive reinforcement from use of substances.)

However, some additional factors have also been found to stratify the risk of developing an
addiction. In particular, impulsivity also appears to be a signi cant risk factor for addictive
disorders. In a classic experiment, children were given access to a sweet treat (a
marshmallow) and told that they could either eat it immediately or wait 15 minutes to be
given a second marshmallow. Children who were able to delay grati cation for longer (an
indicator of low impulsivity) were found to have lower rates of addiction as adults,
suggesting that impulse control and the ability to delay grati cation are protective against
developing addictive disorders. In contrast, the children who ate the marshmallow right
away were noted to be at much higher risk of addiction later in life, suggesting that their
inability to refrain from activities which provided immediate positive reinforcement is
related to problems with impulse control (which you can think of as “impos control” to
connect the two concepts).
 

Addiction often involves poor impulse control or a

tendency to seek
immediate positive reinforcers without
consideration of consequences.
 

Impos control problems are related to immediate positive

reinforcement (even if there are long-term negative
consequences later).

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However, a later variant of this experiment found that intrinsic personality factors do
not tell the whole story, as people’s perceptions of how reliable their environment is also
plays a strong role. For example, if prior to the experiment a child is made a similar promise
by an adult (“If you wait, then you will be rewarded”) but then fails to receive it (“I’m sorry,
we are out of any additional marshmallows today”), they are more likely to decide against
delaying grati cation again and would instead eat the marshmallow right away, as they now
believe that promises of future gains cannot be reliably counted on. is suggests that
growing up in chaotic or unstable environments can also play a large role in impulsivity and
the later development of addictive disorders. Under these kinds of conditions, a greater
focus on immediate gains may actually be an adaptive response to an unreliable
environment.
e combination of a tendency towards negative emotions (which makes use of drugs
both positively and negatively reinforcing from the get-go) along with a greater focus on
immediate rewards over long-term gains appears to predispose certain individuals over
others to developing addictive behaviors. Once exposure to these reinforcers has occurred,
however, a different set of processes involving the protein Delta FosB (or ΔFosB) take over.
ΔFosB appears to play a critical role in all forms of addiction by acting as a “molecular
switch” that is turned on following exposure to a reinforcer. Interestingly, ΔFosB appears to
be involved in all addictions regardless of the speci c reinforcers involved, including drugs
like heroin and cocaine or behaviors like gambling and shopping. You can remember the
association of ΔFosB with addiction by thinking of the Δ as a triangle with the three Re’s at

each corner:

Δ
 

ΔFosB acts to stimulate neuronal growth in dopamine-producing neurons in the

ventral tegmental area which itself projects to the nucleus accumbens, the primary region
of the brain where many addictive substances act. ese brain areas, known collectively as
the reward circuitry, have played a key role in the evolutionary success of our species as
they are involved in promoting many of the behaviors (such as eating nutrient-rich food,
seeking sexual partners, and gaining possessions) that are not only pleasurable but also
necessary for survival. ese “normal” reinforcers are nely tuned to be just rewarding
enough that we will spend some of our time seeking it (but not so rewarding that we spend
all of our time seeking it). However, in the case of addiction, exposure to “supernormal”
reinforcers like heroin hijacks this otherwise helpful brain circuitry by creating an
experience that is so pleasurable and rewarding that seeking out this particular reinforcer
becomes an all-consuming obsession. Compared to the arti cially pleasurable experience of
being on heroin, normal reinforcers like food, sex, and attaining life goals simply cannot
compare. With enough exposure, the reward circuitry soon becomes non-responsive to
anything but the target of addiction, leading to a state of anhedonia (“Nothing else in my
life feels good—only heroin.”). is anhedonia can present a major obstacle to abstinence,

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as the things that normally bring people pleasure have been rendered ineffective for
someone with long-term exposure to supernormal reinforcers. is has important
implications for treatment, as healthcare providers must be mindful and empathetic about
how difficult it can be to live without pleasure and to nd speci c things (like socializing or
exercise) that still feel good.
 

ΔFosB is involved in both substance-related and

behavioral addictions.
 

ink of the Δ in ΔFosB as a triangle with the three

Re’s of addiction at each corner.

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DIAGNOSING ADDICTIVE DISORDERS
Addiction is not hard to diagnose. As long as all three Re’s are there (Repeated use, positive
Reinforcers, and negative Repercussions), you can diagnose addiction. In clinical practice, a
diagnosis of addiction is often made on the basis of supporting history, including
psychological symptoms (like cravings), speci c behaviors (such as spending a lot of time
attempting to obtain the reinforcer), and consequences of that behavior (including lost jobs,
legal penalties, and medical problems). You can systematically gather a complete substance
history using the mnemonic TRAPPED which stands for Treatment history, Route of
administration, Amount used, Pattern of use, Prior abstinence, Effects of use (both positive
and negative), and Duration of use.
 

A complete substance history should systematically

evaluate the pattern of the patient’s substance use
and their attempts at sobriety, if any.
 

TRAPPED: Treatment history Route of administration

Amount used Pattern of use Prior abstinence Effects of
use Duration of use

Historically, the DSM made a distinction between substance abuse (repeated use of a
substance despite adverse consequences) and dependence (needing to use a substance to
avoid a withdrawal state). However, in the DSM-5 this distinction was dropped in favor of
a single diagnosis: substance use disorder. A diagnosis of a substance use disorder should
specify the speci c substance involved (such as alcohol use disorder or opioid use disorder).
People with multiple substance use disorders should have them listed separately, as each can
be at a different level of severity. For example, someone could have “alcohol use disorder,
severe, active,” “opioid use disorder, in partial remission on maintenance therapy,” and
“methamphetamine use disorder, in long-term remission” all at the same time. Because of
this, for a patient with multiple substance use disorders, you should list each of them
separately rather than using a broad and unhelpful term like “polysubstance use disorder.”
In this section, we will revisit each of the major classes of psychoactive drugs through
the lens of how they appear in cases of addiction, including their diagnosis, prognosis, and
treatment. We will also touch brie y on behavioral addictions.
 
STIMULANT USE DISORDER
Stimulant use disorder generally refers to addiction to either methamphetamine or
cocaine, as caffeine use generally does not result in signi cant pathology and nicotine
addiction differs enough in its prognosis and treatment that it is considered separately as
tobacco use disorder. Because stimulants provide a subjective sense of energy and euphoria,
they can be very positively reinforcing, making stimulants among the most addictive
substances. Despite several studies, no medications have been shown to be helpful with

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treating stimulant use disorder. Instead, a variety of therapies (such as cognitive behavioral
therapy and/or motivational interviewing) have shown some minimal efficacy. Nevertheless,
stimulant use disorder tends to have an overall good prognosis, with around 80% of
methamphetamine-dependent patients achieving remission within 5 years of diagnosis.
 
TOBACCO USE DISORDER

Nicotine (the active ingredient in tobacco products like cigarettes) is

the single most addictive substance known to man. However, tobacco use is also associated
with a host of health problems, including an increased risk of cardiovascular disease and
various types of cancer. For this reason, smoking cessation is the single most effective
lifestyle modi cation you can encourage for your patients in nearly all cases.
Smoking cessation can be incredibly difficult. Not only is nicotine incredibly addictive
through its rapid absorption into the brain, it is also legal and widely available, making
maintaining abstinence even more challenging. Nicotine withdrawal is also associated with
particularly severe cravings.
Effective treatment strategies for tobacco use disorder exist and include medications,
therapy, or both. Nicotine replacement therapy (including nicotine gums or patches), the
nicotinic receptor partial agonist varenicline, and the antidepressant bupropion have all
shown efficacy at improving quit rates, with varenicline being the most effective.
Psychosocial treatments are also helpful by providing personal support and teaching
patients how to cope effectively with cravings. However, even with treatment, smoking
cessation is a long process. For many people, it can take several years and multiple attempts
to quit before sustained abstinence is achieved.
 
ALCOHOL USE DISORDER

Alcohol causes the most harm of any single

psychoactive substance due to its legal status, wide availability, and severe medical, social,
and societal consequences of misuse. Because of this, identifying and treating alcohol use
disorder is of primary importance. A specialized screening tool has been developed to help
identify patients with an active alcohol use disorder. Anyone who answers “Yes” to 2 or

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more of the following CAGE questions has a high likelihood of having an alcohol use
disorder: “Have you ever felt you ought to Cut down on your drinking?” “Have people
Annoyed you by criticizing your drinking?” “Have you ever felt Guilty about your
drinking?” and “Have you ever had an Eye-opener (a drink rst thing in the morning)?”

Screen for alcohol use disorder using the four

CAGE questions.
 

CAGE: Cut down Annoyed Guilty Eye-opener

Alcohol is a highly toxic substance that has been linked to increased rates of metabolic
diseases, brain damage, and various kinds of cancer. However, the most commonly affected
organ is the liver, which metabolizes alcohol. People with extensive histories of alcohol use
often have signs of liver damage including elevated hepatic enzymes. While there are
increases in both aspartate transaminase (AST) and alanine transaminase (ALT), a greater
increase in AST compared to ALT (known as the AST/ALT ratio) is characteristic of
chronic alcohol abuse. You can remember the greater increase in AST by thinking of
drinking and getting wASTed.
 

A high AST-to-ALT ratio is characteristic of

alcohol use disorder.
 

Getting wASTed raises your AST.

Another liver enzyme known as gamma-glutamyl transferase (GGT) is a highly sensitive

marker of chronic alcohol use. Combined with a high AST/ALT ratio, it is highly
suggestive of chronic alcohol intake. You can remember the association of GGT with
alcohol by thinking that it is elevated in people who are Gonna Get Trashed.
 

Elevated gamma-glutamyl transferase is a sensitive

index of alcohol use disorder.
 

Gonna Get Trashed and raise my GGT!

175
  

Effective treatments are available for alcohol use disorder. As mentioned previously,
alcohol withdrawal is potentially deadly, so detoxi cation programs with close monitoring
of vital signs is often necessarily (particularly in cases where there is a history of complicated
withdrawal). Benzodiazepines can be used to treat vital sign abnormalities or seizures if
they occur. Once the patient is successfully detoxi ed off of alcohol, a variety of
rehabilitation strategies are available, including both individual and group therapy. A
variety of medications are also available for chronic treatment of alcohol use disorder,
although these must generally be paired with other forms of support to be effective. ese
medications work by a variety of mechanisms. Some, like disul ram, introduce an element
of positive punishment to drinking by causing a build-up of toxic metabolites whenever
someone drinks, making them feel incredibly sick. Another, known as naltrexone, blocks
the ability of alcohol to activate opioid receptors and thereby reduces the pleasurable
sensation that one gets from drinking. Finally, acamprosate acts by opposing glutamate, a
neurotransmitter that is hyperactive in people who have previously been alcohol dependent.
ese three medications each can play a role in treatment of alcohol use disorder, though
generally they have low effect sizes in the range of 0.1 to 0.4.
 
BENZODIAZEPINE USE DISORDER
Use of benzodiazepines is common, with up to 15% of adults having taken at least one dose
in the past year. When used on a short-term basis for treatment of anxiety, these
medications can be very effective. However, with long-term use a number of worrying
patterns emerge, including memory impairment, disinhibition, depression, emotional
blunting, and psychological and physiologic dependence resulting in a tendency to make
anxiety worse rather than better. e majority of benzodiazepine misuse also occurs in the
context of use of other substances (often alcohol and opioids) that can increase the toxicity
of these drugs in overdose signi cantly. While dependence upon benzodiazepines is
common (with 1-2% of adults in the United States taking them on a daily basis), true
addiction is uncommon because the desired effect of these medications is often to remove a
state of anxiety, making them negatively (rather than positively) reinforcing. For this reason,
for most people chronic misuse of benzodiazepines represents a compulsive behavior rather
than an addictive behavior (people take them to not feel bad rather than to start feeling good).
e best way of preventing benzodiazepine misuse is to avoid prescribing them in
anything but short courses with the smallest amount possible and only when there are no
better alternatives. For someone who is already misusing benzodiazepines, a taper should be
scheduled. While this can result in an uncomfortable and protracted withdrawal state, many
people notice that their depression and anxiety both improve considerably once the taper is
completed, making it a worthwhile effort.
 
OPIOID USE DISORDER
Misuse of opioids is increasingly common in the United States, with up to 2% of adults
having used heroin at some point in their lives. On a clinical level, there is no difference
between prescription painkillers and illicit narcotics, and many people will transition from
one to the other. Opioids can be extremely dangerous in overdose due to their tendency to
cause respiratory depression, and deaths related to opioid overdoses have reached crisis
levels in many parts of the country.

176
 Treatment for opioid use disorder involves an initial phase of detoxi cation. Opioid
withdrawal can be incredibly uncomfortable, including emotional dysphoria, restlessness,
muscle aches, nausea, vomiting, abdominal cramping, and diarrhea. While this is not
dangerous, treating withdrawal symptoms with symptomatic treatments can facilitate
abstinence by reducing the drive towards using again (essentially, you are removing the
positive punishment for abstinence). Following detoxi cation, patients with opioid use
disorder often need long-term efforts to prevent relapse. e evidence suggests that the best
treatments involve a combination of medications and psychosocial treatment rather than
either alone. Medications can either block the opioid receptor directly, as in naltrexone, or
bind to the opioid receptor in a way that doesn’t induce euphoria or interfere with
functioning in the way that addictive opioids do, as in methadone or buprenorphine.
 
CANNABIS USE DISORDER
Cannabis is signi cantly less addictive compared to other substances like opioids or
nicotine. However, because cannabis is widely used (with over half of American adults
having tried it at some point), cannabis dependence has a relatively high base rate in the
population at around 4%. e majority of people who are dependent upon cannabis begin
before the age of 25, and most use it in addition to other substances. While cannabis is not
particularly dangerous in either overdose or withdrawal, it can lead to dysfunction in life
due to persistent apathy and low motivation. Treatment strategies for cannabis use disorder
have been poorly studied, although motivational interviewing and CBT appear most
effective so far.
 
BEHAVIORAL ADDICTIONS
Behavioral addictions involve speci c reinforcers that are not biologically active substances
but can still be powerfully rewarding. While the DSM-5 makes a distinction between
substance use disorders and behavioral addictions, research on the underlying neural
mechanisms has shown that substance use disorders and behavioral addictions are much
more alike than they are different, as both activate ΔFosB and stimulate neuronal changes in
the reward circuitry.

Gambling is the best studied of the behavioral addictions

and the only one listed as a discrete diagnosis in the DSM-5. Gambling is particularly
addictive because it operates on a variable reinforcement schedule. To understand what is
meant by this term, compare a slot machine to a vending machine. A vending machine acts
in the same way every time: if you put in $1, you will get a can of soda. erefore, you go to
a vending machine when you want a drink but not at any other times. In contrast, a slot
machine is inherently unpredictable: if you put in $1, you don’t know if you will get $0, $1, or

177
$100 back. Variable reinforcement schedules seem to intrinsically be much more addictive
than predictable reinforcement schedules and make the rewards seem much more enticing
and valuable. is unpredictability is incredibly salient to our brains and motivates us to act,
and for this reason variable reinforcement schedules are often highly addictive. Because of
this, addiction to SLOt machines and other forms of gambling are much SLOwer to go
away than addiction to vending machines. While a slot machine is a classic example,
variable reinforcement schedules are increasingly found in other media including video
games.
 

Variable reinforcement schedules can lead to

behavioral addictions.
 

Addiction to SLOt machines goes away much SLOwer

than a vending machine.

While gambling is the only behavioral addiction officially recognized in the DSM, a variety
of other behavioral addictions have been studied including addiction to sex, pornography,
food, shopping, and the internet, among other things. What each of these things has in
common is that they represent a supernormal stimulus, or something that has long been
adaptive for humans to desire but is now available in such concentrated form that our
attraction to it leads to unhealthy patterns. Food is a good example. roughout our species’
history, it has made sense for humans to seek out the most highly caloric and nutrient-
dense foods to ensure sufficient energy reserves during the times when access to food was
more limited. However, following the agricultural revolution, food is now readily available
around the clock in many societies, making obesity a greater threat to health than starvation
in most places. However, our reward circuitry is still programmed to desire the highest
calorie foods available to prevent starvation. Whereas before this was meat, nuts, fruits, and
vegetables, in the modern day there are cookies, chips, and ice cream, each of which
combines fat, sugar, and salt into a hyper-appetizing delicacy that evolution has not
prepared us for. In this way, an easily available and highly concentrated version of a natural
resource is able to hijack the reward circuitry and create maladaptive patterns. Pornography
is another example. It is evolutionarily advantageous for humans to place a high priority on
seeking out sexual partners and to devote signi cant time and resources to attracting a mate.
However, in an age where the internet provides easy access to millions of perceived potential
sexual partners at all times of the day, our adaptive desire to bond and procreate has been
co-opted by concentrated stimuli that, at least for some, becomes excessive and unhealthy,
leading to addictive behavior.
While there is controversy in the eld of psychiatry about whether behavioral addictions are
“true” addictions in the same way as substance use disorders, the fact that they t the same
pattern (repeated use of positive reinforcers despite negative repercussions) and involve the
same biological mechanisms (ΔFosB and the reward circuitry) argues for a shared diagnostic
approach. Treatment for behavioral addictions also resembles substance use disorders to a
large degree, with motivational interviewing, CBT, and psychosocial therapies being

178
helpful. While no medications have been approved speci cally for treating behavioral
addictions, some (including naltrexone) have been shown in a few studies to reduce
pathological gambling, shopping, sexual behavior, and internet use.

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DIFFERENTIAL DIAGNOSIS OF ADDICTIVE DISORDERS
Addiction is not difficult to diagnose. Unlike depression, bipolar disorder, and
schizophrenia where a precise understanding of the phenomenology of these conditions is
necessary (“Is it decreased sleep or decreased need for sleep?” “Are the voices coming from
inside or outside their head?”), cases of addiction can largely be diagnosed simply by using
the three Re’s and systematically reviewing each of the common substances and behaviors
that are often the targets of addiction. Because of this, the primary pitfalls to avoid when
diagnosing addiction are missed diagnoses rather than misdiagnoses. Due to the high
comorbidity between addiction and other mental disorders, anyone presenting with an
addiction should be carefully screened for the presence of other psychiatric syndromes (such
as mood disorders, anxiety, schizophrenia, personality disorders, PTSD, and OCD) and
vice versa.
While misdiagnosing an addiction as a different disorder is rare, the opposite is not true, as
the effects of substance use are commonly mistaken for a primary psychiatric disorder. is
is because the effects of speci c substances can mimic nearly any psychiatric syndrome. In
addition, many substances can increase the risk of developing various mental disorders such
as an alcohol-induced depressive disorder or cannabis-induced psychotic disorder. ere is
often a “chicken or egg?” question intrinsic to the discussion of any substance-induced
disorder (“Did this person become depressed because of
their addiction, or did they get addicted because they were
depressed?”). While the answer to this question can be
helpful to guiding treatment (“Do we treat the depression or
alcoholism rst?”), a clear and unambiguous answer is not
always found. In these cases, it is generally best to treat the
addiction rst and see whether the psychiatric symptoms
resolve accordingly. In cases where they do not, separate
treatment of a mental disorder may be necessary.
 
NORMALCY
Engaging in “vices” like drug use or gambling is not inherently pathological. Recall from
the three Re’s that negative repercussions are a necessary component for diagnosing
addiction, so in the absence of any signi cant consequences, you should not diagnose
addiction even if someone is engaging in repeated use of positive reinforcers. It’s also
worthwhile to keep in mind that negative repercussions from substance use do not exist in a
vacuum. For example, someone who has a medical condition like multiple sclerosis may use
cannabis as an evidence-based way of relieving spasticity. However, in many places, use of
cannabis for any reason remains illegal, making it possible that this person could get red
from their job or sent to prison. If this happens, can we now diagnose this person as having
a disorder? is position seems difficult to hold, especially considering that this exact same
person would not have had the same repercussions if they lived in a different place where
cannabis use was legal. In these cases, the negative repercussions of addiction can be more
accurately attributed to societal (rather than personal) dysfunction, yet our diagnostic system
is designed in such a way that a diagnosis is always personal (rather than societal). ese grey
cases reveal the limits of an arti cial diagnostic scheme that attempts to impose strict limits
upon an inherently messy subject. For this reason, always use your judgment on where to
draw the line between normalcy and addiction, and try your best to avoid knee-jerk

180
diagnoses of addiction (such as diagnosing “cannabis use disorder” for someone who uses
cannabis but has no problems from it).
 
MOOD DISORDERS
e speci c behavioral effects of particular substances can often be mistaken for mood
disorders. Stimulants like methamphetamine can resemble mania, while depressants can
obviously resemble depression. Paying close attention to the timing of symptom onset in
relation to substance use can help to resolve this ambiguity.
Mania deserves special mention, as the impulsivity and hyperhedonia seen in mania can
manifest in excessive use of drugs and other reinforcers. For some people, this
“pseudoaddictive” behavior will go away with resolution of mania, making it more likely
that the addictive behaviors can be attributed entirely to the recklessness of mania.
However, in other cases, substance use that began during mania can develop into a “full
blown” addiction that persists even after the mood episode resolves. Be cautious when
diagnosing addiction during a manic state, but don’t rule out the possibility entirely.
 
PSYCHOSIS
A variety of drugs can induce a state that strongly resembles psychosis, including drugs like
methamphetamine that result in excessive release of dopamine. Always have substance-
induced psychotic disorder on the differential for anyone presenting with psychotic
symptoms, especially if they appear suddenly, resolve quickly, or occur along with objective
signs of pathology (such as decreased orientation or changes in vital signs) that suggest
something more may be going on. In addition, keep in mind that chronic use of
methamphetamine and cannabis have been associated with development of persistent
psychotic syndromes, so in these cases the symptoms may remain even once the substance is
stopped.
 
OBSESSIVE-COMPULSIVE DISORDER
e repetitive harmful behaviors seen in OCD can sometimes be mistaken for the repetitive
harmful behaviors seen in addiction. Pay close attention to whether the behavior is positively
reinforcing (in which case it is likely an addiction) or negatively reinforcing (in which case
OCD or a related disorder is more likely). While the point can seem technical, it carries
signi cant implications for prognosis and treatment, with medications that work on the
reward circuitry (like naltrexone) being more helpful for addictive behaviors while
medications that modulate serotonin (like SRIs) are more helpful for compulsive behaviors.
 

ANXIETY
Use of stimulants and withdrawal from depressants can both induce very strong feelings of
anxiety that may be mistaken for a primary disorder. In addition, people with an anxiety
disorder are at higher risk of substance misuse, particularly with substances like alcohol or
benzodiazepines that are intrinsically anxiety-relieving (making them both positively and
negatively reinforcing at the same time).
 
PAIN
Reasonable use of opioids to relieve pain is medically and ethically justi ed. In these cases,
opioids are being used for their negatively reinforcing qualities (removing pain) instead of

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their positively reinforcing traits (inducing a feeling of euphoria). Because of this, don’t
assume that everyone who seeks out opioids is suffering from an addiction. However, it’s
also dangerous to assume that everyone who seeks out opioids is doing so for a legitimate
medical reason. As with so many things in psychiatry, the line separating normalcy from
pathology is blurry, and even someone who starts out using opioids for “legitimate” medical
reasons can transition to problematic use.
 

TRAUMA Trauma and addiction are highly comorbid conditions, with current symptoms
of PTSD being 3 times more common in people suffering from an addiction. In addition, it
is more difficult to treat addiction in people who have untreated symptoms related to
trauma. For this reason, it is helpful to keep PTSD (as well as closely related disorders that
also are linked to trauma including cluster B personality disorders, somatoform disorders,
and dissociative disorders) on the differential for anyone with an addiction.

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PUTTING IT ALL TOGETHER
Addiction is one of the largest problems facing society today, and it is estimated that 20% of
all deaths in the United States are related to this disorder. Addiction exacts further costs on
society in terms of high medical costs, broken families, and increased rates of accidents,
overdoses, suicide, and violence. Despite these costs, barely over 10% of people struggling
with addiction receive high-quality treatment. Because of this, it is essential to evaluate for
addiction in every patient presenting with a psychiatric issue (remember the N in
CHAMPION FISH CALLER).

When assessing for substance use, it is helpful to have a

systematic framework to screen for each of the major reinforcers. To give you this
framework, picture someone who is currently destroying their life due to an uncontrolled
addiction. eir friends stage an intervention and successfully get him into rehab. However,
they realize that now there is no one to take care of his dog. e friends look at each other,
with nobody quite yet willing to step up and volunteer to care for the dog. e question on
everyone’s mind naturally is, “ is guy’s out of control, but CAN HIS DOG Behave?” is
phrase can remind you of the major classes of addictions to remember: Cannabis, Alcohol,
Nicotine, Hallucinogens, Inhalants, Stimulants, Depressants, Opioids, Gambling, and
other Behavioral addictions.
 

Having a framework for the various types of

addictions can be helpful when evaluating a patient’s
substance history.
 

CAN HIS DOG Behave?: Cannabis Alcohol Nicotine

Hallucinogens Inhalants Stimulants Depressants
Opioids Gambling Behavioral

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REVIEW QUESTIONS
1. A 44 y/o M comes into an addiction medicine clinic for an initial evaluation. He
recently went through a divorce and lost custody over his two twin daughters in
the process (“the judge says it was mostly due to my drinking”). He reports alcohol
intake on most days. He is asked several times to quantify exactly how much he
drinks per day but consistently avoids the question by giving tangential responses;
the clearest answer he gives is “a lot.” When asked about his reason for drinking,
he says that he nds that drinking “has always been there at the happiest moments
of my life” and that he nds himself going to bars primarily out of boredom and a
desire to socialize. He is motivated to stop drinking (“I don’t give a shit about my
ex but I have to get my daughters back”) and has been attending Alcoholics
Anonymous meetings every day for the past week. His last drink was 10 days ago.
He has never seen a psychiatrist before or taken psychotropic medications. Vital
signs are all within normal limits. Which of the following is the best single
treatment recommendation at this time?
A. Refer for inpatient detoxi cation
B. Prescribe a benzodiazepine
C. Prescribe naltrexone
D. Prescribe acamprosate
E. Prescribe disul ram
F. Psychosocial support and therapy
2. (Continued from previous question.) To rule out medical complications of alcohol
use, a variety of blood tests are ordered. Which of the following laboratory values
is least likely to be elevated in this patient?
A. Gamma-glutamyl transferase (GGT)
B. Aspartate transaminase (AST)
C. Alanine transaminase (ALT)
D. ALT-to-AST ratio
E. All of these are likely to be elevated
3. (Continued from previous question.) e patient reports increasing feelings of
depression over the past 2 weeks since being told that he was losing custody of his
daughters. His speci c symptoms include poor appetite, difficulty falling and
staying asleep, feeling guilty, having poor energy, and nding it difficult to
concentrate on other things. He denies suicidal ideation, and there is no evidence
of psychomotor slowing on exam. In addition to alcohol use disorder, which of the
following diagnoses is most appropriate at this time?
A. Major depressive disorder
B. Bipolar depression
C. Substance-induced mood disorder
D. Adjustment disorder
E. No additional diagnoses should be assigned
4. A 35 y/o M begins seeing a therapist for “sex addiction.” He reports spending up
to 5 hours each day on the internet looking for potential sexual partners. He
typically contacts several hundred women per day and meets with new partners
two or three times each week, although he says “sometimes it’s like a buffet and

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other times it’s a drought.” He has contracted several sexually transmitted
infections as he prefers not to use condoms because “it dulls the reworks.” He has
occasionally attempted to “play it straight” and see the same partner multiple times
but nds that he often suffers from erectile dysfunction when he does so. He feels
guilty about his behavior but nds himself unable to stop. Which of the following
features of his behavior makes it most difficult for him to stop?
A. Ease of looking for partners online
B. Unpredictable nature of seeking new partners
C. Pleasurable sensation of orgasm
D. Sense of danger from contracting sexually transmitted infections
E. Presence of erectile dysfunction when seeing the same partner
 

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1. e best answer is F. is patient is likely suffering from an alcohol use disorder.
While he does not quantify the amount he is drinking, it is clear that there is
repeated use of alcohol despite negative repercussions (such as losing custody of his
daughters). Treatment for alcohol use disorder involves an initial period of
detoxi cation. However, the window for acute withdrawal symptoms is generally
one week after the last drink. Given that his last drink was over on week ago, it is
likely unnecessary in this case (answer A). Benzodiazepines would also be
unnecessary given his lack of vital sign instability or other symptoms suggestive of
withdrawal (answer B). Each of the other listed medications can play a role in
treatment of alcohol use disorder; however, they must generally be paired with
psychosocial rehabilitation to be effective (answers C, D, and E). erefore, the
best single treatment option for this patient is psychosocial rehabilitation.
2. e best answer is D. Chronic use of alcohol is associated with increases in
multiple laboratory values, including gamma-glutamyl transferase (answer A),
aspartate transaminase (answer B), and alanine transaminase (answer C). However,
it is the ratio of AST to ALT that is reliably elevated in alcohol use disorder, not
the ratio of ALT to AST.
3. e best answer is C. While the patient technically meets criteria for a major
depressive episode (including 5 out of 9 symptoms for at least 2 weeks), the
presence of excessive alcohol intake around the same time period precludes a
diagnosis of a primary mood disorder, including both major depressive disorder
(answer A) and bipolar depression (answer B). Instead, a diagnosis of a substance-
induced mood disorder should be given. It is possible that these symptoms will
persist even once sustained abstinence from alcohol has been achieved, at which
time a diagnosis of a primary mood disorder could be considered; for the time
being, however, the most likely explanation for his mood symptoms is his recent
substance use, especially considering his lack of prior psychiatric history. While
there is a recent major life stressor, the patient’s current symptoms are too severe to
qualify for a diagnosis of adjustment disorder which by de nition is subsyndromal
(answer D) or for no additional diagnosis to be given (answer E).
4. e best answer is B. While all of these factors likely play a role in maintaining
this patient’s behavior (with the likely exception of a sense of danger from
contracting new infections, or answer D), it is the unpredictability of a variable
reinforcement schedule that has been found to correlate most strongly with which
behaviors develop into an addiction. e pleasure of an orgasm (answer C) acts as
a positive reinforcer for sex while the presence of erectile dysfunction (answer E)
acts as a negative punishment for seeing the same partner, which can support the
current pattern of the patient’s behavior but likely does not contribute to his high
degree of use to the same extent as the variable reinforcement schedule. e ease of
looking for new partners online (answer A) may have played a role in initiating this
behavior but likely does not account for why it has developed into an addiction.

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9 ANXIETY

Anxiety is an unpleasant mental state involving persistent

worrying about the possibility of future dangers, threats to safety, or upsetting events.
Anxiety manifests physiologically, psychologically, and behaviorally with speci c signs
and symptoms, including an increased heart rate, pessimistic thought patterns, and
avoidance of particular places or situations. Despite being unpleasant, anxiety is not an
intrinsically pathological state. Indeed, anxiety is often adaptive by allowing us to foresee
possible negative outcomes and take steps to avoid them. For example, someone who begins
going to the gym and eating a better diet is likely motivated at least in part by anxiety about
becoming unhealthy. In this way, anxiety is similar to pain: both are experienced as
distressing and unpleasant, but both serve a practical purpose by motivating us to avoid
harmful things or situations.
However, for some people anxiety becomes extreme and excessive to the point that it
is no longer helpful but instead causes the person to act maladaptively. ese people are said
to be suffering from anxiety disorders. As a group, anxiety disorders are the most common
type of mental disorder, making it essential for anyone studying psychiatry to understand
these conditions. Anxiety disorders involve exaggerations or abnormalities in the way that
humans process alarm signals, leading to the development of irrational beliefs as well as
maladaptive coping behaviors that, while intended to avert bad outcomes, instead end up
causing more dysfunction than they prevent. e goal in diagnosing and treating anxiety
disorders is not to eliminate anxiety altogether, as a life that is completely free of anxiety
would likely be equally problematic (not to mention unattainable). Instead, the goal should
be to restore a pattern in which anxiety is a helpful signal rather than a harmful one.

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SIGNS AND SYMPTOMS OF ANXIETY
e signs and symptoms of anxiety are not hard to recognize, as everyone has experienced
them at some point in their lives. In describing the signs and symptoms of anxiety, it is
important to distinguish between the states of anxiety and fear. Anxiety and fear are both
part of our body’s stress response, or the physical and mental changes that occur when
encountering a challenge in our environment. However, in anxiety the focus is a perceived
future threat whereas in fear the focus is on a current threat. For example, a deer who is
suddenly attacked by a cougar jumping at them from behind the bushes will enter a state of
fear, while a deer who walks around worrying about a cougar jumping out at any time is
experiencing anxiety. While both are uncomfortable, fear and anxiety can each serve a
purpose by motivating the organism to behave in an adaptive way (such as encouraging the
deer to run away from the cougar or to avoid places where cougars are more likely to be
found).
 

Fear Anxiety

Fear is related to current threats, while anxiety

focuses on future threats.
 

Fear is for what’s here and now, anxiety’s for the future.

Biologically, both anxiety and fear activate the rapid-acting sympathetic nervous system
which immediately puts the body into “ ght or ight” mode. In response to the release of
epinephrine and norepinephrine, muscles tense up, the heart beats faster, breathing
becomes rapid, pupils dilate, and sugar is released into the bloodstream in an effort to
prepare the organism to either face down its threat or get away from it as quickly as
possible. Activation of the sympathetic nervous system also shuts down other organ systems
such as the gastrointestinal tract and reproductive organs that are less essential for
immediate survival. On a cognitive level, fear and anxiety are often experienced as “racing”
or “loud” thoughts, extreme unease, and/or a sense of impending doom. Compared to fear,
anxiety tends to activate the sympathetic nervous system to less of an extent (which makes
sense, as the body’s response to the thought of a cougar jumping out at you should naturally
be less than a cougar actually jumping out at a you).

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 Anxiety is both a state and a trait—it can be both an
immediate mental state in response to current circumstances (“I’m feeling very anxious right
now.”) as well as a chronic and enduring disposition towards anxiety (“I’m kind of an
anxious person.”). (In contrast, fear can only be a state.) While activation of the sympathetic
nervous system explains the signs and symptoms of anxiety in the immediate “state” sense,
it does little to account for the “trait” signs and symptoms of anxiety that are persistent over
months or years. Instead, chronic anxiety is generally mediated by the slower-acting
hypothalamic-pituitary-adrenal axis (or HPA axis). Activation of the HPA axis induces
long-term changes in physiology, cognition, and behavior via the release of the hormone
cortisol. Cortisol has many functions, including reducing in ammation, breaking down
connective tissues, regulating blood pressure, and altering the metabolism of carbohydrates,
protein, and fat. Psychologically, chronic activation of the HPA axis has been linked to
irritability, restlessness, muscle tension, insomnia, and poor mood as well as a heightened
sensitivity to a variety of physical symptoms. oughts in anxiety are often ruminative,
which can make it difficult to concentrate on other things. e signs and symptoms of
chronic anxiety can be memorized easily using the mnemonic MISERA-ble, which stands
for Muscle tension, Irritability, difficulty with Sleep, low Energy, Restlessness, and poor
Attention. (If these symptoms sound familiar, that is because we have discussed many of
them previously in the context of depression. Indeed, chronic activation of the HPA axis is
also found in people who are depressed, which likely accounts for the similar symptoms,
overlap in treatments, and links to adverse childhood events that are shared between the
two disorders. is makes activation of the HPA axis a sensitive, though not very speci c,
marker of chronic anxiety.)
Chronic anxiety is associated with both physical and
physiologic symptoms, including muscle tension,
restlessness, and irritability.
 

MISERA-ble: Muscle tension Irritability Sleep

(decreased) Energy (decreased) Restlessness Attention
(decreased)

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 e sympathetic nervous system is involved in
acute fear and anxiety, while the hypothalamic-
pituitary-adrenal axis is activated in chronic
anxiety.
 

e SNS is activated by both types of Stress, while the

HPA is activated only by Anxiety.

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ANXIETY ACROSS THE LIFESPAN
Whether as a trait or a state, anxiety is common, with over 10% of people having had an
anxiety disorder within the past year and up to 30% meeting criteria for one during their
lifetime. is makes anxiety disorders the most common group of mental disorders
(although depression is still the most common individual mental disorder). is gives
anxiety a high base rate in the population, making it liable to underdiagnosis (especially
considering that the symptoms of anxiety are often less noticeable or overtly impairing than
those seen in mania or psychosis). Like with depression, women are diagnosed with anxiety
disorders more than twice as often as men. Anxiety disorders often begin during childhood
and adolescence, with almost all cases beginning by the age of 25.
 
PROGNOSIS
Without treatment, anxiety disorders tend to become chronic and persist throughout life
(rather than being episodic in the same way that mood disorders are). While some degree of
anxiety is almost always present for someone with an active disorder, there is often a natural
waxing and waning of severity from day to day or even year to year. e severity of
symptoms often levels off with aging, as the prevalence of clinically signi cant anxiety
disorders begins to decrease after the age of 55. However, some degree of impairment often
remains even into old age.
While anxiety disorders are associated with a lower risk of suicide compared to mood
disorders, the risk is still present. In addition, untreated anxiety disorders often lead to more
social and occupational disability than mood disorders by virtue of their being a chronic
(rather than episodic) disorder. e disability associated with depression, for example, often
resolves once the depressive episode ends (usually within one year) whereas for an anxiety
disorder the dysfunction can continue unabated for years on end.
 
TREATMENT
As with most mental disorders, treatment involves psychotherapy and medications.
However, in contrast to depression (where either medications, therapy, or both are
appropriate) as well as bipolar disorder and schizophrenia (where medications are almost
always used with therapy being an adjunct), for anxiety disorders psychotherapy should be
the rst-line treatment in nearly all cases. CBT in particular shows a large effect size
(above 0.8) for the majority of anxiety disorders.
Medications should be used more sparingly, as they tend to have smaller and more
transient effects on anxiety. Antidepressants like SRIs are most commonly used and have a
small effect size (around 0.3 or 0.4). ey appear to be effective regardless of the speci c
anxiety disorder that is diagnosed (they are “broad-spectrum antineurotics”).
Benzodiazepines are often used for acute treatment of panic attacks, but they should not be
used for chronic treatment of any anxiety disorder as they tend to actually worsen long-
term outcomes. Benzodiazepines not only induce a state of psychological and physiologic
tolerance that makes the brain more susceptible to anxiety, they can also interfere with
someone’s ability to engage in the psychotherapy that is required for de nitive treatment of
an anxiety disorder. Because of this, benzodiazepines should be avoided for chronic
treatment of anxiety.

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MECHANISMS OF ANXIETY
Understanding the underlying pathophysiologic mechanisms of anxiety disorders is helpful
insofar as it assists in con rming a diagnosis and providing speci c targets for treatment. In
this way, the alarm—beliefs—coping (ABC) model of anxiety disorders provides a helpful
framework for understanding the speci c symptoms and behaviors seen in each individual
type of anxiety disorders.

In this model, the starting point for any and all

anxiety disorders is an internal alarm signal. Something (either in the environment or an
internal sensation) is telling us that there is cause for concern. Perhaps it is an oddly colored
mole on our skin that we never noticed before or the sound of a window breaking at night.
Regardless of the speci c stimulus that triggers it, the alarm signal instantly activates the
sympathetic nervous system, leading to the immediate symptoms of anxiety. Cognitively,
thoughts tend to become singularly focused on interpreting the alarm signal and developing
a set of speci c explanatory beliefs about the alarm (“Does this mole mean I have cancer?”
or “Oh shit, is somebody breaking in?”). ese beliefs form the basis upon which we
consciously act in response to the alarm signal (“I need to go see a doctor,” or “I have to get
out of here!”). is experience then forms the basis of our coping strategies, including
taking steps to either avoid this situation altogether or to plan for what we would do should
we ever nd ourselves in a similar situation (“I should wear more sunscreen,” or “I’m buying
a security system!”).
Viewed from this perspective, all anxiety disorders are characterized by a defective
alarm signal, including overactive alarms that won’t turn off or “false alarms” that go off for
unknown reasons. All of the variations in thought and behavior that de ne the traditional
separations between different types of anxiety disorders are ultimately just downstream
consequences of this core abnormality. On a biological level, hyperactivity of the HPA axis
appears to be the mechanism by which a defective alarm signal arises, and individuals with a
wide variety of anxiety disorders all appear to share some degree of overactivity in one or
more components of the HPA axis. A hypersensitive HPA axis has been linked to adverse
events during childhood, including abuse, neglect, parental death, or a caregiver with a
severe mental illness. Exposure to adverse events appears to induce long-lasting changes
during the development of the HPA axis, leading to the hyperactivity seen in anxiety
disorders.
As we explore each of the speci c patterns of anxiety disorders (including generalized
anxiety disorder, panic disorder, speci c phobias, and social anxiety disorder), try to view
each of them though the lens of the ABC model and look closely at how the alarm system
has become dysfunctional in each.
 

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Anxiety disorders involve a consistent pattern of a
defective alarm signal followed by explanatory
beliefs and compensatory coping strategies.
 

Anxiety is as easy as ABC: Alarm—Beliefs—Coping.

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DIAGNOSING ANXIETY DISORDERS
Like most mental disorders, anxiety disorders are diagnosed using the psychiatric interview
and mental status exam. While the current signs and symptoms of anxiety that are elicited
during the evaluation process (the “state”) are important in pointing towards a diagnosis,
you must take into account the longitudinal pattern of anxiety across the lifespan as well
(the “trait”).
Unlike depression, mania, and psychosis, there is no single disease prototype against which
all other related disorders are measured. Instead, the major subtypes of anxiety disorders—
including generalized anxiety disorder, panic disorder, speci c phobias, and social anxiety
disorder—are more like addictive disorders in that they are a heterogeneous group of
conditions, each with their own diagnostic, prognostic, and treatment considerations.
However, they all share a similar fundamental pattern: persistent and excessive worrying
about the future that results in maladaptive belief systems and coping strategies.
Because of this shared pattern, it is perhaps no surprise that the majority (over two-
thirds) of people who are diagnosed with one anxiety disorder also meet criteria for another.
is makes being diagnosed with a single anxiety disorder the exception rather than the
rule. ( ere is also a high rate of comorbidity with for other conditions, like depression, that
also involve HPA axis hyperactivity.) In addition, people with one anxiety disorder will
often “convert” to another during their lifetime, reinforcing further the notion that
someone’s trait anxiety (an overactive alarm signal) can produce various state abnormalities
(the speci c beliefs and coping behaviors that characterize each individual anxiety disorder).
In clinical practice, you will encounter many people who clearly suffer from excessive
and debilitating anxiety but do not quite t a particular diagnosis. However, you will also
run into people who seem to have “read the textbook” on each of these disorders and t
their patterns to a tee. In general, don’t get too caught up in the idea of adhering strictly to
the diagnostic criteria found in the DSM, as it’s ultimately more important to identify the
overall process of pathologically extreme or dysfunctional levels of anxiety than it is to “nail
the diagnostic criteria.”
 

GENERALIZED ANXIETY DISORDER

Generalized anxiety disorder (GAD) is characterized by chronic anxiety in multiple areas
of life, including—but de nitely not limited to—work, home, family, friends, nances,
health, politics, and transportation. ( is places generalized anxiety disorder in contrast to
other anxiety disorders, such as speci c phobias or social anxiety disorder, where severe
anxiety is limited only to a single domain.) It is the persistence and pervasiveness of the
anxiety that truly de nes generalized anxiety disorder, which in the ABC model of anxiety
is akin to an alarm that rings all the time for no clear reason. ese worries are not only

194
distressing to experience but can also result in signi cant impairment. For example,
someone with generalized anxiety disorder may end up having problems with social
relationships (“I can’t get married, she will cheat on me!”), difficulty at work (“I can’t do this
project, I’ll screw everything up!”), trouble getting around (“I can’t drive, the bridge will
collapse!”), and complications even with things that most people would nd exciting (“I
can’t buy a house, a hurricane is bound to hit soon!”). Left unchecked, these worries can
prevent someone from engaging in the very parts of life that people nd meaningful.
In addition to signi cant social and occupational dysfunction, people living in a state
of chronic anxiety often suffer from the symptoms inherent to chronic overactivation of the
HPA axis, including the Muscle tension, Irritability, impaired Sleep, low Energy,
Restlessness, and poor Attention captured in the MISERA-ble mnemonic. As mentioned
previously, these symptoms are not unique to generalized anxiety disorder (or even anxiety
disorders as a whole), but they can help to characterize the effect that the disorder has on
each person’s life and to provide speci c areas for treatment.
Diagnosing generalized anxiety disorder is not complicated. Asking even a single question
(“Do you worry excessively about minor matters?”) is a highly sensitive screening
instrument for generalized anxiety disorder, making it a quick and easy way to rule out the
disorder. For people who answer yes, the presence of chronic anxiety symptoms can help to
rule in the diagnosis provided that they have been present for at least 6 months. To
remember the overall pattern of generalized anxiety disorder, think of the phrase A-mos
Mo-six (also a reference to an old country song by Jerry Reed) to remember that
generalized anxiety disorder involves Anxiety about most things Most of the time for six
months.
 

Generalized anxiety disorder is diagnosed when

someone has anxiety about most things most of the
time for six months.
 

A-mos Mos-six: Anxiety about Most things Most of the

time For six months

Generalized anxiety disorder affects around 1-3% of the population at any given time,
making it relatively uncommon (though by no means rare). As with most anxiety disorders,
women are diagnosed twice as often as men. e diagnosis is highly comorbid with
depression and dysthymia which suggests shared genetic, mechanistic, and environmental
vulnerabilities. It is also often found in combination with addiction to speci c substances,
especially those that are inherently anxiety-relieving such as alcohol and benzodiazepines.
Without treatment, the symptoms of generalized anxiety disorder tend to persist for years,
if not decades.
Treatment for generalized anxiety disorder consists of psychotherapy. CBT is a
particularly effective modality with a large effect size around 0.7 or 0.8. Medication
treatment for generalized anxiety disorder generally involves either an SRI or buspirone, a
medication that also interacts with serotonin receptors. While both have been shown to be

195
helpful (with a small effect size around 0.2 or 0.3), like most medications for anxiety they
should primarily be used in combination with therapy to ensure that the effects of treatment
are sustained.
 
PANIC ATTACK
A panic attack is a brief period of intense mental and physical discomfort that results from
sudden activation of the fear response. Symptoms during a panic attack are consistent with
overactivation of the sympathetic nervous system and include palpitations, shortness of
breath, hyperventilation, chest pain, dizziness, sweating, headache, paresthesia, vertigo,
lightheadedness, choking, derealization, fears of dying, and a sense of impending doom.
ese symptoms tend to follow a crescendo-decrescendo pattern where symptoms peak
within a few minutes and then slowly subside after that. Panic attacks typically last for 5 to
10 minutes, although they can be as short as 1 minute or as long as an hour.

Panic attacks differ from normal fear reactions in

terms of their severity. It is natural that the fear response should be greater or lesser
depending on the circumstances. For example, seeing a spider across the room should
naturally provoke a lesser fear response than pulling back the shower curtain to reveal a
killer clown holding a knife. During a panic attack, however, the fear response loses its
connection to the external circumstances and hits its maximum severity every time. With
apologies to Spinal Tap, during a panic attack, the fear response goes to eleven. For
example, it is natural that someone experiencing a major natural disaster (like a sudden
earthquake) would have a major fear response provoked. However, people with panic
attacks who have lived through a natural disaster have reported that what they felt during
the disaster was “basically nothing” compared to what they experience even during a
“routine” panic attack.
Panic attacks also differ from natural fear in their timing. A normal fear response
occurs in direct response to an external stressor. However, while some panic attacks can be
provoked by stress, the majority come “out of the blue.” is is especially true for people
who have had multiple previous panic attacks: the more panic attacks that people have had,
the more likely they are to be “uncued.” Being in this state of panic often leads people to
believe that there must be something wrong, and many will call 911 or go to the hospital.
However, even with extensive history taking, no trigger for the fear response is found in
most cases. With further apologies to Franklin D. Roosevelt, in the case of panic attacks,
the only thing to fear is the fear response itself.
Panic attacks are quite common, with over 25% of all people having had a panic attack in
their lifetime. Despite being incredibly aversive, panic attacks are not in and of themselves

196
an anxiety disorder, as they do not involve anxiety (they involve fear) and there is often no
evidence of dysfunction (many people who have had panic attacks continue to lead normal
lives). However, for some people, this dysfunctional alarm signal goes on to produce
disabling beliefs and coping strategies that do represent a disorder, as we will explore next.
 

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PANIC DISORDER

While not everyone who has panic attacks is signi cantly

disabled by them, for some people the onset of Sudden Unexpected Recurrent Panic attacks
gives rise to speci c beliefs and coping strategies, including constant worrying about when
they will have their next attack and avoiding places where they have previously had attacks.
is is when panic disorder emerges. In this way, the distinction between fear and anxiety
becomes important: while a panic attack is a state of extreme fear, panic disorder results
from anxiety about having future panic attacks. Following the ABC model of anxiety
disorders, panic disorder is akin to an overactive alarm system that goes off randomly,
leading to a state of perpetual anxiety about when the alarm will ring next. While these
beliefs and coping strategies are in many ways a logical response to the experience of having
panic attacks, the constant anxiety and avoidance of going to speci c places (including
work, school, or even the grocery store) can become incredibly impairing and directly
impact one’s ability to lead a normal life. You can remember the overall pattern of panic
disorder by thinking of the word SURPrise: Sudden Unexpected Recurrent Panic attacks
that give rise to excessive and dysfunctional anxiety even between attacks. Just having panic
attacks is not enough for the diagnosis; you need both the SURP and the rise.
 

Panic disorder is when sudden unexpected

recurrent panic attacks give rise to long-lasting
negative consequences.
 

SURPrise! Sudden Unexpected Recurrent Panic attacks

that give rise to anxiety.

While over a quarter of the population has had a panic attack, only one in six go on to
develop panic disorder, giving it a moderate base rate of around 5% of the population. Like
most anxiety disorders, panic disorder is diagnosed in women twice as often as in men. It
generally begins in the late teenage years or young adulthood.
While panic attacks do not necessarily become more severe or frequent with each additional
occurrence, the anxiety surrounding the panic attacks and the resultant dysfunction can
worsen over time and become increasingly impairing. However, panic disorder also has a

198
high rate of spontaneous remission, with over 75% of people diagnosed with panic disorder
becoming free of symptoms within 3 years.
On an acute basis, benzodiazepines are very effective at rapidly terminating panic
attacks. However, while effective for short-term treatment, over the long-term chronic use
of benzodiazepines often makes panic attacks more frequent and severe. Preventive
treatment involves looking for any contributing lifestyle changes (such as caffeine intake)
and changing them. SRIs are helpful for reducing the frequency and severity of panic
attacks when taken daily, with a moderate effect size of around 0.5. However, like most
anxiety disorders, the best treatment for panic disorder is CBT, with the vast majority of
patients achieving full remission from panic attacks within several months of initiating
treatment (with a large effect size around 0.7) and maintaining these bene ts even years
after nishing therapy.

AGORAPHOBIA
Agoraphobia (literally “fear of the marketplace”) is a disorder where people feel extreme
anxiety in public places, causing them to remain in the safety of their own home. In severe
cases, people with agoraphobia have not left their home for several years. Agoraphobia is
almost always preceded by a history of panic attacks and can best be understood as a speci c
coping strategy that arises in response to Sudden Unexpected Recurrent Panic attacks.
Staying home is a viable coping strategy because panic attacks tend to happen less
frequently at home and, if they do happen, are often less severe because the person feels that
they are in a safe place. In contrast, when a panic attack happens in a public place where the
victim does not feel that they can escape from easily (like in a busy shopping mall), it can
lead to feelings of being trapped or vulnerable, increasing the level of anxiety and making
the panic attack even more aversive. is creates a pattern of avoidance of places that
people have had a panic attack in the past, and for some this pattern becomes
overgeneralized to the point where it includes any and all places that are not their own
home.
Agoraphobia develops in around a quarter of all people with panic disorder, giving it a
base rate of around 1%. It is generally considered to be a marker of severe panic disorder as
evidenced by a spontaneous remission rate of only 25% (compared to 75% for panic disorder
without agoraphobia). Treatment is the same as for panic disorder, although CBT is
generally less effective, with an effect size under 0.3.

SPECIFIC PHOBIA
Speci c phobias are characterized by an intense fear response to a speci c object or
situation that approaches the level of (or can even turn into) a “full blown” panic attack. In
the ABC model of anxiety disorders, it is akin to an alarm that goes off too strongly in
response to a speci c stimulus. Speci c phobias involve a variety of feared objects, each
with its own fun-to-memorize name such as ophidiophobia (fear of snakes), thalassophobia
(fear of the ocean), nyctophobia (fear of the dark), or trypanophobia (fear of needles). is
dysfunctional alarm signal gives rise to particular beliefs and coping strategies aimed at
avoiding the stimulus, and many people with a speci c phobia will put forth signi cant
effort to avoid any situation that could possibly result in exposure to it, such as a woman

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with gephyrophobia (fear of bridges) driving two extra hours per day to avoid going over the
bridge that is the shortest route between her home and her work.

Speci c phobias are likely adaptive to some degree. For

example, someone with arachnophobia (fear of spiders) is more likely to survive than
someone who has no fear of spiders. However, where speci c phobias diverge from adaptive
fear is in terms of severity, as the fear response experienced by those with a speci c phobia
is greatly out of proportion to what is helpful for survival. Many people with a speci c
phobia report an inciting incident that likely led to the development of that phobia, such as
a child who is attacked by a dog who later develops cynophobia (fear of dogs). However, this
isn’t found in every case, and some speci c phobias appear to develop completely “out of the
blue.”
Speci c phobias are common, with around 10% of people having a speci c phobia at some
time during their life. ey usually begin in childhood or adolescence and affect women
twice as often as men. Treatment consists of a speci c type of CBT known as exposure
therapy in which the patient is intentionally exposed to the object of their fear with
gradually increasing intensity. For example, someone with a fear of snakes may play with a
toy snake until they no longer feel afraid around it, at which point they would progress to
looking at pictures of real snakes. e goal of exposure therapy is to make the patient feel
uncomfortable but not overwhelmed with each exposure so they can gradually be able to
tolerate being in the presence of the object of their fear. Exposure therapy is extremely
effective at treating speci c phobias, with a large effect size over 1.0 and bene ts that last
even after the therapy is completed. Medications do not play a signi cant role in treating
speci c phobias.

SOCIAL ANXIETY DISORDER

People with social anxiety disorder have chronic and persistent

anxiety. However, unlike generalized anxiety disorder, this anxiety is focused entirely around
one speci c area: the possibility of interpersonal rejection. People with social anxiety

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disorder constantly worry that they will say or do something embarrassing or humiliating,
leading to severe discomfort during even routine social situations. is hyperactive alarm
system leads to speci c beliefs (“I am unlikable, boring, and stupid.”) and coping strategies,
including avoiding most or even all social situations. People with social anxiety disorder
often have particularly pronounced anxiety about speci c situations (such as public speaking
or musical performances) that could potentially invite criticism from many people at once.
Social anxiety disorder is common, affecting around 10% of the population. It must be
carefully differentiated from introversion or shyness which are normal personality traits.
Separating social anxiety disorder from shyness requires clear evidence that the trait is
impairing one’s ability to function. While it is important to be mindful of the potentially
stigmatizing nature of diagnosis, diagnosing social anxiety disorder can also have positive
effects by providing a pathway for treatment, as CBT for social anxiety disorder is very
effective (with a large effect size over 0.9) and produce long-lasting results. SRIs can also
help (with a smaller effect size in the range of 0.3 or 0.4) but should generally be seen as a
second-line intervention.

SELECTIVE MUTISM
Selective mutism is a condition in which people who are physically capable of speech have
difficulty speaking in speci c situations, often out of fear of being seen as stupid or silly.
Paradoxically, being silent can itself lead to social judgment, creating a vicious cycle. It is
most often diagnosed in children. Despite being listed by the DSM as a separate disorder,
selective mutism is more likely a speci c behavioral manifestation of severe social anxiety
disorder, as nearly 100% of people who are diagnosed with selective mutism also meet
criteria for social anxiety disorder. In addition, treatment strategies and response rates are
largely the same between the two. You can think of selective mutism as a particular
manifestation of severe social anxiety disorder.

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DIFFERENTIAL DIAGNOSIS OF ANXIETY DISORDERS
ere are a variety of psychiatric conditions that closely resemble anxiety or have anxiety as
a prominent symptom, including depression, OCD, PTSD, somatoform disorders, and
certain personality disorders (particularly those in cluster C). In the case of OCD and
PTSD, both were actually considered to be anxiety disorders for a long time even though
they are now conceptualized as being on their own spectrum. To help make sense of this,
we will rst develop a framework for assessing someone who comes to us with severe or
persistent anxiety and then explore the speci c misdiagnoses and missed diagnoses that are
often associated with anxiety.
It is incredibly common for anxiety to be the primary presenting complaint of a
patient seeking psychiatric treatment. However, just like depression (where someone saying
that they are “depressed” is no guarantee that they should ultimately be diagnosed with
depression), a chief complaint of “anxiety” does not guarantee that the person in front of
you actually has a diagnosable anxiety disorder. Even once normalcy has been ruled out,
there are a variety of mental disorders that can present with anxiety as a chief complaint.
Having a structured framework for approaching these patients can be essential. To
systematically evaluate any patients presenting with anxiety, use the mnemonic ONSTAGE
which stands for Obsessive (as in OCD and related disorders), Normalcy, Somatization,
Trauma, Attributable (as in anxiety that is attributable to a medical problem, use of
substances, or speci c life events as in adjustment disorder), Generalized (versus speci c to
certain situations or stimuli like in speci c phobia and social anxiety disorder), and Episodic
(as in panic attacks). We will go over each of these now.
 

Disorders that commonly present with anxiety as the

chief complaint include obsessive-compulsive,
traumatic, and somatoform disorders.
 

Use ONSTAGE to characterize the nature of anxiety:

Obsessive Normalcy Somatization Trauma Attributable
Generalized Episodic
 

NORMALCY

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Fear and anxiety are both normal and adaptive states that everyone experiences throughout
their lives. erefore, the mere presence of either fear or anxiety is not enough to diagnose
an anxiety disorder. In fact, the majority of people experience anxious thoughts throughout
the day, and this is not inherently impairing or pathological. However, when anxiety
becomes extreme, the quantitative becomes qualitative (as in one of the principles of
psychodiagnostic introduced in Chapter 2), and certain people absolutely qualify for a
diagnosis of an anxiety disorder. e line between adaptive and maladaptive anxiety is not
always clear, and careful consideration of both the advantages and disadvantages of
diagnosis should be given at all times. For example, diagnosing an extremely shy person
who doesn’t think that their behavior is a problem with social anxiety disorder may instead
stigmatize and alienate the patient. In contrast, if that same person had come to you
speci cally for help with this problem, then the diagnosis may be more appropriate as it
allows them to access helpful treatments.
Anxiety can also intersect with normalcy in that the language of anxiety can be an idiom of
distress as often as it is a disorder in and of itself. e language of anxiety is frequently used
to communicate distress, such as someone saying that they are having a panic attack due to
a bad day (even though, objectively speaking, there are no objective signs that what they are
experiencing is in any way a panic attack). Keep in mind that taking someone seriously does not
always mean taking them literally. You should always take the distress of someone you are
treating seriously, but that does not mean abandoning the knowledge of these disorders that
is necessary for clarity in diagnosis, treatment, and research.
 
DEPRESSION
Depression is so frequently comorbid with anxiety disorders that the presence of one
should always prompt an assessment for the presence of the other. ere appears to be a
shared pathophysiologic mechanism between depression and anxiety, as HPA axis
abnormalities are seen in both and could account for many of the symptoms that they share
in common (including irritability, fatigue, insomnia, and difficulty concentrating). In
addition, many of the same treatments (including SRIs and CBT) are highly effective for
both. However, we should not go so far as to assume that depression and anxiety are the
same disorder. e episodic nature of depression is distinctly different from the enduring
and persistent nature of symptoms seen in many anxiety disorders. In addition, while
comorbidity is the rule rather than the exception, we cannot ignore the fact that many
people have “just depression” or “just anxiety.”
 
ADJUSTMENT DISORDER
Anxiety is frequently reported as a primary symptom in adjustment disorder. e same rules
apply here as for depression: the patient must not meet criteria for a “full blown” anxiety
disorder, and the anxiety must have started after (and be directly related to) a signi cant life
change or stressor. Adjustment disorder is best thought of as a non-stigmatizing “diagnosis
of normalcy” that allows the patient to access helpful treatment (in this case, a type of
psychotherapy known as supportive therapy).

POST-TRAUMATIC STRESS DISORDER

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 e relationship between PTSD and anxiety is complex. Indeed, for many years PTSD was
considered to be an anxiety disorder. However, recent research has suggested that, while fear
and anxiety can be core symptoms of PTSD, they are not the only emotions experienced by
survivors of trauma and, indeed, it is possible to have PTSD without experiencing either
fear or anxiety (which makes it really hard to argue that PTSD is an anxiety disorder).
Instead, the predominant symptom of PTSD is the re-experiencing of trauma. For some,
this manifests as fear and anxiety, but not necessarily for everyone. Nevertheless, be on the
lookout for a history of trauma if a patient presents with anxiety, as anxiety may be the
presenting symptom of PTSD.
 
OBSESSIVE-COMPULSIVE DISORDER
OCD is another disorder that was long thought to be an anxiety disorder. After all, the
obsessions found in OCD are often clearly de nable as anxiety (“If I don’t wash my hands,
then I will get sick and die!”). However, obsessional thoughts do not always involve anxiety.
For example, someone who needs to count up the number of letters in each sentence they
speak is not necessarily anxious about something bad happening; it just bothers them
severely if they don’t. In this way, OCD is revealed as a disorder of error signaling rather
than a dysfunctional alarm system. In some cases, error signaling and alarm signaling
overlap, but not always. Making a distinction between the error signaling of OCD and the
dysfunctional alarm system in anxiety disorders is supported by an accumulating body of
evidence showing that OCD and related disorders comprise their own “OCD spectrum” of
disorders with substantially different diagnostic, prognostic, and treatment-related
considerations.
 
PERSONALITY DISORDERS
Cluster C personality disorders (including avoidant, obsessive-compulsive, and dependent
personality disorders) all feature worrying and anxiety to some degree, but each of them has
a different link to existing anxiety disorders. As we will discover in Chapter 12, avoidant
personality disorder is best conceptualized as a particularly severe variant of social anxiety
disorder (similar to selective mutism in some ways), while obsessive-compulsive personality
disorder is more similar to perfectionistic disorders like anorexia nervosa than it is to anxiety
disorders. Finally, dependent personality disorder is a manifestation of an extremely high
level of trait agreeableness which can present with signi cant anxiety symptoms (“I worry
all day that my partner is going to leave me.”). However, these worries all fall within the
domain of interpersonal dependency.
 
SOMATIZATION
People with somatoform disorders (discussed further in Chapter 15) experience frequent
physical symptoms for which no underlying medical cause can be found. Because physical
symptoms are often taken to be a sign of medical illness, people who somatize often come
in with anxiety as a presenting symptom. In cases of somatization, however, the anxiety is
limited to only physical symptoms. Somatization differs enough from primary anxiety
disorders in its prognosis and treatment requirements that it warrants separate
consideration.
 
SUBSTANCE-INDUCED ANXIETY DISORDER

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 Anxiety (including both formal diagnoses like panic disorder
and generalized anxiety disorder as well as people with an overall trait of high anxiety) can
often be related to substance intake. Anything with a stimulating effect on the central
nervous system can create anxiety, including prescription medications like thyroid hormone,
albuterol, steroids, and stimulants. However, any discussion of substance-related anxiety
would be incomplete without mentioning caffeine. Caffeine is ubiquitous, with over 85% of
the United States population consuming at least one caffeinated beverage per day. Given
this, it is by far the most common reason for substance-induced anxiety disorders. Multiple
studies have shown a clear link between caffeine use and anxiety. In many cases, anxiety
disorders can be treated or even cured completely by stopping all caffeine intake, so it is
worthwhile to ask any patients suffering from an anxiety disorder to consider keeping of log
of caffeine intake to see if there is any correlation.
 

ANXIETY DISORDER DUE TO A GENERAL MEDICAL CONDITION

A host of physical diseases can produce symptoms that closely resemble primary anxiety
disorders. At times, the conditions themselves (such as hyperthyroidism and
pheochromocytoma) produce chemicals that have a net stimulating effect on the central
nervous system. In other cases, the pathophysiologic link between the physical disease and
the patient’s symptoms of anxiety are not as clear. In any case, you can remember some of
the most common medical diseases that frequently present as anxiety using the mnemonic
Physical Diseases That Have Commonly Appeared Anxious, which stands for
Pheochromocytoma, Diabetes mellitus (typically during hyper-or hypoglycemic episodes),
Temporal lobe epilepsy, Hyperthyroidism, Carcinoid, Alcohol withdrawal, and
Arrhythmias. Clues that someone may be suffering from a medically-induced (rather than
primary) anxiety disorder include an atypical onset of symptoms (such as someone in their
late sixties who never had problems with anxiety until a month ago), the presence of
objective physical ndings or vital sign abnormalities, or an episodic (rather than chronic)
pattern of anxiety symptoms.
 

Several medical conditions can produce symptoms

resembling anxiety disorders.
 

Physical Diseases That Have Commonly Appeared

Anxious : Pheochromocytoma Diabetes mellitus

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Temporal lobe epilepsy Hyperthyroidism Carcinoid
Alcohol withdrawal Arrhythmias

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PUTTING IT ALL TOGETHER
Anxiety disorders are best conceptualized as various beliefs and coping strategies that arise
in response to a dysfunctional alarm system. e alarm is either going off all the time
(generalized anxiety disorder), goes off randomly for unclear reasons (panic disorder), or is
vastly out of proportion to the trigger (speci c phobia and social anxiety disorder). Given
that a dysfunctional alarm signal is at the heart of each of these conditions, it is no surprise
that someone with one anxiety disorder is likely to have another, and this is exactly what we
see, with comorbidity being the rule rather than the exception.
Use your knowledge of the sympathetic nervous system as well as the MISERA-ble
mnemonic to remember the signs and symptoms of both acute and chronic anxiety. From
there, use the ONSTAGE mnemonic to systematically approach the diagnosis for anyone
coming in with anxiety as a major or presenting symptom, including assessing the
Normalcy, Attributability, Episodicity, and Generalizability of the complaint (as well as
whether a different type of condition that commonly presents with anxiety, such as
Obsessive-compulsive, Traumatic, or Somatoform disorder, would be more diagnostically
appropriate). For most forms of anxiety, CBT is going to be your rst-line intervention,
although in some cases SRIs or other medications can be used as well. Benzodiazepines are
incredibly helpful for rapid treatment of anxiety (like during a panic attack) but tend to
make anxiety worse in the long-term and should generally be avoided as a chronic
treatment.
 

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REVIEW QUESTIONS
1. A 10 y/o F is brought to see a psychologist for an initial evaluation by her mother.
e girl has tears on her face and looks drowsy; she refuses to speak to the
psychologist. e mother reports that the patient has stopped leaving the house for
the past 2 weeks after a friend’s pet parrot ew out of its cage and bit her several
times on the arm. e mother says that even bringing her to the psychologist’s
office was a struggle (“I had to sneak Benadryl into her food or else there would be
no way I could get her here!”). Prior to the incident 2 weeks ago, the patient was
doing well in school and was well-liked by her peers. Because the patient is not
talking to the psychologist, he brings in some stuffed animals for her to play with.
She then begins screaming loudly and hyperventilating after seeing a stuffed bird
in the pile of toys. What is the most likely diagnosis?
A. Generalized anxiety disorder
B. Panic disorder
C. Speci c phobia
D. Social anxiety disorder
E. Selective mutism
F. None of the above
2. (Continued from previous question.) At the next appointment, the psychologist
asks the girl to write down ten bird-related objects or situations that cause her to
feel fear and then rank them in terms of how much fear they make her feel. She
indicates that drawing a bird is associated with “a little fear,” while seeing a toy
bird is associated with “some fear” and having a bird sit on her arm would make
her feel “like I’m going to die.” Which of the following would be the next best
step?
A. Ask her to draw a bird
B. Bring in a toy bird
C. Bring in a real bird
D. Prescribe a benzodiazepine
E. Discontinue treatment
3. A 25 y/o M presents to his primary care provider complaining of insomnia. He
says that he rst noticed difficulty sleeping one year ago but that it has steadily
gotten worse since then. He primarily has difficulty falling asleep as he “cannot
shut my brain off.” He reports constant ruminative thoughts that his parents will
die somehow (“like in a car crash, or they’ll both get cancer, or someone will break
in and murder them in their sleep”). He has not applied for a job since graduating
from college last year as he is “sure that any employer is going to laugh at my paltry
résumé.” He describes feeling “stressed” most of the day and feels that he cannot
relax. He has yelled at his parents several times over the past month when they ask
him about his life, which he says he has never done before. He denies use of
substances. He has never taken psychiatric medications before but saw a therapist
for several years as a teenager after the death of his grandmother. Which of the
following systems is most likely overactive in this patient?
A. e hypothalamic–pituitary–adrenal axis
B. e sympathetic nervous system
C. e parasympathetic nervous system

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 D. e orbitofrontal cortex
E. e ventral tegmental area
F. None of the above
4. A 19 y/o F is brought to the emergency department by her roommate after she
started experiencing chest pain, difficulty breathing, dizziness, and “feeling like I
was going to die.” It took them 20 minutes to drive to the hospital, and by the
time they arrived the patient reported that her symptoms had resolved. Vital signs
at the time of initial examination are HR 118, BP 128/72, RR 20, and T 98.9°F.
On interview, she describes having had similar episodes three times over the past
month, including at work, at school, and while visiting friends. She denies having
any major changes during that time period other than taking a new job; however,
she says that overall she enjoys her job and doesn’t feel that this is a major stress.
Outside of needing to leave work early once, she has remained functional at her
job and is performing well in her evening classes. She feels that overall her life is
“good except for when stuff like this happens.” Chest x-ray, EKG, and cardiac
markers are all normal. She desires an explanation for her current symptoms.
What is the most likely diagnosis?
A. Panic disorder without agoraphobia
B. Panic disorder with agoraphobia
C. Generalized anxiety disorder
D. Speci c phobia
E. None of the above
 

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1. e best answer is C. is girl appears to have developed a speci c phobia of birds
(ornithophobia). People with speci c phobias sometimes, but not always, develop
this fear response following a speci c incident. While the signs and symptoms
seen in someone who is exposed to the object of their fear can be the same seen
during a panic attack, the fact that these attacks only happen when exposed to the
object rules out panic disorder (answer B). While the phobia has caused
impairment even when the girl is not exposed to the object (she has stopped
leaving the house or going to school), this is not consistent with generalized
anxiety disorder as there is only a single object that is feared (answer A). e girl is
not speaking which raises the possibility of selective mutism, but the fact that this
has only occurred in the past 2 weeks and is not accompanied by any evidence that
she suffers from a fear of interpersonal rejection or humiliation argues against
either selective mutism or social anxiety disorder (answers D and E) as the
explanation for her behavior.
2. e best answer is A. e psychologist is attempting to perform exposure therapy,
which is an effective treatment for speci c phobias. With each exposure, the goal is
for the patient to feel uncomfortable but not overwhelmed to allow them to
gradually reduce the fear response associated with the feared stimulus. In this case,
starting with the stimulus that provokes the least fear (drawing a bird) would be
the next best step. Medications do not play a signi cant role in treating speci c
phobias (answer D), while treatment should not be discontinued when there is an
effective form of therapy available (answer E).
3. e best answer is A. is patient appears to be suffering from generalized anxiety
disorder as evidenced by the presence of anxiety about multiple areas of his life that
manifest in chronic symptoms of HPA axis activation including insomnia,
restlessness, muscle tension, and irritability. e sympathetic nervous system is
generally more involved in acute fear states like a panic attack (answer B), while
the parasympathetic nervous system tends to reduce arousal rather than increase it
(answer C). e orbitofrontal cortex is involved in prediction of rewards and is
generally associated with mood episodes such as depression and mania (answer D),
while the ventral tegmental area is implicated in addictive disorders (answer E).
4. e best answer is E. is patient has likely experienced a panic attack as
evidenced by the presence of signs and symptoms of sympathetic nervous system
activation, including tachycardia, chest pain, dizziness, and a feeling of impending
doom. However, while she suffers from sudden, unexpected, and recurrent panic
attacks, it is not clear that these have directly caused distress or dysfunction nor
have they given rise to maladaptive behaviors (such as avoiding places, like work or
school, where she has had a panic attack before). erefore, it is not correct to say
that she suffers from panic disorder (answers A and B). ere is no evidence of
chronic anxiety as would be seen in generalized anxiety disorder (answer C), nor
do the panic attacks appear to be directly associated with speci c objects or
situations as would be seen in a speci c phobia (answer D).

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10 OBSESSIONS AND COMPULSIONS

Obsessions are intrusive and unwanted thoughts that

continue to recur despite attempts to resist them. Obsessive thoughts are disturbing and
unpleasant, and someone who develops obsessive thoughts often begins to feel distressed as
result. is leads them to use compulsions, or speci c thoughts and behaviors that help to
reduce the distress caused by obsessions. While compulsions are effective at reducing this
distress, this relief is only temporary. In addition, because compulsions don’t actually
eliminate the obsessions driving the distress (if anything, obsessions are reinforced by
compulsions), they up the potential for an endless loop between obsessions and
compulsions that begins to take up more and more time, leading to dysfunction and
disability.
Obsessive-compulsive disorder (commonly abbreviated as OCD) is considered the
prototypical disorder involving both obsessions and compulsions, and we will start off our
discussion by learning about this disorder in some detail. However, there are a number of
other disorders that also involve obsessive thoughts, compulsive behaviors, or a combination
of the two, including body dysmorphic disorder, hypochondriasis, trichotillomania, and tic
disorder. ese disorders are considered to be part of an “obsessive-compulsive spectrum”
that bears a strong resemblance to “textbook” OCD in terms of phenomenology, prognosis,
and treatment response. We will also look closely at the underlying mechanisms of
obsessions and compulsions. Pay close attention here, as it is the core pattern that ties these
seemingly disparate conditions together as part of the same spectrum.

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SIGNS AND SYMPTOMS OF OBSESSIONS AND
COMPULSIONS
OCD is a disorder in which someone has developed obsessive thoughts. In many cases,
these obsessions give rise to speci c compulsive behaviors, and a dysfunctional loop is
created between the two. Because both obsessions and compulsions are central to
understanding this disorder, let’s make sure we know exactly what we mean when we use
these two terms.
 
OBSESSIONS
Obsessions are de ned as mind-based, unwanted, resistant, distressing, ego-dystonic,
recurrent thoughts. ey are often intrusive, appearing suddenly and interrupting one’s
normal stream of consciousness. Obsessive thoughts can take on any number of forms,
including checking (“Did I forget to turn off the stove?”), contamination (“I will get sick if
I don’t clean my hands after touching a doorknob.”), symmetry (“ ese books have to line
up exactly.”), and taboo thoughts involving topics such as sex and religion (“I can’t stop
thinking about having sex with the Virgin Mary.”). e majority of people with OCD will
have obsessions in more than one of these forms. However, despite these variations in the
content, they all t the same underlying pattern.

To get a better feel for what experiencing an obsessive

thought is like, picture a young mother playing with her baby outside. Suddenly, a random
thought passes through her mind: “You should kill your baby.” She immediately reacts to this
thought with a feeling of revulsion as well as some anxiety about what the thought might
mean (“Why am I having this thought? Am I a baby murderer?”). She tries to reassure
herself by saying, “ at's ridiculous, that’s not the kind of person I am,” and reminding
herself that she has never done something that like before. While this initially works to
bring her anxiety down, soon the thought comes back (“You should kill your baby…”) which
causes her to feel even more distress, as she now worries about what it means that the
thought has come back twice. Her anxiety continues to rise, making the thought seem even
scarier than it initially was. Over the next few days, she nds herself avoiding going near
her child out of fear that she might act on these thoughts (even though she has no desire
to). ese intrusive thoughts have now become an obsession.

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Let’s go back through this example and use it to illustrate each of the key characteristics of
obsessive thoughts. Handily (or scarily), these attributes form the word MURDER (as in
“murder your baby”):
M is for Mind-based. People who experience obsessional thoughts recognize that they
originate from their own mind (“It’s just a thought that I have a lot”). is sets them apart
from the auditory hallucinations found in schizophrenia which are experienced as
originating outside of one’s head and are genuinely believed to be an accurate perception of
the real world.
U is for Unwanted. Obsessions are by their very nature unwanted, and people who have
these thoughts often try to ignore them or put them out of their mind. Paradoxically,
however, attempts to suppress obsessive thoughts often seem to make them even stronger,
and in severe cases no amount of self-reassurance can make a dent in how frequent or
intrusive the obsessions are.
 

R is for Resistant. Obsessive thoughts are remarkably resistant to efforts to ignore or

suppress them. If the thought of killing your baby could be resisted easily through self-
reassurance (as this girl initially tried to do), then it would likely be regarded as an
unpleasant but ultimately meaningless occurrence (“ otsam in the stream of
consciousness”). However, in the case of obsessions, these thoughts aren’t “defeated” so
easily. Even if people are able to self-reassure initially, when the thought becomes
unsuppressible it crosses the line into being an obsession.
 

D is for Distressing. Obsessional thoughts are often inherently

upsetting and cause signi cant distress to the person experiencing them. While most people
have intrusive thoughts from time to time, it is the thoughts that are most distressing—
those that are felt to be highly inappropriate, disgusting, or immoral—that are the most
likely to develop into obsessions. (No one comes into clinic complaining of intrusive
thoughts about cute kittens.) is explains why obsessional thoughts often t the worries
and anxieties of the person who develops them, with someone growing up with a very clean
mother being more likely to develop obsessions about symmetry and orderliness while
someone with a religious worldview may be more likely to develop obsessions around
blasphemous thoughts.
 

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E is for Ego-dystonic. Someone having obsessional thoughts is generally able to recognize
that, despite being based in their own mind, the intrusive thoughts are not re ective of their
true desires. In this example, the mother is able to say very clearly that she has no desire to
act upon these thoughts and that she nds them incredibly disturbing (“ at’s not the kind
of person I am!”). e word ego-dystonic is used to describe these thoughts, as they are
discordant with someone’s self-concept (or their “ego” in psychiatric jargon).
 

R is for Recurrent. It is the recurrent nature of obsessive thoughts that truly de nes them
as a disorder. After all, even the most disturbing thoughts will be quickly forgotten unless
they begin to happen repeatedly. Frequent recurrence of obsessive thoughts directly sets the
stage for someone to seek out speci c thoughts or actions they can do to help ght these
thoughts when they recur, creating fertile ground for the development of compulsions
(discussed next).

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 Obsessions are mind-based, unwanted, resistant,
distressing, ego-dystonic, recurrent thoughts that
are often sudden and intrusive.
 

MURDER: Mind-based Unwanted Resistant

Distressing Ego-dystonic Recurrent

COMPULSIONS
Because obsessions tend to provoke feelings of intense anxiety or distress, people with
frequent or severe obsessions will often begin to seek out speci c thoughts or actions that
they can perform to relieve their distress. ese neutralizing behaviors are known as
compulsions. Compulsions are quite effective at relieving the distress related to obsessions.
However, this relief is only temporary, and the person soon experiences a return of the same
obsessive thoughts (and often at a higher intensity than before). is leads to further use of
compulsions to neutralize these thoughts, creating a vicious cycle between obsessions and
compulsions. Compulsions also have the bad habit of reinforcing the beliefs that
necessitated them in the rst place, effectively feeding the very beast that they were
intended to defeat.

To illustrate this with an example, let’s say that a young man is

about to go to bed, as he has an important exam early the next morning. As his head hits
the pillow, he has a sudden thought: “Did I forget to lock the front door?” He initially puts
the thought out of his mind, but it won’t go away and he begins to feel increasingly anxious
about what might happen if the door is left unlocked the whole night (an obsession). To
counter the anxiety from this obsession, he gets up to check the door (a compulsion), which
immediately relieves his anxiety (making the compulsion a negative reinforcer). However,
as soon as he climbs back into bed, the thought suddenly comes back: “Did I forget to lock
the door?” Despite telling himself over and over that he knows that he checked the lock, he
cannot put the thought out of his mind (the thought is resistant). His anxiety continues to
rise until he cannot take it any longer, and he gets up to check the lock again. is again

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temporarily reduces his anxiety. However, just as before, this relief is not sustained, and the
obsession recurs the moment he returns to his room and begins the cycle anew. He becomes
increasingly frustrated with himself for continuing to check the door over and over, but due
to the ever-rising levels of anxiety, he cannot actually keep himself from doing so. (As with
obsessions, compulsions are typically ego-dystonic: someone knows that their behaviors are
excessive, but they are unable to stop themselves from engaging in them.) As a result, he
spends the next ve hours repeating this cycle, which keeps him up all night and prevents
him from getting any rest. e next morning, he fails his test as he is too tired and fatigued
to concentrate effectively on the material. In this way, the loop between obsessions and
compulsions has set the stage for a pattern of behavior that takes up more and more time
and leads to distress, disability, and dysfunction.
It is worthwhile to spend a few moments distinguishing compulsivity from
impulsivity, as both involve the inability to inhibit an action (someone can’t not do
something). However, compulsivity and impulsivity differ in regards to the reason why the
person can’t not do the behavior. As discussed in Chapter 8, impulsivity involves repeated
use of positive reinforcers despite negative repercussions and is associated with a lack of
deliberation that leads to prioritizing of short-term bene ts over long-term consequences.
In contrast, compulsions represent repeated use of negative reinforcers despite negative
repercussions. Unlike the positive reinforcers that are the target of addictions, compulsive
behaviors are not inherently pleasurable (there is no “thrill” or “rush” to be found in
checking a lock repeatedly). Instead, the behaviors are performed as a consequence of
de cits in recognizing completion of tasks (as in the inability to assure one’s self that the
door is locked despite having checked it multiple times in the same night) which leads to a
desire for behaviors that will calm an internal sense of anxiety. It is this calming function
that makes compulsions so difficult to resist. To remember this distinction, think of
calmpulsions as working to calm an internal sense of anxiety while impos’es provide
immediate positive reinforcement when they are indulged.
 

Impulses and compulsions both involve an inability

to inhibit an action but differ in whether the
behaviors are positively reinforcing or negatively
reinforcing.
 

Calmpulsions are done to calm an internal sense of

anxiety, while impos’es happen because of the immediate
positive reinforcement that occurs.

To be clear, the line between impulsivity and compulsivity is not always neatly de ned.
Some behaviors that are initially quite pleasurable lose their pleasurable properties over
time, making it so that an action initially done impulsively becomes compulsive. For
example, someone who initially takes heroin for its euphoric rush may soon nd that they
are now using it primarily to avoid the uncomfortable state of withdrawal—in effect, their
impulsive use of drugs has now become compulsive. In other cases, speci c behaviors appear

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to have properties of both positive and negative reinforcements. For example, someone who
is so angry after an argument with their spouse that they throw a brick through a nearby
window is likely to experience not only a lessening of their internal sense of agitation (a
negative reinforcement) but also an emotional “thrill” that feels inherently pleasurable (a
positive reinforcement). If this person were to then continue to act out whenever they
became angry in the future, it would be difficult to say de nitively whether this represents
impulsive or compulsive behavior (it is likely both to some extent). Despite the boundaries
between these concepts not being completely clear cut, knowing these de nitions can still
help to guide diagnosis and subsequent treatment decisions in the majority of cases.
 

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OBSESSIONS AND COMPULSIONS ACROSS THE LIFESPAN
OCD is a relatively rare disorder with a low base rate in the population, with around 1%
having clinically signi cant symptoms of OCD at any given moment and up to 3% being
diagnosed at some point in their life. is makes it more liable to overdiagnosis than
underdiagnosis. Men and women have an equal chance of being affected. Onset of
symptoms is often during childhood and adolescence, with most people developing
symptoms before the age of 20 and almost all before age 30.
PROGNOSIS
Symptoms generally come on gradually but soon become chronic and enduring. OCD is
not considered an episodic disorder, although there may be times when symptoms
temporarily worsen (often in response to life stressors). e severity of OCD occurs on a
spectrum, with some people only mildly affected whereas others are completely disabled as a
result. For example, some people engage in checking behaviors for hours each and every day,
preventing them from engaging in any kind of work, school, or social life. (In fact, the
amount of time that one spends engaging in compulsive behaviors can be a helpful proxy
for how severe their disorder is.) In other cases, a patient may not have touched another
human being for years out of fear of contamination, leading to frayed relationships and
unimaginable loneliness. Left untreated, OCD can reduce one’s quality of life and ability to
function for years or even decades. However, even without treatment, a small but signi cant
lessening of symptoms occurs over time.
TREATMENT

e rst-line treatment for OCD is psychotherapy, with CBT

being the modality most clearly linked to improved outcomes. In particular, a form of CBT
known as exposure and response prevention is used in which patients are encouraged to
expose themselves to the object of their obsessional thoughts without resorting to use of
compulsions to reduce their anxiety. For example, someone who believes that all doorknobs
are contaminated and feels compelled to wash their hands after touching even one would be
encouraged to touch a doorknob and then delay hand washing for as long as possible. e
length of time between the obsession and compulsion is made longer and longer until the
link between them is eventually broken. By doing this, people with OCD begin to learn
that the behavior does not actually lead to the feared outcomes (they don’t actually get sick
if they don’t wash their hands) and that compulsions are unnecessary for preventing harm.
Even in cases where exposure to the object of the obsession cannot be done directly (you
can’t ask someone to hold a knife to their baby in the same way that you could ask them to

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avoid washing their hands), just imagining the feared scenario via talking or writing about it
can cause signi cant reductions in symptoms. Exposure and response prevention is
incredibly effective at treating OCD, with a very large effect size over 1.0.
Medications can also be used to treat OCD. Serotonergic medications are most
helpful, with SRIs being frequently used. ese medications must often be used at higher
doses than those used for depression. e use of SRIs for OCD has a large effect size
(compared to the small to medium effect size seen when using SRIs for depression or
anxiety). Compared to CBT, however, medication treatment of OCD has a few drawbacks.
It produces only transient improvement in symptoms and is associated with a high
recurrence rate when the medications are discontinued. In addition, it is unclear that
combining medications with therapy leads to improved outcomes over therapy alone.
Because of this, medications should mostly be used as a second-line option in cases where
therapy has been ineffective, more rapid treatment is necessary, or the patient is unable to
participate in therapy for whatever reason.
 

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MECHANISMS OF OBSESSIONS AND COMPULSIONS
e key to understanding both OCD and the other disorders on the obsessive-compulsive
spectrum (which we will discuss in the next section) is to focus in on the underlying
pattern of the disorder. is pattern has been established from the very rst descriptions of
OCD, including one in the early 1900s that described people with the disorder as being
“continually tormented by an inner sense of imperfection connected with the perception
that actions or intentions have been incompletely achieved.” ese two components (a
sense that something is imperfect or wrong as well as a feeling that actions have been
incompletely achieved) are found in all obsessive-compulsive spectrum disorders.
e inner sense of imperfection is related to dysfunctional error signals that generate
a distinct sense that something is wrong. To understand what is meant by an error signal
better, consider the following picture:

Looking at the picture, most people are quick to recognize that something strange is
going on: the man is about the lick the toilet paper he has just used. is is not only
disgusting, it is wrong, and our brains need a way of alerting us when it has recognized this
kind of error. Error signals are processed in a part of the brain known as the anterior
cingulate cortex (or ACC). e discrepancy between two situations that we know should not
go together (such as “eating” and “toilet paper”) makes the anterior cingulate cortex light up
like a Christmas tree, creating a feeling of psychological and physiological arousal. is state
of motivational arousal prompts us to act (“If I don’t do something, something bad will
happen!”). In the case of this particular situation, we may yell at the man to stop. You can
remember the function of the anterior cingulate cortex by thinking that it’s the part of the
brain that yells, “Acc! at’s so wrong!”
 

e anterior cingulate cortex is involved in error

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 recognition and is believed to be hyperactive in
obsessive-compulsive disorder.
 

e anterior cingulate cortex makes you think, “Acc!

at’s so wrong.”

is pattern is core to the idea of obsessions, with the sensitivity of the anterior
cingulate cortex determining how likely someone is to experience motivational arousal in
response to an error signal. To use another example, consider this image:

How do you feel when looking at this image? Some people feel upset by the perceived
error in this image due to activation of their anterior cingulate cortex. is creates a state of
motivational arousal that prompts them to want to turn the O tile 90° so it will t with the
rest of the tiles. However, other people will look at the image and not feel upset or bothered
by it in any way. For them, this image does not activate the anterior cingulate cortex or
generate an error signal. It is this spectrum of sensitivity to error signaling that puts people
at higher or lower risk for obsessive-compulsive disorders. It is here that the difference
between obsessive-compulsive disorders and anxiety disorders becomes most apparent:
obsessions involve error signaling (a sense that something is wrong) while anxiety involves
alarm signaling (a sense that something bad will happen). ere are de nitely times when
the two signaling systems overlap (such as someone with a contamination obsession who is
worried about getting an infection if they don’t follow strict hygiene). However, there are
other times when they don’t (as in the prior image, where someone who is bothered by the
out-of-place tile is not necessarily worried about anything bad happening because of it—it is
simply an error). In some cases, the sensitivity to error signaling is so strong that people
with obsessive-compulsive disorders will perceive errors where none exist (as we will discuss
further when talking about body dysmorphic disorder and hypochondriasis).

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 e relationship between error signaling and motivational arousal explains how
obsessions give rise to compulsions, as recognition of an error signal practically demands
action. However, there is nothing inherently pathological about either error signaling or
motivational arousal, and we often use these processes to govern our behavior. For example,
someone who is bothered by the O tile in the previous picture can simply turn it 90°,
eliminating the error signal and returning to a non-aroused state. In a more real-world
example, someone who is procrastinating on ling their taxes may start to feel more and
more motivational arousal (“I can’t keep putting my taxes off.”) until they nally take action.
Upon completion of this task, they receive a signal of satisfaction (or a “feeling of
knowing”) that turns off the motivational arousal and allows them to return to doing what
they really want to do (like watching television). is “feeling of knowing” is registered in
the prefrontal cortex, a region of the brain which (among many other things) links
motivational arousal to a speci c task. In both of these cases, the link between the error
signal and its associated behavior is linear—once the task is completed, the error signal goes
away.

However, what makes OCD dysfunctional is that the

behavior is not linear but rather occurs in a loop, with the error signal persisting even once
the task is completed. People with OCD appear to have a de cient “feeling of knowing” and
experience only a fraction of the relief from motivational arousal that most people receive
upon completing a task (or even no relief at all). is leads to a distinct and unpleasant
sensation that the behavior has not been not done even though they know intellectually that
it has (the “perception that actions or intentions have been incompletely achieved”
referenced earlier). is was demonstrated directly in a study in which two groups of people
(one with OCD and one without) were asked to immerse their hands in a soiled diaper.
Compared to people without OCD, people with OCD did not necessarily experience more
motivational arousal when touching the dirty diaper (unsurprisingly, both groups wanted to
wash their hands as soon as possible). However, people with OCD differed from normal
controls in that they were less able to reduce this state of arousal by washing their hands. is
sense of being dirty and contaminated persisted much longer than for people without
OCD, leading to more hand washing. Because performing the compulsive behavior is only
transiently effective at knocking out the sense of motivational anxiety driving the behavior
(the “feeling of knowing” doesn’t stick), the behavior continues.
 

In this way, compulsions are revealed to result from a “problem with stopping” due to
an ineffective “feeling of knowing.” is pattern is supported by evidence. For one, people
with OCD often report a conscious sense that they are unable to stop (“I can't move on
because I can't convince myself that I've nished what I'm doing.”). In addition, people
with OCD do not repeatedly engage in frequent sessions of compulsive behavior; rather,
they tend to engage in few but extended sessions of compulsive behavior. (In contrast,
addiction and other impulsive disorders involve a “problem with starting” where the

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problem lies in repeatedly starting a behavior.) is overall pattern (hypersensitive error
signal → motivational arousal → compulsive behavior → lack of “feeing of knowing” →
continuation of error signal) is key to understanding not only OCD but also the other
disorders on the obsessive-compulsive spectrum. While learning about the obsessive-
compulsive disorders in the next section, try to think about how each of them ts into this
model.

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DIAGNOSING OBSESSIVE-COMPULSIVE DISORDERS
While OCD is the prototypical disorder involving obsessions and compulsions, there are
several other related conditions including body dysmorphic disorder, hypochondriasis, tic
disorders, and trichotillomania. Like OCD, they all involve either an obsessional
preoccupation with an idea (as in body dysmorphic disorder and hypochondriasis) or
recurrent uncontrollable behaviors that appear more compulsive than impulsive (as in tic
disorders or trichotillomania). ese disorders also co-occur in the same person more often
that would be predicted by chance and tend to respond to similar kinds of treatment,
suggesting a shared mechanism. For these reasons, these conditions are considered to be
sufficiently similar to OCD to warrant inclusion in an “obsessive-compulsive spectrum.”
We’ll go over each one now in turn.
 
OBSESSIVE-COMPULSIVE DISORDER
As mentioned previously, OCD is de ned by the presence of obsessions, compulsions, and a
loop between the two. While obsessions are a necessary aspect for diagnosis, compulsions
are optional. is is because compulsions are a speci c behavioral outcome of obsessions
which often (but do not always) develop. Because of this, everyone with clinically
signi cant compulsions will have obsessions as well; however, not everyone with obsessions
will develop compulsions. ( is is roughly analogous to the development of agoraphobia in
panic disorder or selective mutism in social anxiety disorder, as both are behavioral outcomes
of another cognitive process.) Cases of obsessions without compulsions are sometimes
known as purely obsessional (or “pure-O”) OCD. e lack of compulsions does not mean
that purely obsessional OCD is any less impairing; if anything, purely obsessional OCD is
considered to be more impairing than “textbook” OCD and is signi cantly more difficult to
treat.
 
BODY DYSMORPHIC DISORDER
Body dysmorphic disorder is an obsessive-compulsive spectrum disorder involving an
obsessional preoccupation that speci c aspects of one’s appearance are incredibly awed or
deformed, such as a nose that is too big or a head that is too small. is is

distressing, and people with body dysmorphic disorder fear that this
will cause other people to reject or make fun of them. However, the key is that these aws
in appearance are entirely imagined, and no objective outside evaluator would nd them
deformed. It’s important to recognize that body dysmorphic disorder is not just vanity:
people with body dysmorphic disorder want to normalize their appearance, as opposed to

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vanity where the goal is to make yourself look better than others. Unlike obsessions in
“textbook” OCD, preoccupations about appearance in body dysmorphic disorder are ego-
syntonic, and the person does not admit that their fears are extreme or excessive in any way.
People with body dysmorphic disorder have a tendency to frequently engage in speci c
compulsive behaviors such as body measuring, mirror checking, excessive grooming, and
reassurance seeking that are aimed at hiding or xing their perceived aws. However, no
amount of reassurance or covering up can convince the person that their features are not
deformed—just like in OCD, the “feeling of knowing” that the defect has been xed never
comes. is sets up the potential for an endless loop between obsessions and compulsions.
What makes this loop particularly troubling in body dysmorphic disorder is the fact that
many people will go on to seek plastic surgery in an attempt to “de nitively” correct the
aw. However, less than 5% of people with body dysmorphic disorder report feeling
satis ed that their appearance has been xed after undergoing plastic surgery, making
surgery a high-risk intervention with a low likelihood of bene t. Nevertheless, because
people with body dysmorphic disorder seek surgery compulsively, they may end up going
under the knife dozens of times throughout their life without ever nding relief.

Body dysmorphic disorder is relatively rare in the

general population and is found in only around 1-2% of the population. However, its
prevalence may be signi cantly higher in certain settings (including 10% of patients in
dermatology clinics and up to one-third of all patients seeking cosmetic surgery). e
disorder often begins during adolescence or early adulthood, with a mean age of onset of
16 years. However, many do not seek their rst surgical consultation until later in life.
Despite societal stereotypes, body dysmorphic disorder is equally common among both men
and women. However, the content of dysmorphic beliefs tends to vary between the genders,
with men being more likely to perceive parts of themselves as being too small (most often
their muscles or genitals) while women are more likely to perceive body parts (such as their
nose or ears) as being too large or dis gured.
Without treatment, body dysmorphic disorder tends to remain and become chronic, with
less than 10% of people experiencing remission within one year. Treatment of body
dysmorphic disorder is the same as for OCD, with a very large effect size for CBT (over
1.5) and a large effect size for SRIs (around 0.9).

HYPOCHONDRIASIS
Hypochondriasis (called “illness anxiety disorder” in the DSM-5) involves an obsessional
preoccupation that one has a medical illness. While everyone has physical symptoms at
various points throughout the day (including random pains, stomach aches, diarrhea,
constipation, headaches, vision problems, tingling, and ringing in the ears), people with

226
hypochondriasis are likely to interpret these sensations as error signals (“I’ve had this
headache for a few hours now. is must mean that I have brain

cancer!”). is leads them to spend lots of time and energy in

compulsive behaviors such as researching possible causes of their symptoms on the internet
or frequently going to the doctor for evaluation. However, just like in OCD, no amount of
reassurance will lead to a “feeling of knowing” that they don’t have an illness, and their
obsessional preoccupation with the idea of having a medical condition will persist no matter
how much evidence is presented to the contrary (“I don’t care what all the doctors and labs
and imaging reports say! I know that I have cancer!”). is leads to endless use of medical
resources and puts the patient at risk of unnecessary medical harm (such as use of
medications with side effects or high doses of ionizing radiation from repeated radiographic
studies). is obsessional preoccupation can often begin to affect the patient’s life as well,
preventing them from engaging in normal activities, socializing with others, and remaining
active due to the obsessional belief that they are sick.
 

Hypochondriasis involves a persistent belief that

one has a physical illness despite reassurance and
evidence to the contrary.
 

In hypo—conned-riasis, the patient believes that the

doctor is being conned by the normal signs and lab
ndings.

While certain forms of OCD involve fears of becoming sick or contaminated, in

hypochondriasis the person isn’t worried that they will get an illness, they are worried that
they have an illness. In addition, the preoccupation with having a medical disease in
hypochondriasis is ego-syntonic, and people with hypochondriasis have no conception that
their interpretation of physical symptoms is in any way excessive or unreasonable (even
though they often appear that way to an outside observer).
Clinically signi cant hypochondriasis appears to be relatively uncommon, with a
prevalence of around 0.5% of the general population. Like other obsessive-compulsive
disorders, hypochondriasis most commonly begins in early adulthood and is found equally

227
among men and women. Clinical features that suggest hypochondriasis include a history of
extensive work-ups for symptoms for which no medical cause is ever found (often involving
consultation with multiple clinicians) as well as a pattern of the patient becoming more
dissatis ed and anxious in response to negative ndings (for someone with hypochondriasis,
no news is actually bad news). Once diagnosed, treatment for hypochondriasis should
consist of CBT as a rst-line intervention, as it is associated with a large effect size (around
0.8 or 0.9). Use of SRIs appears to be helpful as well and can represent a reasonable
treatment option.
A diagnosis of hypochondriasis should be given cautiously. Given its low base rate, it
is more likely to be overdiagnosed than underdiagnosed. More importantly, however,
diagnosing someone with hypochondriasis can be stigmatizing and can severely jeopardize
the therapeutic relationship. ere is also the risk of missing a medical condition that is
actually present. For all these reasons, make sure that you have fully ruled out all other
possibilities before diagnosing hypochondriasis, and always try to validate your patient’s
concerns while trying to point towards interventions that will be the most likely to lead to
positive outcomes.
 
TIC DISORDERS

Tics are sudden contractions of speci c skeletal or vocal muscle

groups that tend to occur in repetitive bouts. Tics may involve simple movements (such as
eye blinking, grunting, or throat clearing) or more complex actions (such as arm jerking,
foot stomping, or forming a whole word or sentence). On a cognitive level, tics are preceded
by a conscious sensation of rising inner tension (often described as an “urge”) that is
relieved by performing the tic. Tics are neither entirely voluntary nor entirely involuntary;
instead, tics are best thought of as irresistible in the sense that they can be delayed with
mental effort but not repressed entirely.
 

Tics are transient irresistible contractions of

speci c muscle groups that occur suddenly in
repetitive bouts.
 

A TIC is a Transient Irresistible Contraction.

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 Tics are believed to be related to OCD in that they both follow a similar pattern (a
state of increasing mental tension that must be discharged through performing a compulsive
act). However, they differ from OCD in that they don’t necessarily involve speci c types of
thoughts such as contamination or blasphemy.
Tics often begin in childhood between the ages of 3 and 8. Motor tics often precede
the development of vocal tics. For the majority of people with this condition, tics occur in a
waxing-and-waning course throughout childhood and adolescence, with bouts of tics
occurring for a few months followed by periods of relative remission. ere is often a
gradual lessening of tics throughout adolescence such that by the age of 20 tics are
signi cantly reduced, if not gone entirely. Tics are relatively common, with around 20% of
school-age children experiencing transient tics and 5% experiencing chronic tics. However,
it is only a minority (around 1%) of children who develop tics that are severe enough that
they interfere with functioning and would therefore be said to have a tic disorder. A speci c
form variant of tic disorder known as Tourette syndrome involves a combination of
multiple motor tics and at least one vocal tic. Despite popular media portrayals of Tourette
syndrome often involving sudden shouts of profanity (known as coprolalia), this
phenomenon occurs only in a minority of children with the disorder (around 10%).
 

Tourette syndrome is characterized by multiple

motor tics and at least one vocal tic.
 

Two-rette syndrome involves two forms of tics (both

motor and vocal).

Tics are not inherently pathological, and many people with tics do not need treatment. In
cases where the tics are signi cantly impairing or disruptive (such as someone whose tics are
dramatic, intrusive, or disruptive to others), treatment involves a speci c type of CBT
known as habit reversal training. is form of therapy involves learning to recognize the
build-up of an urge and then to voluntarily perform a “competing” act that physically
cannot be done at the same time as the tic (such as someone with a shoulder shrug tic
instead pushing their shoulders downward). e competing act should be held until the
urge goes away. Habit reversal training is associated with a large effect size (0.8) not only
for tics but for a variety of related conditions including stuttering, nail biting, and thumb
sucking. While antipsychotics are reasonably effective at reducing tics (with an effect size
around 0.6), their high side effect burden should limit their use to only unusual
circumstances.
 

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TRICHOTILLOMANIA Trichotillomania (roughly
meaning “hair pulling madness”) is a condition in which people repeatedly pull out their
hair, leading to skin damage and hair loss. Many people with trichotillomania say they have
no desire to lose their hair and wish that they could stop engaging in this unwanted
repetitive behavior. However, just like tics, hair pulling is preceded by an urge that is
irresistible. is places trichotillomania more in line with compulsive disorders than
impulsive disorders (as the act of pulling hair out is not positively reinforcing). e link
between trichotillomania and obsessive-compulsive disorders is further reinforced by the
fact that this condition is found in higher rates in people with OCD or in relatives of those
with OCD. Treatment involves habit reversal training. Medications like SRIs are only
minimally effective at best and should generally not be used to treat trichotillomania.
 

Disorders that are related to OCD are tic disorders,

trichotillomania, hypochondriasis, and body
dysmorphic disorder.
 

ink of the icks: tic, trich, sick, and dysmorphic.

A few other conditions (including dermatillomania and hoarding disorder) have previously
been considered for inclusion in the OCD spectrum of disorders, but further research has
revealed that they are likely separate conditions. So that we are not tormented by an inner
sense of incompleteness, we will brie y review them now.
DERMATILLOMANIA Dermatillomania (also known as pathologic skin picking or
excoriation disorder) is a condition in which people repeatedly pick at their skin, resulting
in injury. It is similar to trichotillomania as both involve repetitive acts of damage to one’s
own body. However, available evidence suggests that in most cases pathologic skin picking
may be driven more by impulsivity than compulsivity. Support for this comes from the facts
that the majority of people who engage in skin picking report nding it to be a pleasurable
activity (making it positively reinforcing), that there is no link between skin picking
behaviors and obsessive thoughts, and that treatments for OCD are signi cantly less
effective for dermatillomania compared to the disorders in the obsessive-compulsive
spectrum. It’s unclear why skin picking differs so much from hair pulling on a biological
level as they seem pretty similar at rst glance, but at least for now we’ll just have to accept
that “they just do.”
 

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COMPULSIVE HOARDING
Hoarding, or the continuous accumulation of possessions to the point that it creates
signi cant dysfunction in one’s life, has a complex relationship to OCD. Like OCD, this
behavior appears to be largely compulsive in nature and is driven by a sense of inner anxiety
(“I can’t throw this magazine away! I might need it later!”). However, unlike OCD,
hoarding is ego-syntonic, as the person truly believes that hoarding these items is necessary
and important.
For a long time, hoarding was simply seen as a type of OCD (similar to
“contamination OCD” or “symmetry OCD”). However, emerging research is showing that
hoarding is more likely a separate entity. Key to this separation is the fact that hoarding and
OCD appear to be associated with a different prognosis (OCD tends to improve across
decades while hoarding generally worsens), different responses to treatment (with hoarding
being poorly responsive to both CBT and serotonergic medications), and distinct neural
mechanisms.
Just to add to the complexity, for a minority of people with OCD, hoarding can be a
manifestation of OCD. In these people, hoarding is notably ego—dystonic and follows the
pattern of OCD: an intrusive thought that can’t be cleared away (“If you throw that book
away, your mother will hate you.”) leading to repeatedly engaging in a compulsive behavior
(hoarding). is is rare, however, and in most cases hoarding should be considered a related,
but ultimately separate, diagnosis from OCD.

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DIFFERENTIAL DIAGNOSIS OF OCD
Super cially, obsessive-compulsive disorders resemble a variety of other psychiatric
syndromes that either feature distressing thoughts (such as anxiety or traumatic disorders)
or involve rigid or repetitive behaviors (including the restricted activities seen in autism or
the non-suicidal self-harm of borderline personality disorder). Having a clear concept of the
phenomenology of both obsessions and compulsions is the best way to protect against
diagnostic confusion, so take the time to make sure that these concepts are straight in your
head (including the MURDER and calmpulsion mnemonics). In addition, obsessive-
compulsive disorders are highly comorbid with many other disorders such as depression,
making it essential to remain vigilant for signs and symptoms that could suggest other
forms of distress.
 
NORMALCY
As we discovered when talking about mechanisms of OCD, it is normal and adaptive to
recognize errors, to experience motivational arousal, and to perform speci c actions to
reduce this arousal. However, the difference between normalcy and pathology lies in
whether the connection between obsessions and compulsions is a line or a loop. It is only
when the “feeling of knowing” breaks down and the compulsive actions start becoming
repetitive and maladaptive that the disorder occurs.

Like depression or panic, the term

“OCD” is often misused by people both inside and outside the medical community, leading
to diagnostic confusion. Despite popular conceptions, OCD is not synonymous with being
“clean” or “orderly” (although the concepts are not entirely unrelated). In addition, some
degree of obsessiveness is likely adaptive, as people who maintain good hygiene are more
likely to avoid illness, and a desire for cleanliness and order can be highly desired
characteristics especially in certain elds of work like engineering or healthcare where being
detail-oriented is essential. Because of this, avoid thinking that all people who are orderly or
methodical have (or “are”) OCD.
 
ANXIETY
OCD has long been classi ed as an anxiety disorder in the DSM, and the links between the
disorders are numerous. For one, anxiety can often be the presenting symptom of OCD
(remember that OCD is the O in the ONSTAGE mnemonic). In addition, OCD follows a
very similar Alarm—Beliefs—Coping pattern that characterizes other anxiety disorders.
Despite these similarities, however, OCD is best thought of as a separate condition. is
re ects the fact that while anxiety is sometimes a prominent feature of this disorder, it is not
the core pathology, and there are some cases of OCD that do not involve anxiety in any way.
ese two conditions also differ in their underlying mechanisms, as obsessive-compulsive

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disorders result from a dysfunctional error system while anxiety disorders result from
dysfunctional alarm systems even though both can lead to similar beliefs and maladaptive
coping mechanisms.
 
OBSESSIVE-COMPULSIVE PERSONALITY DISORDER
We have not talked about obsessive-compulsive personality disorder yet (it will be discussed
more fully in Chapter 12), but it is characterized by extreme and in exible traits of high
conscientiousness and low openness to new experiences that manifests in rigid and
perfectionistic beliefs and behaviors. Despite being named obsessive-compulsive
personality disorder, this condition is not characterized by either obsessions or compulsions,
making it one of the worst named disorders in the DSM. Don’t let the words “obsessive”
and “compulsive” in the name distract you: obsessive-compulsive personality disorder is an
entirely separate condition from OCD.
 
ADDICTION
Obsessive-compulsive disorders and addictive disorders both share a pattern of repeatedly
engaging in speci c behaviors despite negative repercussions. Because of this, it is easy to
get the terminology confused (people will sometimes say that someone “uses cocaine
compulsively” or that someone is “addicted to washing their hands”). It’s important to get
this distinction right because the prognosis and treatment considerations for impulsive
disorders like addiction differ signi cantly from those for compulsive disorders like OCD.
Pay attention to whether the speci c behaviors are immediately positively reinforcing (in
which case they would represent dysfunctions in impos control) or whether they serve to
calm an internal sense of anxiety (in which case they would likely represent calmpulsions).
 
PSYCHOSIS
Both OCD and primary psychotic disorders can include beliefs that others nd odd or
delusional. In some cases, it is impossible to tell whether a belief is related to OCD or
psychosis just from the belief alone. As one example, consider someone who believes that
looking into any re ective surface would cause someone to murder them in the night,
leading to anxiety when someone buys them a shiny new toaster. On the surface, most
people would agree that this belief likely represents some form of psychiatric pathology.
When looking deeper, however, it is not immediately clear whether it represents an
obsessional thought or a paranoid delusion. As usual, the content of the delusion tells us very
little while the process tells us much more.
A key differentiating factor between OCD and psychotic disorders is that bizarre beliefs in
OCD are notably ego-dystonic while those in psychosis are ego-syntonic. is helps to
distinguish obsessive thoughts from delusions because the person who has these thoughts
knows that they are excessive, odd, or bizarre. In contrast, people who have delusions do not
necessarily see them as being strange and sincerely believe that they represent an accurate
view of reality. Using the example from earlier, if you asked the person with anxiety about
re ective surfaces if this belief is strange, they would reply with, “Absolutely.” In contrast, if
you ask someone with schizophrenia the same question, they would say, “No, this is real,
don’t you get it?”
 
AUTISM

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Obsessive-compulsive disorders and autism can both be characterized by repetitive or rigid
behaviors, and just like with psychosis and OCD it is not always possible to tell from the
behavior itself which disorder it belongs to. For example, someone who organizes all the
items on their bathroom sink every single morning without fail may be diagnosed with
either OCD, autism, or even plain old normalcy depending on the reasons why they do this
behavior. If they engage in the behavior to neutralize obsessive beliefs, a diagnosis of OCD
should be considered. If they do it to provide sensory stimulation or out of a preference for
sameness, this is in line with an autism spectrum disorder. If they do it because they like to,
it’s probably just normal.
 

TRAUMA PTSD and OCD share more than a few similarities. Both are characterized by
recurrent, intrusive, and unwanted thoughts, and both were considered to be anxiety
disorders before being split off into their own categories (with trauma being the T in the
ONSTAGE mnemonic). In addition, PTSD and OCD are frequently comorbid, and at
least in some people, a traumatic event appears to be able to “trigger” development of OCD.
Because of this, a history of trauma should be assessed in all patients presenting with
obsessive-compulsive symptoms (and vice versa), with up to 30% of people diagnosed with
one having the other as well. In patients where only one disorder is suspected, one clinical
feature that can help to differentiate between the two is age of onset, as OCD generally
begins in adolescence whereas PTSD tends to begin later in life (even when trauma is
experienced during childhood).
 
DEPRESSION
Depression and OCD are frequently comorbid. In addition, the ruminative thoughts in
depression appear to share phenomenological and treatment similarities with OCD,
suggesting at least some overlap in etiology. For this reason, it is helpful to rule out a
diagnosis of depression when someone presents with OCD.

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PUTTING IT ALL TOGETHER
Obsessive-compulsive disorders can be initially difficult to understand, as many of the
conditions that fall within this group do not appear to have much in common (“What does
hair pulling have to do with feeling that your nose is too big?”). However, by looking at the
underlying pattern of these disorders (error signal → motivational arousal → compulsive
behavior → lack of “feeling of knowing” → continuation of error signal), we can begin to see
how the full spectrum of these disorders ts together.
Looking at OCD in particular, the MURDER and calmpulsion mnemonics can help
to remind you of the core phenomenology of this condition. For the other disorders in the
obsessive-compulsive spectrum (remember tic, trich, sick, and dysmorphic), try to think
through how each of them ts this underlying pattern. In body dysmorphic disorder, the
error signal is a persistent belief that some part of their body is dis gured which leads to
excessive grooming and other behaviors intended to hide the perceived defect. In hypo—
conned-riasis, the error signal is that the person believes they have a medical disease
regardless of what the evidence says (they think that doctors are all conned by the negative
work-up). In tic disorder, these transient irresistible contractions do not revolve around any
speci c thought pattern but still can be conceptualized as a compulsive behavior intended to
reduce a state of inner tension. Finally, in trichotillomania, there is also a sense of
motivational anxiety that is only transiently relieved by engaging in compulsive hair
pulling. Always do your best to view obsessive-compulsive spectrum disorders through the
lens of this core underlying pattern, as this will help you to identify cases that are likely to
respond well to appropriate forms of treatment (speci cally, a robust effect from certain
forms of CBT like exposure and response prevention, with serotonergic medications being
used as an adjunctive or second-line treatment).
 

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236
REVIEW QUESTIONS
1. A 23 y/o F presents to a psychiatrist’s office for an initial evaluation. She was
recently red from her job after she arrived more than an hour late for the third
time in a single week. When asked why she was late, she replies with some
embarrassment that for the past year she has been spending several hours each
morning cleaning her rectum using toothbrushes and enemas, as she feels
“unclean” following a bowel movement. Recently she noticed that the amount of
time that it takes for her to feel clean has been increasing. While she tried to
accommodate this by both setting her alarm for 4:00 in the morning as well as
reducing the amount of food she is eating to prevent bowel movements, she still
nds that the process takes more time than she thought, resulting in her being late.
e psychiatrist then asks the patient why she engages in this behavior. Which of
the following responses is least consistent with a diagnosis of OCD?
A. “I know it’s weird, but I can’t stop doing it.”
B. “I can’t get these thoughts to go away.”
C. “If I don’t spend hours cleaning, then God will view me as unworthy.”
D. “I don’t understand what you’re asking. is is completely normal.”
E. All of these responses are consistent with a diagnosis of OCD
2. (Continued from previous question.) Which of the following regions of the
patient’s central nervous system is most likely activated following a bowel
movement?
A. e anterior cingulate cortex
B. e orbitofrontal cortex
C. e prefrontal cortex
D. e hypothalamus
E. e ventral tegmental area
3. An 8 y/o M is brought into the pediatrician’s office by his father who is concerned
about his “weird movements.” One month ago, the father noticed his son making
sudden jerking movements of his neck while at soccer practice. e father says that
his son “looks like a crazy person” and is worried that he will become the target of
bullying by other children. When asked about the movements, the patient says
that he feels that he has little control over them. He denies involuntary
vocalizations. Which of the following statements is true?
A. ese movements would be diagnosed as Tourette syndrome
B. It is rare for children to experience these types of movements
C. ese types of movements often decrease in frequency and severity in
response to serotonergic medications
D. ese movements are often accompanied by an inner sense of tension
or anxiety
E. ese types of movements are generally permanent once they begin
F. None of these statements are true
 

4. A 23 y/o M makes an appointment with a plastic surgeon but does not write down
the reason for his visit on the intake form. When the surgeon asks him why he is
here, the patient looks down and embarrassedly says, “I would like for my penis to

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 be bigger.” He says that he has tried various methods of enlarging his penis,
including using pumps, traction devices, and “jelqing.” He has also bought and
consumed pills claiming to increase penis size from various sources. However,
none of these efforts have resulted in substantial increases in the size of his penis.
Which of the following would argue most strongly against a diagnosis of body
dysmorphic disorder in this patient?
A. Low self-reported frequency of masturbation
B. A penis that is 2 inches (5 cm) in length
C. A belief that women will reject him because of his penis size
D. A self-reported “high sex drive”
E. Homosexual orientation
5. A 30 y/o M with a long history of untreated OCD comes to his psychiatrist’s
office for a follow-up appointment. At the last visit, the psychiatrist explained the
various treatment options that were available to him, and the patient requested
time to research each of these options and make a decision. At this visit, the
patient says that he does not believe that he will have time to engage in CBT given
his busy work schedule but is interested in starting a serotonin reuptake inhibitor.
After discussing the risks and bene ts, the patient and his psychiatrist decide on
sertraline. Which of the following conditions would be least likely to respond well
to sertraline if they were also comorbid in this patient?
A. Body dysmorphic disorder
B. Trichotillomania
C. Dermatillomania
D. Major depressive disorder
E. Generalized anxiety disorder
F. All of the above conditions would be expected to respond well to
sertraline

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1. e best answer is D. Obsessions in OCD are often ego-dystonic, meaning that
the person who has these thoughts recognizes that they are excessive or unrealistic.
is makes someone who responds by saying that they perceive their actions to be
normal or reasonable less likely to have OCD. Obsessive thoughts are
characteristically ego-dystonic (answer A) and recurrent (answer B). It is also not
unusual for someone to have obsessions involving multiple themes, which in this
case would be both cleanliness and religiously-oriented thoughts (answer C).
2. e best answer is A. e anterior cingulate cortex is involved in recognition of
perceived errors and the generation of motivational arousal, which in this case
takes the form of the patient believing that she is dirty following a bowel
movement and feeling the urge to take steps to make herself feel clean again. e
prefrontal cortex is involved in OCD, but its role appears most related to de cits in
recognizing completion of tasks (the lack of any “feeling of knowing”) rather than
error recognition (answer C). e orbitofrontal cortex is implicated in mood
disorders (answer B), while the hypothalamus is involved in anxiety disorders
through its place in the hypothalamic–pituitary–adrenal axis (answer D). e
ventral tegmental tract is part of the reward circuitry and is more related to
addictive disorders than compulsive disorders (answer E).
3. e best answer is D. Tics are often accompanied by a sense of inner tension that
is relieved by engaging in the movement. is case would not be diagnosed as
Tourette syndrome, as Tourette syndrome speci cally involves the combination of
both motor and vocal tics (answer A). Tics are common, with around 20% of
children experiencing them (answer B). For most children, they are transient and
will resolve on their own (answer E). Medication treatment generally involves
antipsychotics rather than SRIs (answer C).
4. e best answer is B. A diagnosis of body dysmorphic disorder is based on the
presence of beliefs that certain aspects of one’s body or appearance are awed.
However, an important point is that these aws are imagined and are not
reasonable by any objective standard. In contrast, a penis that is 2 inches in length
is small by any objective standard and would likely meet common medical criteria
for a diagnosis of a micropenis. For this reason, it cannot be said that he suffers
from body dysmorphic disorder, as his perceived views are not necessarily
imagined. None of the other factors listed has any bearing on a diagnosis of body
dysmorphic disorder.
5. e best answer is C. Body dysmorphic disorder, trichotillomania, major
depressive disorder, and generalized anxiety disorder (answers A, B, D, and E) are
all expected to respond well to starting an SRI (although the size of the effect will
differ between them). In contrast, dermatillomania is associated with a poor rate of
response to SRIs and may be more related to impulse control disorders than
compulsive disorders.
 

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11 TRAUMA

In psychological terms, trauma is de ned as an event that is

violent or life-threatening to the extent that it evokes intense feelings of fear,
helplessness, and terror in the people experiencing it. Common examples of trauma
include war, combat, violence, assault, crime, terrorism, and accidents. Traumatic
experiences are common, with the majority of people experiencing at least one major
trauma in their lifetime. Experiencing trauma is not inherently pathological, and not
everyone develops distressing or disabling symptoms after trauma. For some people,
however, exposure to a traumatic event can provoke a characteristic syndrome of trauma-
related signs and symptoms that can be incredibly impairing. ese people are said to be
suffering from a trauma or stressor related disorder, the prototype of which is post-
traumatic stress disorder (or PTSD).
For this and the next few chapters, we will talk about disorders that are strongly
related to trauma. ere is a key distinction that needs to be made here. A history of trauma
elevates the risk for nearly all mental disorders, including anxiety, depression, bipolar
disorder, OCD, and schizophrenia. However, these disorders can and do occur in the
absence of a history of trauma. In contrast, PTSD, dissociative disorders, some personality
disorders (primarily those from cluster B), and somatoform disorders tend to occur almost
exclusively in the context of trauma (and, in the case of PTSD, cannot be diagnosed without
it). Because of this, these disorders can be conceptualized as various emotional, cognitive,
and behavioral manifestations of the effects of trauma. While PTSD is the “textbook”
trauma-related disorder, keep in mind that personality disorders, somatoform disorders, and
dissociative disorders are all directly related to trauma as well. For the moment, however, we
will limit our discussion to PTSD.

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SIGNS AND SYMPTOMS OF TRAUMATIC DISORDERS
While not everyone develops a disorder following exposure to a traumatic event, those who
do tend to experience a remarkably consistent set of signs and symptoms. In fact, while the
term “PTSD” was not used until the 1970s, this particular constellation of signs and
symptoms has been referenced throughout history under various other names, including
“railway spine” for victims of the frequent railroad collisions that occurred in the early
1800s, “shell shock” in World War I, and “combat stress reaction” in World War II. e
primary symptoms required for a diagnosis of PTSD can be captured in the acronym
TRAUMA:
T is for Trauma. Exposure to a traumatic event is required for a diagnosis of PTSD, and the
characteristic signs and symptoms of PTSD must not have been present prior to this event.
Despite a general consensus that traumatic events exist, it has been much more difficult to
de ne what exactly constitutes a traumatic event. Do we de ne trauma based on
characteristics of the event itself, or is it de ned based on a person’s reaction to that event?
Modern approaches attempt to take both into account. e event must either be life-
threatening and/or involve actual or threatened physical and/or sexual violence, while the
response must involve signi cant feelings of fear, helplessness, and terror. is means that
other events (such as harassment, non-violent bullying, or having nude images of yourself
posted online by an ex-boyfriend) do not “qualify” as trauma per the DSM-5 despite the
fact that these experiences can often result in signs and symptoms indistinguishable from
“textbook” PTSD. Secondary exposure to a traumatic event (such as hearing about a spouse
or family member who was robbed at gunpoint) still quali es per DSM-5 standards. e
trauma can be a single event (as in a car crash) or it can be chronic (such as childhood
abuse). e nature of the trauma has important considerations for the development of
PTSD, as less than 10% of people experiencing a non-intentional trauma such as a
workplace accident develop PTSD while nearly 50% of those experiencing intentional
trauma such as rape or assault do.
 

R is for Re-experiencing. People with PTSD often re-

experience their trauma in various ways. is primarily takes the form of ashbacks, which
are sudden and unexpected re-experiencings of the trauma. Flashbacks can be either cued
(“triggered” by certain stimuli that are reminiscent of the trauma, such as a Vietnam War
veteran hearing a helicopter) or uncued (occurring seemingly at random or “out of the
blue”). Flashbacks are not thoughts so much as experiences, and someone in the midst of a
ashback tends to experience them in highly emotional and sensory terms (including

241
speci c images, sounds, or smells) rather than verbal or narrative memories (“I remember
that one time in Vietnam…”). is appears to be related to how stress affects the ability to
encode memories, with traumatic events often being encoded in a “ ashbulb” manner rather
than being stored in terms of a personal autobiographical narrative as most memories are.
Flashbacks are experienced as occurring in the “here and now” and appear to be a form of
dissociation (discussed more in Chapter 14). Re-experiencing can also occur in the form of
nightmares, which are common in individuals diagnosed with PTSD (with over 70% of
people who have experienced trauma reporting frequent nightmares compared to only 5% of
the general population). Nightmares are often, though not always, related to the trauma
itself and can result in signi cant disruptions in the quality of sleep or even attempts to
avoid sleep due to anxiety about having more nightmares.

A is for Arousal. People with PTSD often develop a state of

increased anxiety and awareness of their surroundings known as hyperarousal. is is
similar to the state of arousal seen in fear that is mediated by the sympathetic nervous
system (as discussed in Chapter 9). However, unlike adaptive fear, in PTSD this state of
arousal becomes persistent and generalized, occurring most of the time and in multiple
environments regardless of whether there is reason to be fearful or not. For example,
someone who was robbed while traveling in another country may begin carrying forms of
protection with them at all times and keeping these at their side before answering the
doorbell at home. People in this state of arousal often engage in constant scanning of their
environment for possible clues to the presence of any danger (known as hypervigilance).
During a mental status exam, this may manifest in an exaggerated startle reaction (“Hi, I’m
Dr. Sm…” “Holy shit! Don’t scare me like that!”). Due to the involvement of the HPA axis,
people in a state of hyperarousal related to PTSD often experience similar symptoms as are
seen in states of chronic anxiety as captured in the MISERA-ble mnemonic, including
Muscle tension, Irritability, trouble with Sleep, low Energy, Restlessness, and inability to
pay Attention to non-trauma related stimuli.

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U is for Unable to function. e re-experiencing, hyperarousal, and avoidance patterns

experienced by people with PTSD can be incredibly impairing in terms of both social and
occupational functioning. Many people often nd themselves unable to concentrate at work
or have no interest in maintaining relationships with “normal people” who cannot
understand the experiences that they have been through, leading to difficulty in maintaining
a job or an adequate social support system.
 

M is for Month. By de nition, PTSD is a chronic disorder, meaning that trauma-related

symptoms must be present for a certain period of time. In the DSM-5, this period of time
is arbitrarily de ned as one month. (People showing signs and symptoms related to trauma
for less than one month would be diagnosed as having acute stress disorder, discussed later
in this chapter.) To be clear, this does not mean that symptoms have to be present in the
rst month after the trauma occurs. In fact, a delayed onset is most characteristic of PTSD,
with nearly 80% of those who eventually receive this diagnosis not showing any symptoms
within the rst month after the trauma.
 

A is for Avoidance. Haunted by frequent re-

experiencing of unpleasant memories, people with PTSD will often go to great lengths to
avoid people, places, or things associated with those memories so as to not trigger a
ashback. For example, someone with PTSD from a construction-related accident may nd
themselves avoiding tall buildings, while someone who was kidnapped while walking out of
a friend’s house at night may nd it difficult to return to that part of town. Avoidance can
go beyond physical avoidance to include a more psychological avoidance of emotions known
as numbing. Emotional numbing helps to protect against strong negative emotions such as
fear, helplessness, or anxiety, but it can also interfere with the ability to experience positive
emotions such as joy, satisfaction, or love. is results in a attening of affect which can
impair one’s ability to interact with other people and engage in meaningful relationships.
 

Post-traumatic stress disorder is characterized by

exposure to a life-threatening and/or violent event

243
that results in re-experiencing, hyperarousal, and
avoidance.
 

TRAUMA: Traumatic event Re-experiencing Arousal

Unable to function Month or more of symptoms
Avoidance

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TRAUMATIC DISORDERS ACROSS THE LIFESPAN
Approximately 3% of the population is affected by PTSD at any given time, with up to 10%
experiencing symptoms during their lifetime. is makes it a relatively common syndrome.
Women are affected twice as often as men even after accounting for signi cant differences
in the nature of trauma experienced by each gender (such as sexual assault being more
common in women). Unlike other psychiatric syndromes we have discussed so far, the age
of onset of PTSD is quite variable. Logically, this makes sense, as traumatic events are
generally unplanned and would be expected to occur on a seemingly random basis, making
it understandable that there is no clearly established age of onset for PTSD. However, there
do appear to be upper and lower limits, with children under the age of 10 being highly
unlikely to develop PTSD (at least in the “textbook” sense) and adults over the age of 55
showing a dramatic decrease in rates of the diagnosis.
Exposure to trauma is common, and the majority of people will experience at least
one traumatic event in their lifetime. However, not everyone exposed to trauma will develop
PTSD. For example, while 20% of soldiers exposed to combat develop PTSD, the other
80% do not. In non-military populations, up to 60% of people experience at least one major
trauma in their lives, but only 8% go on to develop PTSD. is can be confusing for
someone learning about PTSD, as the medical model of illness often assumes a simple
cause-and-effect explanation (“trauma → PTSD”, just as “virus → infection”). However, the
wide variation in human responses to trauma argues against this idea.

Traumatic disorders make much more sense when

viewed through the lens of a core principle of psychodiagnostics: it’s never just one thing.
Like many psychiatric syndromes, PTSD requires both a stress and a diathesis. While
most people would expect that the severity of PTSD symptoms would be most related to
the nature of the traumatic event itself, research has found that non-trauma related factors
(including personality traits, psychological coping styles, presence of social support, and
number of pre-trauma mental disorders) matter just as much as the details of the traumatic
event. For someone who is particularly vulnerable to stress, even a relatively minor trauma
(such as having their car broken into while at work) can be enough to induce PTSD. In
contrast, someone who is relatively immune to the effects of stress may still develop PTSD
provided that the event they experience is distressing enough (such as being the victim of a
violent assault). Most cases fall somewhere in between these two extremes. Nevertheless,

245
approaching PTSD from this vantage point will provide additional insight into the
multifactorial nature of trauma’s effects on the mind.
Other factors can also predict an increased risk of developing PTSD after trauma. In
particular, people who are younger at the time of trauma, experience trauma alone, have
little time to process, and have low social support tend to be at the highest risk for
developing PTSD. ese factors together help explain why soldiers who fought in the
Vietnam War developed PTSD at much higher rates than those returning from World War
II. Compared to World War II veterans, soldiers in the Vietnam War were younger (19
years compared to 26), served in predetermined and variable timeframes which broke up
social cohesion (as opposed to those in World War II who trained, fought, and returned
home largely with the same group), had little time to process (a 16-hour ight from
Vietnam to the United States compared to a 30-day boat ride home with your comrades),
and received little social support upon returning home (many were greeted with protestors
rather than parades). ese same risk factors also appear to apply in non-military
populations as well.
 
PROGNOSIS
Without treatment, PTSD is often chronic and enduring, with about 50% of cases
showing continued symptoms and impairment over a 5 year period. In the other 50% of
cases, the severity of PTSD symptoms appears to decrease over time. e distinction
between intentional and non-intentional trauma appears to be important for the prognosis
of PTSD, as symptoms related to non-intentional trauma appear to decrease over time
while those associated with intentional trauma remain constant or even increase as time
goes on. It’s also important to realize that mental dysfunction is not the only possible
outcome of trauma. In fact, around a third of people who experience a signi cant trauma go
on to attribute that event to positive changes in their perspective on life (a phenomenon
known as post-traumatic growth). However, post-traumatic growth appears to be more
common following non-intentional trauma (such as a natural disaster or a diagnosis of
cancer) compared to intentional trauma.
 
TREATMENT
Speci c treatments for PTSD have been shown to be effective at reducing the distress and
dysfunction related to trauma. e primary form of treatment for PTSD is trauma-focused
CBT. In particular, a form of CBT known as exposure therapy helps to overcome
avoidance by encouraging patients to intentionally come into contact with places and things
that remind them of their traumatic experiences (such as driving a car in the area where an
accident previously occurred) to re-encode these memories in a way that is less “ ashbulb”
and more “narrative,” leading to fewer re-experiencing episodes. CBT for PTSD is very
effective, with a large effect size over 1.0.
Medications (particularly SRIs) can be helpful as an adjunct to psychotherapy.
However, they are generally not preferred as a rst-line treatment given that they are not
only less effective (with a smaller effect size around 0.5) but also produce effects that tend to
disappear after treatment has ended (as opposed to the longer lasting bene cial effects
associated with psychotherapy). In addition to SRIs, another drug known as prazosin
(which works by blocking the sympathetic nervous system and its associated “ ght or ight”
response) has been shown to be helpful for preventing PTSD-related nightmares when
taken before bed, with a large effect size of 1.0. Benzodiazepines rapidly reduce the anxiety

246
and hyperarousal associated with PTSD, but they should generally be avoided as they
appear to worsen many outcomes (including rates of depression, aggression, and substance
abuse following a trauma).
 

Treatment for PTSD consists of CBT, with SRIs

as an adjunctive treatment.
Prazosin can be used to reduce PTSD-related
nightmares.
 

Post Traumatic Stress? Try Prazosin, Therapy, and

Serotonin.

While much is known about treatment of PTSD once it has occurred, recent research
has focused on preventing PTSD following exposure to a trauma. Studies have shown that
trauma-focused CBT can reduce the rate of developing PTSD, at least for “single exposure”
traumas such as a car crash. In contrast, medications have not been shown to be helpful for
preventing PTSD following exposure to a trauma.

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MECHANISMS OF TRAUMATIC DISORDERS
When looking at the mechanisms underlying PTSD, it soon becomes clear that PTSD is
an incredibly complex and multifactorial disorder. One thing that complicates the matter
signi cantly is the fact that many of the systems involved in PTSD are also implicated in
other psychiatric syndromes as well. For example, people with PTSD display persistent
overactivation of both the sympathetic nervous system and the HPA axis which is also
seen in anxiety and depression as well. ( e involvement of these two systems explains why
medications that interact with them such as prazosin appear to be effective in treating
particular symptoms of PTSD.) In addition, negative affective biases (which you’ll
remember from the chapter on depression) appear to be present in PTSD as well which
could account not only for the persistently poor mood associated with the disorder but also
for the bene ts observed with CBT and SRIs. Finally, dissociative mechanisms (discussed
in Chapter 14) appear to account for re-experiencing symptoms such as ashbacks and
nightmares. Because the various symptom domains of PTSD each have their own
mechanisms, it seems unlikely that there is going to ever be a single unifying mechanism for
the disorder.

However, despite this overlap in symptoms and

mechanisms with other disorders, there do appear to be two consistent neurobiological
ndings that are both quite speci c and sensitive for a diagnosis of PTSD: increased activity
in the amygdala and decreased activity in the medial prefrontal cortex. e amygdala is a
part of the brain clusters that works to quickly generate emotional responses to stimuli
(particularly those associated with fear), while the medial prefrontal cortex helps to police
the amygdala’s response by integrating higher-level information about the environment. For
example, say that we suddenly hear the sound of a loud explosion. e amygdala
immediately kicks in and suggests unconsciously that “explosion = bad” and activates the
sympathetic nervous system’s ght-or- ight response, inducing a state of fear. However, if
the sound of the explosion happens during the Fourth of July, then the medial prefrontal
cortex is able to take higher-level sensory information (such as visuals of American ags and
the emotional context of smiling faces around us) and integrate them into an unconscious
thought of “explosion = okay for now.” e medial prefrontal cortex then steps in to tell the
amygdala to back off a little bit, reducing the fear response and allowing us to enjoy the
reworks. In the picture to the right, the dad’s medial prefrontal cortex has been able to
integrate higher-level sensory information and tell the amygdala to turn off, while the boy is

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clearly disturbed by the experience (his amygdala is running rampant, unhindered by his
medial prefrontal cortex). It is the boy’s response that is most typical of PTSD: an
overactive amygdala that is insufficiently regulated by an underactive medial prefrontal
cortex.

A second brain structure known as the hippocampus also helps to regulate the
amygdala in response to accumulated memories. An underdeveloped hippocampus has
been found to be a risk factor for developing PTSD, even in people who have never
experienced trauma (suggesting that it forms part of the diathesis for PTSD). Someone
with an underdeveloped hippocampus would be less able to use memories of the past to
control the emotional response to current stimuli. Using the same example, someone may
remember based on their memories of the Fourth of July over their entire life that the sound
of an explosion is not always bad, and this information can help to regulate an overactive
amygdala as well. is partly explains why the dad in the picture is having a good time with
the reworks while the boy (who, due to his age, hasn’t had the time to develop his
hippocampus) seems much more scared.
Someone with this characteristic combination of an overactive amygdala, an
underactive medial prefrontal cortex, and an underdeveloped hippocampus is at high risk
for developing the signs and symptoms of PTSD, as they are more likely to react to trauma
with strong negative emotions, less able to integrate sensory information from the
environment, and less able to use memories of happier times in their lives to lessen the sting
of a traumatic event. You can remember the association of these brain structures with
PTSD by thinking of a girl named Amy who sees an M-shaped (two-humped) Pretty
Frightening Camel and a hippopotamus. Knowing that these animals can be aggressive
(especially the hippo, which is considered one of the most dangerous large animals in
Africa), her fear response is activated in response to this perceived life-threatening
situation. However, the camel and the hippo try to calm her down by reminding her that
she’s in a private park with only tame animals (they are using contextual information to
bring down her fear response). Use this situation to help you remember the relationship
between the Amygdala (which is prone to be frightened) and the Medial PreFrontal Cortex
and the hippocampus (which try to calm the amygdala down using contextual information).
 

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PTSD involves an overactive amygdala that is

inadequately regulated by an underactive medial
prefrontal cortex and an underdeveloped
hippocampus.
 

Remember Amy, the woman who encounters an M-

shaped Pretty Frightening Camel and a hippopotamus
while visiting the zoo.

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DIAGNOSING TRAUMATIC DISORDERS
PTSD is a highly variable condition that encompasses a wide spectrum of possible
cognitive and behavioral responses to trauma. Because the variations in the clinical
presentation between different people with PTSD depend not only on each individual’s pre-
existing vulnerabilities but also on the nature of the trauma (including whether the trauma
occurred only once or over a long period of time, whether it was intentional or accidental,
and whether it involved the patient personally or was instead experienced vicariously), it was
possible for a diagnostic scheme for traumatic disorders to have become endlessly complex.
Instead, the DSM-5 takes a broader and more inclusive approach to diagnosing
traumatic disorders by offering a single diagnosis that encompasses a wide range of
pathological experiences following trauma. is makes diagnosing PTSD relatively simple.
In fact, while the speci c symptom domains of PTSD are helpful for understanding the
disorder, from a diagnostic standpoint simply asking two questions (“Have you experienced
a life-threatening or violent event? If so, does the memory of this event interfere with your
life?”) can be a very sensitive test for PTSD. People who answer no to both of these
questions are quite unlikely to have PTSD, while those who answer yes should be further
evaluated to understand the nature of their dysfunction and whether they would qualify for
a diagnosis of PTSD. However, keep in mind that many people won’t feel comfortable
sharing their experiences of trauma, especially if it makes them feel vulnerable or ashamed
(as can occur with domestic violence or sexual assault).
 
POST-TRAUMATIC STRESS DISORDER
PTSD is the prototype traumatic disorder and is diagnosed based on a history of a
traumatic event as well as the characteristic signs, symptoms, and dysfunction that tend to
follow, including re-experiencing, avoidance, and hyperarousal. By de nition, these
symptoms must be present for at least one month. ese criteria are captured in the
TRAUMA mnemonic described previously.
 
ACUTE STRESS DISORDER
For some people who have experienced trauma, severe emotional and cognitive problems
can begin almost immediately following the event. However, until the symptoms have been
present for at least one month, you cannot diagnose PTSD. Nevertheless, you also should
not ignore these patients, so in these cases a diagnosis of acute stress disorder would be
given. ( is time-based distinction is similar in nature to the boundaries between
schizophrenia, schizophreniform disorder, and brief psychotic disorder.) While it is easy to
assume that acute stress disorder is synonymous with “pre-PTSD,” this is not the case.
Many people who are diagnosed with acute stress disorder will go on to develop PTSD
after a month has passed, but not all of them do. In addition, the majority of people with
PTSD did not qualify for a diagnosis of acute stress disorder within the rst month, with
many showing a delayed onset of symptoms occurring months or even years after the initial
trauma. erefore, the presence of acute stress disorder immediately following a traumatic
event does not rule in later development of PTSD, nor does its absence rule it out.
 
ADJUSTMENT DISORDER
Given that both adjustment disorder and PTSD involve mental responses to stress, they can
easily be confused. However, two differentiating factors are the nature of the stressful event

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as well as the speci c signs and symptoms involved. Trauma is somewhat narrowly de ned
by the DSM as speci cally a life-threatening or violent event, so someone who becomes
depressed or anxious after a different type of experience (such as losing a job or being
cheated on by their spouse) would not qualify for a diagnosis of PTSD. In addition, the
symptoms encompassed by the PTSD diagnosis are often speci c to the domains of re-
experiencing, hyperarousal, and avoidance whereas adjustment disorder encompasses
broader forms of mental distress including anxiety and depressed mood.
 

“COMPLEX PTSD”

A growing body of research suggests that exposure to chronic

trauma can lead to a set of signs and symptoms that is similar to, but ultimately distinct
from, those found in “single exposure” traumas, especially when it occurred at a young age
(such as someone who endured years of child abuse). e terms “complex PTSD” or
“complex developmental trauma” have been used to describe these cases, which often
involve severe and pervasive problems in affect regulation, sense of identity, and ability to
maintain interpersonal relationships. e relationship of complex PTSD to other
psychiatric syndromes (such as cluster B personality disorders, somatoform disorders, and
dissociative disorders, all of which share similarities in phenomenology and have a clear
relationship to histories of childhood trauma) is unclear, and a diagnosis of “complex
PTSD” is not officially recognized in the DSM-5. Nevertheless, from a practical clinical
perspective, differentiating between adult-onset “single-exposure” PTSD and
developmental trauma does appear to increase the prognostic value of both diagnoses and
suggest different treatments. When working with a patient who has experienced chronic
childhood trauma, you can use the mnemonic PTSD to remember the “abuse cluster” of
possible diagnoses to consider.
 

e “abuse cluster” of disorders related to chronic

developmental trauma includes PTSD, personality
disorders, somatoform disorders, and dissociative
disorders.
 

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PTSD: Personality disorders (primarily cluster B)
“Textbook” PTSD
Somatoform disorders Dissociative disorders

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DIFFERENTIAL DIAGNOSIS OF TRAUMATIC DISORDERS
Because PTSD is only one manifestation of the effects of trauma in an individual with a
high diathesis for developing mental disorders, the rate of comorbidity with other
psychiatric syndromes is high. In fact, studies have suggested that “just PTSD” is the
exception rather than the norm and that people with PTSD often meet criteria for several
other diagnoses even prior to trauma exposure. Given this, PTSD is rarely a misdiagnosis,
but there can be a broad range of missed diagnoses if care is not taken to do a thorough
psychiatric interview. In this section, we’ll go over some of the most common disorders that
can be mistaken for or are frequently comorbid with PTSD.
 
NORMALCY
Exposure to trauma (or even experiencing some degree of distress as a result) is not
pathological in any way. (Indeed, what would be strange would be for someone to go
through an incredibly frightening and life-threatening event and come out the other side
exactly the same as before). is is a crucial distinction to make, as the term “PTSD” is
often used loosely to refer to anyone who experiences any sort of symptoms following a
trauma. What is missing from this discussion is a focus on the disorder part of “post-
traumatic stress disorder,” as we should be exceedingly careful not to medicalize ordinary
responses to extraordinary events (even if they are experienced as painful or distressing). Be
vigilant about searching for concrete evidence of dysfunction as a result of trauma-related
symptoms rather than focusing too much on whether the symptoms themselves are present.
 
DEPRESSION
PTSD is frequently comorbid with depression, with approximately half of all patients with
PTSD also having depression. Despite this, depression should not be seen as a “natural
consequence” of having PTSD, as people with both PTSD and depression are characterized
by greater symptom severity, lower levels of functioning, worse response to treatments, and
a reduced overall likelihood of symptom remission compared to patients with either
disorder alone. While there are some symptoms that overlap between the two disorders
(including anhedonia, insomnia, and reduced range of affect), try to focus on the non-
overlapping symptom domains such as re-experiencing, hyperarousal, and avoidance in
PTSD and episodic changes in mood and neurovegetative functioning in depression to
differentiate between mere diagnostic overlap and true comorbidity.
 
ANXIETY
Like OCD, PTSD was once considered to be an anxiety disorder, as symptoms of anxiety
are often prominent (“I’m scared to sleep in the same bed as my wife for fear that I’ll have
another nightmare and attack her again.”), the same neurobiological systems (including the
sympathetic nervous system and HPA axis) are implicated in both, and for some people the
disorder follows a clear Alarm—Beliefs—Coping pattern. However, while anxiety is often
found in the disorder, it is not always seen. Instead, the core symptoms of PTSD are re-
experiencing, hyperarousal, and avoidance. While for some people these symptoms can lead
to anxiety, this is not always true, making it difficult to consider a disorder that doesn’t
always feature anxiety to be an anxiety disorder. Despite now being considered its own
diagnostic category, PTSD remains highly comorbid with anxiety disorders, making it
essential to screen for possible comorbid diagnoses.

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PERSONALITY DISORDERS
A history of childhood trauma is associated with the development of certain personality
disorders, particularly those in cluster B. In addition, many symptoms (including a
proneness to negative emotions and dissociative states) are shared between PTSD and
cluster B personality disorders. From a clinical standpoint, it is absolutely possible for
someone to “have” both PTSD and a personality disorder, and these disorders should both
be seen as possible cognitive and behavioral outcomes of trauma.
 
DISSOCIATION
Dissociation is common following exposure to trauma. Interestingly, it tends to appear more
often in the initial period following a traumatic event (during the time when someone
would be diagnosed with acute stress disorder) than in the months or years following (when
they would be diagnosed instead with PTSD). Nevertheless, for some people (especially
those who have experienced traumatic events during early developmental periods)
dissociation can become chronic and disruptive. ese people would likely be diagnosed
with a dissociative disorder. e boundary between dissociative disorders and PTSD (and
when you should diagnose both instead of just saying that one is a manifestation of the
other) remains murky and unclear. For now, it is enough to remember that the vast majority
of people diagnosed with a dissociative disorder meet criteria for one or more other trauma-
related disorders, which should put each on the differential for the other.
 
SOMATIZATION
Somatization is common in people who have experienced trauma, so consider evaluating
anyone with a suspected somatoform disorder for a history of trauma. Out of all the
somatoform disorders, the one most associated with a history of trauma is conversion
disorder, in which patients experience a sudden loss of neurologic function (such as the
sudden inability to move their legs). People with conversion disorder score highly on tests of
dissociation, suggesting a shared mechanism between other disorders that are characterized
by trauma exposure.
 
PSYCHOSIS
While they are not included in the diagnostic criteria for PTSD, psychotic symptoms
(including paranoia, delusions, and auditory hallucinations) are not uncommon in people
with PTSD and are reported by around one-third of patients with the diagnosis. On closer
evaluation, however, the details of these symptoms differ signi cantly from “classic” primary
psychosis. Paranoid delusions tend to be non-bizarre (“Everyone is trying to screw me over
all the time!”), while voices are often directly related to the trauma and are recognized as
coming from inside one’s head (“I hear my dead husband asking me why I didn’t take a
different route home that night…”).

ADDICTION
Use of substances and other potentially addictive reinforcers is exceedingly common in
PTSD. Due to its anxiety-relieving effects and wide availability, alcohol is the most
commonly used substance (with around 35% of people with PTSD meeting criteria for an

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alcohol use disorder) although a wide variety of substances can be used. For this reason, it is
essential to screen everyone with a trauma-related disorder for addiction and vice versa. In
cases where both are present, treatment of addiction must often take priority, as frequent
intoxication tends to interfere with meaningful efforts to engage in therapy and other
treatments for PTSD.
 
OBSESSIVE-COMPULSIVE DISORDERS
e relationship between trauma and obsessive-compulsive disorders was explored in more
depth in the previous chapter. For now, it’s enough to remember that OCD and related
disorders are more common in people who have experienced trauma (and in some cases may
even be “brought out” by a traumatic event in someone who has never had symptoms of
OCD before).
 
MALINGERING
One of the main bene ts of diagnosis is that it validates distress on not only a personal level
but also societally as well, resulting in special privileges (such as time off work or disability
payments) being given to those with a diagnosis but not to those without. PTSD is
particularly vulnerable to malingering for several reasons. For one, as with any psychiatric
syndrome the primary symptoms are subjective and are therefore easy to mimic but difficult
to verify (as no objective signs are required). In addition, a diagnosis of PTSD is relatively
non-stigmatizing, as most people view it as a diagnosis of victimhood (“I didn’t do anything
wrong! I’m the victim here!”). Finally, there is often a clear secondary gain available from
receiving the diagnosis (such as higher damages being awarded in workers’ compensation
lawsuits when symptoms of PTSD are present or military veterans being provided with
direct nancial compensation for being disabled as a result of PTSD). erefore, it is
imperative to keep malingering on the differential for anyone presenting with symptoms of
PTSD. More than simply being a moral issue, malingered PTSD diminishes the tangible
and intangible bene ts that people who truly suffer from PTSD receive from society.
Your suspicion for malingering should be increased whenever there is clear evidence of
potential secondary gain (such as someone currently involved in legal proceedings), when
someone eagerly volunteers their symptoms from the beginning of your evaluation (“Oh
yeah, I totally have PTSD or whatever.”) but then is unwilling to cooperate with further
exams or treatment, or when symptoms are vague, nebulous, or do not match what is
known about the phenomenology of this condition. When evaluating PTSD (or really any
disorder with the potential for malingering), it can be helpful to ask open-ended questions
as much as possible (“How has the trauma affected your life?”) rather than unintentionally
educating the patient on what symptoms to report (“Do you ever have times when you
suddenly re-experience the trauma out of nowhere? is is often a sign of PTSD.”). In
difficult cases, formal assessment using psychodiagnostic testing in a clinic that specializes
in compensation evaluations may be warranted.

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PUTTING IT ALL TOGETHER
Trauma is painful and unsettling for almost everyone who experiences it. However, for some
people, a traumatic event becomes an unfortunate “gift that keeps on giving,” leading to
severe and disabling symptoms for months, years, or even decades past the event itself. e
link between trauma and mental dysfunction has long been established. However, the
precise ways in which trauma manifests itself are still in the process of being understood.
Patients with trauma will present in different ways. Some patients will require a “top-down”
approach (evaluating symptoms from a known trauma) where the history of trauma is clear
from the beginning, such as someone coming in for medical treatment after an assault. For
other patients, however, your approach will be more “bottom-up” (evaluating trauma from
known symptoms) where it is unknown if there is a history of trauma but the symptoms
present are telling you that there is a possible chance of traumatic exposure in the past, such
as someone who comes in with affective attening, frequent nightmares, and a hyperactive
startle response. In both of these cases, your task is to determine whether their traumatic
exposure has resulted in clinically signi cant signs and symptoms that warrant diagnosis
with a disorder (rather than representing a normal and expected response to a tragic event).
You can use the TRAUMA mnemonic to provide a systemic framework for recognizing the
signs, symptoms, and timeframe seen in PTSD.
In all cases of trauma, it is essential to keep in mind that PTSD is just one possible
manifestation of trauma. It is absolutely incorrect to say that everyone who has been
exposed to trauma has PTSD (or even that everyone who has problems as a result of trauma
has PTSD). Instead, do your best to conceptualize PTSD as a disorder of re-experiencing,
hyperarousal, and avoidance related to differences in emotional processing in the
amygdala, medial prefrontal cortex, and hippocampus. is is not to say that other people
who have experienced trauma but don’t have these speci c symptoms are any less deserving
of the positive bene ts of diagnosis! Someone who has experienced trauma but instead
expresses their distress through feelings of unreality or depersonalization (as in a dissociative
disorder), medically unexplained symptoms (as in a somatoform disorder), or
hypersensitivity to interpersonal rejection and abandonment (as in a cluster B personality
disorder) deserves just as much empathy, validation, and treatment as someone who
experiences “textbook” PTSD. Try your best to strike a balance between keeping a strict
de nition of PTSD (in order to increase the reliability and validity of the diagnosis as much
as possible) while also having compassion and empathy for people who manifest trauma in
other ways.
 

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REVIEW QUESTIONS
1. A 33 y/o F is seen for a workers’ compensation evaluation. Two months ago, she
was working at a tire repair shop when a tire exploded and sent a piece of the rim
ying at high velocity. e object lodged in the patient’s left thigh, and she was
rushed to the hospital. She has since had to undergo four separate surgeries. She
currently is unable to walk and uses a wheelchair to get around. Upon evaluation,
she reports thinking frequently about the incident, saying that the event “replays”
in her mind “all the time.” She denies nightmares or any changes in mood. She
denies anhedonia, feelings of hopelessness, or thoughts of suicide. She does
endorse feeling fatigued but attributes this to “those painkillers you guys have me
on.” Her affect is reactive with a full range. She is accompanied by her partner
who, when interviewed separately, says that the patient is handling the trauma
“overall fairly well, there are good days and bad days.” What is the most
appropriate diagnosis at this time?
A. Post-traumatic stress disorder
B. Acute stress disorder
C. Major depressive disorder
D. Speci c phobia
E. None of the above
2. (Continued from previous question.) Six months after the incident, the patient has
recovered enough to return to work. Her mood has remained stable, and her
episodes of re-experiencing have diminished. As the patient’s partner is driving her
to her rst day back at work, the patient experiences a sudden ashback to the
trauma and feels her heart begin to race. Hyperventilating, she yells, “Turn around!
Turn around!” She begins to feel lightheaded and dizzy. Which of the following
structures is most likely overactivated in this patient’s brain?
A. e amygdala
B. e anterior cingulate cortex
C. e medial prefrontal cortex
D. e hypothalamus
E. e hippocampus
3. An 18 y/o M graduates from high school and moves across the country to attend a
prestigious college. He does not know any other people at this college but decided
to go after being offered a full scholarship. On the weekend before school starts, he
goes to a welcome party at a local fraternity and is sexually assaulted by another
student there in a private room. In the days following the assault, he misses all of
his classes as he feels afraid to leave his room. He frequently experiences a
sensation that he does not know who he is or whether or not he is in a dream. His
sleep is disturbed by nightmares every night. One week after the incident, the
college’s student life center contacts him to inquire about his having missed so
many days of school. Two days later, he is in the school psychologist’s office. He
endorses a lack of appetite, inability to concentrate, lack of enjoyment of any
activities, and feelings of restlessness, anger, and irritability. He reports that he was
diagnosed with social anxiety disorder during his teenage years and underwent
therapy two years ago. Which of the following is the most appropriate diagnosis at
this time?

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 A. Post-traumatic stress disorder
B. Acute stress disorder
C. Major depressive disorder
D. Adjustment disorder
E. Panic disorder
F. None of the above
4. (Continued from previous question.) Which of the following features of this case
does not predict a higher chance of having PTSD one year from the incident?
A. e intentional nature of the assault
B. Experiencing the trauma alone
C. Lack of social support network since moving across the country
D. Presence of at least one pre-trauma psychiatric diagnosis
E. Presence of symptoms soon after the onset of the traumatic event
F. All of the following predict a higher chance of PTSD one year from
the incident
5. (Continued from previous question.) One month after the initial trauma, the
patient continues to experience daytime re-experiencing and severe nightmares.
Which of the following medications would be the best option for improving the
amount and quality of his sleep?
A. Fluoxetine (a serotonin reuptake inhibitor)
B. Ziprasidone (an antipsychotic)
C. Prazosin (a sympatholytic)
D. Lorazepam (a benzodiazepine)
E. All of the above would be equally effective
F. None of the above would be effective
 

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1. e best answer is E. is patient has de nitely experienced a traumatic event as
de ned in the DSM, and she currently exhibits signs and symptoms consistent
with PTSD (such as frequent re-experiencing). However, by de nition PTSD
cannot be diagnosed unless there is evidence of dysfunction as a result, and in this
case her reaction to her circumstances appears to be appropriate (answer A). is
also rules out acute stress disorder, as does the length of time that has passed since
the trauma (answer B). ere is no evidence of major depressive disorder (answer
C) or a speci c phobia (answer D). It is possible that this patient may meet criteria
for an adjustment disorder, although this would still be considered within the
realm of normalcy.
2. e best answer is A. is patient is experiencing signi cant distress while
returning to her rst day back at the place where she experienced a traumatic
event. Her fear response likely represents overactivation of the amygdala, which
generates emotional reactions to stimuli. In contrast, the medial prefrontal cortex
and the hippocampus appear to be underactive in PTSD (answers C and E).
While the hypothalamus is associated with PTSD through the hypothalamic–
pituitary–adrenal axis, it plays a larger role in chronic responses to trauma rather
than the immediate fear reaction that this patient is experiencing (answer D). e
anterior cingulate cortex is more strongly linked to OCD than PTSD (answer B).
3. e best answer is B. e patient’s history is consistent with an acute stress
disorder given the onset of signs and symptoms of psychological distress following
exposure to a trauma. Given that it has been less than one month since the trauma,
a diagnosis of PTSD should not be given (answer A). While the patient has many
symptoms of depression, the timing of their onset strongly suggests that they
should be attributed to the trauma rather than an entirely separate diagnosis
(answer C). e patient’s distress is also constant rather than episodic, arguing
against a diagnosis of panic disorder (answer E). Finally, the presence of signi cant
distress and functional impairment as well as the traumatic nature of the inciting
event all argue against a diagnosis of adjustment disorder (answer D).
4. e best answer is E. Acute stress disorder does not predict a higher rate of PTSD
in the months or years following the traumatic event, and the majority of people
diagnosed with PTSD did not meet criteria for acute stress disorder in the month
after the trauma occurred. Intentional violence, experiencing trauma alone, having
a poor social support network, and having a pre-trauma psychiatric diagnosis are
all associated with an increased risk of developing PTSD (answers A through D).
5. e best answer is C. Prazosin is a helpful medication for reducing the severity
and frequency of nightmares related to PTSD. While benzodiazepines are
effective at reducing anxiety and inducing sleep, they are associated with overall
worse outcomes in PTSD and should generally be avoided (answer D). SRIs like
uoxetine can improve overall outcomes in PTSD but are not helpful speci cally
for either sleep or nightmares (answer A). Finally, antipsychotics like ziprasidone
have no role in treating PTSD (answer B).

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 5.

12 PERSONALITY
Personality is de ned as a consistent and
enduring pattern of behavior, thought, and
emotion that a person demonstrates. While there
is often considerable stability in these patterns,
most people also show a certain degree of range
and exibility when interacting with the world.
For some people, however, this pattern of
interacting with the world has become in exible
and maladaptive, resulting in distress, disability,
and dysfunction. ese people are said to have
personality disorders. Personality disorders are
incredibly complex. More than any of the
psychiatric syndromes that we have discussed so
far, personality disorders exist on a continuum
with normalcy without a clear line demarcating
what is “abnormal.” In addition, most personality
disorders involve multiple domains of mental health that often overlap with or are easily
mistaken for other syndromes. For example, borderline personality disorder involves
persistent feelings of emptiness and dysphoria (which can resemble depression), wild swings
of emotion (which can resemble mania), stress-induced paranoia (which can resemble
psychosis), frequent worrying (which can resemble anxiety), impulsivity (which can lead to
addiction), a history of trauma (which can overlap with PTSD), and so on. Because
personality disorders lie at the boundary not only of normalcy but also of nearly every other
psychiatric syndrome as well, they are among the most frequently misdiagnosed forms of
mental pathology. erefore, a thorough understanding of personality disorders (and their
associated personality traits) will improve your diagnostic skills in every area of psychiatry
and enable you to provide tangible help to some of your most troubled patients.

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PERSONALITY TRAITS

To understand what happens when personality becomes disordered,

we must rst have a basic knowledge of what is meant by “normal” personality. ere have
been many attempts to describe patterns of personality going back thousands of years. e
majority of diagnostic schemes have attempted to divide people into distinct personality
types. For example, the famous Greek physician Hippocrates attempted to describe
personality in terms of four “humors,” including sanguine (social, extroverted, and fun-
loving), choleric (hot-tempered, quick-thinking, and strong-willed), melancholic (artistic,
introverted, and private), and phlegmatic (calm, easy-going, and con ict-averse). More
recent personality typing schemes, including the well-known Myers–Briggs Type Indicator,
similarly attempt to group people into distinct categories.
However, personality is best viewed through the lens of personality traits rather than
types. is is because personality characteristics (like basically everything else in psychiatry)
are not binary but rather exist on a spectrum. While qualitative personality types may do a
good job of explaining the extremes of personality, they do a poor job of capturing the
majority of people who live somewhere in the middle. For these people, more quantitative
personality traits (which better capture the nuances seen in real life) are preferred. For
example, someone who is extremely withdrawn socially and prefers to spend most of their
time alone could be called “an introvert” while someone else who is more outgoing and
tends to be the life of the party could be called “an extrovert.” However, most people fall
somewhere in between by spending some of their time with others and some time alone.
For these people, dimensional descriptions of personality do a much better job than discrete
categories.
ere are ve core personality traits (known as the ve factor model or the “Big
Five”) that have been shown to be both reliable and valid. ey are also remarkably stable
over time, staying consistent from childhood through adulthood and even into old age. In
addition, someone’s self-assessment of their scores on these traits is likely to agree with
ratings by signi cant others, family, friends, and healthcare providers. Finally, these traits
have each been shown to have a strong heritable component and have been replicated in
multiple different societies and cultures. ese traits can be represented by the acronym
OCEAN:
O is for Openness to experience. People who rate highly on measures of openness to
experience are generally imaginative and tend to be interested in novel experiences, whether
that involves the arts, travel, or new ideas. Conversely, those who score low on this trait
tend to be more conventional and traditional in their outlook.
 

C is for Conscientiousness. Conscientiousness is the tendency to act in accordance with

both personal and societal expectations, including following rules, working to meet goals,

263
and keeping things orderly. In general, people who are highly conscientiousness tend
towards planned behaviors (though they perhaps risk being overly rigid) while those who
are less conscientious are more often spontaneous and free-spirited (though they may risk
being impulsive or disorganized). Of note, low conscientiousness is associated with
disorders related to impulsivity and conduct (such as addiction and conduct-related
disorders) while high conscientiousness is correlated with depression and obsessive-
compulsive disorder.
 

E is for Extroversion. Extroversion (also spelled “extraversion”) refers to the tendency to

engage with others in the external environment. It exists on a continuum with introversion,
or a tendency to focus on one’s inner mental and emotional state. At its core, extroversion
means that you gain mental energy from interacting with others, while introversion means
that being with others depletes your mental energy. Because of this, extroverts tend to spend
more time with others while introverts need some time away from others to “recharge.”
 

A is for Agreeableness. Agreeableness refers to the priority that one places on getting along
with other people. ose with high agreeableness tend to place others’ interests ahead of
their own and are seen as helpful, kind, and trustworthy (though they may be more prone to
social pressure and groupthink as a result). In contrast, those who score low on
agreeableness tend to be less willing to expend effort to help others and may view other
people’s motives with skepticism or suspiciousness. Disorders related to conduct are more
common in people with low agreeableness while anxiety disorders are more common in
people with high agreeableness.
 

N is for Neuroticism. Neuroticism refers to the tendency to experience negative emotions

such as anger, sadness, and anxiety over positive emotions such as happiness, joy, and
contentment. People with high neuroticism tend to spend more time focusing on negative
stimuli in the present, thinking of mistakes from the past, and worrying about bad things
happening in the future. Because of this, people with high neuroticism are much more
vulnerable to stress (though they may also be more perceptive of reality as a result). On the
other hand, those who score low on neuroticism are less emotionally reactive and tend to
become upset less often. It’s important to note that low neuroticism does not mean a
perpetually positive mood; rather, it implies freedom from persistent negative moods.
Unsurprisingly, neuroticism is associated with both mood and anxiety disorders.
 

e ve factor model is a reliable and valid model

of personality traits.
 

OCEAN: Openness to experience Conscientiousness

Extroversion Agreeableness Neuroticism

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From a clinical perspective, assessing the Big Five personality traits does not often come
into practice directly (personality assessments are not routinely done in most psychiatric
clinics). However, understanding these personality traits will help to provide a better
perspective on what occurs when personality becomes disordered.

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SIGNS AND SYMPTOMS OF PERSONALITY DISORDERS
Personality disorders are a heterogeneous group of conditions that are ultimately more
different than they are alike. Traditionally, the DSM has categorized personality disorders
into three distinct groups: cluster A (the “weird” cluster of paranoid, schizoid, and
schizotypal personality disorders), cluster B (the “wild” cluster of borderline, antisocial,
narcissistic, and histrionic personality disorders), and cluster C (the “worried” cluster of
dependent, avoidant, and obsessive-compulsive personality disorders). Because personality
disorders differ signi cantly from one cluster to the next (and even from disorder to disorder
within the same cluster), we will wait until we discuss each personality disorder individually
to talk about the speci c associated signs and symptoms. For now, we will focus primarily
on the core features shared by all personality disorders—in essence, what makes any
personality disorder a disorder.
If personality is de ned as the enduring and consistent patterns of behavior, thought, and
emotion that an individual person shows, then a personality disorder is what happens when
those patterns becomes maladaptive. Personality disorders are not based solely on the
content of one’s personality—in other words, a personality disorder is not de ned by the
presence or absence of any particular personality trait. Instead, personality disorders are
de ned by the process by which those personality traits are expressed. Two key characteristics
of maladaptive personality traits are those that are in exible and extreme.

Most people have personality traits that,

while generally consistent, are exible depending on the situation. For example, someone
who is spontaneous and free-spirited may frequently bring joy to their group of friends with
their exciting and fast-paced lifestyle. However, they would likely still be able to reign in
their impulsive side in situations where this is necessary, such as being at work or giving
testimony in a court case. In contrast, someone with a maladaptively in exible level of
impulsivity may be spontaneous and careless in all areas of their life, which can make it
difficult for them to maintain relationships or hold a job.
In addition, maladaptive personality traits are de ned by how extreme they are. While
no personality traits are inherently “good” or “bad,” any personality trait can become
dysfunctional when taken to an extreme degree. As we will see soon, even traits that appear
mostly positive on the surface (such as conscientiousness or agreeableness) can lead to severe
dysfunction when taken to an extreme.
In contrast to normal aspects of personality, the in exible and maladaptive traits seen in
personality disorders are not only distressing to the individual but also to those around
them, resulting in signi cant social and occupational dysfunction. However, because these
traits are a core part of their personality (they are ego—syntonic), people rarely seek medical
attention saying, “ ere’s something wrong with my personality.” Rather, most people with
personality disorders come in complaining of depression, anxiety, or stress due the effects of

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their personality (such as con icts at work or a lack of close friends due to an inability to
hold relationships).

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PERSONALITY DISORDERS ACROSS THE LIFESPAN

Personality disorders are common, with a relatively high base

rate in the general population between 10 and 15%. However, in certain settings the
prevalence is even higher, with up to 25% of people in primary care clinics and up to 50% of
those in outpatient psychiatric settings meeting criteria for a personality disorder.
Personality disorders as a whole are also found with roughly the same frequency in both
men and women, although the gender ratio varies signi cantly between particular disorders
(such as antisocial personality disorder being more common in men while borderline
personality disorder is more common in women). However, in clinical settings, women tend
to be diagnosed more often than men (likely because the personality disorders that are more
common in women tend to come more often to medical attention while those affecting men
are more likely to be seen in legal settings).
 
PROGNOSIS
As with all things related to personality, the dysfunction seen in personality disorders is
chronic and enduring (rather than transient or episodic). e characteristic patterns of
disordered personality tend to develop early in life, with most people showing signs by their
teenage years if not earlier. Without treatment, personality disorders tend to remain,
although for some personality disorders (particularly those in cluster B) there is a natural
leveling off of symptom severity that occurs as one enters later adulthood and old age.
People with personality disorders tend to have higher rates of illness, disease, and even
death compared to their peers, with some estimates placing the decrease in life expectancy
as high as 20 years. Like with schizophrenia, the reasons for this gap in expected lifespan
are not clear, although higher rates of suicide and substance abuse, the deleterious effects of
chronic stress on one’s physical health, and the frequent lack of social support due to
difficulties in interpersonal relationships all likely play a role.
 
TREATMENT
Available evidence on effective treatment of personality disorders is severely lacking, as
personality disorders remain one of the most understudied groups of disorders in psychiatry.
e problem is compounded further by the fact that effective treatment tends to differ
signi cantly from one personality disorder to the next. However, what evidence exists tends
to suggest that personality disorders are difficult to treat. When treatment is used, it
appears that psychotherapy as a whole is signi cantly more effective than medications and
should be the primary form of treatment. Because personality disorders are chronic and
pervasive, treatment should be aimed at improving the speci c aspects of the personality
disorder that create the most distress and dysfunction (such as thoughts or behaviors that

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prevent meaningful work or social relationships from forming). If medications are used,
they should generally be seen as symptomatic (rather than curative) treatments.

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DIAGNOSING PERSONALITY DISORDERS
Correctly diagnosing a personality disorder is one of the most challenging tasks in
psychiatry. Because personality disorders are chronic and enduring conditions, they require
an understanding of the disorder across the lifespan (rather than just knowing how the
syndrome appears during an episode like with mood disorders). Many personality disorders
also have aspects of both a trait and a state which strongly in uence each other (for
example, someone with a personality trait of high neuroticism is more likely to nd
themselves in a state of depression).
is complexity is compounded further by the fact that the current diagnostic scheme
for personality disorders in the DSM-5 is, frankly, kind of a mess. e DSM does not base
its diagnoses on any speci c framework of personality like the OCEAN personality traits.
Instead, the theoretical framework for personality disorders in the DSM is based largely on
outdated psychological theories. Like a broken clock that happens to be right several times
a day, at times the DSM’s diagnostic scheme works, with some personality disorders
mapping neatly onto extremes of speci c traits (such as dependent personality disorder
being an extreme of agreeableness or obsessive-compulsive personality disorder being an
extreme of conscientiousness). For other personality disorders, however, the relationship
with OCEAN traits or any other validated theoretical framework is tenuous at best.
e DSM’s focus on symptoms (rather than the patterns underlying those symptoms) also
leads to personality disorder diagnoses that are highly comorbid with each other. In fact,
the majority of people diagnosed with one personality disorder will meet criteria for at least
2 others, with many meeting criteria for even more than that. is likely re ects a shared
tendency towards extreme and in exible personality traits rather than truly distinct
pathologies (even though the DSM treats them as separate). e problem of comorbidity is
further compounded by the fact that personality disorders are highly comorbid with other
mental disorders, including depression, bipolar disorder, anxiety disorders, addiction,
PTSD, and ADHD.

To further add to the challenge, personality disorders

are highly stigmatizing, making many clinicians reluctant to diagnose them. For a long
time, it was believed that by the age of 30 one’s personality had set “like plaster” and would
never soften again. is made giving a patient a diagnosis of a personality disorder akin to
sentencing them to a lifetime of an incurable and untreatable disease. However, recent
evidence suggests that, while changes are slower to happen after a certain age, personality
remains malleable over the entire lifespan. is means that personality disorders are no
longer a “life sentence,” and for certain conditions like borderline personality disorder, rates
of remission within 10 years exceed 80%.

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 e outdated notion that personality cannot change in adulthood was accompanied by the
equally incorrect idea that personality is completely uid during childhood. is idea made
clinicians similarly reluctant to diagnose personality disorders before the age of 18, as they
wanted to avoid diagnosing such a “permanent and unchanging disorder” at a time when
personality was thought to be entirely uid. However, just as we now know that personality
isn’t completely “hard” in adulthood, we also know that it isn’t completely “soft” in
childhood. While it is important to allow for variations in personality during childhood and
adolescence, it does a disservice to our patients to ignore clear signs of a personality disorder
(which would generally begin in childhood and adolescence) when they are present.
Finally, many clinicians avoid diagnosing personality disorders because people with
personality disorders can be difficult to work with. It is challenging for clinicians to set
aside their own feelings when working with patients who are often perceived as being
extremely self-centered (narcissistic personality disorder), manipulative (antisocial
personality disorder), rigid (obsessive-compulsive personality disorder), or clingy
(dependent personality disorder). Accordingly, many clinicians prefer not to work with
these patients or, if they do, to focus on speci c symptoms (such as insomnia or low mood)
that are seen as “treatable.” However, this can lead to a cycle of ineffective treatment, as the
presence of a comorbid personality disorder is a major risk factor for treatment failure when
trying to treat other conditions. Because of this, it is helpful to conceptualize the negative
feelings you may have towards a patient with a personality disorder (such as frustration,
rage, or annoyance) as being a direct result of their disorder. If the patient is making you feel
this way, it is likely that they are making everyone else in their life feel this way as well,
leading to fractured relationships and social isolation. In contrast, by determining the
correct diagnosis, educating the patient on what the diagnosis means, and using it to guide
appropriate treatments, you can make a huge impact on their ability to function in the
world.
Due to all of these challenges, personality disorders are often underdiagnosed compared to
other mental disorders such as depression, bipolar disorder, and schizophrenia. While some
people believe that they are doing patients a service by avoiding the potentially stigmatizing
diagnosis of a personality disorder, the fact of the matter is that doing so also deprives them
of the bene ts of diagnosis, including providing information about their prognosis,
predicting their response to treatment, allowing for referrals to evidence-based forms of
therapy, and relieving distress through psychoeducation. For personality disorders in
particular, a diagnosis often provides a helpful unifying framework for why someone is
experiencing multiple different types of symptoms at once.
 
PERSONALITY DISORDER CLUSTERS
As mentioned before, the DSM-5 groups its personality disorders into three main groups
which we will learn about now. However, it’s important to note that these clusters are based
more on super cial resemblances between the disorders than on actual shared pathological
processes. For example, cluster A personality disorders are grouped together because they
are most likely to resemble psychotic disorders such as schizophrenia. However, analysis of
the personality traits and genetic factors related to each has shown that they all have distinct
causes and etiologies despite the super cial resemblance each has to certain aspects of
psychotic disorders. is is a terrible way to categorize mental pathology, and when learning
about personality disorder clusters, you should not assume that these clusters re ect any sort
of shared genetic, symptomatic, or prognostic factors between the disorders within them.

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CLUSTER A PERSONALITY DISORDERS
Cluster A personality disorders include paranoid, schizoid, and schizotypal personality
disorders. As you might inter from their names, these disorders have the highest chance of
being misdiagnosed as psychotic disorders like schizophrenia due to some overlap in their
symptoms (at least on a super cial level) and their tendency to cause restrictions in affect
rather than the wild swings of emotion seen in cluster B personality disorders. In actual
practice, cluster A disorders rarely come to clinical attention as many of the disorders have
features that make people less likely to seek clinical care (such as pervasive distrust in
paranoid personality disorder, a preference for being alone in schizoid personality disorder,
and fear of social ostracism in schizotypal personality disorder).
 
PARANOID PERSONALITY DISORDER

Paranoid personality disorder is characterized by

a persistent pattern of fear, mistrust, and suspiciousness of other people. e level of
paranoia is often excessive and is directed towards most, if not all, of the people in their
lives. e predominant OCEAN personality trait in people with paranoid personality
disorder is extremely and in exibly low agreeableness. People with paranoid personality
disorder tend to become quite socially isolated, although given that they think that everyone
else is only out to get them, they say they don’t mind too much (even if they also commonly
report a sense of loneliness). In contrast to the paranoid delusions seen in primary
psychosis, paranoid personality disorder tends not to involve a single complex delusional
belief system. Instead, people with paranoid personality disorder are constantly jumping
around between multiple paranoid ideas without sticking to any one belief for too long,
suggesting a stable pattern of paranoia (even if the beliefs change too frequently to be
considered a stable delusion).
 
SCHIZOID PERSONALITY DISORDER

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 Schizoid personality disorder is characterized by a
consistent lack of interest in social relationships, which maps to the OCEAN trait of
extremely and in exibly low extroversion. People with schizoid personality disorder
commonly lead solitary lives and are aloof or detached from others. Unlike in avoidant
personality disorder (a cluster C personality disorder), this lack of social contact doesn’t
appear to bother them. is isn’t to say that people with schizoid personality disorder don’t
get lonely—sometimes they do, but they generally nd that being alone is preferable to the
constant demands for intimacy that others put upon them. Schizoid personality disorder is
often accompanied by other symptoms, including emotional coldness, restricted affect,
anhedonia, and apathy. In the absence of relationships, people with schizoid personality
disorder often develop a strong interest in ctional or fantasy worlds with which they
engage through imagination and media such as books and movies (although, unlike
schizophrenia, their ability to differentiate reality from fantasy remains intact).
 

People with schizoid personality disorder tend to

avoid social relationships and do not often seek out
the presence of others.
 

Schizoid avoids.
 
SCHIZOTYPAL PERSONALITY DISORDER
Schizotypal personality disorder is de ned by the presence of odd beliefs and difficulty
relating to other people that strongly resembles, though is not quite as impairing as,
schizophrenia. Like other cluster A personality disorders, schizotypal personality disorder
tends to lead to loneliness and isolation, although in this disorder the avoidance is often out
of fear that others will judge them for their odd beliefs, strange mannerisms, or
unconventional manner of dress.

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 Despite its classi cation in the DSM as a personality
disorder, in reality schizotypal personality disorder is not really a personality disorder. For
one, it doesn’t map to extremes of any speci c personality traits in the same way that
paranoid and schizoid personality disorders do. In addition, studies have shown that
schizotypal personality disorder is phenomenologically and genetically linked to
schizophrenia itself (unlike the other cluster A disorders which have only a super cial
resemblance to schizophrenia). Further reinforcing the idea of a link between those two
disorders is the fact that about a third of adolescents with schizotypal personality disorder
“progress” to a diagnosis of schizophrenia (whereas rates of progression to schizophrenia
from paranoid or schizoid personality disorder are no higher than the general population).
Based on these studies, it may be more accurate to think of schizotypal personality disorder
as a low-grade schizophrenia that, at least in some cases, has not yet “declared itself.”
Due to both schizoid and schizotypal personality disorder having “schizo-“ in their
name, it can be easy to confuse the two. You can remember that people with schizoid
personality disorder prefer to avoid other people while schiz-o-typal is a type-o’-schizo
that has clear links to schizophrenia.
 

Schizotypal personality disorder is genetically and

phenomenologically
related to schizophrenia.
 

Schiz-o-typal is a type-o’-schizo.

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CLUSTER B PERSONALITY DISORDERS
Cluster B includes borderline, narcissistic, histrionic, and antisocial personality disorders.
is cluster is sometimes known as the “wild” group due to the emotional instability
associated with them. Indeed, one of the core factors linking all cluster B personality
disorders together is a sense that one’s emotions are unbalanced. e involvement of
extreme emotional states makes these disorders commonly misdiagnosed as mood disorders
like depression and bipolar disorder. However, it’s important to realize that cluster B
personality disorders are not de ned by a single mood state in the same way as depression or
mania but rather by a tendency towards negative emotions (which maps to the OCEAN trait
of extremely and in exibly high neuroticism). is tendency manifests in chronic feelings
of dissatisfaction, anger, irritability, and sadness. Accordingly, people with cluster B
personality disorders often suffer from low self-esteem and an unstable sense of identity,
which is less surprising when you consider that cluster B disorders (with the exception of
histrionic personality disorder) have a strong statistical association with histories of
childhood abuse or neglect.
All personality disorders are not created equal, and those in cluster B deserve a greater
level of attention as they are the group that is most likely to come to clinical attention as a
primary diagnosis (rather than an ancillary diagnosis discovered by diligent clinicians
taking a thorough history). Because of this, we will cover these disorders in a greater level of
detail, including devoting the entirety of the next chapter to borderline personality disorder
as well as discussing different forms of antisocial personality disorder in Chapters 20 and
21.
 
BORDERLINE PERSONALITY DISORDER
Borderline personality disorder is a syndrome of chronic instability in multiple areas of life,
including poor emotion regulation, impulsivity, difficulty forming relationships, an
inconsistent sense of self, and impulsive or self-destructive behavior. Viewed through the
lens of the OCEAN personality traits, borderline personality disorder maps neatly to an
extreme and in exible trait of high neuroticism, including a disposition towards feelings of
anxiousness, depression, anger, and shame. Borderline personality disorder shares with other
cluster B disorders a strong desire for approval from others, an intolerance of criticism, and
a low sense of self-worth and identity. In many ways, it is the prototypical cluster B
personality disorder, and learning more about this condition (as we will in the next
chapter) will facilitate a deeper understanding of the other cluster B disorders.
 
HISTRIONIC PERSONALITY DISORDER
Histrionic personality disorder is de ned as a pattern of excessive or exaggerated behaviors
intended to draw attention to one’s self or to gain the approval of others. Speci c behaviors
include being very dramatic, irtatious, or sexually provocative as a way of commanding
attention. ese gestures, which can come across as shallow or manipulative to people
around them, appear to stem from an intense desire to be loved which is itself related to
poor self-esteem and an unstable sense of self. Histrionic personality disorder maps to an
extreme and in exible trait of high extroversion. It is four times as common in women as
men.

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 Histrionic personality disorder is the only cluster B disorder that
does not have a clear relationship to a history of childhood abuse. It is likely that people
with histrionic personality disorder share a similar diathesis to other cluster B disorders
(including the same underlying need for approval and desire to avoid rejection) but take a
different path in life due to a lack of major environmental stressors during development (like
childhood abuse). Because of this, histrionic personality disorder lacks the anger,
destructiveness, and inability to empathize seen in the other cluster B disorders. Overall,
the behavior of people with histrionic personality disorder can come across as obnoxious to
others, but it is seldom associated with severe impairment in the same way that the other
cluster B disorders are. For this reason, histrionic personality disorder is rarely given as a
primary diagnosis.
 
NARCISSISTIC PERSONALITY DISORDER
Narcissistic personality disorder is characterized by a pattern of exaggerated behaviors
intended to draw attention to one’s self, to gain the approval of others, or to make one’s self
appear superior to others. ese behaviors are often accompanied by an inability to
empathize with other people’s feelings, leading to trampling upon the emotions of others
(although not to the same extent as the reckless disregard for the rights of others seen in
antisocial personality disorder). e key to understanding narcissistic personality disorder is
that, while these individuals act or speak in a way that suggests that they see themselves as
the greatest person ever, this is an illusion as just below the surface lurks a pervasive sense of
insecurity and a debilitating fear that they are unloved. Accordingly, people with
narcissistic personality disorder often have difficulty tolerating criticism or not being the
center of attention. In this way, narcissistic personality disorder is revealed to be a
maladaptive way of arti cially in ating a sense of self-worth to mask an inner insecurity. It
is almost twice as common in men as in women.

276
 If this pattern sounds familiar after reading
about histrionic personality disorder, you are not far off. In a lot of ways, the core pattern of
narcissistic personality disorder is very similar to histrionic personality disorder in that both
are characterized by a sense of inner insecurity for which they make compensatory
attempts to gain attention or approval. In histrionic personality disorder, this takes the
form of dramatic, irtatious, or sexually provocative behaviors while in narcissistic
personality disorder it involves repeatedly boasting about one’s accomplishments or self-
worth. Based on this, some have hypothesized that histrionic personality disorder and
narcissistic personality disorder are essentially different expressions of the same core
disorder with the differences largely being mediated by culture-bound expectations for each
gender (such as Western cultures nding it more acceptable for women to engage in
sexually provocative behaviors while men are encouraged to brag or boast).
ANTISOCIAL PERSONALITY DISORDER

Antisocial personality disorder is characterized by a

persistent pattern of behavior that infringes on the rights of others, including purposeful
deception, aggression, theft, and violence. People with antisocial personality disorder are
often described as having no sense of loyalty and will use or manipulate others to get what
they want. Viewed through the lens of the OCEAN personality traits, antisocial personality
disorder is de ned by a combination of both low agreeableness and low conscientiousness.
In an attempt to make the diagnosis more reliable, the DSM has placed the diagnostic focus
for antisocial personality disorder exclusively on the supposedly objective presence of
frequent “bad behavior” without making reference to the less objective (though perhaps
more relevant) question of why someone is engaging in this behavior. After all, people
commit “bad behavior” for any number of reasons. For example, a man who frequently
steals from his work may be pilfering because he lives in poverty and has a hungry family, or
perhaps he suffers from an addiction to heroin and needs money to fuel his addiction, or
maybe he comes from a privileged background and instead steals for the “thrill” of it, or
possibly he never developed an inner conception of morality and views it as his right to take
things that do not belong to him. Because the reasons for “bad behavior” are so numerous,

277
it seems ludicrous to attempt to lump all of them together under a single diagnosis. Yet that
is what the DSM attempts to do, and the results are telling: antisocial personality disorder
as a diagnosis has very poor validity and little prognostic value.
It is only when you break down cases of antisocial personality disorder and separate them by
the reasons why someone engages in bad behavior that clear patterns begin to emerge. For
people who consistently and repeatedly engage in antisocial behaviors regardless of the
speci c circumstances, two consistent patterns are seen, known as psychopathic and non-
psychopathic forms of antisocial personality disorder. ese two patterns will be discussed
extensively in Chapters 20 and 21, but we will brie y go over them here.
People with psychopathic antisocial personality disorder are characterized by a distinct lack of
emotionality that manifests in indifference towards others and an absence of empathy or
remorse (together referred to as callous-unemotional traits). Antisocial behavior is often of
a greater severity and frequency than in non-psychopathic forms of the disorder and can
involve things like robbery, rape, and murder (rather than “just” anger outbursts and petty
theft). People with psychopathic forms of antisocial personality disorder are more likely to
engage in “cold-blooded” or instrumental violence with the goal of obtaining something
tangible (like killing a stranger to take their purse or wallet).
In contrast, people with non-psychopathic antisocial personality disorder engage in bad
behavior as a result of overemotionality, with a tendency towards affective instability and
negative emotional states in response to speci c interpersonal triggers such as feeling
rejected, devalued, or humiliated. People with non-psychopathic antisocial personality
disorder engage in aggressive behaviors as a way of externalizing negative emotions by
expressing them outwardly. ( is is in contrast to internalizing which is the process of
directing negative emotions inward towards the self, which instead results in disorders like
anxiety or depression.) In this way, non-psychopathic antisocial personality disorder reveals
the “cluster B-ness” that it shares with other disorders in its class, including the same
difficulties in interpersonal relationships (such as a need for attention and a fear of
abandonment) as well as disruptions in mood (including swings of emotion mixed with
chronic feelings of emptiness, boredom, meaninglessness, and alienation).

On a psychological level, most people with non-psychopathic

antisocial personality disorder do not go around trying to be “bad people.” Rather, most of
the violent or aggressive acts done by people with this disorder are done impulsively in
response to emotional triggers. However, this does not account for the whole picture. Many
people with non-psychopathic antisocial personality disorder also commit premeditated
acts such as stealing or defrauding others. ese acts are normally justi ed on the basis of

278
saying that “I need to look after myself because no one else will,” a rationalization that
makes more sense when you consider the history of both parental and societal neglect that
characterizes the backgrounds of many people with antisocial personality disorder.
Antisocial personality disorder is common, with as much as 5% of people having it.
However, in certain populations such as prisons or jails it is even higher, with up to 60% of
criminal inmates meeting criteria for the diagnosis. It is up to 5 times more common in
men than in women. By de nition, antisocial personality disorder cannot be diagnosed until
the age of 18. However, the majority of people with antisocial personality disorder have
concerning behaviors beginning in childhood and have often been previously diagnosed
with an externalizing disorder such as oppositional de ant disorder or conduct disorder
(both discussed more in Chapter 20).
As mentioned before, a diagnosis of non-psychopathic antisocial personality disorder has
little prognostic value. While a history of violence is by far the biggest risk factor for future
violence, once that is controlled for as a confounding variable, the presence of this diagnosis
does not independently predict a higher rate of future violence or criminal acts compared to
people who do not meet criteria for the diagnosis. (In contrast, psychopathic forms of
antisocial personality disorder are associated with a higher rate—up to 4 times greater—of
returning to violent criminal acts following release from custody.) Antisocial personality
disorder in either of its forms is considered to be a difficult mental disorder to treat, as no
medications or psychotherapies have consistently been shown to be effective at reducing
rates of reoffending, increasing life satisfaction, or improving one’s level of social or
occupational functioning. Treatment is limited further by the fact that people with
antisocial personality disorder often show very little motivation for treatment, as their
behavior is often ego-syntonic (they do not believe that their lives are deprived in any way
by their actions). Nevertheless, it is possible that better treatment paradigms will be
developed in the future, with some evidence suggesting that reinforcement-based behavioral
therapy may be more effective than the punishment-heavy approach that is used today.

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CLUSTER C PERSONALITY DISORDERS
Finally, we arrive at cluster C of the personality disorders which includes dependent,
obsessive-compulsive, and avoidant personality disorders. If cluster A disorders resemble
psychosis and cluster B disorders resemble mood states, then cluster C disorders resemble
anxiety. Because of this, the cluster C personality disorders are sometimes called the
“worried” group. However, just like in cluster A the similarities between the disorders in
this group are ultimately super cial, and their inclusion together should not make you think
that there is any shared genetic or phenotypic diathesis between them. In contrast to cluster
B disorders (which often come to clinical attention) and cluster A disorders (which rarely
come to clinical attention), cluster C disorders sometimes come to clinical attention.
 
DEPENDENT PERSONALITY DISORDER

Dependent personality disorder is characterized by an

overreliance upon other people in multiple areas of life. People with dependent personality
disorder often feel unable to live life on their own and instead rely on others for any number
of things, including making decisions (both large and small), having a sense of purpose, or
believing in their own self-worth. ey will often be extremely deferential in most of their
relationships in order to avoid even the slightest possibility of con ict. In the OCEAN
model, dependent personality disorder is conceptualized as an extreme and in exible trait of
high agreeableness. While at rst it may seem odd that high agreeableness could be
pathological, in reality even agreeableness can become maladaptive when present in extreme
forms, as trust becomes gullibility, cooperation becomes subservience, and thoughtful
consideration of others becomes subservience. Treatment of dependent personality disorder
is very poorly studied. In the absence of more concrete data, it seems reasonable to suggest
that treatment should be focused on addressing the cognitive biases that are found in the
disorder (including automatic thoughts like “I am weak and ineffectual”), addressing
relationship dynamics that contribute towards this pattern, and working towards promoting
independence and self-efficacy.
 

Dependent personality disorder is caused by

pathologically high agreeableness.
 

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 ink of someone who fake-laughs at all of your lame
jokes (HA-HA-HA) to avoid con ict. is person has
extremely High Agreeableness.
 
OBSESSIVE-COMPULSIVE PERSONALITY DISORDER
Obsessive-compulsive personality disorder (or OCPD) is characterized by intense
emotional and behavioral rigidity, resulting in a need for things to be controlled and
orderly at all times. Viewed through the lens of the OCEAN personality traits, this involves
extreme and in exible traits of high conscientiousness with low openness to new
experiences. is combination of traits manifests itself in an overreliance on structure (such
as rigidly adhering to a checklist to complete a task without ever questioning if the task
needs to be done in the rst place).
Despite having “obsessive-compulsive” in the name, this disorder does not involve
either obsessions or compulsions as de ned in Chapter 10. Instead, the rigid and repetitive
tasks that people with this disorder engage in are distinctly ego-syntonic. People with
obsessive-compulsive personality disorder truly feel that the way they are doing things is the
“right” or “correct” way to do them. In contrast, people with OCD have ego—dystonic
rituals that tend to cause feelings of distress rather than satisfaction. In this way, obsessive-
compulsive personality disorder more closely resembles anorexia nervosa (which we will
discuss more in Chapter 16), and some studies have found that over 50% of people with
anorexia meet criteria for obsessive-compulsive personality disorder. Don't let yourself get
confused: OCD and obsessive-compulsive personality disorder should be considered
separate syndromes despite the similarities in name, and obsessive-compulsive personality
disorder is a good candidate for renaming (“perfectionistic personality disorder” would be a
better t).
 

Obsessive-compulsive personality disorder is

characterized by rigidness and excessive adherence to
structure related to high conscientiousness.
 

OCPD = Overly Conscientious Personality Disorder

 
AVOIDANT PERSONALITY DISORDER
Like schizoid personality disorder, people with avoidant personality disorder are
characterized by their chronic avoidance of other people. However, what sets them apart is
that people with avoidant personality disorder still desire human companionship whereas in
schizoid personality disorder the interest is not even there in the rst place. What holds
people with avoidant personality disorder back from seeking companionship is a severe and
crippling sense of self-doubt and inadequacy which is often related to extreme sensitivity
to rejection.
Like schizotypal personality disorder, avoidant personality disorder is not really a
personality disorder. For one, it does not map clearly to extremes of any particular
personality traits. More telling, however, is the fact that the diagnosis is basically redundant,

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as the core symptoms of the disorder are almost exactly the same as those of social anxiety
disorder. In fact, studies have suggested that comorbidity between social anxiety disorder
and avoidant personality disorder is over 90% (and may even be as high as 100%). Shared
genetic vulnerabilities between the two disorders as well as signi cant overlap in treatment
(primarily SRIs and CBT) further support the hypothesis that avoidant personality disorder
is best conceptualized as a severe and chronic form of social anxiety disorder rather than as
a personality disorder.
 

Avoidant personality disorder is best conceptualized

as a severe and chronic form of social anxiety
disorder.
 

Avoid using avoidant personality disorder! Use social

anxiety disorder instead.

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DIFFERENTIAL DIAGNOSIS OF PERSONALITY
DISORDERS
As mentioned earlier, many personality disorders have speci c symptoms that resemble
nearly every other mental disorder. is makes them among the most chronically
misdiagnosed disorders in all of psychiatry. However, this also means that if you have a
good grasp of personality disorders, your diagnostic abilities in nearly every area of
psychiatry will improve. Because of this, pay careful attention to personality disorders when
learning about the differential diagnosis of each major class of mental disorders.
 
NORMALCY
All personality traits exist on a spectrum with normalcy, so normalcy should always be on
the differential when evaluating for a personality disorder. e key is to avoid xating on the
presence of any speci c personality traits and instead focus on the process by which those
traits manifest (such as being particularly extreme or in exible). Indeed, even supposedly
“good” personality traits like agreeableness and conscientiousness can go awry when present
to a severe degree (as in dependent and obsessive-compulsive personality disorders,
respectively). As with other mental disorders, use the presence of clear dysfunction as a
benchmark to determine whether personality pathology is actually present, and avoid using
the term pejoratively to refer to people whose personalities you might nd distasteful but do
not actually result in any dysfunction.
 
DEPRESSION AND MANIA
Mood disorders are most often confused for cluster B personality disorders due to the
involvement of emotional extremes. However, many people with cluster A or C personality
disorders also experience depression as a result of the impairments present in their
conditions (including social isolation or chronic worry). Mood disorders can easily be
differentiated from personality disorders in that they are episodic rather than chronic. In
addition, affect in personality disorders is often reactive to external events (versus being
non-reactive in depression or mania). Finally, it’s wise to be cautious with diagnosing a
personality disorder when someone is in an acute mood episode. Speci cally, the grandiosity
and in ated self-image seen during a manic episode can super cially resemble narcissism,
but unlike with narcissistic personality disorder, these characteristics will go away with time
or treatment. (In contrast, studies suggest that cases of borderline personality disorder that
are diagnosed during depressive episodes—provided they are based on the presence of
speci c signs and symptoms such as affective instability, non-suicidal self-harm, and
unstable relationships—are more likely to re ect enduring pathology rather than an
“artifact” of being in a depressive episode.)
 
PSYCHOSIS
While it makes sense that cluster A personality disorders would easily be confused for
psychotic disorders, it is not uncommon for cluster B personality disorders to be confused as
well. e aggressive behavior seen in antisocial personality disorder can at times be mistaken
for the agitated or paranoid states seen in schizophrenia, while the dissociative and paranoid
symptoms of borderline personality disorder can resemble psychosis as well. e lack of
other symptoms of psychosis (such as thought disorganization or negative symptoms) can

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help to clarify, as can the increased range of affect seen in cluster B personality disorders
(compared to the restricted range seen in schizophrenia).
 
ANXIETY
e personality disorders in cluster C are most often confused for anxiety disorders, though
anxiousness and worry are also found frequently in clusters A and B as well (especially in
the latter given their general tendency towards negative emotions). erefore, careful
assessments for symptoms of anxiety is warranted in most people who have a personality
disorder.
 
OBSESSIVE-COMPULSIVE DISORDERS
As discussed previously, obsessive-compulsive personality disorder should be carefully
distinguished from OCD and its related disorders, as they differ signi cantly in
phenomenology, prognosis, and treatment response despite having a similar name.
Determining whether rigid behavior (which is seen in both conditions) results from ego—
syntonic or ego—dystonic thoughts can be illuminating (with the former being seen in
obsessive-compulsive personality disorder and the latter being seen in OCD).
 
TRAUMA
A history of trauma is associated with most personality disorders, although the presence of
extended abuse or neglect (especially in early childhood) is most strongly associated with
cluster B personality disorders. For this reason, keep personality disorders on the differential
when evaluating someone with traumatic complaints or other related conditions such as
dissociation or somatization (and vice versa).
 
ADDICTION
Most personality disorders are associated with higher rates of substance use, so keep this on
your differential to avoid addiction becoming a “missed diagnosis” that is interfering with
effective treatment.
 
EATING DISORDERS
Both major forms of eating disorders (anorexia nervosa and bulimia nervosa) are strongly
linked to speci c personality disorders. Anorexia shares phenomenological and genetic links
to obsessive-compulsive personality disorder, while bulimia is associated with cluster B
personality disorders in the vast majority of cases.
 
ATTENTION DEFICIT HYPERACTIVITY DISORDER
Cluster B personality disorders share a high degree of impulsivity with ADHD, making it
easy to confuse them. Diagnostically, the boundaries between the two disorders are not
entirely clear, and rates of comorbidity are high. In general, you should avoid giving a
comorbid diagnosis of ADHD unless there is clear evidence that the dysfunction started in
childhood, and a diagnosis of a personality disorder should be avoided in someone who is
merely impulsive unless the other signs and symptoms characteristic of personality
pathology are present.

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PUTTING IT ALL TOGETHER
Personality disorders are one of the most challenging groups of disorders to study. is is
largely because no other category of disorders attempts to lump so many disparate and
unrelated conditions into a single category. Even past attempts to draw some connections
between the disorders (including the “cluster” system used by the DSM) seem to introduce
more problems than they solve. e best unifying framework appears to be the OCEAN
model of personality traits which provides an explanatory framework for some personality
disorders including low agreeableness in paranoid personality disorder, low extroversion in
schizoid personality disorder, high neuroticism in borderline personality disorder, high
extroversion in histrionic personality disorder, low agreeableness with low conscientiousness
in antisocial personality disorder, high agreeableness in dependent personality disorder, and
high conscientiousness with low openness to new experiences in obsessive-compulsive
personality disorder. However, this model doesn’t capture schizotypal or avoidant
personality disorders which instead appear to be related to other existing psychiatric
conditions (schizophrenia and social anxiety disorder, respectively).
Because of the high variability between each personality disorder, it hasn’t been possible to
delve deeply into each condition the same way we have with the other disorders we have
discussed so far. However, there is some comfort in knowing that with personality disorders
in particular it is not so important that you remember each and every individual symptom of
the disorder. You’ll notice that there aren’t a lot of mnemonics in the style of SIGECAPS or
DIG FAST in this chapter, and that is because using a “cookbook” approach for personality
disorders is largely a waste of time. Rather, focus on the underlying process of extreme and
in exible personality traits seen in each disorder, and the other pieces will fall into place.

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REVIEW QUESTIONS
1. A 45 y/o M comes to see a psychotherapist specializing in relationship issues. He
tells the therapist at the beginning of the appointment, “I’ve read a lot about you
and believe that you are the most quali ed person to help me right now.” He works
as an entrepreneur and has been very successful in various aspects of his life,
including winning several marathons in the past few years. He is nancially well-
off and is able to afford the $500 hourly rate that the therapist charges. He
describes himself as an “incredibly competent” person who has “many, many
friends—if you can’t tell already, people like to be around me.” His company is
“one of the best, I’m sure you’ve heard of it. We’re constantly making headlines.”
His primary concern right now is his relationship with his wife whom he says
“doesn’t appreciate me for who I am.” ey have been married for 12 years. Early
in their relationship, his wife was “very subservient and demure,” but recently she
has begun “talking back to me and belittling me all the time” which infuriates him.
ey have not had sex in over 3 years, and he has had “literally dozens” of sexual
partners over this time period without his wife’s knowledge or consent. He
describes his wife’s current behavior as being similar to his mother who was
frequently critical of him throughout his childhood. He asks the therapist, “I feel
like I can do better than my wife. I am used to having the best at work. Why can’t
I have the best in my marriage?” As the 90-minute time slot is running out, the
therapist attempts to interject and bring the session to a close; however, the patient
continually interrupts, leading to the session running 30 minutes over and making
the therapist late for his next session. As the therapist is ending the session, he
asks the patient to bring in his wife to the next appointment. e patient replies by
saying, “Why? Don’t you trust what I am telling you? If you can’t take me at face
value, then you’re not the therapist I thought you were, and I will be going
elsewhere.” e therapist watches the patient leave her office and return to his car
to discover a parking ticket on the window. He immediately rips it up and throws
it in the trash. As he backs his sports car out of the parking spot, he hits another
car’s bumper and leaves a dent; however, he then drives off without getting out to
inspect the damage or leaving a note. Which of the following statements is most
likely to be true of this patient’s case?
A. He is likely to meet criteria for more than one personality disorder
B. He was almost certainly abused as a child
C. His company is unlikely to be as successful as he claims
D. His wife likely believes that their relationship is “ ne”
E. None of the above statements are likely to be true
2. (Continued from previous question.) Which of the following would most argue for
a diagnosis of bipolar disorder in this case?
A. Being arrested for a hit-and-run
B. Going from laughing one minute to crying the next
C. A history of having seen a therapist for a year in high school
D. Coming in 3 months later with none of the same signs
E. Reporting current symptoms of depression
3. A 38 y/o F presents to her therapist complaining of “stress” and a desire to “ x my
husband.” She is a stay-at-home mother and says that she tries to be the “best

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 mom I can be for my kids.” She spends several hours a day researching the
nutritional information for all food she packages for her children and ensures that
the meals not only follow the age-speci c recommended ratios for fat,
carbohydrates, and protein but also are arranged in a variety of fun shapes. She
sometimes stays up until 2:00 or 3:00 in the morning working on making sure that
each lunch is perfect, saying, “It’s how I show my love to my children.” Despite her
children’s requests, she does not permit them to eat candy or dessert at any time,
saying, “ at stuff is grade A garbage.” In regards to her husband, she says that “he
needs help” as he has called off work three times over the past year “when he’s not
even sick!” She has extensively researched this behavior online and has concluded
that he is “a malingerer” and that he “needs to seek psychiatric help but won’t do it,
so I’m coming in on his behalf.” When asked, she says that neither she nor her
husband have taken a vacation since they had children 10 years ago, as “it’s best for
children to be raised in a consistent environment.” She says, “Sometimes I feel like
I’m the only one holding this ship a oat, and if I stop for even one second then
everything will fall apart.” She describes constant muscle tension and says that she
often feels like yelling at other people, although she will only yell at her husband
“because he made a vow saying that that was okay.” She denies that she needs
psychiatric help of any kind, saying, “I told you, there’s nothing wrong with me.
I’m just here on behalf of my husband who is too lazy to help himself.” Which of
the following quotes from the vignette most argues for a diagnosis of obsessive-
compulsive personality disorder over an anxiety or obsessive-compulsive disorder?
A. “Sometimes I feel like I’m the only one holding this ship a oat, and if
I stop for even one second then everything will fall apart.”
B. “[Candy and desserts are] grade A garbage.”
C. “[Making perfect lunches] is how I show my love to my children.”
D. “I told you, there’s nothing wrong with me. I’m just here on behalf of
my husband who is too lazy to help himself.”
E. “It’s best for children to be raised in a consistent environment.”
4. Which of the following personality disorders is incorrectly paired with its
corresponding personality trait?
A. Dependent personality disorder – High agreeableness
B. Avoidant personality disorder – Low extroversion
C. Borderline personality disorder – High neuroticism
D. Paranoid personality disorder – Low agreeableness
E. Histrionic personality disorder – High extroversion
F. All of the above are correctly paired

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1. e best answer is A. is patient shows signs of narcissistic personality disorder
including excessive self-praise, grandiose statements, and interpersonal
exploitation. People with one personality disorder often meet criteria for another,
and narcissistic personality disorder is no exception. While a history of child abuse
is more common in cluster B disorders, it is by no means almost certain (answer
B). In addition, while many people with narcissistic personality disorder will
exaggerate their claims, the disorder does not preclude them from being highly
successful, and it should not be assumed that he is making up or embellishing the
success of his company (answer C). People with narcissistic personality disorder
often have dysfunctional interpersonal relationships, and it is likely that his wife
believes there is a problem in their relationship, possibly even mores than the
patient does (answer D).
2. e best answer is D. Narcissistic personality disorder can occasionally be
confused for bipolar disorder, as some of the same signs can be found in both.
However, the key is to look at the timing of the signs and symptoms as these will
be enduring in narcissistic personality disorder and episodic in bipolar disorder.
erefore, for the patient to return in 3 months with none of the same symptoms
would strongly suggest bipolar disorder. Reckless behavior (answer A), onset of
symptoms during adolescence (answer C), and comorbid depressive symptoms
(answer E) can all be found across both disorders, while affective lability is more
characteristic of cluster B personality disorders than bipolar disorder (answer B).
3. e best answer is D. is patient is likely suffering from obsessive-compulsive
personality disorder as evidenced by her high degree of conscientiousness in
combination with her rigid and controlling behavior. Obsessive-compulsive
personality disorder is notably ego-syntonic, so her continued insistence that there
is nothing wrong with her is most consistent with this diagnosis. Feeling like the
only person holding everything together can be seen in cases of obsessive-
compulsive personality disorder but can also be found in anxiety disorders as well
(answer A). In exibility in choosing food for others can sometimes be found in
anorexia nervosa, which is frequently comorbid with obsessive-compulsive
personality disorder; however, it is not inherently suggestive of the disorder
(answer B). Neither showing love for children through spending extra effort on
making school lunches nor wanting children to be raised in a consistent
environment are inherently pathological, and neither argue for a diagnosis of
obsessive-compulsive personality disorder (answers C and E); however, in the
context of in exible and rigid behavior (such as staying up late each night making
the lunches or desiring consistency to the extent that the children are never
exposed to new experiences such as a vacation) these can be signs of pathology.
4. e best answer is B. Avoidant personality disorder does not map neatly to an
extreme or in exible personality trait and is best conceptualized as a severe
manifestation of social anxiety disorder. Instead, low extroversion is most
characteristic of schizoid personality disorder. All of the other personality disorders
are correctly paired with their corresponding traits.

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13 BORDERLINE
Borderline personality disorder is a complex syndrome of speci c signs, symptoms, and
behaviors that result in chronic instability in multiple parts of one’s life, including
emotions, identity, relationships, and motivation. In many ways, it can be seen as the
prototypical cluster B personality disorder, and you may often hear the term “cluster B”
used nearly synonymously with borderline personality disorder, as the persistent and
enduring forms of dysfunction seen in this condition epitomize the difficulties faced by
people with other cluster B diagnoses.
Borderline personality disorder is among the most challenging conditions in all of
psychiatry, both in terms of diagnosis and treatment. e signs and symptoms of the
disorder cover a vast array of symptoms and can easily be confused for just about every other
psychiatric diagnosis, making it the great imitator of mental health. In addition, working

with people who have bor derline personality disorder can be

emotionally demanding, as the core features of the disorder (such as hostility,
destructiveness, and impulsivity) can make maintaining a therapeutic relationship with
someone who has the disorder a major challenge. However, it is helpful to keep in mind
that these difficulties in the patient-provider relationship are a core feature of the disorder
itself. Just as it would be ludicrous to give up on working with a person who has
schizophrenia because they “kept hearing voices,” so too is it ridiculous for clinicians to
avoid patients with borderline personality disorder because of their persistent difficulties in
interpersonal relationships. At the end of the day, people with this condition deserve the
same level of compassionate and evidence-based care as anyone else despite the challenges
that the disorder presents. To help prepare you as much as possible to approach this
condition with clarity and compassion, we will spend quite some time understanding
borderline personality disorder.

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SIGNS AND SYMPTOMS OF BORDERLINE PERSONALITY
e range of signs and symptoms that can be attributed to borderline personality disorder is
vast. In fact, the word “borderline” was initially used to describe this syndrome because it
was seen to be at the border between psychotic disorders like schizophrenia and neurotic
disorders such as depression by encompassing aspects of each. Because of this, the range of
symptoms covered by borderline personality disorder can seem overwhelming and difficult
to tell apart from the other disorders that we have studied so far.

Despite the wide variation in symptoms, however, there are

a few broad themes that emerge. ese core symptom domains can be encapsulated in the
mnemonic phrase “Unstable waters make for HARD SHIPS to steer.” e word unstable
should help you associate borderline personality disorder with instability, as many of the
symptoms are characterized by their consistent instability (you might even say that they are
“stably unstable”). Instability is so core to the disorder that other diagnostic schemes (such
as the World Health Organization’s ICD coding system) refer to the syndrome not as
borderline personality disorder but as “emotionally unstable personality disorder.”
We’ll go over each of the symptom domains in the HARD SHIPS mnemonic one by
one. ese symptom domains are highly interrelated, and we will make frequent references
between symptom domains as we explore each one.
 

H is for Hostility. Hostility and anger are hallmark emotions of

borderline personality disorder. People with borderline personality disorder have a strong
tendency towards negative emotions (they routinely score very high on personality
assessments of neuroticism) which makes anger, irritability, and hostility among the most
common emotions experienced by people with borderline personality disorder on a daily
basis (“I hate you! I wish you had never come into my life, you asshole!”). However, it’s also
important to point out that not all people with borderline personality disorder have overt or
obvious expressions of anger and hostility. While some people with the condition are

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frequently yelling or engaging in aggressive behavior, other “quiet borderlines” instead hold
these emotions inside and do not express them. is makes outward displays of anger a
marker of the disorder that is not very sensitive, although even “quiet borderlines” will tend
to report frequent angry or hostile thoughts when asked.
 

A is for Affective instability. e emotional state of individuals with borderline personality

disorder is characterized by sudden and drastic swings between extremes of emotion known
as affective instability. People with borderline personality disorder can easily “ y off the
handle” and may quickly go from laughing to crying to yelling to worrying and back again.
ese shifts tend to happen within seconds or minutes, which helps to differentiate them
from the mood changes in depression and mania which occur over weeks or months.
People with borderline personality disorder also feel emotions very strongly and have
been said to experience “grief instead of sadness, humiliation instead of embarrassment, rage
instead of annoyance, and panic instead of nervousness.” ( is is not to suggest that people
with borderline personality disorder cannot experience positive emotions as well—they
absolutely do and will feel those strongly as well, such as elation instead of happiness or
extreme pride instead of contentment.) Changes in affect are often precipitated by
interpersonal events, either positive (such as being thrown a surprise birthday party) or
negative (like being stood up for a date). ese emotional responses can often come across
as wildly out of proportion to the actual events that prompted them, at least to an outside
observer. For this reason, living with affective instability can be incredibly disorienting not
only for the person experiencing these emotional shifts but also for those around them,
leading to confusing and unstable relationships.
 

R is for Relationships. Relationships are difficult for people with

borderline personality disorder. ey often show a pattern of short-lived and unstable
relationships with all but a few people in their lives. Difficulty in relationships involves not
only romantic relationships but also other types as well, including family, friends, and co-
workers. ere are several patterns that help to explain why people with borderline
personality disorder tend to have unstable relationships. For one, like in other cluster B
disorders people with borderline personality disorder are extraordinarily sensitive to
interpersonal rejection. While being rejected, dumped, or abandoned doesn’t feel good for
anyone, people with borderline personality disorder often react to these circumstances in an
extreme way and may lash out with angry or violent behavior, threaten suicide, engage in

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self-harm, or ask to go to a monitored environment (such as a hospital) in order to feel safe.
Because being rejected is such an aversive feeling for people with borderline personality
disorder, they will often engage in frantic efforts to avoid abandonment (“If you leave me, I
will take this knife and kill myself, I swear it!”). Much of the interpersonal rejection
sensitivity that people with borderline personality disorder experience is likely related to a
fundamental intolerance of being alone, as these individuals often rely upon others to feel a
sense of identity and to lessen feelings of chronic dysphoria. Relationships for people with
borderline personality disorder are also complicated by their tendency to see the world in
extreme or black-and-white terms, known as splitting. Friends, relatives, and healthcare
providers interacting with people with borderline personality disorder often nd themselves
on one side or the other of a split: they are either “the best person ever” or “the cruelest
person ever to walk the face of the earth.” is overall pattern of unstable relationships
involving extremes of idealization and devaluation is both highly sensitive and highly
speci c for the disorder, with a sensitivity of 75% and a speci city over 85%.
D is for Dysphoria. Dysphoria is a state of profound internal pain or emotional aching that
is found in basically all people with borderline personality disorder, with some studies
estimating a frequency of nearly 100%. Chronic dysphoria is often described as persistent
feelings of “emptiness” or being “lost.” is sensation is typically accompanied by a sense of
boredom, alienation, apathy, despair, and anhedonia (“I feel like I don’t belong anywhere on
the earth.”). Dysphoria differs from depression and dysthymia in that it is a reactive state
whereas depression and dysthymia are generally non-reactive to circumstances. Dysphoria is
often quite stable and is found across the lifespan (in contrast to other symptoms of
borderline personality disorder, such as impulsivity and self-harm, that tend to “burn out” as
time goes on). Because of this, chronic dysphoria can be seen as an enduring hallmark of
the disorder, making it a sensitive marker of the diagnosis.
 

S is for Self-image. Many people with borderline

personality disorder have an unstable identity that manifests in an unclear or inconsistent
sense of self and purpose. While everyone has aspects of their personality that change
depending on the time and circumstances, most people are able to see these seemingly
contradictory states as still being rooted in the same core identity. In contrast, people with
borderline personality disorder have difficulty seeing themselves as the same consistent
person throughout their lives. Instead, their sense of identity may change entirely
depending on whom they are around, such as appearing to like particular hobbies when
they are with one group of friends but then showing no interest in those same activities on
their own. is manifests in a lack of long-term goals which leads to an agonizing sense of

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purposelessness or “drifting” over time known as painful incoherence. is fragmentation
of self-image is likely related to the feelings of depersonalization seen in dissociative states
which explains the strong association between dissociative disorders and borderline
personality disorder.
 

H is for Harm. People with borderline personality disorder often engage in self-destructive
behaviors that directly lead to harm. Self-harm can include overt suicide attempts (such as
overdosing on medications) but more often involves non-suicidal self-injury (such as
repeatedly making shallow cuts on their arms with no clear intention of actually wanting to
die). e question of why people with borderline personality disorder repeatedly hurt
themselves can seem initially like a difficult one to answer. However, some research suggests
that people with the disorder self-harm as a way of managing psychological pain, as cutting
actually appears to relieve suffering rather than exacerbate it. Interestingly, rates of self-
injurious behavior correlate strongly with one’s tendency to dissociate, suggesting that
cutting may actually act as a catalyst for allowing someone to mentally distance themselves
from emotional pain. While self-harm is neither perfectly sensitive nor speci c for
borderline personality disorder, a history of non-suicidal self-harm should put this disorder
high on your differential. People with borderline personality disorder also have frequent
suicidal thoughts or intentions. However, in contrast to the episodic suicidality seen in mood
disorders, people with borderline personality disorder are chronically suicidal. is makes
the decision to hospitalize someone more difficult than with depression or bipolar disorder,
as suicidality in borderline personality disorder tends to be more of a constant rather than a
modi able risk factor.

I is for Impulsivity. Emotions drive behavior, so it is no surprise that someone with extreme
and erratic emotions would also engage in extreme and erratic behavior. People with
borderline personality disorder have a tendency to act quickly without fully considering
the consequences of their actions, leading to substance abuse, unsafe sex, reckless driving,
loss of jobs, running away from home, lashing out at others, and frequent self-harm. is
also manifests in a higher rate of comorbid disorders that are also characterized by
impulsivity such as addiction and bulimia nervosa. ere is often an element of
compulsivity as well, as many of these actions help to temporarily relieve the chronic state of

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dysphoria. However, the negative consequences of impulsive behaviors often end up
exacerbating the pain even further, leading to a vicious cycle. Like hostility, impulsivity is
frequently associated with borderline personality disorder but tends to “burn out” as people
get older, so the absence of impulsivity should not rule out this diagnosis.
 

P is for Psychosis-like symptoms. Up to half of all people with borderline personality

disorder will experience symptoms that appear psychotic in nature at some point in their
lives, including auditory hallucinations, paranoia, and delusions. However, while these
symptoms super cially resemble those seen in schizophrenia, they ultimately do not t the
known phenomenology of primary psychosis. For example, people with borderline
personality disorder who experience auditory hallucinations will say that the voices are inside
their heads or that they are vague. e psychosis-like symptoms experienced by people with
borderline personality disorder are often transient and tend to occur primarily in times of
severe interpersonal stress; when the stress decreases (often in several hours or days), the
symptoms will remit as well. ( is is in stark contrast to a disorder like schizophrenia where
auditory hallucinations are persistent and only somewhat related to stress, if at all.) Paranoid
ideation does not typically involve complex delusional belief systems as in schizophrenia but
rather is more often related to extreme interpersonal sensitivity (“I think my classmates are
spying on me just to laugh at what a failure I am.”).
 

S is for Somatization. Borderline personality disorder is associated not only with persistent
emotional pain but also with chronic physical pain and distress as well. People with the
disorder tend to report higher than average levels of pain, and around a third of all people
with chronic pain are also diagnosed with borderline personality disorder. People with this
disorder also frequently experience medically unexplained symptoms, leading to a high rate
of comorbid somatoform disorders. Clinically, you should consider the possibility of
borderline personality disorder in patients presenting with chronic pain or unexplained
symptoms.
Borderline personality disorder is characterized by
chronic instability in the
domains of mood, affect, behavior, relationships,
and identity.
 

Unstable waters make for HARD SHIPS to steer:

Hostility Affective instability Relationships Dysphoria
Self-image Harm Impulsivity Psychosis-like
Somatization

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BORDERLINE PERSONALITY ACROSS THE LIFESPAN
While all personality disorders require an understanding of the illness across the lifespan,
borderline personality disorder is signi cantly more complicated because its symptoms can
present clinically not only as a trait but also as a state. For example, you may see someone
coming into the hospital in a state of extreme distress after cutting themselves repeatedly
following a break-up. However, if you saw them several months later, these state-speci c
behaviors would not necessarily be present. At that time, they may instead present with
feelings of emptiness and dysphoria (the chronic traits of the disorder). Perhaps the best
analogy with another condition can be drawn with schizophrenia, which is similarly
characterized by chronic de cits with occasional exacerbations. Also like schizophrenia,
the most well-known symptoms of borderline personality disorder (including impulsivity,
hostility, and dramatic suicidal gestures) are very speci c for the disorder but tend to be
present primarily in the early stages of life such as adolescence or young adulthood. In
contrast, the chronic and enduring features of the syndrome are often present throughout
life and are associated with signi cant and lasting dysfunction, making them sensitive
markers of borderline personality disorder no matter what stage of the disorder the patient
is in.
Borderline personality disorder is relatively common, with between 5 and 10% of the
population showing signs and symptoms that are severe enough to cause dysfunction. In
populations of people seeking mental health treatment, borderline personality disorder is
signi cantly more common and may account for up to one-third of all patients in an
outpatient psychiatric clinic. is high prevalence combined with the fact that it is a chronic
rather than episodic disorder gives it a high base rate and makes it liable to underdiagnosis
rather than overdiagnosis.
Borderline personality disorder is commonly associated with women, and it tends to
be diagnosed in women three times as often as men in clinical settings. However, recent
research suggests that borderline personality disorder affects men and women equally. e
historical association of borderline personality disorder with women appears to be related to
the fact that women are more likely to seek medical and psychiatric care in general, leading
to higher rates of clinical diagnosis. However, when men have borderline personality
disorder, they are more likely to come to clinical attention for substance abuse or reckless
behavior which are more often treated in legal settings than medical ones. ere is also
reason to believe that the diagnostic criteria for borderline personality disorder themselves
may be biased towards a greater rate of diagnosis in women, as nearly all features of the
disorder (with the exception of hostility) are seen as being more common in women than
men. Because of this, gender should not play a large role in evaluating the likelihood of a
diagnosis of borderline personality disorder despite the long-standing historical associations
with women.
Like other personality disorders, signs and symptoms of borderline personality
disorder most often begin in adolescence (although onset either earlier in childhood or
later in young adulthood is not uncommon).
 
PROGNOSIS
Conventional wisdom has long held that borderline personality disorder is a chronic and
unchanging diagnosis. is makes clinicians quite reluctant to diagnose it, as it was felt that
assigning the diagnosis would “doom” the patient to a lifetime of misery and distress.

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However, systematic studies that have followed people with borderline personality disorder
over decades have revealed that the condition is not persistent and unchanging. In fact, 50%
of people who initially meet criteria for the diagnosis no longer do by 2 years, with 85%
being in remission by 10 years even without treatment. e fact that the majority of people
enter remission from the disorder strongly argues against the idea that it is an
unchangeable condition.
Looking more closely at the data, however, it appears that complete remission from
symptoms is quite rare. e more intense and dramatic symptoms (including impulsivity,
self-harm, and overt hostility) tend to remit, but others remain (including affective
instability, chronic feelings of emptiness, somatoform complaints, difficult relationships,
and issues with self-image). Because of this, even if people no longer technically meet DSM
criteria for borderline personality disorder, this does not mean that they are completely
“free” from the disorder, a fact which is re ected in lower than average rates of employment
and life satisfaction even after remission. While the prognosis for borderline personality
disorder is not as bad as it was once thought to be, there is often some level of persistent
dysfunction even after active symptoms have disappeared.
 
TREATMENT

Borderline personality disorder is a treatable condition, with

psychotherapy being by far the most effective modality of treatment. Studies have shown
that speci c forms of psychotherapy that are geared towards patients with borderline
personality disorder appear to be the most helpful. e most well-known of these is
dialectical behavior therapy (DBT) which teaches speci c cognitive and behavioral skills to
allow people with borderline personality disorder to better regulate their emotions, tolerate
distress, avoid splitting, and reduce impulsive or self-destructive behaviors. In well-designed
studies, dialectical behavior therapy has been shown to decrease rates of self-harm, suicide
attempts, and hospitalizations. Other forms of therapy for borderline personality disorder
such as mentalization-based treatment have been shown to work as well. e downside of
these treatments is that they tend to be costly and time-consuming, often requiring one to
two years in specialized treatment before meaningful and sustained effects are observed.
While specialized forms of treatment like dialectical behavior therapy can be incredibly
helpful, the fact remains that the vast majority of people with borderline personality
disorder are seen in general psychiatric or medical settings, making it essential for all
clinicians to have speci c principles on which they can rely to guide treatment. e
following interventions can be practiced by any healthcare provider who believes that the
patient they are treating has borderline personality disorder and could bene t from
treatment. e mnemonic DEEP SALT can help you to remember what to do when
working with a patient who has borderline personality disorder:

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 D is for Diagnose. Most providers’ initial tendency is to
avoid a diagnosis of borderline personality disorder and instead focus on speci c symptoms
(like depression or anxiety) that are seen as “more treatable” or “less stigmatizing.” Do not
give into this impulse. Telling your patient about the diagnosis and the reasons why you
believe they likely have it is one of the most helpful things you can do, as it provides a
unifying framework for the multiple concerns (like depression, chronic pain, difficulty
holding a job, and unstable relationships) that the patient likely has. It also helps both you
and your patient to avoid spending years trying treatments that work for other people (such
as antidepressants) but are known to be ineffective for people with borderline personality
disorder.
 

E is for Educate. Educating a patient on borderline personality disorder and its relationship
to extreme interpersonal sensitivity provides a helpful explanatory model that allows them
to place their symptoms in context when they experience them.
 

E is for Expect change. Make it clear to the patient from the outset that you are committed
to helping them change whatever they are most concerned about (whether that is depressed
mood, persistent anxiety, frequent self-harm, or repeated suicide attempts). However, you
must also make it clear that you will not be the sole source of change and that you will
expect meaningful efforts from the patient in exchange for providing guidance about
treatment options.
 

P is for Prioritize. e majority of people with borderline personality disorder meet criteria
for multiple other conditions as well, including depression, anxiety, PTSD, dissociation,
somatization, bulimia nervosa, and more. Because of this, it becomes essential to prioritize
all of their conditions and triage which ones should receive treatment rst. As a general rule
of thumb, treatment of borderline personality disorder should take priority over most other
conditions, as active symptoms of borderline personality disorder tend to prevent adequate
treatment of comorbid conditions such as depression or anxiety. However, there are a few
exceptions to this, including active substance abuse, acute mania, and severe eating disorders
(all of which may represent an immediate threat to health or would interfere with the ability
of the patient to engage in therapy).
 

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S is for Safety plan. Given the high rates of suicidality, self-harm, and reckless behavior
seen in borderline personality disorder, coming up with a good safety plan is essential.
Determine the patient’s current level of safety, then make plans for what to do if the patient
develops an acute crisis, including explaining when it is (and is not) appropriate to go to the
hospital or call 911.
 

A is for Avoid medications. Medications should generally be avoided for patients with
borderline personality disorder, as a higher number of medications often predicts a lower
chance of clinical improvement. If medications must be used, they should only be for
symptomatic treatment of speci c symptoms (such as insomnia or impulsivity) rather than
being seen as something that will fundamentally alter the trajectory of the condition.
Anticonvulsants and antipsychotics are the most frequently used medications, with
anticonvulsants helping to reduce anger and impulsivity and antipsychotics helping to
alleviate paranoid or dissociative symptoms.
 

L is for Life outside of treatment. Because the effects of borderline personality disorder can
often extend into every area of someone’s life, you can and should provide guidance on
things besides just therapy and medications. Inquire about the patient’s life outside of
treatment, encourage them to engage in work or volunteering activities that they nd
meaningful, and support the development of healthy interpersonal relationships.
 

T is for erapy if possible. All patients with borderline personality disorder should be
encouraged to engage in therapy (preferably one that is speci c to the disorder like
dialectical behavior therapy or mentalization-based treatment). However, these forms of
intensive treatment are not always available due to cost, location, or other factors. In that
case, consider other forms of therapy (such as supportive therapy or CBT) which can also
be helpful for teaching coping skills and treating individual symptoms.
 

Treatment of borderline personality disorder

consists of more than just medications and therapy
and often requires a comprehensive approach.
 

DEEP SALT: Diagnose Educate Expect change

Prioritize Safety plan Avoid medications Life outside of
treatment Therapy if possible

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MECHANISMS OF BORDERLINE PERSONALITY
Many of the signs and symptoms of borderline personality disorder are found across other
psychiatric conditions as well (including impulsivity in addiction, affective extremes in
mood disorders, and a tendency towards negative emotions in anxiety). erefore, in order
to truly understand the mechanisms underlying the disorder, we need to look at the
characteristics that are most unique. e one pattern that is most speci c to borderline
personality disorder and other cluster B disorders is extreme interpersonal sensitivity, as
the symptoms of the disorder can almost always be traced back to interpersonal sensitivity
(such as changes in affect often being triggered by relational con ict). In addition, this
pattern tends to persist throughout life (in contrast to the symptoms mentioned before that
tend to “burn out” with time), suggesting that it is directly linked to the underlying
pathophysiology of the disorder.

To gain a better understanding of what is meant

by “extreme interpersonal sensitivity,” think back to the rst experience you ever had with
heartbreak. Perhaps a cute new boy or girl joins your class after their family moves from
across state. You think constantly about going up to them to say hi, but your stomach gets
tied up in knots every time you do, so you hold back. Later that day during algebra, your
eyes meet during one of your nervous glances. ey smile and blush, but you aren’t sure
whether they are responding to your looks or are creeped out by them. Days and weeks pass.
Desperate for their affection but too scared to make a move, you cozy up to their best friend
in an attempt to get closer. After a while, you can’t take the uncertainty anymore and you
ask their friend point-blank if they like you. (And not just like but, like, like you.) eir
friend embarrassedly looks down and says, “ ey actually just started dating someone else.”
Take the emotion you were feeling at that exact moment and put it in a bottle labeled
“dysphoric state” (you can place that bottle on the same shelf as the one labeled “pro-salient
state”). While most people feel this sort of dysphoria for a few days or weeks following
rejection or a major break-up, this is the mental state in which people with borderline
personality disorder live chronically. Having this dysphoric state as their baseline makes it so
that when someone with borderline personality disorder experiences further rejection, it
hurts twice as bad (if not more). is leads to levels of emotional pain and turmoil that

301
people without the disorder will likely never experience or be able to understand. It also
explains why people with borderline personality disorder go to such extreme lengths to
avoid abandonment or other circumstances that make them feel this way. However, to
understand why the speci c behaviors that are often seen in a “borderline crisis” (including
self-harm, suicidal threats, attention-seeking, and dissociation) are used, we need to look at
the underlying neurobiology of the disorder.
 

On a biochemical level, the endogenous opioid system appears to be involved

in borderline personality disorder. e endogenous opioid system is

responsible for releasing peptides in response to physical strain. ese morphine-like
substances (such as endorphins or “endogenous morphine”) act as natural painkillers to
help reduce the perception of pain. For example, long distance runners often report feeling
the most pain at the beginning of a marathon. However, as they continue their run,
endorphins and other endogenous opioids are released and result in reduced pain perception
and a pleasant, almost euphoric feeling (known as a “runner’s high”). In this way, runners
are able to engage in a speci c activity (exercise) that boosts signaling in the endogenous
opioid system as a way of off-setting incoming pain signals.
While the link of the endogenous opioid system to physical pain is well-known, this
system appears to play a central role in social pain as well. Social pain describes the aversive
emotional state that someone experiences in response to social rejection (such as being
excluded from a group or feeling devalued by another person). It is no coincidence that the
words used to describe social pain—including “broken-hearted,” “burned,” “slapped in the
face,” or “wounded”—are the same used to describe physical pain in a more literal sense (a
pattern that remains true across many different cultures and languages worldwide). Studies
suggest that social pain causes an immediate decrease in the release of endogenous opioids,
leading to feelings of dysphoria (rather than the euphoria caused by the increase in
endogenous opioid release that occurs during a runner’s high).
People with borderline personality disorder are believed to have an endogenous opioid
system that is chronically underperforming, leading to feelings of chronic dysphoria and
emptiness at baseline (two symptoms that are reported by almost everyone with the
disorder). However, this baseline level of hypoactivation makes it so that when someone
with borderline personality disorder experiences social rejection, their release of endogenous
opioids plummets even further, prompting an immediate emotional crisis state. (To be clear,
social rejection feels terrible for everyone, but for someone with an endogenous opioid
system that is already underresponsive, it throws an already dysregulated system even

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further off track.) is explains why “borderline crises” are almost always precipitated by
threats of social exclusion or rejection and often appear to be extremely out of proportion to
the circumstances to most outside observers.
To help offset this state of severe endogenous opioid depletion during a crisis, people
with borderline personality disorder often engage in a variety of behaviors to stimulate
release of endogenous opioids in an attempt to restore balance and bring some relief from
the intense dysphoria. ese behaviors include:
Seeking comfort from others. Neuroimaging studies show that endogenous opioids are
released in higher amounts during hugs, talking about your problems, or even just thinking
about being loved and supported. For most people, this is an essential part of feeling better
after social exclusion. For people with borderline personality disorder, however, this need
for social connection is so extreme that it can almost resemble an addictive disorder
(another condition that causes people to engage in frequent destructive behaviors in order to
ful ll an inner need). is explains the great lengths to which people with borderline
personality disorder will go (such as making an exaggerated show of threatening to kill
themselves if their partner doesn’t stick around) in order to obtain this feeling from their
partners, families, and friends.

Engaging in self-harm. Non-suicidal self-injurious behavior is common in borderline

personality disorder, and as mentioned before people with the disorder tend to report that it
helps relieve pain rather than cause it. Neuroimaging studies have shown that self-harm
induces the release of endogenous opioids in response to physical pain (similar to how the
strain of running also causes endogenous opioid release). In icting physical pain upon one’s
self to cause the release of endogenous opioids is an effective method of relieving social
pain, and people who self-harm often report that it makes them feel “normal” or “forget
about their pain” at least for a few minutes.
 

Dissociating. Dissociative symptoms in people with borderline personality disorder are

often immediately precipitated by traumatic events or threats of social exclusion.
Interestingly, endogenous opioids appear to be involved in generating feelings of both
derealization and depersonalization, as speci c medications that block the opioid receptor
(such as naltrexone or naloxone) have been shown to reduce dissociative symptoms in
people with these disorders.
 

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Using drugs or other substances. Perhaps the most direct way to activate one’s opioid
receptors is through substances like prescription painkillers, illicit opiates, or other drugs
(such as alcohol) that all appear to help someone in a dysphoric state feel “normal” again.
is explains the high rates of substance use and addiction in people with borderline
personality disorder, as use of these drugs is not only positively reinforcing but also quite
negatively reinforcing by providing immediate relief from the feelings of dysphoria and
emptiness that these individuals experience chronically.
 

In this way, we see how most of the signs and symptoms of borderline personality
disorder can be traced back to dysregulation of the endogenous opioid system. But where
does this dysregulation come from in the rst place? As with many things in psychiatry, it’s
never just one thing, and there are likely both biological and environmental factors at play.
Research has shown that differences in opioid receptor activity appear to be at least
somewhat heritable, with genetic differences appearing to correlate with speci c behaviors
(such as infants showing higher reward system activation during maternal contact and
greater distress upon separation) that mirror the interpersonal patterns seen in borderline
personality disorder. On the other hand, common environmental precipitants of the
disorder, such as a history of trauma and abuse, may exacerbate these underlying
vulnerabilities to the point where they become clinically signi cant. e release of
endogenous opioids appears to mitigate perception of both physical and emotional pain in
response to trauma. However, this is only a short-term x, and if the pain of the trauma
goes on for too long (such as under conditions of abuse and neglect), long term changes can
occur in the opioid system, leading to receptors that become persistently desensitized and
unresponsive.
e concepts of extreme interpersonal sensitivity and its rooting in a dysregulated
endogenous opioid system explain much of what we see in borderline personality disorder,
including its lasting traits (such as chronic dysphoria, affective instability, and sensitivity to
abandonment), its crisis states (such as self-harm, dissociation, and attention-seeking
behaviors), and its relationship to histories of chronic trauma. By tying together these
seemingly disparate traits and patterns, you will be better able to recognize borderline
personality characteristics when they occur in your patients. To associate this syndrome with
interpersonal hypersensitivity, use the phrase “With borderline (inter)personality disorder,
it’s always (inter)personal.”
 

Borderline personality disorder involves extreme

interpersonal sensitivity that appears to stem at
least partially from a dysregulated endogenous
opioid system.
 

With borderline (inter)personality disorder, it’s always

(inter)personal.

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305
DIAGNOSING BORDERLINE PERSONALITY DISORDER
When diagnosing borderline personality disorder, use the mnemonic HARD SHIPS to
remember the wide variety of signs and symptoms encompassed by this condition as well as
their “stably unstable” nature. As a personality disorder, a diagnosis of borderline
characteristics is based not only on a “snapshot” view of the patient’s presentation at a
particular moment in time but also on the presence of extreme and in exible patterns of
personality across the lifespan. ere should also be evidence that the dysfunctional traits
are persistent and enduring across years or decades. (After all, almost everyone becomes “a
little bit borderline” at various times in their lives after experiencing social rejection.)
Borderline personality disorder (or at the very least borderline personality traits) can be
accurately diagnosed in children and adolescents. Because of what we know about the
malleability of personality across the lifespan, a diagnosis of borderline personality disorder
should not be avoided simply because someone is less than the age of 18 when the speci c
signs, symptoms, and patterns are clearly present and are not better accounted for by other
explanations.
Finally, using a diagnosis of borderline personality disorder as a shorthand for people who
can come across as infuriating, manipulative, entitled, demanding, or frustrating should
absolutely be avoided. While these characteristics can sometimes be found in people with
borderline personality disorder, they fail to differentiate patients with borderline personality
disorder from people who have these characteristics for other reasons. erefore, consider
this diagnosis in people for whom these traits appear to directly stem from a pattern of
extreme interpersonal sensitivity, but avoid adding to the stigma by using the diagnosis
pejoratively.

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DIFFERENTIAL DIAGNOSIS OF BORDERLINE
PERSONALITY
e differential diagnosis for borderline personality disorder is as wide as the ocean.
Because the disorder is pervasive and touches on every aspect of one’s life, it frequently
overlaps with nearly every other psychiatric syndrome. In addition, people with borderline
personality disorder are prone not only to somatoform symptoms (those that resemble but
do not actually stem from a medical condition) but also to “psychoform” symptoms (those
that super cially appear to be, but are ultimately distinct from, symptoms of other
psychiatric illnesses). As the great imitator of mental health, borderline personality disorder
should almost always be on your differential diagnosis.
 
NORMALCY
e traits of borderline personality disorder are on a spectrum with normalcy, as feeling
emotions strongly, valuing relationships, and having one’s identity be at least partially
dependent upon the people around you are not inherently negative traits. Indeed, these
traits often make people with borderline personality disorder quite passionate about things
or people that they love, and it is not uncommon to nd people with these traits excelling in
creative elds like the arts because of their greater ability to feel emotion. As it so often
does, the key here involves looking at the level of dysfunction in someone’s life that can be
attributed to these traits as well as a pattern of in exibility that causes these same traits to
be maladaptive rather than helpful. In cases where someone has borderline traits but hasn’t
quite reached the point where these have caused problems, you can always recommend
speci c readings or techniques from dialectical behavior therapy (such as learning about
emotion regulation or mindfulness) that can be helpful for just about anyone regardless of
whether they technically meet criteria for the disorder or not.
 
DEPRESSION
Depressed mood is incredibly common in people with borderline personality disorder, and
some estimates place the rate of comorbid depression at over 90%. However, it’s not always
clear that people with borderline personality disorder have depression in the “textbook”
sense of an episodic mood disorder. Rather, in the vast majority of cases comorbid
depression is more likely to be a manifestation of chronic dysphoria than it is a truly
comorbid depressive disorder. is has important implications for treatment, as
conventional treatments for depression (such as SRIs and CBT) are generally not effective at
relieving depressive symptoms in people with this disorder. erefore, avoid diagnosing a
comorbid depressive disorder in someone with borderline personality disorder unless if it is
clear that their particular presentation cannot be entirely explained by chronic dysphoria
(such as a clear episodic pattern to symptoms with pronounced mood non-reactivity). In
addition, the longstanding belief that you should not diagnose borderline personality
disorder during a depressive episode does not appear to hold water, as personality
assessments performed both during and after depressive episodes show considerable stability
within the same person. erefore, you should not avoid diagnosing borderline personality
disorder when there are highly speci c and sensitive features present (such as extreme
interpersonal sensitivity, self-harm, or dissociation).
ATYPICAL DEPRESSION

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Recall from Chapter 5 that interpersonal rejection sensitivity is also a core feature of
atypical depression, suggesting at least some degree of diagnostic overlap. Indeed, up to half
of all people with atypical depression also meet criteria for borderline personality disorder,
making it unclear whether the two are separate disorders with overlapping features or two
ways of describing the same thing.
 

MANIA Cases of borderline personality disorder have been misdiagnosed as bipolar

disorder for as long as both disorders have been around. Much of the confusion stems from
the fact that common misconceptions about the word “bipolar” (often used to refer to
someone who is affectively labile) apply much more to borderline personality disorder than
to bipolar disorder. Differentiating between borderline personality disorder and bipolar
disorder should be done on the basis of their underlying mechanisms (such as looking for
patterns of extreme interpersonal sensitivity for the former or increased goal-directed
activity for the latter). In addition, the timing of symptoms is crucial, as affective changes
occur over minutes or hours in borderline personality disorder but weeks or months in
bipolar disorder (even in the rapid-cycling subtype).
 
PSYCHOSIS
Psychosis-like symptoms are common in borderline personality disorder and occur in up to
half of all people with the diagnosis. e phenomenology of psychotic symptoms in
borderline personality disorder differs signi cantly from schizophrenia. In addition,
“micropsychotic” phenomena are often transient (rather than ongoing) and tend to occur
primarily in times of interpersonal stress.
 
ADDICTION
Given the impulsivity found in borderline personality disorder, it is no surprise that rates of
comorbid addiction are high, with nearly two-thirds of those with the disorder developing a
substance-related disorder at some point in their lives. e presence of negative emotions at
baseline in borderline personality disorder also predisposes further to addiction by making
use of substances not only positively reinforcing but also negatively reinforcing as well.
Because of this, it is worthwhile to screen patients with borderline personality disorder for
the presence of comorbid addictions and to have a frank discussion about a higher risk of
dependence when prescribing controlled substances.
 
ANXIETY
Consistent with the nding that high neuroticism is a core characteristic of borderline
personality disorder, anxiety is incredibly common and occurs in nearly 90% of those with
the disorder. Social anxiety disorder is particularly common, with nearly half of all people
with the disorder meeting criteria for this comorbidity. Keep in mind that people with
borderline personality disorder will often use the language of psychiatry to communicate
idioms of distress, so someone simply saying “I had a panic attack” should not always be
taken literally.

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TRAUMA As one of the disorders in the abuse cluster, it is no surprise that PTSD is
common in patients with borderline personality disorder, with over half meeting criteria for
a diagnosis of PTSD. Related conditions, including dissociative and somatoform disorders,
are quite common as well.
 
EATING DISORDERS
Comorbidity between borderline personality disorder and eating disorders is high. Bulimia
nervosa is much more commonly associated with borderline personality disorder compared
to anorexia nervosa (which is itself more often associated with obsessive-compulsive
personality disorder).
 
AUTISM
You may think that borderline personality disorder and autism would rarely be confused
since the former is associated with increased affect and desire for the affection of others
while the latter is characterized by decreased affect and a generally low desire to socialize.
However, both borderline personality disorder and autism are linked by de cits in
mentalization, or an inability to correctly determine the mental state of others. For
example, people with borderline personality disorder or autism can both have difficulty
correctly guessing someone’s emotions based on their facial expression. However, the
reasons for this differ signi cantly. Individuals with autism tend to hypomentalize by failing
to accurately “read” facial expressions and showing a lack of consideration of situational
context. In contrast, people with borderline personality disorder tend to hypermentalize by
overinterpreting facial expressions or making overly complex assumptions based on context
and social cues. While both conditions have the same result (decreased ability to accurately
read the emotions of others), the underlying reason is quite different, making a
differentiation between hypomentalization and hypermentalization crucial.
 
PSEUDOBULBAR AFFECT

Pseudobulbar affect is a neurologic condition in which one experiences

uncontrollable and inappropriate outbursts of emotion such as suddenly crying or laughing.
ese episodes of “emotional incontinence” can resemble the affective instability that is a
core trait of borderline personality disorder. However, they differ in a few key ways. For one,
changes in expression in pseudobulbar affect are incongruent with the underlying
emotional state (even though someone is laughing or crying, that doesn’t mean that they are
happy or sad). In addition, changes of affect in pseudobulbar affect are not precipitated by
environmental triggers (unlike the affective lability seen in borderline personality disorder).
Using these clues to accurately recognize pseudobulbar affect is important as it can often be
a sign of an underlying neurologic disorder such as amyotrophic lateral sclerosis or stroke
(so misdiagnosing it as borderline personality disorder could mean missing a potentially
serious neurologic condition).

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PUTTING IT ALL TOGETHER
Borderline personality disorder doesn’t enjoy the same amount of attention or public
awareness as the “big ones” in psychiatry like depression, schizophrenia, or bipolar disorder.
However, this does not make it any less impairing, and people with the disorder often suffer
persistent dysfunction across their lifespan. Because of the mismatch between the
seriousness of the condition and the low level of interest in it, borderline personality
disorder has been described as a disorder in search of advocacy. Clinicians are reluctant to
talk about it, patients are averse to hearing about it, and insurance companies often do their
best to avoid covering effective treatments. Yet ignoring borderline personality disorder does
a disservice not only to patients but to society as a whole, as the majority of research seems
to indicate that it is a treatable condition with a much better prognosis than originally
thought.
Being educated about this disorder helps to prevent diagnostic reluctance and allows
you to provide patients with an accurate view of their condition. To remember what you
have learned about how to diagnose and treat borderline personality disorder, picture a eet
of HARD SHIPS sailing across the unstable waters of a DEEP SALTy ocean.
Recognizing the key role that extreme interpersonal sensitivity plays in the phenomenology
of the disorder can also help you to be sure of your diagnosis and to educate your patients
on the nature of their symptoms. By doing this, you can avoid the cycle of failed treatments
and unmet expectations that occurs when people try to call borderline personality disorder
by any other name.

310
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REVIEW QUESTIONS
1. A 28 y/o F suddenly moves across the country after meeting “the man of my
dreams” at a music festival. She moves in with him, and they enjoy several weeks
of passionate romance. However, after one month of living together, she begins to
suspect that he is cheating on her. He works at a consulting rm and often has to
stay at the office until 10:00 or 11:00 at night which leaves her at home by herself.
During her time alone, she thinks constantly about other women that he might be
sleeping with and vividly imagines them making love. She develops narratives
about each of these women and even names them. She cries frequently when he
works late and accuses him of in delity every night when he walks through the
door. However, upon being hugged and reassured that he has been faithful, she
instantly begins smiling and laughing. One night, her partner returns home to nd
her in the bathtub with super cial cuts on her wrists and the words “LOVE ME”
written in red ink on the bathroom mirror. Which of the following is the least
likely function of this patient’s self-injurious behavior?
A. Attempting to distract from emotional pain
B. Ful lling a desire to be dead
C. Demanding that her partner provide reassurance and comfort
D. Making the current situation feel less real
E. Stimulating the release of endogenous opioids
2. (Continued from previous question.) Her partner calls 911, and she is soon
admitted to a local psychiatric hospital. During the initial evaluation, the treating
psychiatrist asks her, “Do you sometimes hear voices of people who aren’t there or
see things that other people don't?” e patient responds by saying that she hears
voices inside her head belonging to “all the people that he’s cheating on me with
telling me what a stupid ugly whore I am.” She denies ever having heard voices
before in her life. What is the best interpretation of this symptom?
A. Evidence of schizoaffective disorder
B. Evidence of a primary psychotic disorder
C. Evidence of a comorbid psychotic disorder
D. Evidence of malingering
E. None of the above
3. (Continued from previous question.) With the patient’s consent, the treating
psychiatrist calls her mother to obtain collateral information. During their
conversation, the psychiatrist asks when the patient rst began to show signs of a
psychiatric condition. What is the mother’s likely response?
A. “She’s been like this as long as I can remember.”
B. “It probably started when she was in elementary school.”
C. “ ings took a turn for the worse when she was in high school.”
D. “I only really noticed anything different in the past few years.”
E. “She has never been this way before.”
 

4. (Continued from previous question.) On the rst morning of her admission, the
patient meets with her treatment team to discuss goals of hospitalization. Upon
sitting down, she immediately says, “Look, I’ve been through this song and dance

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 before. You’re going to tell me I’m depressed and then medicate me and send me to
a therapist, but nothing’s going to help and I’ll end up back here again in a few
weeks. You all seem nice but let’s face it, it’s not like you’re doing me any favors by
keeping me here in this hideous hospital gown eating shitty hospital food.” She
laughs sarcastically and then looks up at the ceiling in the room for a few seconds
before tears start coming down her face. Which of the following is most likely to
reduce her chances of hospital readmission?
A. Taking a thorough medication history and prescribing a medication that
has not been tried before
B. Telling the patient of her diagnosis of borderline personality disorder
C. Working with a social worker to nd local therapists who specialize in
dialectical behavior therapy
D. Discharging the patient from the hospital as soon as possible
E. None of the above are likely to reduce her chances of readmission
5. (Continued from previous question.) e patient is treated in the hospital, and
soon both the inpatient team and the patient feel that she is ready for discharge.
On her last day in the hospital, she asks the team if she is going to “be this way
forever.” What is the most appropriate response?
A. “Yes, this is an unchangeable part of your personality.”
B. “Yes, most likely. If you had gotten the right help earlier it might have
been different, but given your age it is unlikely to change.”
C. “No, you are suffering from an episode of this disorder. It will likely
pass soon, but there is always the possibility of future episodes.”
D. “No, you are likely to get better, but only if you stay in treatment.”
E. “No, you are likely to get better, but it will likely take a few years.”
 

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1. e best answer is B. is patient is likely suffering from borderline personality
disorder given the presence of self-harm, hostility, affective instability, unstable
relationships, and impulsivity. While the functions of self-harm are complex, it
appears to serve multiple purposes including distracting from emotional pain
(answer A), forcing others to provide comfort (answer C), and inducing a state of
dissociation (answer D). Each of these purposes is mediated at least in part
through the increased release of endogenous opioids (answer E). In contrast, it is a
minority of people who engage in this form of self-harm who have a genuine
desire to commit suicide.
2. e best answer is E. e patient’s reported auditory hallucinations are not
phenomenologically consistent with a primary psychotic disorder and are most
likely a representation of the transient, stress-induced micropsychotic symptoms
that are common in borderline personality disorder. erefore, a diagnosis of a
diagnosis of schizoaffective disorder or either a primary or comorbid psychotic
disorder appears unwarranted in the absence of other symptoms (answers A, B,
and C). It is unclear that these symptoms represent malingering, and the severity
of her self-harming behaviors suggests a level of distress that argues against her
primarily seeking some form of secondary gain (answer D).
3. e best answer is C. As with most personality disorders, the age of onset for
borderline personality disorder is generally during adolescence. While cases of
borderline personality disorder beginning in childhood or later adulthood are not
unheard of, the most common pattern is onset during one’s teenage years.
4. e best answer is C. Out of the listed options, only dialectical behavior therapy
has been demonstrated to reduce rates of hospitalization in people with borderline
personality disorder. While educating the patient on the nature of borderline
personality disorder can be helpful, it has not been shown to make a clinically
signi cant impact on readmission rates in and of itself (answer B). Prolonged
admissions are generally advised against in borderline personality disorder to avoid
creating behavioral dependency on the structured setting of a hospital, but early
discharge has not been shown to reduce rates of hospitalization (answer D).
Medications on the whole are unlikely to signi cantly alter the clinical trajectory
of someone with borderline personality disorder (answer A).
5. e best answer is E. Borderline personality disorder is characterized by chronic
de cits with occasional exacerbations. However, it is not considered to be an
episodic disorder given that signs and symptoms often remain across the lifespan
(answer C). Contrary to previous conceptions of the disorder, longitudinal studies
have found that the majority of people with borderline personality disorder enter
remission from the disorder during their lifetime (answers A and B) and that this
pattern is seen even in people who do not receive evidence-based treatments for
the disorder (answer D). erefore, it is most accurate to say that the patient will
likely enter remission but that this will take a period of several years.

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14 DISSOCIATION

Dissociation refers to a feeling of being detached

from one’s sense of reality. Similar to anxiety, dissociation is both a state and a trait as the
term can be used to describe both a transient phenomenon (“She dissociated for several
minutes following the car crash.”) as well as a long-term predisposition towards these
experiences (“He is highly prone to dissociating when under stress.”). Dissociation can take
two forms: derealization, or a feeling that one’s experience of reality is fake or “unreal,” and
depersonalization, or a feeling that one has become separated from their sense of self and
identity.
While dissociation can often be experienced as confusing, bewildering, or shocking, it
is not an inherently pathological state. In fact, up to 20% of people have experienced
depersonalization or derealization in the past year. However, for some people, dissociative
experiences can become frequent or severe enough to form the basis of a dissociative
disorder. Dissociative disorders are recognized in the DSM and include dissociative
amnesia, depersonalization-derealization disorder, and dissociative identity disorder.
Each of these conditions features dissociative experiences in some form, but they differ
signi cantly from each other in terms of their cause, severity, and prognosis.
As mentioned previously, dissociative disorders are highly correlated with a history of
trauma (especially when it occurred chronically during early development), placing them
alongside PTSD, cluster B personality disorders, and somatoform disorders in the “abuse
cluster.” In addition, dissociative states are believed to play a role in the pathophysiology of
each of these conditions, so learning about dissociation will be helpful in understanding the
effects of trauma as a whole (even when working with someone who is not formally
diagnosed with a dissociative disorder).

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SIGNS AND SYMPTOMS OF DISSOCIATION

Dissociative experiences occur primarily in two main forms:

derealization and depersonalization. Derealization involves a sudden or profound sense
that one’s current experience of the world is illusory or fake. People often describe
derealization as a mental “fog” or “veil” that suddenly descends and makes their
surroundings seem alien or dream-like (even if they are in a familiar place like their own
home). People in a state of derealization also report that they often feel unsteady or uneasy
(“It’s like I am walking on shifting ground.”). Dissociation can also be subjectively
experienced as depersonalization, or the feeling of having become mentally detached from
one’s sense of self. People experiencing depersonalization may look at their body and think,
“I’m not myself,” or “ at isn’t me.” is is experienced as a sense that their body is out of
their conscious control or that they are observing their body from an outside perspective.
Depersonalization and derealization are not mutually exclusive states, and people will often
feel both at the same time.
If you’re feeling confused at this point, you’re not alone, as the signs and symptoms of
dissociation are notoriously difficult to explain. (In fact, one of the most common words
that people who have dissociated use to describe the experience is “indescribable.”) Much of
this difficulty comes from the fact that the vast majority of people have not had the
experience of dissociating. In fact, some research suggests that less than a quarter of the
population even has the capacity to spontaneously dissociate without any outside in uence,
which makes the concept of dissociation quite difficult to grasp for the other 75% of people.
is difficulty is compounded further by the fact that dissociation is not a “severe” variant of
a common emotion (in contrast to something like depression which can be understood as an
extreme version of sadness even by people who have not personally experienced a depressive
episode during their lifetime).
Nevertheless, there are clues that can help anyone to better understand the experience
of dissociating. e closest experience that most people have had to dissociation is the
transient “head rush” that occurs upon standing up too quickly and becoming lightheaded.
When this happens, there is often a distinct but ineffable sensation of unreality that is
similar to what is described by people in a state of derealization or depersonalization. Like
lightheadedness, the onset of dissociative experiences is often sudden, startling, and
somewhat unsettling. Interestingly, symptoms of dissociation—including both
depersonalization and derealization—can also be experimentally induced in healthy
volunteers by injecting warm or cold water directly into the external auditory canal (please
don’t try this at home). In addition, drugs known as dissociative hallucinogens (including
ketamine, dextromethorphan, and phencyclidine) can also induce a state of dissociation in

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most people who take them, suggesting that all people have the ability to dissociate even if
it is only a minority of people who do so spontaneously.
 

While derealization and depersonalization are the two primary ways in which dissociation is
subjectively experienced, there are often other signs as well. Most prominently, lapses in
memory are a key clinical symptom of dissociation. Memory loss during dissociation is
characterized by retrograde amnesia, or the loss of previously encoded memories (as
opposed to anterograde amnesia where new memories cannot be encoded). For example,
someone diagnosed with dissociative amnesia may be unable to remember any signi cant
events in the month-long period after the death of her son but would be able to encode and
memorize new information such as a shopping list or the name of the therapist she is seeing
next week.
Memory lapses in dissociation are also characterized by the presence of both omission and
commission errors. Omission errors are things that happened that you cannot remember
(you have omitted the information from your mind) whereas commission errors are false
memories of things that didn’t actually happen (you remember yourself committing an act
that you haven’t committed). Human memory is far from perfect, and omission errors are
incredibly common (can you remember what you ate for dinner exactly one year ago?). In
contrast, commission errors appear to be speci cally related to the capacity to dissociate, and
evidence suggests that people who score high on measures of dissociation differ from
healthy controls primarily in the increased number of commission errors (rather than
omission errors) that they make. is is not to say that “normal” people don’t make
commission errors of memory as well (they absolutely do, which is a key part of the reason
why eyewitness testimony in legal cases is so often unreliable). However, people with a high
degree of trait dissociation appear to remember false or suggested memories with a much
higher frequency than most and with an intensity similar to their memories of actual events.
 

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DISSOCIATION ACROSS THE LIFESPAN
As a class, dissociative disorders have not bene tted from the same amount of research
attention that has been given to other psychiatric disorders, resulting in little being known
about the epidemiology, prognosis, and treatment of these disorders. Nevertheless, based on
what data are available, a few themes have emerged.
As mentioned previously, dissociation is a relatively common experience, with around
20% of people experiencing dissociative states. However, dissociative disorders appear to be
much more rare, with estimates placing the prevalence at around 1-3% of the population.
ey are most commonly diagnosed in early adulthood, with very few cases beginning after
one’s 20s or 30s.
Non-pathological dissociation occurs with approximately the same frequency in both
women and men. However, pathological dissociation appears to be much more common in
women, with diagnoses such as dissociative identity disorder being found up to 10 times
more frequently in women than men. is discrepancy is believed to be at least partially
related to higher rates of abuse histories in women compared to men, as a history of trauma
(especially during early childhood) is a major risk factor for developing a dissociative
disorder. In fact, over 90% of people diagnosed with a dissociative disorder report a history
of childhood trauma.
PROGNOSIS
At the time of diagnosis, dissociative disorders are generally associated with high levels of
disability and dysfunction, including psychiatric symptoms in multiple domains (such as
mood, anxiety, sleep, and cognition), unstable interpersonal relationships, increased rates of
physical illness, frequent substance abuse, and an elevated risk for suicide. Dissociative
disorders also appear to be some of the most disabling conditions, with studies consistently
nding low rates of employment and high utilization of social welfare. However, how much
of this comes from the dissociative symptoms themselves (as opposed to the fact that people
with dissociative disorders also tend to have multiple comorbid diagnoses such PTSD,
depression, substance abuse, and personality disorders that are each signi cantly impairing
as well) remains unclear. While all of this together would seem to suggest a poor prognosis
for dissociative disorders, studies have suggested that dissociative symptoms and disability
tend to decrease with age even in the absence of treatment, although long-term naturalistic
outcome studies are lacking.
 
TREATMENT

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 Like other aspects of dissociative disorders, treatment for
these conditions is severely under-researched. Part of the problem is that it is not always
clear what the speci c targeted outcomes of treatment should be (“Are we trying to reduce
episodes of dissociation or simply trying to eliminate distress and dysfunction related to
them?”). Treatment studies on dissociative disorders also have an unfortunate tendency to
refer to “treatment” in a general sense and rarely clarify the exact type of interventions used.
Because of this, there is a lack of clearly de ned treatment strategies for dissociative
disorders. However, available evidence suggests that the most effective treatments generally
consist of trauma-focused psychotherapy in a variety of modalities (including CBT,
dialectical behavior therapy, supportive therapy, hypnosis, and psychoeducation) in both
group and individual formats. Interestingly, therapy appears to be only somewhat effective
at addressing the symptoms of dissociation themselves; instead, the most robust effects of
therapy tend to involve reducing comorbid depression, anxiety, suicidality, trauma-related
symptoms, and symptoms of borderline personality disorder. Studies have suggested that
effective therapy for dissociative disorders typically requires long-term treatment in the
order of years rather than weeks or months. However, given what we know about the
natural lessening of dissociative pathology even without treatment, it remains unclear
whether the bene cial effects observed with therapy over time are a direct result of therapy
or simply the natural course of the disorder. is demonstrates a clear need for more
rigorously designed and controlled trials.
Medication treatment has not been found to be helpful at improving functional
outcomes for dissociative disorders. When medications are used, they are generally focused
at alleviating speci c symptoms rather than targeting the underlying process of dissociation
directly.
 

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MECHANISMS OF DISSOCIATION
e phenomenology of dissociation largely involves two domains: subjective feelings of
unreality mixed with objective de cits in memory. However, it is not immediately obvious
what ties these two domains together, nor is it clear why they tend to happen around times
of particularly traumatic events. One theory that attempts to bridge this gap suggests that
dissociation results from an unstable sleep-wake cycle that causes intrusions of the
dreaming state into waking life.
During waking life, we are generally responsive to most external stimuli, and our
memories of these experience are relatively stable and durable. During dreaming, however,
the brain enters a unique state in which vivid images and experiences are generated in the
absence of any external stimuli. For the most part, we are unaware of the fact that we are
dreaming and will react emotionally to what we see as if it were a genuine perception of the
world. In contrast to memories from waking life, however, the memories from our dreams
tend to be exceptionally fragile and are often forgotten quickly.
Dissociation appears to involve sudden activation of the neural networks responsible
for the dreaming state during normal waking life, leading to a sort of halfway point
between dreaming and wakefulness. During dissociation, consciousness and an awareness
of one’s surroundings are preserved (as in wakefulness); however, there is also an ability to
generate and react emotionally to internally generated stimuli (as in dreaming). ese
“dream attacks” are involuntary and often occur quite suddenly (similar to the sudden
episodes of re-experiencing seen in PTSD which are believed to also be a form of
dissociation that operate by similar mechanisms). Someone in a state of dissociation can
often recognize that they are having an odd or unusual experience which is re ected in the
feelings of depersonalization, derealization, and unreality that accompany dissociation
episodes. ( is may account for why insight is often preserved in dissociative disorders yet
lost in other conditions like schizophrenia that also involve the ability to react to internally
generated stimuli.) e activation of dream-related neural networks during waking
consciousness helps to explain how a single mechanism could account for two different
memory errors: retrograde amnesia and memory errors of commission. To understand
this, consider your own experiences with dreams. Upon awaking from a particularly vivid
dream, you likely had in your mind a memory of events that did not actually happen (a
memory error of commission). However, this memory likely faded from your mind over the
next few minutes or hours, even if you tried to mentally hold onto it (retrograde amnesia).
e co-occurrence of both retrograde amnesia and memory errors of commission is highly
speci c for both dreaming and dissociation, suggesting a shared mechanism.
Evidence for the involvement of a disrupted sleep-wake cycle and dreamlike consciousness
in dissociation is found in clinical studies that have subjected healthy subjects to sleep
deprivation. After even a single night of sleeplessness, these participants showed an
increased tendency towards dissociative experiences and a decreased threshold for entering
into a state of sleep and dreaming. is “pro-dissociative state” impacts the way that
memories are encoded in several ways. First, it makes people signi cantly more likely to

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accept false information as true, re ecting a higher
rate of memory errors of commission compared to people who have gotten enough sleep.
Second, it increases the retention of negative memories over positive ones, a role mediated
largely by strengthening of the amygdala with a loss of connection to the medial prefrontal
cortex (a similar pattern to PTSD). ird, it causes a tendency to encode memories in
isolated sensory fragments rather than in cohesive narratives (“On the day he was shot, I
remember the smell of the owers, the breeze from the ocean, the sound of the birds
calling…”). Together, this leads to a pattern of remembering events in so-called “ ashbulb
memories” which are incredibly vivid snapshots of particular moments in time when
something emotional or traumatic occurred. e emotion associated with the memory
enhances one’s ability to recall particular details, but it also makes it more difficult to store
memories in the usual narrative format, leading to memories being stored instead as strong
but isolated sensory fragments.
e involvement of a dreamlike state during dissociation and its associated changes to
how memory functions both have important implications for treatment. One study found
that a program focusing exclusively on sleep hygiene can improve dissociative symptoms
signi cantly, suggesting that sleep patterns should be a crucial aspect of evaluating and
treating dissociative disorders. More broadly, the liability towards memory errors of
commission should make clinicians incredibly cautious to avoid suggesting false memories
either implicitly or explicitly. Refrain from use of leading questions (“When people have
been sexually abused, they often experience strange aches and pains in their genitals. Has
this ever happened to you?”) in favor of open-ended questions (“Tell me about any physical
pains, discomforts, or ailments that you have.”) as much as possible when working with
patients who are prone to these forms of memory errors.
To summarize, dissociation appears to be related to a disrupted sleep-wake cycle
leading to an increased tendency for intrusions of the dreaming state into waking life, which
results in the characteristic combination of feelings of unreality with speci c forms of
memory errors. To remember this association, think of DISsociative disorders as Dreaming
—InSunlight disorders . (Interestingly, daydreaming and imagination both appear to be
related to the capacity to dissociate and likely lie on the same biological spectrum. However,
neither should be considered pathologic in any way.)

321
Dissociative episodes involve sudden intrusions of
dreamlike consciousness into waking life caused by
an unstable sleep-wake cycle.
 

DISsociative disorders = Dreaming—InSunlight

disorders

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DIAGNOSING DISSOCIATIVE DISORDERS
Dissociative disorders are categorized by the DSM-5 into three types: dissociative amnesia,
depersonalization-derealization disorder , and dissociative identity disorder. Dissociative
identity disorder is generally considered to be the prototype disorder. While it is not the
most common (affecting only 1% of the population, in contrast to dissociative amnesia and
depersonalization-derealization disorder which affect up to 5-10%), it is the most impairing
form of dissociative disorder.
 

DISSOCIATIVE AMNESIA Dissociative amnesia refers to

episodes of retrograde amnesia that lead to gaps in one’s autobiographical memory. ese
gaps often occur around the time of severe traumatic events. Episodes can be brief (lasting
only a few minutes or hours), but in other cases they can last for months or years. In severe
cases, amnesia can be so profound that people forget their own name and identity, leading
to a “fugue” state in which they will wander around with no knowledge of who they are or
where they are from. Dissociative amnesia is a diagnosis of exclusion, and biological causes
for memory loss (like structural brain damage) must be ruled out. e prognosis for
dissociative amnesia is good, however, and many people will recover their memories even
without treatment. However, the overall level of functioning for those who have
experienced dissociative amnesia is often poor, though this is more likely related to various
comorbidities (such as PTSD or depression) than from the dissociative amnesia itself.
 
DEPERSONALIZATION-DEREALIZATION DISORDER
Depersonalization-derealization disorder is characterized by depersonalization and/or
derealization symptoms that are severe and persistent enough to result in signi cant distress
and impairment. is diagnosis is broad enough to capture a wide range of pathology
related to dissociation, and accordingly presentations of the disorder are highly variable. For
most people with the disorder, feelings of depersonalization and derealization are chronic
while for one-third they occur in more transient episodes. For those who experience
dissociation in episodes, these can either be spontaneous or preceded by speci c triggers
(including life events, stress, anxiety, depression, or use of drugs like cannabis or
hallucinogens). Age of onset is typically in the teenage years, although some people
describe experiencing depersonalization and derealization as far back as they can remember.
It affects men and women equally.

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As with other dissociative disorders, depersonalization-derealization disorder is correlated
with a history of trauma. Feelings of depersonalization in particular appear to overlap
signi cantly with the poor sense of identity and chronic feelings of emptiness found in
borderline personality disorder. In fact, the co-occurrence of other symptoms common to
borderline personality disorder (including self-harm) raises the possibility that
depersonalization-derealization disorder is likely on a similar spectrum, and a signi cant
proportion of individuals who experience depersonalization will likely meet criteria for both
disorders.
DISSOCIATIVE IDENTITY DISORDER

Dissociative identity disorder involves episodes of

derealization, depersonalization, and memory lapses that are severe enough that someone
experiences them subjectively as completely separate identity states. (After all, if you felt
like a different person at 5 o’clock than you did at 4 o’clock and could not remember what
you did an hour ago, you might also conclude that you were a different person, as a sense of
self and continuous memory are both required to maintain a consistent sense of identity.)
is lack of continuity in accessible memories and sense of self leads to a fragmentation of
identity, resulting in a distinct sensation that one is a completely different person from each
moment to the next.
Because the concepts associated with dissociative identity disorder (like the notion of
identity itself ) can seem vague or ill-de ned, misconceptions about the disorder abound.
For this reason, it can be just as helpful to know what the disorder is not as to know what it
is. Contrary to stereotypical media depictions (ranging from “ e Strange Case of Dr. Jekyll
and Mr. Hyde” in the 19th century and “ e ree Faces of Eve” in the 20th all the way to
Split in the 21st), dissociative identity disorder does not involve switching from one
personality to another in a dramatic or theatrical fashion. e fact that this disorder was
previously named “multiple personality disorder ” in the DSM only further contributed to
this woefully inaccurate conception of the syndrome and paved the way for a diagnostic
“fad” in the United States. During its heyday in the 1980s, rates of multiple personality
disorder in clinical settings approached 10% of all patients, which is over ten times greater
than the 1% prevalence for dissociative identity disorder that has been observed before and
since.
In response to this, some researchers have suggested that dissociative identity disorder
does not exist but rather is an iatrogenic diagnosis (or a disorder that is caused by medical
treatment rather than being cured by it). In support of this theory, they refer to studies
showing that a diagnosis of multiple personality disorder had as much to do with the
clinician’s demographics as it did with the patient’s presentation, with female psychiatrists and
those trained during the 1980s giving out the diagnosis much more frequently than
clinicians trained at other times. Further support for the idea that multiple personality

324
disorder is a fabricated diagnosis comes from the fact that clinical presentations of the
disorder often followed depictions of the disorder in popular media. For example, media
depictions of multiple personality disorder in North America often showed the shifts
between personalities as instantaneous whereas in India the transitions between different
personalities happened during sleep, and patients presented accordingly in each of these
countries. erefore, it seemed logical to conclude that the diagnosis as a whole may have
been created entirely by overzealous clinicians and imposed upon a speci c subset of
patients with a high capacity for dissociation and suggestibility.
However, to throw out the diagnosis of dissociative identity disorder entirely does not
seem wise, as symptoms consistent with the disorder have been described for hundreds of
years across multiple cultures (even those that do not prominently feature media depictions
of the disorder). More than that, however, is the fact that even though rates of the diagnosis
have gone down, they have not gone away entirely, and people still come to psychiatric
clinics reporting these very symptoms. In light of this, it is likely that dissociative identity
disorder does exist but simply not in the form that most people think it does. Rather than
being a “movie-like” syndrome of multiple people inhabiting the same body, dissociative
identity disorder is best described as a syndrome of extreme depersonalization,
derealization, and memory lapses that leads to fragmentation of identity. ese different
identities often correspond to speci c extremes of affective states (for example, presenting
as one identity when angry, another when scared, another when sad, and another when
elated). Fragmentation of identity can even lead to observable changes in mannerisms,
behavior, and speech patterns (in fact, neuroimaging studies of people with dissociative
identity disorder have even shown differences in cerebral blood ow and other physiological
processes between different identity states). However, it is an extreme overliteralization to
conceive of these states as entirely separate people.
 

Absolutely not.

e relationship of dissociative identity disorder to trauma is well established, as

dissociation most often occurs when circumstances are extraordinarily traumatic, stressful,
or fear-inducing. While dissociation is usually a transient state (recall that it is more often

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associated with acute stress disorder than with chronic PTSD), dissociative symptoms can
become persistent when traumatic experiences are especially prolonged or occur during early
childhood development. is is consistent with reports that around 95% of people with
dissociative identity disorder report chronic childhood trauma often beginning before the
age of 6. (In contrast, the rate of child abuse in the general population is around 5-15%.)
Dissociative identity disorder is also highly comorbid with other disorders related to
trauma, including PTSD (up to 100%), depression (90%), substance abuse (90%),
personality disorders (80%), and somatoform disorders (80%). e association with
childhood trauma appears to explain much of the discrepancy in gender ratio, as women
have a history of childhood trauma that vastly exceeds men. Abuse histories in patients with
dissociative identity disorder cannot be attributed entirely to memory errors of commission,
as rigorous studies have found outside evidence corroborating histories of abuse in the
majority of cases.

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DIFFERENTIAL DIAGNOSIS OF DISSOCIATIVE
DISORDERS
Dissociative disorders overlap with other psychiatric syndromes in many ways, making an
understanding of the differential diagnosis essential for coming to the correct conclusion.
 
NORMALCY
Dissociation is not inherently pathological, as up to a quarter of all people experience
dissociative symptoms but are not particularly troubled by them. Even within medical
settings, dissociation is rarely the primary reason that someone seeks mental health care. For
this reason, it is important not to let the mere presence of dissociative symptoms form the
basis for a diagnosis. Instead, a dissociative disorder should only be diagnosed when there is
clear evidence that the episodes of derealization and depersonalization are frequent or severe
enough that they are causing problems in and of themselves.
While dissociative disorders can often present with memory loss, care should be taken to
avoid diagnosing a dissociative disorder in everyone who believes that they have lost their
memory for certain events in their life. Certain forms of memory loss are normal, as most
adults are unable to remember most memories for events that happened when they were
pre-verbal (before the age of ve or six), that occurred long ago (with memories of events
diminishing with time), or were experienced during sleep or dreaming.
Finally, when diagnosing dissociative identity disorder, care should be taken not to
overliteralize when someone says that they act like a “different person” in different
situations. e normal range of personality is large enough to encompass even major
differences in feelings and behavior in different settings (such as someone who is quiet and
reserved with their conservative parents yet outspoken and disinhibited when with friends),
and this type of compartmentalization should not be seen as representing entirely new or
different personalities.
 
PSYCHOSIS
Dissociation is commonly confused for psychosis. In fact, in some studies as many as half of
all patients with dissociative identity disorder had been diagnosed as or treated for
schizophrenia. Some of this has to do with the fact that the terminology used to describe
dissociation (such as “feelings of unreality”) are often quite similar to those used to describe
psychosis (such as “loss of contact with reality”). While both psychosis and dissociation
involve alterations in someone’s subjective experience of reality, they are ultimately quite
different. A person in a state of dissociation is generally able to distinguish between their
own internal experiences and the objective reality of the outside world (their experiences
don’t feel real even though they recognize that they are). In contrast, someone in a state of
psychosis is genuinely unable to tell that their subjective experiences do not represent a
shared reality, and their reality testing ability (or the capacity to tell what is real from what
is fake) is distinctly impaired. Other symptoms, such as thought disorganization and
negative symptoms, can also help to differentiate psychosis from dissociative disorders
(although some symptoms, such as paranoia and auditory hallucinations, can be found in
both, especially if there is comorbid borderline personality disorder).
BORDERLINE PERSONALITY DISORDER
Dissociation is a common symptom of borderline personality disorder, making these two
diagnoses highly comorbid. In fact, some studies have found rates of comorbidity between

327
borderline personality disorder and dissociative identity disorder above 80%. In addition,
the identity disturbance and affective lability that are core symptoms of borderline
personality disorder likely are on the same spectrum as dissociative identity disorder. For
this reason, it is worthwhile to consider borderline personality disorder in someone
presenting with a dissociative disorder and vice versa.
 
DEMENTIA
Dissociative disorders and dementia both share memory loss as a core clinical feature, but
there are enough differences that these two conditions should rarely be confused. Of note,
people with dissociative amnesia show a distinct awareness of (and distress about) their
lapses in memory whereas people with dementia are generally oblivious to the fact that their
memory is fading. In addition, dissociative disorders rarely present with actual de cits on
cognitive tests. Finally, most people diagnosed with dissociative disorders tend to be much
younger (late teens or early adulthood) as opposed to the older ages seen in dementia.
 
TRAUMA
All dissociative disorders are strongly correlated with a history of trauma, making PTSD a
very common comorbidity (approaching 100% of patients in some studies). Given that
dissociation is a symptom of both acute stress disorder and PTSD, the line between when
you consider dissociation to be merely a speci c manifestation of those disorders (as
opposed to a diagnosis in and of itself ) is unclear. is confusion is likely the result of a
messy diagnostic scheme more than it re ects a genuine separation between these clinical
entities. As a practical rule of thumb, consider diagnosing a separate dissociative disorder in
individuals for whom the dissociative episodes exceed the ashbacks and nightmares seen in
“textbook” PTSD, who have speci c forms of dissociative experiences that match these
disorders, or who experience signi cant distress as a direct result of feelings of
depersonalization or derealization rather than from the trauma itself.
 
PANIC ATTACKS
Dissociative symptoms are common during a panic attack, with over two-thirds of all
patients with panic disorder reporting depersonalization or derealization during an episode.
However, for people with panic disorder, dissociative experiences outside the context of a
panic attack are no more common than in the general population. For this reason, a
dissociative disorder should only be diagnosed in someone with panic disorder if there is a
clear history of episodes outside the context of a panic attack.
 
BIPOLAR DISORDER
People with bipolar disorder can appear to be very different people depending on whether
they are depressed, manic, or euthymic. However, these switches between mood states
happen over weeks or months (as opposed to over minutes or hours in dissociative identity
disorder). In addition, people with bipolar disorder rarely report feelings of derealization or
depersonalization, even during mood episodes.
SOMATIZATION
Somatoform disorders are frequently comorbid with dissociative disorders, and you should
keep somatization higher on the differential when evaluating someone with both
unexplained symptoms and a history of dissociation (but take care to always take the
concerns seriously and conduct a thorough work-up no matter what!).

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DEPRESSION
Feelings of unreality and depersonalization have been associated with a state of depression
for as long as this disorder has been described. Dissociative symptoms that occur exclusively
during an episode of depression and disappear when the episode resolves should therefore
be thought of as a particular manifestation of depression rather than requiring a diagnosis of
a separate dissociative disorder.
 
ELECTROCONVULSIVE THERAPY
Retrograde amnesia is a common side effect of ECT and occurs to some degree in almost
everyone who undergoes the procedure. Do not confuse the retrograde amnesia seen in
dissociation with this unfortunate but expected effect of ECT.

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PUTTING IT ALL TOGETHER
Dissociative disorders can be confusing to understand. Rather than face this complexity,
many clinicians have an unfortunate tendency to try and avoid these diagnoses completely.
Given that patients rarely present with dissociation as their primary concern, it is actually
possible to do so, and as a result dissociative disorders are highly underdiagnosed.
However, this does a disservice to the many patients who struggle with dissociation as it
deprives them of evidence-based treatment and further perpetuates stigma. In response to
this situation, some clinicians instead go the opposite direction and attempt to champion
these disorders by searching for evidence of dissociation everywhere they look. While this is
a helpful counterpoint to the status quo, it has the potential to make dissociative disorders
overdiagnosed by certain clinicians, further muddying the waters.
Try to strike a balance between these two extremes by understanding that dissociation
exists, that it often results from trauma, and that for some people it can become severe,
persistent, and impairing. In addition to focusing on the subjective symptoms of
depersonalization and derealization, use the presence or absence of objective abnormalities
in memory (particularly retrograde amnesia and memory errors of commission) to establish
the diagnosis further. Remembering that DISsociative disorders mechanistically resemble
Dreaming—InSunlight via their link to a disrupted sleep-wake cycle can also help to not
only con rm the diagnosis but also provide targets for treatment (which is particularly
helpful considering that treatment strategies for dissociative disorders remain very poorly
understood). Finally, keep in mind that dissociation itself is not inherently bad! Indeed,
dissociative mechanisms appear to be related to processes like imagination and daydreaming
which form the basis of art and creativity—things that most people would agree are the
exact opposite of pathology.

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REVIEW QUESTIONS
1. A 21 y/o M is brought to the emergency department by his parents. ey became
concerned when they called him two days ago and he appeared to have no
knowledge of who they were. ey immediately drove to his university to pick him
up and bring him in for evaluation. On interview, the patient says that he is here
because “I’ve lost my memory.” He says, “People tell me that I was very into a girl
who broke my heart. I wish I could remember her so I could tell her not to do it.
But I can’t even remember her name. It’s completely gone.” He denies feeling
depressed and says, “No, I feel completely ne. Everyone else seems to be
concerned, but I am ne.” Physical and neurologic examination is normal. He is
able to perform a 10-minute recall of 5 words given to him by the psychiatrist.
What term best describes the type of memory error that he is experiencing?
A. Anterograde amnesia
B. Retrograde amnesia
C. Global amnesia
D. Memory errors of commission
E. Aphasia
2. (Continued from previous question.) When interviewed, the patient’s parents
report that he was diagnosed with ADHD as a child but later “outgrew” it. ey
also report that he was hospitalized for one week at the age of 16 after he became
suicidal following a break-up with his high school girlfriend. To their knowledge,
he currently takes no medications other than a few doses of alprazolam (a
benzodiazepine) each month for a diagnosis of panic disorder. During the
interview, his father begins crying and says, “I just hate that he can’t remember
who we are. We raised him. We’re his parents. Will he ever know who we are
again?” What is the best response to his father?
A. “Yes, it is an absolute certainty that he will regain his memories.”
B. “You don’t have to worry. It is very likely that he will.”
C. “It’s tough to say at the moment. ere’s around a 50% chance.”
D. “It’s unlikely that he will regain his lost memories, but we will do our
best to work with him and with you both during this process.”
E. “ is is a hard thing for me to say, but those memories are gone.”
3. A 23 y/o F is admitted to the hospital following a suicide attempt in which she
attempted to overdose on 10 pills of lamotrigine (a mood stabilizer which she has
been prescribed). is is her third hospitalization in the past year. She normally
sees her therapist two times a week but has not been attending sessions for the past
month. During her interview with the hospital psychiatrist, she initially comes
across as lighthearted and irtatious in a way that seems at odds with the
circumstances. When asked about the suicide attempt, her affect immediately
switches to a brooding, serious expression. She responds by saying, “I don’t talk
about that. I don’t want to talk to you anymore,” and asks the psychiatrist to leave.
Later, when talking with the nurses, she says that she has “no clue” why she is in
the hospital but she is “glad to be back.” Which of the following disorders is this
patient least likely to have?
A. Post-traumatic stress disorder
B. Major depressive disorder

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 C. Bipolar disorder
D. A substance use disorder
E. A personality disorder
F. A somatoform disorder
4. (Continued from previous question.) e patient is discharged from the hospital
three days later and begins seeing a new therapist who has extensive experience
working with dissociative disorders and offers trauma-focused psychotherapy. e
patient remains in treatment for two years and is noted to have signi cant
improvements in interpersonal and occupational functioning. Which of the
following symptoms is most likely to still be present at the end of two years?
A. Episodes of dissociation
B. Depressed mood
C. Feelings of anxiety
D. Frequent suicide attempts
E. Frequent non-suicidal self-harm
F. All of the above are equally likely to be present at the end of
treatment
5. A 22 y/o F is robbed at gunpoint on her way home from work. Following this
incident, she begins to feel very depressed and frequently has trouble sleeping.
Normally outgoing and vivacious, she begins to come across as pessimistic and
isolated to the point that her friends have commented to each other that she looks
“like a different person.” She does not seek psychiatric care, nor does she tell
anyone else about the incident. ree months later, her friends receive an invitation
to attend a stand-up comedy gala that she is hosting. At this event, she is
gregarious and warm, laughing and telling jokes as she introduces each new
comedian. While most of the audience is having a wonderful time, her friends feel
uneasy about this “transformation” and worry about her mental health. What is the
most likely diagnosis at this time?
A. Dissociative amnesia
B. Depersonalization-derealization disorder
C. Dissociative identity disorder
D. Bipolar I disorder
E. Bipolar II disorder
F. None of the above
 

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1. e best answer is B. e patient’s inability to recall details from his past suggests
a retrograde amnesia, while his ability to recall new information (such as the 5
words given to him by the interviewer) rule out anterograde amnesia (answer A).
Global amnesia is a combination of both anterograde and retrograde amnesia, but
this patient is only suffering from retrograde amnesia (answer C). Memory errors
of commission involve remembering events that did not happen, and there is no
evidence of that in this case (answer D). Aphasia involves impairments in
comprehending and generating language, both of which are intact in this case
(answer E).
2. e best answer is B. is patient appears to be suffering from dissociative
amnesia which is characterized by loss of memories in a retrograde fashion. e
usual prognosis for dissociative amnesia is for a spontaneous recovery of lost
memories, although it cannot be said with complete certainty that the memories
will return (answer A).
3. e best answer is C. is patient shows signs consistent with dissociative identity
disorder which is strongly correlated with a history of childhood abuse.
Accordingly, this disorder is highly comorbid with other disorders related to abuse,
including PTSD, depression, substance abuse, personality disorders, and
somatoform disorders (answers A, B, D, E, and F). In contrast, while bipolar
disorder is related to stress, it is not associated with childhood trauma in the same
way as the other disorders listed. e mere fact that this patient is taking
lamotrigine (a mood stabilizer) is not enough to con rm that she has bipolar
disorder, as she may have been prescribed lamotrigine to treat another condition
such as epilepsy (not to mention that bipolar disorder itself is frequently
overdiagnosed and overtreated).
4. e best answer is A. While the optimum treatment strategies for dissociative
identity disorder remain poorly de ned, evidence suggests that trauma-focused
psychotherapy is effective at improving outcomes in the disorder. However,
episodes of dissociation themselves appear to be the least responsive to therapy,
while other outcomes including depressive symptoms, anxiety, and frequency of
suicide attempts and self-harm appear to respond much better (answers B through
E).
5. e best answer is F. Despite a history of trauma, there is no indication of either
dissociative or bipolar pathology in this clinical vignette. e changes in affect and
behavior described in this case occur from one setting to another (as opposed to
being in exible across various settings) and are adaptive and appropriate to the
context of the situation. ere is no evidence to suggest amnesia (answer A),
feelings of depersonalization or derealization (answer B), or fragmentation of a
sense of identity (answer C). No form of bipolar disorder is diagnosed based on
the presence of a single evening of different behavior (answers D and E). While it
is possible that this patient is suffering from another disorder (such as PTSD or
depression), these are not available as answer choices.

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 5.

15 SOMATIZATION

Somatization is the process by which mental distress is subjectively

experienced as bodily (or “somatic”) symptoms like pain, fatigue, nausea, soreness, or
discomfort. Mental disorders that have somatization as a prominent feature are known as
somatoform disorders because they resemble (or take the “form” of ) body-based illnesses
like infection, heart disease, stroke, or cancer without actually involving any of the
pathological signs of these diseases. Historically, the starting point for somatoform
disorders was the mere presence of medically unexplained symptoms. However, grounding a
diagnosis on the absence of an explanation is a fundamentally problematic enterprise.
Because of this, attempts have been made to revise the diagnostic criteria to include a
greater focus on maladaptive cognitive patterns, feelings, and behaviors related to the
symptoms, including frequent thoughts about the seriousness of the symptoms, excessive
anxiety about them, and lots of time, energy, and effort being spent on activities related to
the symptoms.
Somatoform disorders are among the most controversial psychiatric diagnoses for several
reasons. For one, interpreting a particular symptom as somatoform in nature is often a
diagnosis of exclusion: it assumes that, once medical explanations have been ruled out, the
only remaining explanation is that the person’s distress related to their symptoms is
psychological rather than physiologic. is can lead to a premature sense of closure,
especially for conditions that are poorly understood. (Consider that asthma was considered
to be a “psychosomatic” disorder up until the 1960s, resulting in some cases being treated
with psychoanalysis rather than medications.) It is possible that with further research we
will discover the roots of other medical syndromes that currently do not have a biological
explanation, including conditions such as bromyalgia, chronic fatigue syndrome, and
irritable bowel syndrome.
Diagnosing a somatoform disorder also has a high chance of invoking the negative
aspects of diagnosis (it is highly stigmatizing) without delivering much in the way of
bene ts (it doesn’t validate distress, and thus far research into causes or effective treatments
has not delivered promising results). Most importantly, telling a patient that “it’s all in your
head” is likely to signi cantly damage the doctor-patient relationship.

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 Nevertheless, there is a reason that the concept of a somatoform
disorder has existed for so long and continues to ll a need even in modern medicine.
Nearly every specialty of medicine frequently sees at least one biologically unexplained
syndrome that often seems to be accompanied by maladaptive cognitive and behavioral
patterns, including bromyalgia (rheumatology), irritable bowel syndrome
(gastroenterology), chronic pelvic pain (gynecology), non-cardiac chest pain (cardiology),
tension headaches (neurology), hyperventilation syndrome (pulmonology), chronic fatigue
syndrome (primary care), multiple chemical sensitivity (allergy), and chronic Lyme disease
(infectious disease). In addition, to completely dismiss any link between physical and
mental health would be to ignore a wealth of research and clinical experience that has built
up over centuries. People with medically unexplained symptoms have a high rate of mental
conditions in other areas, including depression, anxiety, and disorders related to trauma
(including PTSD, dissociative disorders, and cluster B personality disorders). In addition,
treatment of medically unexplained symptoms often involves the same treatments as for
anxiety and depression (speci cally, psychotherapies like CBT and medications like SRIs)
and results in improvement in the physical symptoms themselves (not just the distress
related to them). With all this in mind, it seems reasonable to conclude that a relationship
does exist between medically unexplained symptoms and mental health, even if there are
many potential pitfalls to diagnosing this pattern too easily or often.

As with dissociative disorders, a balanced perspective on

somatoform disorders appears warranted. First, do not be led into thinking that if particular
symptoms are psychological or psychiatric in origin then they are somehow feigned,
imaginary, or non-existent! Somatization is not “acute pretendicitis” as some have joked.
Instead, patients prone to somatization appear to genuinely experience the symptoms that
cause them so much discomfort and distress. erefore, if we apply what we have learned so
far and remember that taking a patient seriously does not always mean taking them literally, we

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can still provide good care for our patients without exposing them to the risks of physical
harm and unnecessary medicalization that would occur by treating their symptoms as
medical illnesses.

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SIGNS AND SYMPTOMS OF SOMATIZATION

e speci c symptoms involved in somatization can encompass

every organ system in the body (including fatigue, fever, headaches, dizziness, visual
problems, wheezing, shortness of breath, diarrhea, constipation, pain with urination,
incontinence, stiffness, weakness, itching, palpitations, and nausea) and can range from
mild to severe. e gastrointestinal tract is the most common location for somatic
symptoms, with over 95% of persistent somatizers experiencing unexplained symptoms
related to these organs. In women, gynecologic complaints (including pelvic pain and
menstrual irregularity) are the second most common symptom and are experienced by over
90% of women with somatoform disorders. Next most common are symptoms of the central
nervous system, musculoskeletal system, and urinary tract. e vast majority of patients
with persistent somatization experience symptoms in multiple organs of the body
throughout their life. However, it is also common for each person to have one or two
“preferred” organs that are most commonly involved.
As mentioned before, symptoms in somatization are genuinely experienced. is contrasts
somatization with other conditions (such as factitious disorder or malingering) where the
signs and symptoms are feigned or intentionally produced as well as with hypochondriasis
(an obsessive-compulsive spectrum disorder) where the primary concern of the patient is the
idea that they have a speci c medical condition (rather than an excessive focus on the
symptoms themselves). However, the line between “real” and “fake” symptoms is not always
clear cut, and around 20% of persistent somatizers have intentionally self-induced a disease
state on at least one occasion.
Behaviorally, people with medically unexplained symptoms often persist in seeking
treatment despite repeated negative examinations and tests. For this reason, people who
experience persistent somatization can incur healthcare costs up to ten times higher than
people who do not, including more primary care appointments, more specialist
consultations, more emergency department visits, and more hospital admissions. ese
patients are also much more likely to be prescribed unnecessary medications and be
subjected to invasive tests, procedures, and even surgical operations. People with frequent
and severe somatization undergo a median of eight surgical procedures over their lifetime,
with procedures on the uterus and gastrointestinal tract being the most common. ese
surgeries are much more likely to be diagnostically and therapeutically unhelpful, with over

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60% of surgeries in persistent somatizers showing no abnormal ndings (compared to 20%
for non-somatizers). Because of this, people with persistent somatization are at high risk for
iatrogenic injuries including surgical accidents, complications from anesthesia, medication
side effects, and radiation exposure. is makes understanding, preventing, and treating
somatization a major personal and public health concern.

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SOMATIZATION ACROSS THE LIFESPAN

Somatization is universal. Every person alive has experienced

distressing medical symptoms for which no cause was ever found. Somatization as a
primary reason for seeking care is also incredibly common. In fact, it is believed that around
one-third of all primary care visits are for medically unexplained symptoms. For the vast
majority of these patients, these symptoms are transient and resolve on their own. For a
small portion of these patients, however, somatization becomes persistent and leads to
signi cant distress and dysfunction. ese people are said to be suffering from somatoform
disorders.
e prevalence of somatoform disorders in the general population is about 5%,
making it neither as common as disorders like depression and anxiety nor as rare as
disorders like bipolar disorder and schizophrenia. Women are affected vastly more often
than men, with some estimates placing the gender ratio as high as 10 to 1. Persistent
somatization begins as early as childhood, and for people with chronic somatoform
complaints, this pattern almost always begins before the age of 30.
 
PROGNOSIS
For some people, somatization is a transient phenomenon which tends to increase around
times of stress. However, for around 25% of people with somatoform symptoms severe
enough to go to a doctor’s office, somatization becomes chronic and enduring. For those
with persistent somatization, the vast majority improve during follow-up, even without
treatment. However, for a minority (10 to 30%), the clinical course is characterized by
worsening symptoms and increasing anxiety. Despite their belief that they are more ill, the
mortality rate of patients who frequently somatize is equal to that of patients in the general
population.
 
TREATMENT

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 Because people presenting with somatoform disorders are
often seen in primary care clinics or other non-psychiatric settings, treatment is often given
by providers who have not received speci c training in these disorders. In addition, patients
with somatoform disorders are often quite hesitant to see mental health providers out of
concern that their somatic complaints will be dismissed as “psychosomatic” or otherwise not
taken seriously. Because of this, somatoform disorders are often trapped in a “no man’s land”
between primary care, neurologists, and other specialists (who are asked to see these
patients but do not believe that they can help) and psychiatrists (who may feel more able to
help but often won’t be seen by the patients). Because of this, treating somatization requires
a fundamentally different approach. Use the mnemonic I Do CARE to remember the
necessary ingredients for successfully treating somatoform disorders: I is for Interface.
Patients who somatize tend to have multiple healthcare providers, including multiple
specialists in various areas of medicine. Work closely to interface with all the medical
providers on the patient’s team, and integrate your ndings so that you are not working in
isolation.
 

Do is for “Do no harm.” Patients who somatize are at high risk for injury, disability, or even
death as a result of frequent tests and treatments. Because of this, keep the dictum “do no
harm” closely held in your mind, and always weigh the potential risks of treatment against
the bene ts to avoid doing more harm than good.
 

C is for CBT. CBT is the best studied treatment for somatization, with a small to
moderate effect size and bene ts that are durable (lasting years after treatment has
stopped). Mindfulness-based therapies have also been shown to be helpful, with a similar
effect size.
 

A is for Antidepressants. Antidepressants are the best studied pharmacologic treatment for
somatization, and evidence suggests that they can be effective (though with a smaller effect
size compared to CBT). However, their potential bene ts must be weighed against the
possibility that the medications themselves can cause side effects which may further trigger
or exacerbate somatization. Nevertheless, for some cases antidepressants can be a helpful
adjunctive treatment.
 

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R is for Regular visits. For someone suffering from severe anxiety about physical symptoms,
a visit to the doctor can be very comforting. However, this can have the effect of
inadvertently providing negative reinforcement for having experienced severe symptoms in
the rst place, as it is easy for the patient to think (even unconsciously) that “I get to go to
the doctor only when I’m sick.” You can reduce this association by scheduling regular visits
rather than only seeing the patient when they have a complaint which avoids sending this
message.
 

E is for Empathy. Try to spend the majority of your time during the appointment listening
to the patient, empathizing with their distress, and educating them on the overall good
prognosis for symptoms that they are concerned about (“In similar cases I’ve worked on,
these symptoms went away on their own without the need for potentially harmful
treatments, and I’m hopeful that this will happen for you too.”).
 

Treatment of somatization involves therapy,

antidepressants,
scheduling regular appointments, and avoiding
iatrogenic harm.
 

I Do CARE: Interface “Do no harm”

CBT
Antidepressants Regular visits Empathy

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MECHANISMS OF SOMATIZATION

If people who somatize genuinely experience the pain and

other bodily sensations that cause them so much distress, then the next question naturally
becomes: why? ere are two possible explanations. One is that people who somatize
receive more pain signals than people who do not (in which case somatization would be a
peripheral problem of too many signals being generated). e other explanation is that
people who somatize are excessively focused on and overreact to existing signals (in which
case it is a central problem of hypersensitivity to noxious stimuli). Between these two views,
the overwhelming amount of evidence supports the latter hypothesis. In studies that have
been performed, people with somatoform disorders who were given the exact same stimulus
(a painful but ultimately harmless electric shock) were signi cantly more likely to react to
this with distress, anxiety, and other negative emotions than people who did not have a
somatoform disorder.
e key to understanding this process is the concept of interoception, or the ability
to sense one’s internal bodily state (as opposed to exteroception, which is the ability to focus
on stimuli outside of the body). People differ in their interoceptive abilities (for example,
some people are more able to sense their own heartbeat than others). A brain region known
as the insula appears to be the central player involved in interoception, with the activity of
this region correlating to the degree of pain that is reported. People who experience
persistent somatization appear to have hyperactive signaling pathways connected to the
insula which manifests as a heightened awareness of, and a tendency to overfocus on,
signals from one’s own body.
However, this is only half of the story. Someone with a hyperactive insula may be
more prone to pay attention to somatic sensations, but this doesn’t necessarily need to be
distressing or impairing. In people who somatize, however, the increased perception of
somatic signals is accompanied by a tendency to overinterpret these bodily signals as being
“bad.” For example, someone who is resting and notices that they can hear the sound of
their heartbeat in their ears may either think, “Oh that’s interesting,” or they could think,
“Oh no, what does this mean? Am I having a heart attack?” It is the latter response that is
typical of somatization. On a biological level, the anterior cingulate cortex is believed to be
involved in this process. As you’ll recall from the chapter on obsessive-compulsive disorders,
the anterior cingulate cortex is responsible for recognizing error signals. When the insula
passes along interoceptive information to the anterior cingulate cortex, the anterior
cingulate cortex interprets that signal as representing an error (or “something bad”) and
generates alarm signals. is creates a state of motivational arousal that prompts the person
to take action (such as seeing a doctor or asking a friend for reassurance).

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 In this way, somatization is revealed to be a two-step process between increased
interoception in the insula along with a tendency for the anterior cingulate cortex to
overinterpret these signals as representing a problem and then take acc-tion on them. You
can remember this by thinking that these abnormalities together cause someone to generate
in-acc-urate self-diagnoses.
Somatization involves hyperactivity of the insula,
which mediates interoception, and the anterior
cingulate cortex, which interprets the signal as an
error.
 

When someone’s self-diagnosis is repeatedly In-ACC-

urate, consider abnormalities in the Insula and Anterior
Cingulate Cortex.

On a behavioral level, somatization is believed to be at least

partially a learned behavior. Much of this has to do with the speci c actions that signal to
others that one is sick (known as illness behavior) as well as the responses that others give
to people who are ill, including favors (bringing chicken soup), increased leniency with
responsibilities (being given a day off of school or work), and increased care, attention, and
affection from friends and family. Many children can relate to feeling a bit of jealousy when
a schoolmate comes to school in a cast due to having broken a bone. e increased attention
and affection given to these individuals are enviable (even if the experience of having a
broken bone is not).
It’s important to note that the presence of illness behavior is completely unrelated to
whether someone has an illness or not. Instead, what is relevant is whether someone believes
that they have an illness. Somatization appears to be a mechanism by which people have
learned to obtain speci c needs in their life. Evidence for this comes from the fact that
many people with persistent somatization have had family members with severe illnesses
during their childhood, which increases exposure to the dynamics of (and bene ts
associated with) the sick role. An increased need for social attachment is frequently found in
persistent somatizers, a feature that overlaps signi cantly with cluster B personality
disorders. Someone’s need for social support is a major predictor of somatization. In fact, in
a group of people experiencing acute stress, social support was found to be associated with
less symptom reporting (even though it had no effect on one’s actual physical health).

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 In this way, somatization provides both positive and negative reinforcement for
illness behavior: the increased affection from others is powerfully rewarding, while being
excused from unwanted responsibilities can be negatively reinforcing. Doctors and other
healthcare providers can unwittingly play into this dynamic just by trying to be empathic
and provide a high quality of care. By seeing people only when they have an illness, doctors
reinforce the idea that symptoms are required for their attention. is underscores why
scheduling regular visits is so important when working with someone who experiences
persistent somatization: it helps to break the positive reinforcement of somatization by
providing the patient with attention even when no symptoms are present.
In summary, somatization is a complex phenomenon that involves both biological and
behavioral processes. While the neurobiological ndings have yet to play a signi cant role
in elucidating treatments for somatoform conditions, understanding the behavioral
dynamics of somatization can help to inform treatment on a day-to-day clinical level.

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DIAGNOSING SOMATOFORM DISORDERS
As mentioned previously, somatoform disorders all involve the presence of medically
unexplained symptoms. e point of differentiation between each individual somatoform
disorder, then, is why these symptoms are believed to be present. As we discuss each of
these disorders, keep this framework in mind:
 
Medically unexplained symptoms + Y
 
e medically unexplained symptoms are the constant found in all somatoform
disorders, so it is the Y (or the putative reason “why” these symptoms are present) that is
the unique calling card of each condition.
 
SOMATIC SYMPTOM DISORDER
Somatic symptom disorder is the prototype somatoform disorder and is characterized by
persistent and impairing somatization as described previously in this chapter. As with all
forms of true somatization, these symptoms appear to be genuinely experienced by the
person. ( is is in contrast to medically unexplained symptoms that are intentionally
produced as in factitious disorder or malingering.) If our framework for somatoform
disorders is “medically unexplained symptoms + Y,” then in the case of somatic symptom
disorder the Y is biology and behavior (as discussed in the section on mechanisms). e
mere presence of medically unexplained symptoms is not enough to diagnose somatic
symptom disorder; rather, the symptoms must be accompanied by signi cant worry about
the possible implications of the symptoms as well as speci c and maladaptive behaviors in
response to this anxiety (such as frequent healthcare seeking leading to unnecessary
treatments and invasive diagnostic tests).
 
CONVERSION DISORDER

Conversion disorder (also called “functional neurological symptom

disorder” in the DSM-5) is less about medically unexplained symptoms than it is about
medically unexplained signs. Cases of conversion disorder are characterized by focal
neurologic de cits that are unexplainable by known medical or neurologic causes. Speci c
examples of neurologic de cits include focal muscle weakness or paralysis, difficulty with
speech, gait abnormalities, memory loss, and seizures. In this way, conversion disorder goes
beyond mere somatization (which is associated only with the subjective reporting of speci c
symptoms) into the realm of objectively observed neurologic de cits. Given that the majority

347
of neurologic de cits involve areas that we have voluntary control over, it is easy to come to
the conclusion that people with conversion disorder are either “faking it” or not trying hard
enough. However, there is no evidence that people with conversion disorder produce or fake
their symptoms. In fact, the preponderance of evidence suggests that conversion disorder is
a form of dissociation over which people have little control.
 

For conversion disorder, the Y behind the symptoms is a recent stressor, as the
neurologic de cits in conversion disorder are often triggered by a speci c event. For
example, someone whose parents were killed in a car crash may suddenly develop leg
weakness and become unable to walk. is external stressor has been “converted” into a
physical de cit (hence the name “conversion disorder”). While a clear psychological trigger
is found in almost all cases, it is not a prerequisite for diagnosis.
Conversion disorder has a decent prognosis, although it is variable depending on the
symptoms. Cases of conversion disorder that involve the absence of function (such as the
inability to walk or talk) have a better prognosis than those that involve the presence of
dysfunction (such as a tremor or seizures). e majority of cases resolve by the time of
discharge from the hospital, although around 25% relapse within a year. Treatment consists
of educating the patient and their family about the nature of conversion disorder. Typical
treatments for somatization, such as CBT, are not very helpful here (underscoring the idea
that conversion is possibly closer to dissociation than it is to somatization). When doing so, it
is important not to “confront” the patient or in any way imply that they are lying or not
trying hard enough, as this can be extremely counterproductive. Instead, emphasize that the
lack of objective medical lab or imaging results is good news, and be optimistic that their
condition will improve with time. Always assess for comorbid psychiatric syndromes such as
depression or anxiety disorders, and offer treatment as necessary (though make it clear that
you are offering this treatment to treat those disorders, not to treat the conversion disorder
itself ). In some cases, physical and/or occupational therapy has been shown to improve
functional outcomes.
As with other somatoform disorders, be extremely cautious not to allow a diagnosis of
conversion disorder to lead you into a sense of premature closure. Studies on conversion
disorder have revealed that a medical or neurologic cause is ultimately found in up to 30%
of all cases, so always keep your mind open to alternative explanations.
 
FACTITIOUS DISORDER

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 Unlike somatic symptom
disorder and conversion disorder (in which the unexplained symptoms are believed to be
genuinely experienced by the patient), in factitious disorder the medically unexplained
symptoms are intentionally produced or exaggerated, with the Y being primary gain. e
term primary gain is used to refer to all of the intangible bene ts associated with being
sick, including sympathy and nurturance. For example, someone with factitious disorder
may complain of severe abdominal pain that they aren’t actually experiencing in order to be
admitted to the hospital and receive medical attention. In some cases, people with factitious
disorder will even permit signi cant dis gurement and disability (such as undergoing
multiple surgeries) because they desire to remain in the “sick role” over and above preserving
their own bodily integrity. Frequent visits to the hospital can also result in a signi cant
nancial toll, as can overuse of medical treatments.
In extreme cases, people with factitious disorder may even intentionally harm themselves to
provide evidence that they are truly sick. For example, someone in the hospital claiming to
have an infection may begin injecting their own feces into their bloodstream to actually give
themselves an infection. is is known in the medical eld as Munchausen syndrome (or
“factitious disorder imposed on self ” in the DSM-5). At other times, someone may harm
their child or other dependent for similar purposes, as they strongly desire the sympathy and
attention that accompanies having a sick child. is is known as Munchausen syndrome by
proxy (or “factitious disorder imposed on another”) and is one of the deadliest forms of
abuse that exists. As in other cases of abuse, once a diagnosis is strongly suspected,
immediate steps to protect the child should be taken.
It’s difficult to study factitious disorder directly because a true diagnosis requires clear
evidence (whether by verbal admission, physical ndings such as track marks indicating
self-injection, or, in the case of Munchausen syndrome, directly witnessed injurious
behavior) that someone is intentionally fabricating their symptoms, which cannot always be
found. Nevertheless, some patterns of epidemiology and prognosis have been consistently
found. People who engage in factitious behavior are more often female (with a gender ratio
of 2 to 1) and typically in their 30s. Interestingly, more than 50% of people with factitious
disorder work in a medical eld (with nursing being the most common occupation),
suggesting that exposure to the dynamics of the sick role may play a part in the
development of the disorder. Cases of factitious disorder are usually diagnosed based upon
an unsubstantiated presentation, although other patterns (including excessive healthcare
utilization in the past, atypical presentation of symptoms, recurrent failure of medical
treatments, and questionable behaviors) can often provide clues as well.

349
 Factitious disorder is a syndrome with a relatively poor prognosis, in large part
because people with factitious disorder tend to have many other mental disorders as well
(predominantly personality, trauma-related, mood, and anxiety disorders). e presence of
suicidal thoughts or a history of suicide attempts in people with factitious disorder is high
(around 15%), placing it on par with the mood disorders. Treatment for factitious disorder
is difficult, as neither medications nor psychotherapy have been shown to be effective in
any large study. In addition, it is unclear whether confronting the patient about known or
suspected factitious behavior is helpful or harmful, as studies have shown no difference
between confrontational and non-confrontational approaches. Nevertheless, it seems
reasonable to try to approach patients with factitious disorder from the perspective of trying
to create a safe and therapeutic relationship while acknowledging that allowing the patient
to continue their unsafe behavior is likely to result in harm.
 
MALINGERING
Like factitious disorder, malingering involves the intentional production or exaggeration of
medically unexplained symptoms. However, malingering differs from factitious disorder in
the reasons for producing the symptoms. In contrast to factitious disorder where the main
draw is the bene t intrinsic to being in the sick role, in malingering the Y is secondary
gain. Secondary gain refers to an extrinsic bene t that someone is getting from the sick role,
including obtaining disability payments, an excuse from work or military service, a lighter
sentence in a criminal case, nancial compensation for a fake injury, or admission to a
hospital with its associated food and shelter. It’s important to note that malingering does
not always involve complete fabrication of symptoms. Often, at least some of the symptoms
do exist but are signi cantly played up or exaggerated (known as partial malingering). For
example, someone involved in a workplace accident may indeed have back pain related to
the injury; however, if they intentionally exaggerate their back pain and say that it prevents
them from moving at all (when they are actually able to move), this would be considered
partial malingering.

Even more so than factitious disorder,

malingering is a difficult entity to study. is is largely because malingering is not
considered to be a mental disorder, as people will exaggerate, fabricate, or lie for various
reasons (not all of them related to mental health). For this reason, there are no clear
patterns of epidemiology, prognosis, or treatment associated with malingering. Several
tests have also been developed to help identify malingering such as the Structured Inventory
of Malingered Symptomatology (SIMS), although these are used more often in forensic
settings than clinical ones.
One key difference between factitious disorder and malingering is in terms of how the
person behaves once their need has been met. Someone who is Malingering Always Leaves
once their need has been met (for example, if disability payments have been approved)
because there is no longer a reason for them to seek medical treatment. In contrast,

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someone with Factitious disorder Always Comes back for more treatment because their
primary motivation is in the medical care itself.
 

Factitious disorder and malingering both involve

intentional production of medically unexplained
symptoms but differ in regards to the reason why.
 

Malingering Always Leaves once their need has been

met whereas Factitious disorder Always Comes back for
more.

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DIFFERENTIAL DIAGNOSIS OF SOMATOFORM
DISORDERS
By their very nature, somatoform disorders are highly liable to misdiagnosis. e best
defense against misdiagnosis is for healthcare providers to have a rm grasp of the disorders
that they are treating. For example, a neurologist should know the features that are
commonly associated with a generalized tonic-clonic seizure (such as biting the inside of
the mouth, urinary incontinence, the presence of automatisms during the seizure, and a
distinct postictal period) and use this knowledge to be able to pick up on cases where
enough non-associated features (such as seizures involving side-to-side head movements,
closing of the eyes, or a duration of more than 2 minutes) are present to suggest a probable
somatoform etiology.
 

While we have largely talked about somatization in terms of bodily symptoms, some
of the conditions we have mentioned can involve psychiatric symptoms as well (such as
someone who feigns hearing voices in an attempt to be admitted to the psychiatric
hospital). As with any specialty, the key to picking up on these cases remains a fundamental
knowledge of the syndromes that we treat. For example, knowing that someone with
schizophrenia will often try to hide the fact that they are experiencing auditory
hallucinations can help raise your suspicions that something else may be going on when
someone spontaneously and repeatedly tries to tell you about “voices in my head.”
While misdiagnoses are the most common problem facing someone with a diagnosis
of a somatoform disorder, missed diagnoses are a very real problem as well. In fact, one
study found that 99% of all people diagnosed with a somatoform disorder had at least one
additional psychiatric diagnosis, with over 90% having depression and 60% having a
personality disorder. Because of this, be mindful not to prematurely conclude that someone
with a somatoform disorder does not have other areas in which you can intervene.
 
NORMALCY
Like all psychiatric disorders, somatization exists on a spectrum. Everyone experiences
symptoms from time to time that they cannot explain, and most people have intentionally
produced or exaggerated symptoms at least once in their life so they could stay in bed all day
eating saltine crackers and chicken soup. However, at extremes the quantitative becomes
qualitative, and some people have such severe or recurrent somatization that it leaves no
doubt that there is a disorder. (One recorded case of factitious disorder involved a single
patient undergoing over 40 surgical procedures over the course of 850 admissions to 650
different hospitals, leading to permanent disability and dis gurement but, amazingly, not
death.) While the line between normalcy and somatization is never clear, look for clear
evidence of dysfunction to make this distinction.
 

TRAUMA As part of the “abuse cluster,” somatoform disorders are frequently found in
people with a history of trauma. A diagnosis of PTSD also appears to increase the risk for
developing a somatoform disorder even after controlling for baseline comorbidities such as
depression and anxiety. In fact, of all the psychiatric disorders, PTSD is perhaps the one

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with the strongest relationship to somatization and medically unexplained pain. Always
remain vigilant to assess for possible histories of abuse so you can provide meaningful
interventions (such as referring someone to trauma-focused CBT or dialectical behavior
therapy) when appropriate.
 
DEPRESSION
e majority of people who experience persistent somatization are either currently
depressed or have been at some point in their lives. However, this “depression” more closely
resembles the chronic dysphoria found in borderline personality disorder (as discussed in
Chapter 13) than episodic major depressive disorder, resulting in higher rates of treatment
failure. On a clinical level, it may make sense to generally consider depressive symptoms in
somatoform disorders to represent chronic dysphoria (rather than “textbook” major
depressive disorder) unless it becomes evident that there is a clear episodic pattern to the
mood states.
 
PSYCHOSIS
Due to stigma, many people (including medical professionals) tend to take psychosis more
“seriously” than disorders like depression or anxiety. is makes schizophrenia an attractive
condition to be feigned, and accordingly it is one of the mental disorders that is most
commonly malingered. Schizophrenia can be distinguished from malingering or factitious
disorder through a good understanding of its usual phenomenology (as covered in Chapter
7). In particular, people with schizophrenia have a tendency to hide their symptoms whereas
people who are feigning psychosis want to make sure that you are aware of their symptoms.
 
OBSESSIVE-COMPULSIVE DISORDERS
e DSM chapter on somatoform disorders previously included hypochondriasis, as it
seemed logical that a disorder based on an excessive fear of illness would be closely related
to other conditions involving concern about somatic symptoms. However, this resemblance
is only super cial, and the phenomenology of hypochondriasis (involving obsessional and
intrusive thoughts about having an illness) as well as its treatment requirements more
closely resembles an obsessive-compulsive disorder. For this reason, distinguishing between
somatization and hypochondriasis is crucial. In somatization, the focus is on the symptoms
themselves along with anxiety about what these symptoms might represent (“Why do I feel
tired all the time?”). In contrast, hypochondriasis is characterized by the obsessive belief
that one has a disorder even when presented with con icting evidence (“Feeling tired all the
time is a sure sign that I have a colon cancer! I don’t care what the colonoscopy report
says!”). While there is some overlap between the two (including abnormalities in the
anterior cingulate cortex), they should ultimately be conceptualized as separate conditions.
 

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DEMENTIA While it’s rare for someone to feign dementia per
se, evaluating memory impairments following an injury is a common task in certain settings
(such as a disability evaluation clinic). People who are feigning memory de cits are likely to
overplay their hand by reporting symptoms that are vastly in excess of what people with
genuine disability report. For example, most people will have some memory de cits
following a car crash (such as being unable to remember new items on a shopping list).
However, someone trying to feign memory de cits may say that the car crash caused
complete and total amnesia to the point where they forget their own name and are unable to
recognize family and friends. As with many somatoform conditions, it also makes sense to
put your detective hat on whenever disabling symptoms are eagerly volunteered during an
evaluation.

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PUTTING IT ALL TOGETHER
Somatization is a complex phenomenon involving multiple biological abnormalities that
result in someone having a greater sensitivity to pain and other bodily signals which
manifests clinically as medically unexplained symptoms. While these symptoms must be
present for a somatoform disorder to be diagnosed, the symptoms must also be
accompanied by maladaptive thoughts and behaviors as well.
When evaluating someone with medically unexplained symptoms, it is not a priority
to give an exact diagnosis based on strict adherence to diagnostic criteria. In fact, studies
done on somatoform disorders have found that the vast majority of people who have
medically unexplained symptoms do not meet criteria for a speci c disorder in the DSM
chapter on “Somatic Symptom and Related Disorders.” Instead, it may be more helpful to
think of these separate diagnostic categories as descriptions of behavior with an assumption
about cause (the Y in the “Medically unexplained symptoms + Y” formula). To recap, let’s
review the Y for each condition:
Somatic symptom disorder = Biology and behavior Conversion disorder = Recent stressor
Factitious disorder = Primary gain Malingering = Secondary gain
In the majority of cases, your ability to know the Y is (at best) a wild stab in the dark.
Nobody can read minds, so providing an explanation for someone’s behavior is always going
to be an inexact science. For this reason, somatoform disorders can (and very often do)
overlap. For example, someone may have a history of epileptic seizures (a genuine medical
condition) but then have an increase in both epileptic and non-epileptic seizures following a
traumatic incident (conversion disorder). Due to the worsening in severity of their
condition, they end up spending more time in the hospital and nd that they have learned
to appreciate being cared for by the doctors and staff in the hospital (which could lead to
factitious disorder), especially as it provides them with some time away from their
dysfunctional family. In addition, they are in the process of applying for disability so that
they do not have to return to their stressful job and believe that they cannot stop having
seizures if they are to be successful in this (which could lead to malingering). To accomplish
this goal, they have been purposefully vomiting up their antiepileptic medications in an
attempt to lower their seizure threshold. Although this may be an extreme example, it
illustrates how uid the diagnostic boundaries between somatoform disorders are and that
many people will not t neatly into one category or another.
Treatment of patients with somatoform disorders can be difficult, especially
considering that patients are rarely motivated to engage in treatment. Nevertheless, you can
use the mnemonic I Do CARE to remember the speci c steps you can take to avoid
causing unnecessary iatrogenic harm and to maximize your patient’s chances of recovery and
wellness.
 

355
  
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 

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REVIEW QUESTIONS
1. A 38 y/o F comes to see her primary care doctor complaining of “constant watery
diarrhea” for the past 3 days. She is concerned that she has a “stomach u” and
desires a colonoscopy. Vital signs (including orthostatics) and physical exam are
both completely normal. She was seen last week by the same doctor for a headache
and the week before for a “sharp stabbing pain” in her lower abdomen. She has
been diagnosed with bromyalgia, irritable bowel syndrome, and chronic fatigue
syndrome. ese complaints have resulted in multiple referrals to specialists;
however, all work-ups have returned without signi cant ndings. e staff at the
clinic are frustrated when they see her name on the schedule because they feel
powerless to help her. Which of the following brain regions is most likely involved
in overinterpreting bodily sensations as being symptoms of an illness?
A. e ventral tegmental area
B. e insula
C. e anterior cingulate cortex
D. e orbitofrontal cortex
E. e hypothalamus
2. (Continued from previous question.) Which of the following interventions is least
likely to be effective at reducing the level of distress related to her symptoms?
A. Initiating a work-up for diarrhea including a colonoscopy
B. Referring to a therapist who specializes in CBT
C. Scheduling regular visits
D. Prescribing an antidepressant
E. All of the above are likely to be effective
3. A 41 y/o M sees his primary care provider complaining of a persistent headache.
He is concerned that this headache is a sign of a brain tumor. Family history is
notable for a father who died from glioblastoma multiforme at the age of 66. A full
physical and neurologic exam are normal, as is a complete set of blood tests. He
has undergone both a CT scan and an MRI within the past 3 months, neither of
which showed any signs of pathology. As soon as the doctor walks into the room,
he says, “I know the CT and MRI are normal. You’ve told me before. But I think
we’re missing something! We only did a standard MRI. I’ve been reading about
perfusion MRI and MR spectroscopy which are supposed to be more accurate than
standard MRIs. Do you think we could do that next?” e doctor reviews his chart
and sees that he has been to multiple healthcare providers in the area over the past
2 years with similar concerns despite over a dozen negative head scans and one
brain biopsy. What is the most likely diagnosis at this time?
A. Glioblastoma multiforme
B. Somatic symptom disorder
C. Conversion disorder
D. Factitious disorder
E. Malingering
F. None of the above
4. A 4 m/o girl is brought to the emergency department by her mother. e mother
says that the girl has had “rectal bleeding” for the past two days and provides
several diapers from her bag that contain streaks of blood. e girl is admitted to

357
the hospital and undergoes several diagnostic procedures including a physical
exam, a complete set of blood tests, and endoscopic examination under general
anesthesia. None of these studies reveal any abnormalities, and a plan is made to
discharge the patient for outpatient follow-up. After being told of this plan, the
mother becomes incredibly angry and yells, “How dare you try to kick my kid out
of the hospital! She’s bleeding and she’s going to die! You don’t care about anyone
except yourselves. is is malpractice. I’m going to report you to the medical
board.” Intimidated, the pediatrician agrees to keep the girl in the hospital for
further testing. at night, a nurse walks in on the mother making a cut on her
thigh and using her nger to insert the blood into the infant’s rectum. What is the
best next step?
A. Avoid a confrontational approach and continue the hospitalization
B. Discharge the patient from the hospital to return home with her
mother
C. Contact social and legal services
D. Consult psychiatry to evaluate the mother
E. Prescribe an antidepressant to the mother
 

358
 1. e best answer is C. While the insula is involved in the process of interoception
(or the ability to sense one’s internal bodily state), it is not directly involved in
interpreting these sensations as being representative of a serious medical condition
(answer B). Instead, the anterior cingulate cortex appears to be the region of the
brain that is most implicated in overinterpreting bodily sensations as medical
symptoms. While abnormalities in the hypothalamic–pituitary–adrenal axis have
been observed for people who experience frequent or severe somatization, this
region does not appear to be directly responsible for overinterpretation of
symptoms (answer E). e ventral tegmental area is involved in addictive disorders
(answer A), while the orbitofrontal cortex is involved in mood disorders (answer
D).
2. e best answer is A. Repeated work-ups for somatoform symptoms are unlikely
to relieve the distress associated with the symptoms and may put the patient at
greater risk of iatrogenic harm. For this reason, medical work-ups should generally
be avoided when there is a clear pattern of somatoform complaints and no
evidence of abnormalities (such as vital sign instability or other concerning
ndings). All of the other answer choices have been shown to be at least partially
effective for reducing somatoform symptoms.
3. e best answer is F. is patient is likely suffering from hypochondriasis which is
an obsessive-compulsive disorder characterized by excessive alarm about medical
symptoms that results in a conviction that they either have a serious illness or will
acquire one soon. It differs from somatic symptom disorder in that the concern is
not about the symptoms themselves but rather an obsessional belief that they have
a disorder even in the face of evidence to the contrary (answer B). e lack of any
speci c neurologic de cits rules out conversion disorder (answer C). It is possible
that the patient is feigning this illness either for primary or secondary gain;
however, there is no evidence of this, and his insistent belief that he has a medical
disease (as opposed to seeking the attention or bene ts associated with the sick
role) argues more strongly in favor of hypochondriasis (answers D and E). Finally,
the negative work-up thus far argues against a diagnosis of a brain tumor (answer
A).
4. e best answer is C. is is a textbook example of Munchausen syndrome by
proxy. As with any form of child abuse, the immediate priority is to ensure that the
child is safe. erefore, either continuing hospitalization (answer A) or discharging
the patient to stay with the mother (answer B) would both be inappropriate, as
either option leaves the girl in the care of her mother. Instead, social and legal
services should be contacted immediately to ensure that the girl is safe. While
people with Munchausen syndrome by proxy often have comorbid psychiatric
conditions that may warrant evaluation and treatment, this is not the priority right
now (answers D and E).

16 EATING DIsORDERS

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 An eating disorder is a pattern of dysfunctional food
intake that has the potential to jeopardize one’s physical and/or mental health. Classically,
this term has been used primarily to refer to anorexia nervosa and bulimia nervosa,
although there are other patterns of disordered eating (such as binge eating) that are now
recognized as well. Because they directly impact the ability of the body to maintain physical
health, eating disorders are among the most harmful and destructive of all mental disorders.
Both anorexia and bulimia follow a similar pattern involving two things: overvalued
beliefs about weight (“I am fat”) as well as the maladaptive behaviors that follow (such as
restricting food intake and/or vomiting after eating). From there, however, the similarities
between the two disorders quickly end. In fact, while anorexia and bulimia are often lumped
together in the general category of eating disorders, in practice there are so many differences
between the two that it is helpful to conceive of them as entirely separate disorders despite
the fact that they both involve eating. What is crucial to understand is that the line
separating these two disorders does not lie in the speci cs of the behavior involved. While
popular conceptions generally hold that “restricting = anorexia” and “vomiting = bulimia,”
the fact of the matter is that neither of these behaviors is diagnostic of either condition (as
some cases of anorexia involve purging and some, if not most, cases of bulimia involve
restricting). Instead, what differs between these disorders is not the content of the behavior
but rather the process by which those behaviors come about, as we will nd out over the
following chapter.

360
ANOREXIA NERVOSA

Anorexia nervosa (or just “anorexia”) is a condition in

which people perceive themselves to be signi cantly overweight even when they are
severely underweight by any objective standard. is perception causes them to make
changes to their eating habits such as restricting food intake to include only “healthy” or
low calorie foods (“Did you know that eating celery actually burns more calories than it
gives?”). In severe cases, food intake can be eliminated altogether. ese restrictions in diet
are often accompanied by other behaviors intended to lose weight including excessive
exercise, self-induced vomiting, and/or abuse of laxatives. Even when these measures are
successful at inducing weight loss, however, someone with anorexia still perceives
themselves as being overweight and will continue their efforts, lea ding to further weight
loss, malnutrition, and eventually even starvation. e key to understanding anorexia (as
opposed to normal efforts at losing weight) is that one’s self-perception is distorted, as no
amount of weight loss ever convinces the person that they are at an appropriate weight. is
leads to an endless loop between thoughts about appearance and attempts to lose weight.

Mechanistically, anorexia is best understood through the

lens of obsessive-compulsive disorders as it involves obsessive thoughts about appearance
that lead to speci c compulsive behaviors (including food restriction and excessive exercise)
intended to help calm these thoughts. Just like in obsessive-compulsive disorders, however,
no amount of weight loss ever leads to that “feeling of knowing” that one is nally thin
enough. Neurobiological studies have shown that anorexia shares with OCD both structural
and functional abnormalities in the anterior cingulate cortex. Despite these similarities,
however, anorexia differs from OCD in a few key ways. Most prominently, the obsession
with weight is distinctly ego-syntonic rather than ego-dystonic, as the person does not view
their attempts at losing weight as being in any way excessive or dysfunctional. From this
perspective, anorexia may actually be closer to obsessive-compulsive personality disorder

361
than OCD itself, which is re ected in higher rates of comorbidity with obsessive-
compulsive personality disorder than OCD proper. Anorexia also shares with obsessive-
compulsive personality disorder a characteristic rigidity of behavior (people often eat the
same thing at the same time every day with little variation) and a high level of
conscientiousness that plays directly into the distorted beliefs at the heart of the condition
(“I am fat, and it is wrong to be fat”). To remember the association of obsessions and
compulsions with anorexia, think of someone who has restricted their diet to eat only
OKRA. is person is engaging in Obsessive—Kompulsive Restriction and Avoidance of
food.
Anorexia nervosa is de ned by an obsessive-
compulsive pattern of distorted perception of
weight leading to food restriction and avoidance.
 

ink of someone with anorexia who has restricted their

diet to eat only OKRA: Obsessive—Kompulsive
Restriction and Avoidance of food.

Anorexia is a relatively rare condition that is found in less than 0.5% of the
population. Women are affected by anorexia 10 times as often as men (which contrasts with
OCD, where the gender ratio is about equal even for appearance-related conditions like
body dysmorphic disorder). Anorexia often begins around the time of puberty and young
adulthood, with a median age of onset of 18 years. Social circumstances that can produce
extreme pressure to be thin (such as participating in modeling or dancing) are associated
with higher rates of anorexia, suggesting that environmental and social factors play a large
role in the pathogenesis of the disorder.
e prognosis for anorexia is variable, with some people only engaging in transient
episodes of food restriction while others avoid food entirely for weeks or months at a time.
Complete elimination of food intake can lead to a state of severe malnutrition which can
negatively impact every organ system in the body. People with anorexia often develop
various medical problems including fatigue, amenorrhea, infertility, osteoporosis, electrolyte
abnormalities, and cardiac arrhythmias, and it is not uncommon for someone with severe
anorexia to end up in the hospital due to medical complications from persistent
malnutrition. Even when this happens, however, people with anorexia will often deny that
anything is wrong and will continue to refuse food, leading to a state of total starvation in
which damage to essential organ systems begins to occur. Because of the associated medical
complications (as well as a not insigni cant risk of suicide), anorexia is the single most
deadly mental illness, with up 20% of people dying as a result of the disorder (with 5%
dying within a decade of the initial diagnosis).

362
 Treatment of anorexia is another point of divergence from the
obsessive-compulsive disorders, as conventional treatments that work for OCD (like SRIs
and CBT) have not been found to be helpful for anorexia. Instead, treatment for anorexia
involves nutritional rehabilitation, monitoring for medical complications of
malnutrition, and engaging in psychotherapy (with no speci c form of therapy having been
shown to be more or less helpful than any other). Medications play a very limited role in
treatment of anorexia, as none have been shown to improve any clinically signi cant
outcomes. Even with full effort on the part of the clinician, however, anorexia is considered
to be a particularly difficult disorder to treat, as the ego-syntonic nature of the condition
frequently makes patients reluctant to engage in treatment (“Why should I go to therapy?
I’m ne, it’s everyone else in this corn-addicted country who’s got an issue!”).
Treating malnutrition related to anorexia is not as simple as sending someone to the
nearest all-you-can-eat buffet, and reinitiating food intake in someone with severe anorexia
must be done with great caution. While you might think that the goal would be to get
someone who is severely malnourished back to their normal weight as fast as possible, in
practice this is a terrible idea, as people in a state of starvation are at high risk of refeeding
syndrome (which can occur in up to 20% of patients hospitalized for anorexia). Repheeding
syndrome is a potentially phatal condition in which reinitiation of food provokes severe
complications, including hypokalemia, vitamin de ciencies, swelling, muscle breakdown,
seizures, hemolysis, heart failure, and even death. e hallmark of repheeding syndrome is
hypophosphatemia which is the direct cause of most of the ensuing abnormalities. In
someone with chronic malnutrition, phosphate stores are already low. When they are
suddenly fed again, insulin is released which causes further uptake of phosphate into cells
and leads to even greater hypophosphatemia. e low availability of phosphate prevents

metabolic intermediates from being produced, leading to

hypoxia and muscle dysfunction. is is particularly bad for the myocardium and the
diaphragm, and death can rapidly occur when these organs shut down. Given the potential
for serious adverse outcomes, repheeding should be approached with serious phorethought!

363
  

In someone with severe malnutrition as a result of

anorexia nervosa, always reinitiate feeding slowly to
avoid refeeding syndrome.
 

Repheeding syndrome is a potentially phatal condition

caused by hypophosphatemia.

Because of the potentially deadly nature of both severe malnutrition itself as well as
the complications of refeeding, inpatient medical hospitalization may be required in some
cases of anorexia. While there are no consistently agreed upon guidelines for when to admit
someone, the mnemonic CRAVE can help you to remember speci c criteria that should
make you at least consider hospitalization:
C is for Cardiac. Severe malnutrition can cause cardiac complications, including weakness
of the heart muscle and slowed electrical conduction which can both be fatal. In fact, heart
failure is one of the leading causes of death in anorexia, so the presence of cardiac problems
strongly suggests a need for hospitalization.
 

R is for Renal. People with anorexia are often dehydrated, especially when they are
engaging in excessive exercise or abuse of laxatives. is can cause severe kidney damage
which may need to be treated in an inpatient setting.
 

A is for Arrhythmia. Arrhythmias could be included under Cardiac, but they are worth a
separate mention. In particular, it is crucial to assess for bradycardia (or a low heart rate) as
this speci c physical nding is associated with high rates of premature death in anorexia. In
addition, given that people with anorexia tend to be bradycardic at baseline, the presence of
tachycardia (an abnormally elevated heart rate) is almost always pathologic and should
prompt a search for an underlying medical illness.
V is for Vital signs. In addition to bradycardia, people with malnutrition related to anorexia
can have changes in blood pressure (usually hypotension) and temperature (hypothermia)
that can portend a poor prognosis and a need for hospitalization.
 

E is for Electrolytes. Essential nutrients and minerals are often de cient in people with
anorexia, and severe abnormalities such as hypokalemia or hypoglycemia are good reasons to
consider hospital admission.
 

Consider hospitalizing patients with anorexia who

develop cardiac complications (including

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 arrhythmias), renal insufficiency, or electrolyte
abnormalities.
 

When someone’s body CRAVEs food, consider inpatient

admission: Cardiac Renal Arrhythmias Vital signs
Electrolytes

In summary, anorexia is best thought of as being on a similar spectrum to both OCD

(in that it involves obsessive thoughts about weight leading to compulsive restriction and
avoidance of food) as well as obsessive-compulsive personality disorder (in that these
thoughts are distinctly ego-syntonic and are accompanied by rigid thoughts and behaviors).
Prognosis is variable, and treatment can be difficult due to low levels of patient engagement.
However, there is ongoing research into different approaches including early intervention
and family-based approaches which may lead to better outcomes in the future.

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 BULIMIA NERVOSA
Bulimia nervosa is a pattern of disordered eating that involves episodes of binge eating (or
consuming large amounts of food in a short amount of time) followed by purging (or
compensatory behaviors to prevent the food that has just been eaten from being digested
and absorbed into the body). While self-induced vomiting is the most common form of
purging, it is not the only one, and people with bulimia will often engage in other behaviors
that serve the same purpose (such as frequent use of laxatives). In between binge eating
episodes, almost all people with bulimia engage in dieting and food restriction (although
this is not required for a diagnosis of bulimia in the DSM). e overall pattern of bulimia
can be summed up in the mnemonic IBM PC which stands for Impulsively Bingeing
Meals followed by Purging Compulsively.
Bulimia nervosa is characterized by impulsive binge
eating followed by compulsive purging to remove
the food.
 

IBM PC = Impulsively Bingeing Meals followed by

Purging Compulsively.

Like anorexia, the disordered eating behaviors are accompanied by distress about
feeling overweight. For someone with bulimia, however, concerns about being overweight
are often rooted in extreme interpersonal rejection sensitivity (“I am fat, and that will
make other people not want to be around me and I’ll feel like shit and die alone.”). e
presence of interpersonal rejection sensitivity should immediately make you think of
borderline personality disorder and other cluster B personality disorders, and indeed the
comorbidity between these two disorders is incredibly high (over 50%). In fact, people with
bulimia share so many other clinical features with borderline personality disorder (including
impulsivity, chronic dysphoria, poor self-esteem, and extreme fear of abandonment) that it
seems reasonable to suggest that in many cases bulimia can be thought of as a particular
manifestation of that condition.
 

Bulimia nervosa is highly comorbid with borderline

personality disorder and shares many clinical
features.

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Remember the association of Bulimia with Borderline

personality disorder and other cluster B personality
disorders!

e prevalence of bulimia in the general population is around 1%, making it

relatively rare (though still twice as common as anorexia). Like anorexia, bulimia is
diagnosed more than 10 times as often in women compared to men. e age of onset is
roughly the same, with the patterns of bulimia beginning in adolescence or early
adulthood. In contrast to anorexia (where someone must be underweight to be diagnosed),
in bulimia most people have a normal weight or are slightly overweight. In addition, a
variety of ndings from physical exam can argue for the presence of active purging,
including erosion of dental enamel, swollen salivary glands, and injuries on the back of the
knuckles from scraping against the teeth during self-induced vomiting.
Bulimia has a variable prognosis, with some people being able to stop bingeing and
purging immediately while others require intensive treatment. Ten years after their initial
diagnosis, about half of people with bulimia will have recovered fully, one third will have
made a partial recovery, and 10 to 20% will still have disordered eating habits. Medically,
self-induced vomiting is associated with signi cant health problems, including dehydration
(leading to tachycardia and hypotension), electrolyte abnormalities (leading to
disorientation and seizures), metabolic alkalosis related to loss of stomach acid, and gastric
ulcers. Frequent vomiting can also damage the esophagus which can then rupture (known as
Boerhaave syndrome). However, as a general rule the medical complications associated with
bulimia are generally not as severe as those seen in anorexia, and the mortality rate is
signi cantly lower.
 

Frequent self-induced vomiting can lead to

esophageal ruptures which is known as Boerhaave
syndrome.
 

Boerhaave syndrome = Been—heaving syndrome.

Effective treatment for bulimia does exist, as both medications and therapy appear to be
effective (with a combination of the two being superior to either alone). In particular, CBT
and a form of psychotherapy known as interpersonal therapy are both associated with
improvements in symptoms with a moderate effect size. SRIs are also helpful, with a small
effect size. Of note, certain medications (like bupropion, a non-serotonergic antidepressant)
must be absolutely avoided for patients with bulimia who are actively vomiting, as they may
increase the risk of seizures.

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To summarize, bulimia involves a combination of impulsive binge eating episodes followed
by compulsive purging behaviors (including self-induced vomiting) intended to prevent
weight gain. Bulimia involves high sensitivity to interpersonal rejection and is likely on a
similar spectrum to both borderline personality disorder and other disorders related to poor
impulse control such as addiction. Prognosis is better than for anorexia but can still be
associated with poor psychiatric and medical outcomes. Treatment involves psychotherapy
and antidepressant medications.
 
BINGE EATING DISORDER

Binge eating disorder is listed as a separate diagnosis

in the DSM, but in practice it is similar in nearly every way to bulimia except that the
bingeing episodes are not followed by compensatory purging behavior. However, the overall
pattern of the disorder (including a strong association with cluster B personality disorders)
is very similar to bulimia, and the treatments used are generally the same. Due to the lack of
compensatory purging behaviors, people with binge eating disorder tend to be quite
overweight (as compared to underweight in anorexia and normal weight in bulimia).
Interestingly, binge eating disorder is equally prevalent in men and women, suggesting that
purging as a speci c compensatory behavior likely has a large learned component. Binge
eating disorder has a better prognosis compared to bulimia, with 80% of people being in
remission at 5 years. With all of this in mind, it is perhaps best to conceptualize binge
eating disorder as a less severe variant of bulimia without compensatory behaviors (similar to
how agoraphobia is seen as a more severe variant of panic disorder with compensatory
behaviors). Because of this, we will lump binge eating disorder together with bulimia for the
rest of this book.

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DIAGNOSING EATING DISORDERS
When diagnosing eating disorders, it’s helpful to keep in mind that people will not always
meet strict DSM criteria for either anorexia or bulimia. In fact, an eating disorder “not
otherwise speci ed” is the most common diagnosis in this category, suggesting that
someone who doesn’t precisely t diagnostic criteria can still have clear patterns of
dysfunctional eating that warrant medical treatment. On a clinical level, you can use the
mnemonic SCOFF as a screening tool for eating disorders. Answering “Yes” to 2 or more
of these questions is suggestive of an eating disorder.
 

Asking about eating habits, weight changes, and

body image is helpful for
screening patients for eating disorders.
 

SCOFF: Do you make yourself Sick because you feel

uncomfortably full?
Do you worry that you have lost Control over how much
you eat?
Have you recently lost more than One stone (14 lbs.) in a
3-month period?
Do you believe yourself to be Fat when others say you are
too thin?
Would you say that Food dominates your life?

While the SCOFF criteria can help to identify the presence of an eating disorder,
they do not differentiate between anorexia and bulimia. Taking time to do so is important
given the major differences in prognosis and treatment between the two. In fact,
longitudinal studies have shown that people with anorexia rarely “cross over” into bulimia
(and vice versa), further supporting the notion that they are entirely separate conditions.
Because we have already established that the speci c behaviors involved do not differentiate
between anorexia and bulimia (as people with anorexia can both binge and purge while
people with bulimia will often restrict food), use the following clinical features instead to
guide your diagnosis.
First, while people with anorexia and people with bulimia both hold the same
fundamental beliefs about their body (“I am fat”), the reasons why the idea of being fat
causes them distress are different. Someone with anorexia is more likely to believe that it is
wrong to be fat. Like other disorders related to OCD, one’s weight in anorexia is ltered
through the lens of error processing. For someone with anorexia, being fat isn’t just a matter
of not looking attractive enough—it is a fundamental error, an aberration, a moral insult. In
contrast, people with bulimia do not feel distress about their weight due to an overactive
error recognition system. Instead, fears about being overweight are related to the feared

369
effects that being overweight will have on their ability to be loved and accepted by others (it
is socially isolating to be fat).
Second, anorexia and bulimia differ in regards to the underlying reasons for engaging
in disordered eating patterns (even if the behaviors themselves can be identical between
the two disorders). Food restriction and other behaviors in anorexia are highly compulsive (or
Kompulsive if you want to stick with the OKRA mnemonic), and people with anorexia
often exert an incredibly high degree of control over their behavior. In contrast, food intake
in bulimia is primarily impulsive, and people with this disorder often report a distinct lack
of control over eating. is inability to not start a behavior strongly resembles the pattern
seen in addiction. While many people with bulimia will also engage in compulsive food
restriction in an attempt to lose weight, the core behaviors of the disorder (bingeing and
purging) occur primarily due to de cits in impulse control as they are unable to resist the
high level of immediate positive reinforcement that foods (especially sweet or fatty foods
like cake) are able to provide. (Interestingly, people with bulimia appear to have an
overactive endogenous opioid response to food, which provides a clear mechanistic link to
the underlying pathophysiology of borderline personality disorder.) Finally, someone’s body
weight can be an easy way to distinguish between the two disorders as people with anorexia
must be underweight while people with bulimia are often a normal weight or slightly
overweight. is reinforces the idea that anorexia results from distorted self-perception (as
the person is actually underweight despite believing otherwise) while someone with bulimia
or binge eating disorder who thinks they are fat may actually just have an accurate self-
perception.

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DIFFERENTIAL DIAGNOSIS OF EATING DISORDERS
Because the presence of disordered eating (including restriction, avoidance, bingeing, and
purging) is fairly unique to eating disorders, true misdiagnoses are rare. Nevertheless, it is
important to be mindful of the way that other psychiatric syndromes can interact with
appetite and eating patterns to avoid drawing incorrect conclusions. Further, because both
anorexia and bulimia share core mechanisms with other disorders (OCD and obsessive-
compulsive personality disorder for anorexia and borderline personality disorder and
addiction for bulimia), comorbidity is incredibly common, so make sure to be on the
lookout for missed diagnoses.
 
NORMALCY
A desire to be thin or avoid overeating are not pathological. Indeed, restricting caloric
intake to some degree would probably be bene cial for most people in industrialized
countries where obesity is a bigger problem than hunger. In addition, many societies place a
high degree of pressure on individuals (and women in particular) to meet unrealistic
standards of beauty. Because of this, normalcy should always be on the differential for
anyone with restricted food intake patterns, and no one should be diagnosed with an eating
disorder on the basis of their weight alone. Try to focus on the underlying process of each
disorder (a distorted body image leading to compulsive behaviors in anorexia, and extreme
interpersonal rejection sensitivity combined with a high degree of impulsivity leading to
bingeing and purging in bulimia) to make the call. Someone with disordered eating hab

its that are quickly corrected with simple education on

what healthy eating involves is also unlikely to have either anorexia or bulimia, as by
de nition these disorders are characterized by speci c cognitive distortions that prevent easy
xes.
BODY DYSMORPHIC DISORDER
It’s easy to confuse anorexia and body dysmorphic disorder, as both involve an obsessive
preoccupation with perceived bodily dis gurement leading to compulsive behaviors focused
on appearance. In fact, some have argued that anorexia should be seen as a particular form
of body dysmorphic disorder that is focused on weight rather than a speci c body part.
However, a few lines of evidence argue against the idea that anorexia is simply a form of
body dysmorphic disorder, including differences in gender ratio (female-predominant in
anorexia versus balanced in body dysmorphic disorder) and treatment response (CBT and
SRIs working for body dysmorphic disorder but not anorexia). While the precise reasons
are unclear, on a neurobiological level an obsessional preoccupation with thinness seems to
differ enough from an obsessional preoccupation with dis gurement in speci c parts of the
body that the two warrant separate diagnoses.

371
  
OBSESSIVE-COMPULSIVE DISORDERS
As discussed previously, anorexia overlaps considerably with OCD to an extent that it is
perhaps best understood within an obsessive-compulsive framework. e rate of
comorbidity between anorexia and other obsessive-compulsive disorders is also quite high,
suggesting a shared vulnerability between the two. For this reason, it is worthwhile to
consider screening people with OCD and related disorders for anorexia and vice versa.
 
BORDERLINE PERSONALITY DISORDER
Patients with bulimia are 15 times more likely to show cluster B personality pathology than
matched controls, and there are many overlapping symptoms between both. erefore,
careful assessment of personality disorders is needed for people with bulimia, with
treatment considerations being revised to account for these disorders if they are present
(such as making a referral to dialectical behavior therapy or other evidence-based treatments
for borderline personality disorder when available).
 
ADDICTION
e impulsivity seen in bulimia appears to overlap with addiction, and some have argued
that people with bulimia do in fact meet criteria for having an addictive disorder as they
engage in repeated use of positive reinforcers (in this case, food) despite negative
repercussions. Indeed, the neurobiology of bulimia resembles that of addiction, with
increases in ΔFosB being observed in the nucleus accumbens. While the DSM doesn’t
officially recognize “food addiction” as a diagnosis, there is at least some merit to the idea as
some of the same principles apply to both. In addition, the high impulsivity seen in bulimia
likely predisposes to the development of other forms of addiction, making screening for
substance use a good idea for these patients.
 
DEPRESSION
Depression has a complex relationship to anorexia. For one, appetite is often decreased in
people suffering from depression (the A in SIGECAPS) which can lead to large decreases
in weight. However, patients with depression do not suffer from distorted body image and
are not actively attempting to lose weight in the same way that people with anorexia are. To
complicate matters further, the cognitive and neurovegetative symptoms of depression can
be difficult to disentangle from the normal physiologic effects of starvation. However, some
research has suggested that depressive symptoms in anorexia tend to resolve with restoration
of regular eating habits. For this reason, antidepressants are generally indicated only when
there is clear evidence of comorbid depression.
For bulimia, depressive symptoms should be clearly differentiated from chronic dysphoria
related to borderline personality disorder. In cases where mood episodes are present, both
SRIs and CBT have been shown to be effective at not only treating depression but also
reducing the frequency of bingeing-purging episodes, and the combination of medications
and psychotherapy is superior to either alone.
 
ANXIETY
People with both anorexia and bulimia often have severe anxiety related to weight gain and
food intake. However, it’s important to avoid diagnosing a separate anxiety disorder without
clear evidence that this anxiety spreads into other domains outside of eating and weight. In

372
addition, just having anxiety can lead to reduced appetite through activation of the “ ght or
ight” mode. is shouldn’t be diagnosed as an eating disorder, as there is a clear upstream
cause for the change in food intake.
 
AUTISM
While it is not a diagnostic requirement, restricted patterns of food intake are common in
people with autism (they are notoriously “picky eaters”). In contrast to anorexia, however,
overall intake of calories is not compromised, and there is no evidence of distorted body
image in these patients.

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PUTTING IT ALL TOGETHER

For many people, eating (and its associated rituals such as having
dinner with family, making a meal with friends, or experiencing a new type of food while
traveling) are among the most delightful moments of life. If all eating disorders did was rob
these moments of their joy, that would be bad enough. However, because eating disorders
threaten not just the quality of life but even life itself, it is essential to stay vigilant for these
conditions. Use the SCOFF mnemonic to screen for eating disorders, then use what you
know about the underlying pattern of each disorder to gure out what mechanisms are at
play. For anorexia, remember that distorted self-perception leads to Obsessive—Kompulsive
Restriction and Avoidance of food (OKRA) while for bulimia, extreme interpersonal
rejection sensitivity mixed with poor impulse control leads to Impulsive Bingeing of Meals
followed by Purging Compulsively (IBM PC). Keep in mind that not everyone will t
perfectly into the precise patterns we have discussed, but don't let this deter you from
recommending treatment for someone who clearly has disordered patterns of eating yet
doesn’t technically meet criteria for a DSM disorder.

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REVIEW QUESTIONS
1. A 14 y/o F begins following her friends into the bathroom after lunch to purge.
She has done this every day for the past month but has never previously engaged in
this behavior. She reports that she enjoys eating but worries that it will “make me
fat and unpopular.” She denies food avoidance, food restriction, or excessive
exercise. She denies eating past the point that she feels full. When asked, she says
that she believes herself to be “normal” weight but is engaging in these behaviors
to avoid becoming fat. Her BMI is 20.2. What is the most likely diagnosis?
A. Anorexia nervosa
B. Bulimia nervosa
C. Binge eating disorder
D. More than one of the above
E. None of the above
2. A 19 y/o F moves to New York to become a model. She lives with a roommate
who is also a model who gives her advice on what foods to avoid, how frequently
to exercise, and how to use diuretics and laxatives on days when there is a photo
shoot to appear as thin as possible. She begins limiting her food intake to a single
cucumber, a wedge of lettuce, and up to a dozen cups of green tea without sugar or
milk per day. While she initially struggles with this diet, after a few weeks she
nds that her hunger has gone away and that food no longer holds any appeal for
her. Within several months, she has lost over 40 pounds. Her current BMI is 15.9.
While initially she is able to nd modeling contracts, recently she has been told
that she looks “like you have cancer or something” and that she needs to gain
weight. Despite being told this, she continues her attempts to lose weight. During
a photo shoot the next day, she suddenly collapses and is rushed to the hospital.
Vitals signs upon initial evaluation are HR 104, BP 98/60, RR 20, and T 94.9°F.
Which of the patient’s vital signs are least consistent with a diagnosis of anorexia
nervosa?
A. Heart rate
B. Blood pressure
C. Respiratory rate
D. Temperature
E. All of her vital signs are consistent with a diagnosis of anorexia nervosa
3. (Continued from previous question.) e patient is admitted to the hospital and
treated with antibiotics. She is confused and is oriented to person but not place,
time, or situation. As she lacks capacity, a decision is made in consultation with the
ethics department to initiate parenteral feeding given her risk of aspiration. On the
fourth day of hospitalization, she suddenly develops psychomotor agitation, severe
hypotension, and respiratory distress. An echocardiograph shows a left ventricular
ejection fraction of 20%; however, electrocardiogram and cardiac markers are both
normal. She is transferred to the intensive care unit in a state of cardiogenic shock.
Which electrolyte is most implicated in the development of this outcome?
A. Sodium
B. Potassium
C. Chloride
D. Calcium

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 E. Magnesium
F. Phosphate
4. A 30 y/o M arrives for an initial consultation with a dietician. He recently suffered
a heart attack and was found to have coronary artery disease, hyperlipidemia, and
previously undiagnosed diabetes mellitus type 2. His BMI is 38.8. Upon initial
evaluation, he reports having been overweight for as long as he can remember
leading to frequent bullying and loneliness. He has attempted to lose weight at
various times in his life but has been unable to continue these efforts for more than
a few weeks at a time. His current diet consists primarily of prepackaged
microwaveable food from the grocery store. Once or twice per week he will drive
to the grocery store and pick up “all of my favorites,” including ice cream, chips,
and candy, and “ravenously devour” several grocery bags worth of food while
watching television. He denies self-induced vomiting, use of laxatives, or exercise.
He views himself as “hopelessly obese.” Which of the following features of his case
most argues against a diagnosis of bulimia nervosa?
A. Current obesity
B. Self-perception as being overweight
C. Lack of purging
D. Male gender
E. Obesity beginning in childhood
5. A 38 y/o F sees her primary care doctor for an annual physical. Her doctor, who
has known her since childhood, notices immediately that she appears thinner. Her
current weight is 102 pounds, which has decreased from 128 pounds six months
ago. On interview, she appears tired and sullen. When asked about the weight loss,
she says that her appetite has “completely vanished” and that she only eats “when I
feel like it, which is basically never.” Her diet consists largely of granola bars, deli
lunch meats, and “whatever else is around the house that I don’t have to cook.” She
denies eating past the point of feeling uncomfortably full or any sense of having
lost control over her eating habits. She does not exercise. She views herself as
“thin.” BMI is 17.0. She has stopped menstruating for the past three months, but
multiple home urine pregnancy tests have been negative. Her mental status exam is
notable for slowed movements, a restricted affect, absent prosody, and poor ability
to concentrate. What is the most likely diagnosis?
A. Anorexia nervosa
B. Bulimia nervosa
C. Binge eating disorder
D. More than one of the above
E. None of the above

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1. e best answer is E. is girl does not suffer from an eating disorder, as her
purging appears to be related to peer pressure rather than any cognitive or
behavioral factors. Of note, she lacks a distorted body image and is not
underweight, ruling out anorexia (answer A). While she engages in purging
behaviors, she lacks impulsivity or a binge pattern to her food intake, ruling out
bulimia and binge eating disorder (answers B and C).
2. e best answer is A. Vital signs in anorexia are characterized by bradycardia,
hypotension, and hypothermia (answers B and D). Respiratory rate is generally
normal (answer C). In contrast, this patient exhibits signs of tachycardia, which is
extremely unusual and is often a sign of an underlying medical illness such as an
infection.
3. e best answer is F. e diagnostic hallmark of refeeding syndrome is
hypophosphatemia related to reinitiating feeding in someone who is chronically
malnourished. While abnormalities in other electrolytes are often seen in cases of
refeeding syndrome, it is most consistently associated with phosphate.
4. e best answer is C. is patient likely meets criteria for binge eating disorder
which is related to bulimia nervosa but ultimately considered a separate diagnosis.
While this patient engages in impulsive binges, he does not then compulsively
purge as would be required for a diagnosis of bulimia. While people with binge
eating disorder are often signi cantly overweight and those with bulimia are often
a normal weight or just slightly overweight, this is a clinical observation and not
part of the diagnostic criteria (answer A). His self-perception as being overweight
is accurate in this case rather than representing a distorted body image as in
anorexia (answer B). While bulimia is de nitely more common in women
compared to men, this is also not exclusionary (answer D). Finally, the fact that his
obesity began in childhood is diagnostically irrelevant (answer E).
5. e best answer is E. While this patient has been restricting her diet recently, this
appears to be secondary to a change in appetite rather than out of a desire to lose
weight as would be seen in an eating disorder. She sees herself as thin, which
argues against a diagnosis of anorexia (answer A), and does not engage in episodes
of impulsive binge eating, which argues against a diagnosis of either bulimia or
binge eating disorder (answers B and C). In this case, her change in appetite is
possibly due to an episode of depression as evidenced by the ndings on her
mental status exam; however, a medical cause (such as hypothyroidism) cannot be
ruled out at this time.
 

377
17 DEVELOPMENT

We now turn our attention to the process of development which occurs over infancy,
childhood, adolescence, and early adulthood. Development is a complex process that
involves speci c changes in physical attributes, intellectual capabilities, social skills, and
emotional expression that should occur at roughly the same time in every person’s life (such
as learning how to walk, talk, or control one’s bowels). is developmental process is crucial
for creating a physically, intellectually, socially, and emotionally mature adult.
Many of the psychiatric disorders we have discussed so far can have their onset during
development (including anxiety, eating disorders, and schizophrenia), and they will often
present with different signs and symptoms and require distinct treatment considerations
compared to cases beginning in adulthood. ese variations are incredibly important and
form the basis for the eld of child and adolescent psychiatry. However, they are largely
beyond the scope of this book.
Over the next few chapters, we will consider speci c disorders of development that
result in cognitive and behavioral impairment. ese neurodevelopmental disorders
include intellectual disability, autism, and attention de cit hyperactivity disorder (ADHD).
To understand disorders of development, however, you must rst know what is considered
within the realm of normal development. Only once you have that understanding can you
begin to detect and diagnose abnormalities. For this reason, we will begin this chapter with
a discussion of normal development.

378
NORMAL DEVELOPMENT
ere is a wide range of variability in what is considered “normal” development, and
different children progress through development at different rates. However, a few processes
(primarily the development of speci c motor, speech, and social skills) are considered vital
for progressing towards full maturation. ese are known as developmental milestones,
and the typical expectation for children is that they will achieve these by a certain age.
Failure to hit these milestones on time may be a sign of a medical condition that requires
further investigation, so having a solid grasp of these milestones is essential for picking up
on cases where there may be cause for concern.
 
INFANCY

Infancy is de ned as the period between birth and when the child
is able to walk (which roughly coincides with the rst year of life). Developmental
milestones in infancy are primarily motor skills as speech has not yet developed. Infants
should be able to Lift their head while laying prone on the ground at 2 months (notice how
there are 2 brushstrokes in the letter L). By 4 months, they should be able to roll over from
laying on their back to their front (there are 4 letters in both “roll” and “over”). At six
months they can sit upright, and by 9 months they should be able to both stand and crawl.
Finally, at wone year of age, they should be able to walk with assistance.
Speech is fairly limited before the age of 1. At 6 months, infants begin to 6abble, and by 9
months they may say simple syllabic words like “mama” or “dada” (although not always used
correctly). Finally, by age wone they should be able to use at least wone word with intention
and follow wone step commands. While children do not develop full speech until after
infancy, they are still social creatures. Infants demonstrate a preference for the sound of the
human voice over other sounds immediately at birth. ey will begin smiling in response to
others by 4 months and laughing by 6 months. Between 6 and 12 months of age, infants
can distinguish between different people and will form attachments to familiar caregivers
such as parents or others living in the home. Infants often develop stranger anxiety around
this time where the presence of new or unfamiliar people prompts bouts of crying,
becoming unusually quiet, or attempting to nd their primary caregiver. Stranger anxiety is
a completely normal phase of social development and often subsides by 12 months (and
almost always by the age of 2).
 

Infant milestones primarily involve speci c motor

379
 and social skills.
 

Lift head at 2 months (2 brushstrokes in the letter L).

Roll over at 4 months (4 letters in both “roll” and
“over”).
Sit and 6abble at six (6) months.
Walk with assistance, say wone word with intention,
and follow wone-step commands at wone year.
EARLY CHILDHOOD
Early childhood is de ned as the period between 1 and 3 years of age. Children this age are
often called toddlers which underscores the primary importance of walking (or “toddling”)
in this stage of development. Toddlers rapidly develop additional motor and speech skills
throughout these years.
Between the age of 1 and 2, toddlers go from knowing a single word to over 2
hundred words which they can put 2-gether into 2 word sentences such as “Carry me!” or
“Me go.” About 2 out of every 4 words can be understood by strangers, and they should be
able to follow a 2-step command. Cube stacking is often used as a proxy for motor skills,
and the number of cubes they can stack should be approximately equal to their age times 3
(so a 2-year-old should be able to stack 6 cubes). ey should also be able to copy a line
(which is essentially a connection between 2 points). ey can also feed themselves using a
cup and spoon by the age of 2. eir motor abilities are generally well developed to the
point that they can run.
Socially, toddlers will often engage in parallel play rather than actively interacting
with other children (recall that you need 2 lines to be in parallel). Toddlers also develop
separation anxiety between 12 and 15 months of age. During this time, they will show a
strong preference for known caregivers such as parents and will cry or tantrum when these
caregivers leave. (Note that this is different than the stranger anxiety that is normal between
6 and 12 months of age. Stranger anxiety involves distress when new people are introduced
whereas separation anxiety involves distress about when caregivers leave.) Separation anxiety
is completely normal and often goes away by the age of 3.
 

Milestones at age 2 primarily involve speech and

motor skills.
 

Over 2 hundred words put 2-gether into 2-word

sentences.
About 2 of every 4 words understandable by strangers.
Can follow 2-step commands.
Can copy a line connecting 2 points.
Play is in parallel.

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 Cube stacking is a commonly used test of motor
development.
 

Children can stack a number of cubes equal to their age

times 3.

By 3 years of age, speech has progressed to include 3-word sentences

such as “I want milk,” and 3 out of every 4 words should be understood by strangers. Toilet
training occurs during this stage of development, and a 3-year-old should be able to exhibit
both bowel and bladder control (“pee at 3”). A 3-year-old can also ride a tricycle (though
not yet a bicycle). Socially, a 3-year-old will begin to interact with other children their own
age and will typically be able to name one or two people in particular as being friends.
Milestones at age 3 primarily involve speech and
toileting.
 

3-year-olds can say 3-word sentences, with 3 out of 4

words understood by strangers.
ey can ride a tricycle and demonstrtate bowel and
bladder control (“pee at 3”).
 
PRESCHOOL AGE
Years 4 and 5 are often called the preschool age as children this age are often independent
enough to be left outside the immediate company of their parents and can socialize easily
with others their own age, including engaging in cooperative play.

In terms of milestones, by age 4 speech should be fully

understandable with 4 out of 4 words understood by strangers (although there may still be

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some small mistakes with complex grammar like saying, “I goed outside”). Motor skills
include the ability to draw a 4-pointed plus sign. By 5, all basic aspects of language should
be present, and 5peech should be fully comprehensible. ey can also begin to perform
more complex motor tasks including 5kipping and tying their own 5hoes. Children at this
age enjoy both hearing and telling stories, and they can often begin reading (typically very
simple books with lots of pictures). Writing begins around the age of 5 (note that there are
5 points in the letter W), often beginning with letters, numbers, and simple words (with
fully formed sentences coming later).
 

By age 5, complex motor skills are possible, and

speech should be fully formed.
 

A 4-year-old should have 4 out of 4 words understood by

strangers.
A 5—year-old can 5peak fully, 5kip, tie their own 5hoes.
Writing letters, numbers, and simple words begins (5
points in the letter W).
 
SCHOOL AGE

Ages 6 through 12 are when the child begins going to school.

Many basic motor and speech skills are in place by school age (although a few more
complex tasks such as being able to ride a bicycle will emerge during this time). For this
reason, developmental milestones tend to shift towards social and cognitive abilities.
Children of school age tend to be rule oriented and respond to peer pressure. When
interacting with others, they tend to be quite conscience-driven and can sometimes rely on
overly rigid notions of right and wrong. Cognitively, reading and writing abilities become
more fully formed, and by the age of 8 children should be able to read a 8ook
independently.
Following school age, development continues through adolescence and into adulthood.
While there are additional developmental processes during this time such as puberty, most
cognitive, motor, and speech abilities are in place by age 12.
By age 8, children should be able to read a book
independently.
 

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 An 8-year-old can read a 8ook.
 
ADOLESCENCE
Adolescence involves the process of maturation from childhood to adulthood. Puberty can
begin during school age (most often at age 10 for girls and 12 for boys), but the most
dramatic changes are typically not seen until age 13 and after. Puberty most directly
involves maturation of the sexual organs, but this is also accompanied by the development
of secondary sexual characteristics such as growth of body hair, changes in bone structure,
and deepening of the voice.

On a cognitive level, most adolescents are able to

comprehend abstract concepts (rather than just concrete ones) and can read and write
about topics intended for any age. Socially, romantic feelings and exclusive relationships also
emerge during this age. Identity is a key developmental concern during adolescence, and
many teenagers will associate with various peer groups and “try on” different identities to see
what ts. Contrary to what is commonly depicted in popular media, most adolescents feel
close to their parents, although many also feel a need to separate from their parents and
establish their own identity. ere is an increase in risky behavior that occurs during late
adolescence and early adulthood, and many actions are done without taking the time to
fully appreciate the possible consequences, leading to an increased rate of accidents, risky
sexual behavior, and use of drugs. A number of psychiatric conditions can also begin to
emerge during this time, including depression and eating disorders. e mnemonic
HEADSS has been developed to assist in identifying common areas of stress or harm in
adolescents including Home (who they live with), Education (how they are doing in
school), Activities (what they do outside of school), Drugs, Sexuality, and Suicide.
 

e major sources of stress or harm in adolescents

involve the home, school, activities, drugs,
sexuality, and suicide.
 

HEADSS: Home, Education, Activities, Drugs,

Sexuality, Suicide

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While all of the major physical changes of development are in place by the end of
adolescence, a variety of cognitive, social, and emotional changes continue to occur
throughout adulthood and even into older age. For this reason, development should be seen
not as a task that is “completed” but as a continuing process of change that occurs over the
entirety of one’s lifespan.
 

384
NEURODEVELOPMENTAL DISORDERS
Development is a complex process, and there are many places along the way for things to go
awry. While the developmental milestones we have discussed are not hard and fast rules, a
consistent failure to meet milestones should prompt an immediate medical work-up for
possible underlying causes. Start by characterizing the nature of the de cits. Are they
observed only in a single area (such as speech) or is there a broad failure to meet milestones
in other domains like cognition and social skills as well? Is there a sudden slowing of
development for a child who was previously developing without a problem, or has the child
lagged behind their entire life? Is there any evidence that previously achieved milestones
have been lost?
Abnormalities in development can occur for any number of reasons, including a wide range
of genetic, environmental, infectious, anatomical, metabolic, nutritional, and immunologic
diseases. However, most of these are well beyond the scope of this book. Instead, we will
focus speci cally on neurodevelopmental disorders (including intellectual disability,
autism, and ADHD) which either are commonly evaluated by psychiatrists or are most
likely to mimic other psychiatric syndromes. For the rest of this chapter, we will learn about
intellectual disability and the various ways in which this can present, with a full discussion
of autism and ADHD in the next two chapters.
 

385
INTELLECTUAL DISABILITY

Intellectual disability (previously known as mental

retardation, although this term is now considered pejorative and should not be used
clinically) is characterized by signi cant and persistent de cits in cognition that result in a
decreased ability to function independently on a day-to-day basis. Unlike most psychiatric
syndromes, a diagnosis of an intellectual disability is not based upon the presence of speci c
signs or symptoms. Rather, it is based around the two things in its name: assessments of
intelligence (“intellectual”) and evidence of an impaired ability to function independently
(“disability”). Intelligence is generally assessed using the intelligence quotient (or IQ) which
is a general measure of someone’s abilities in multiple domains, including reading, math,
vocabulary, memory, general knowledge, visual skills, verbal uency, and reasoning. IQ tests
are scored in such a way that the average person receives a score of 100, with a standard
deviation of 15. is means that those who score below 70 comprise the lowest 2.5% of the
population. is was chosen to be the cut-off under which someone is said to have an
intellectual disability. However, it is not enough to simply score in the lowest 2.5% of the
population; there must also be evidence of impaired functioning in multiple areas of daily
living (such as interpersonal communication or the ability to care for one’s self ).
 

For unknown reasons, males are affected by intellectual disability more often than
females, with a gender ratio of 2 to 1. By de nition, intellectual disability needs to be
present during early childhood which distinguishes it from other conditions that result in
similar levels of cognitive impairment but only later in life (like dementia).
While all cases of intellectual disability represent lifelong conditions with persistent
de cits, the prognosis can vary widely from one case to the next. Some people with mild
intellectual disability (with an IQ in the range of 50-69) will struggle in certain areas but
can often complete school with some assistance, nd jobs, and engage in meaningful
relationships. ose with moderate intellectual disability (with an IQ in the range of 35-49)
are often more impaired, with de cits in signi cantly more areas that necessitate assistance
with even basic activities of daily living such as cooking or housework. However, they can
often perform some tasks independently. Finally, those with severe intellectual disabilities
may require assistance with every aspect of their lives, including feeding, bathing, and
toileting. e majority of people (over 75%) with an intellectual disability have a mild form,
with moderate and severe forms comprising the other 25%.

386
Intellectual disability is not a medical disease or a disorder, and there is no “cure.”
Management generally involves various forms of behavioral, occupational, physical, and
speech therapy along with individualized educational programs. Management can also
involve training both patients and their caregivers to develop speci c skills that will
enhance adaptive functioning. For example, a child who has difficulty learning to use the
toilet would be given speci c trainings on this and provided with reinforcers when they do
it correctly. In this way, the negative consequences of the intellectual disability are mitigated
as much as possible, with the overall goal of increasing independence and autonomy.
In over half of all cases of intellectual disability, no clear cause is found. is is known as an
idiopathic or non-syndromic intellectual disability. In the other half of cases, however, an
underlying medical cause can be identi ed, which is known as a syndromic intellectual
disability. As a group, syndromic intellectual disabilities are often more severe than
idiopathic cases (although this is not always the case). For the remainder of this chapter, we
will brie y cover some of the most common syndromic causes of intellectual disability. is
is not intended to be a comprehensive list, as a full understanding of all forms of intellectual
disability would require an entire book on its own. Nevertheless, this guide should serve as a
high-yield starting point for recognizing some of the most common causes of syndromic
intellectual disability as well as those with a signi cant behavioral component. ( is
information overlaps signi cantly with the eld of pediatrics and may be beyond the scope
of what is needed for some readers, so feel free to skip ahead to the next chapter if you don’t
think that it will apply to you.)
DOWN SYNDROME
Down syndrome is the single most common cause of genetic intellectual disability and
occurs in around 1 of every 1,000 live births. It is caused by the presence of a third copy of
chromosome 21 known as trisomy 21. (You can remember the association of Down
syndrome with trisomy 21 by thinking of someone going out to hit the bars and Downing
some drinks on their 21st birthday.) e likelihood of having a child with Down syndrome
increases with maternal age, particularly above 35 years old.
Down syndrome is a trisomy disorder caused by a
third copy of chromosome 21.
 

ink of someone hitting the bars and Downing drinks

on their 21st birthday.

387
 Intellectual disability is the predominant clinical feature
of Down syndrome, with signi cant delays in attaining developmental milestones and
mental abilities no greater than an 8-year-old even as an adult. A diagnosis of Down
syndrome is based upon genetic testing (either in utero or after birth) to demonstrate the
chromosomal abnormalities associated with the disorder. However, you can also often make
a clinical diagnosis based upon certain signs. Physical exam often reveals a generally short
stature and distinctive facial features, including attening of the face, prominent eyelid
folds, slanted eyes, a at nose, and a large tongue relative to the small size of their mouth.
People with Down syndrome often have additional medical comorbidities that are
characteristic of the condition, including congenital heart disease and gastrointestinal
abnormalities such as duodenal atresia.
e prognosis for Down syndrome varies on the degree of intellectual disability
present, with some people able to lead fairly independent lives and others being totally
dependent upon others. However, people with Down syndrome have a signi cantly
increased risk of developing Alzheimer’s disease, with over half showing signs of further
cognitive decline during their lifetime.
 
FRAGILE X SYNDROME

Fragile X syndrome is the second most common cause of

genetic intellectual disability after Down syndrome. In addition to cognitive de cits, people
with fragile X syndrome often have additional neuropsychiatric symptoms that may
resemble other psychiatric syndromes, including social withdrawal, repetitive stereotyped
behavior, and poor attention. Physical exam often reveals X-tra large testes (macro-
orchidism), X-tra large jaws (macrognathism), and X-tra large ears (macrotia), all of which
should be easy to associate with fragile X syndrome.
 

388
 Fragile X syndrome is a genetic cause of intellectual
disability characterized by social withdrawal,
repetitive behavior, and enlarged testes, jaws, and
ears.
 

Fragile X syndrome features X-tra large testes, jaws, and

ears.

Fragile X syndrome is caused by an expansion of the trinucleotide repeat CGG on the

X chromosome. While most people have less than 40 CGG repeats, someone with fragile X
syndrome often has over 200. is increase in the number of CGG repeats results in
suppression of a speci c gene (known as FMR1) which produces a protein required for the
development of interneuronal connections. (Suppression of the FMR1 gene changes the
shape of the X chromosome and causes it to appear “fragile” under a microscope which
gives the disorder its name.) e poor connection between neurons is believed to underlie
the intellectual de cits that individuals with this condition display. You can remember the
association of the trinucleotide repeat CGG by associating it with Congenitally Giant
Gonads.
 

Fragile X syndrome is caused by expansion of the

trinucleotide repeat CGG
on the X chromosome.
 

CGG = Congenitally Giant Gonads.

 
FETAL ALCOHOL SYNDROME

Fetal alcohol syndrome is a common cause of

intellectual disability that is related to alcohol exposure in utero. e perinatal period is

389
often complicated by low birth weights, preterm deliveries, and small stature. After birth,
the extent of observed de cits depends largely on the amount of alcohol exposure, with
some people having only mild symptoms and others experiencing profound disability.
People with fetal alcohol syndrome often have problems with attention and behavior as
well, leading to a higher rate of legal, academic, and social difficulties compared to their
peers. Many also suffer from severe problems with motor coordination. Individuals with
fetal alcohol syndrome often have consistent physical characteristics that can help to guide a
clinical diagnosis, including small eye openings, a smooth philtrum (the cleft between the
nose and lips), and a thin upper lip. Like any form of intellectual disability, there is no cure
for fetal alcohol syndrome, so the focus of medical intervention is largely on preventing
prenatal alcohol exposure through public health education programs.
 

PRADER-WILLI SYNDROME
Prader-Willi syndrome is a genetic disorder that results in intellectual disability and speci c
neuropsychiatric signs including frequent tantrums, emotional lability, and self-injurious
behavior such as scratching and skin picking. Physical examination can reveal a short stature
and hypogonadism, with poor muscle sometimes being observed during infancy. However,
by far the most speci c symptom of Prader-Willi syndrome is a persistent and unremitting
state of insatiable hunger that is not relieved by eating. When permitted access to food,
people with Prader-Willi syndrome can continue to eat for hours on end. is directly leads
to various complications, both chronic (including obesity, insulin resistance, and type 2
diabetes mellitus) and acute complications (such as perforation of the stomach wall).
Because of the potential consequences of overeating, access to food must be strictly
supervised at all times.

Prader-Willi syndrome is caused by the deletion of a normally active

Paternal allele on chromosome 15 (although it is still unclear how this deletion leads to the
insatiable hunger that characterizes this syndrome). You can remember the association of P-
rader Willi syndrome by remembering that it involves a Paternal gene deletion that results
in “fridge raider” behavior.
 

Prader-Willi syndrome is a genetic disorder

characterized by insatiable hunger, intellectual
disabilities, short stature, and hypogonadism.
 

390
 P-rader Willi syndrome = Paternal “fridge raider.”
 
ANGELMAN SYNDROME

Angelman syndrome is similar to Prader-Willi syndrome in that

both involve a deletion on chromosome 15. However, whereas in Prader-Willi syndrome
the paternal gene is involved, in AngelMan syndrome the Maternal allele has been deleted.
is results in a characteristic syndrome involving intellectual disability, speech
impairment, and ataxia. People with Angelman syndrome are often noted to have a
generally happy demeanor and frequently laugh and smile in response to attention. ere is
also a characteristic facial appearance in many (though not all) cases. Angelman syndrome
was initially known as “happy puppet syndrome” which captures the speech impairment,
ataxia, and positive affect that characterizes people with this disorder. However, this term is
considered pejorative and should not be used in a clinical setting. You can remember Angel-
Man syndrome by thinking of someone who is angelically happy due to a Maternal gene
deletion.
 

Angelman syndrome is a genetic disorder

characterized by a generally happy demeanor,
intellectual disabilities, speech impairment, and
ataxia.
 

Angel-Man syndrome = Angelically happy due to a

Maternal gene deletion.
 
DIGEORGE SYNDROME
DiGeorge syndrome (also known as velocardiofacial syndrome) is a genetic disorder caused
by the deletion of a few dozen genes in the 22q11.2 region of chromosome 22. It is an
autosomal dominant disease that varies widely in its presentation, with some having only a
mild form of the syndrome and others being severely affected. DiGeorge syndrome causes
abnormalities in multiple areas of physical development including Cardiac malformations
(such as tetralogy of Fallot), Abnormal facies, Thymic hypoplasia, Cleft palate, and
Hypocalcemia (which forms the convenient mnemonic CATCH-22, with the 22
reminding you of the chromosome).
Many people with DiGeorge syndrome have a below average IQ, although their verbal
abilities are often preserved compared to non-verbal domains. Like other aspects of the
syndrome, the intellectual disability present is highly variable, with some having only mild
cognitive de cits and others having severe disabilities. Interestingly, nearly a quarter of all

391
individuals with DiGeorge syndrome go on to develop schizophrenia (a much higher
incidence than in the general population). e exact mechanism linking DiGeorge
syndrome to schizophrenia is unclear, but it remains an area of active research.
 

DiGeorge syndrome is a genetic condition resulting

in intellectual disability and a variety of
characteristic anatomical and physiologic
abnormalities.
 

CATCH-22: Cardiac malformations Abnormal facies

Thymic hypoplasia Cleft palate Hypocalcemia 22nd
chromosome
 
WILLIAMS SYNDROME

Williams syndrome is a genetic condition characterized by

intellectual disability and an exceptionally extroverted and outgoing personality. People
with Williams syndrome are often quite personable and will readily interact with strangers.
(Interestingly, this appears to be related to hypoactivity of the amygdala in response to
socially threatening stimuli such as disapproving faces, which is the opposite of what is seen
in depression and PTSD.) Williams syndrome is generally associated with mild forms of
intellectual disability, with reasoning and verbal abilities both being relatively spared.
Physical exam tends to reveal a small head, a prominent mouth with widely spaced teeth, an
elongated philtrum, and a attened nasal bridge (sometimes known as “el n” features).
Unfortunately, people with Williams syndrome are vulnerable to a host of health problems
including cardiac structural abnormalities (most often supravalvular aortic stenosis),
gastrointestinal problems (such as frequent abdominal pain), and hypercalcemia. Life
expectancy does not appear to be signi cantly impacted, however, and many people with
Williams syndrome live into their 60s and beyond.
e cause of Williams syndrome is a genetic microdeletion on the long arm of
chromosome 7 that leads to the loss of several genes. One of these genes produces the
protein elastin which is found in structural connective tissue, and deletion of the elastin
gene may account for some of the medical complications of Williams syndrome (including
the cardiac structural abnormalities). If you picture a 7riendly person with el7in features,
you can remember the association of Williams syndrome with increased sociability and a
microdeletion of chromosome 7.

392
 Williams syndrome is a genetic cause of mild
intellectual disability resulting in high extroversion
and speci c anatomical abnormalities.
 

If you picture a 7riendly person with el7in features, you

can remember the association of Williams syndrome with
sociability and a microdeletion of chromosome 7.
 
CRI DU CHAT SYNDROME

Like Williams syndrome, cri du chat syndrome (French for “cat’s cry”) is
caused by a genetic microdeletion, this time on the short arm of chromosome 5 (there are 5
letters in “kitty”). Unlike the mild intellectual disability found with Williams syndrome,
however, cri du chat syndrome is associated with severe intellectual disability. People with
cri du chat syndrome often have various cardiac abnormalities (including ventricular and
atrial septal defects) that may require surgical correction. Self-injury is sometimes found in
cri du chat syndrome, with hair pulling being a particularly common behavior. Diagnosis is
based on the disorder’s namesake cat-like mewing which is found as early as birth.
 

Cri du chat syndrome is a genetic disorder resulting

in severe intellectual disability, cardiac
abnormalities, and a characteristic cat-like cry
during infancy.
 

ere are 5 letters in “kitty” (cri du chat results from a

deletion on chromosome 5).
 
HOMOCYSTINURIA
Homocystinuria is an autosomal recessive disorder of metabolism where a de ciency of a
speci c enzyme (cystathionine beta synthase) results in accumulation of a toxic metabolite
(homocysteine) not only in the urine but also throughout the body. If untreated, elevated
homocysteine can lead to developmental delays, intellectual disability, and neuropsychiatric
symptoms resembling other disorders like ADHD.

393
 Physical manifestations of untreated homocystinuria include a long thin
body, genu valgum (also known as “knock knees”), osteoporosis, and ophthalmologic
problems (including lens dislocation, retinal detachment, and myopia). Individuals with
untreated homocystinuria are also at high risk for thromboembolic events such as heart
attacks and stroke, and a signi cant number of people with this condition die before the age
of 30 due to pathological clots. Because of this, your diagnostic suspicion for
homocystinuria should be raised whenever you see a young person present with
thromboembolic events (which are usually only found in older adults). Treatment involves
high doses of vitamin B6 (pyridoxine) and/or a low-sulfur diet.
Homocystinuria can sometimes be confused for Marfan’s syndrome, as both conditions
feature a characteristic long and thin body habitus in addition to lens dislocation. However,
Marfan’s syndrome does not feature intellectual disability and has a different pattern of lens
dislocation (with the lens moving away from the midline, or “up and out”). In contrast,
homocystinuria does feature intellectual disability, and the lens moves towards the midline
(“down and in”). Focus on the “in” of homocystinuria to remember the intellectual
disability, down-andin lens dislocation, and thromboembolic infarction events like heart
attack and stroke seen in this condition.
 

Homocystinuria is a genetic disorder resulting in

intellectual disability, lens dislocation,
thromboembolic events, and a long thin body.
 

Homocystinuria causes intellectual disability, down-

andin lens dislocation, thromboembolic infarction, and a
long thin body.
 
ADRENOLEUKODYSTROPHY
Adrenoleukodystrophy is an X-linked genetic disorder in which fatty acids cannot be
properly metabolized, leading to their toxic build-up in tissues throughout the body.
Deposition of fatty acids into the white matter of the brain results in neuronal dysfunction
which leads to hyperactivity, emotional instability, and disruptive behavior. e excess

394
fatty acids also have a tendency to deposit in the adrenal cortex where they can cause
adrenal insufficiency. ( ese two patterns are re ected in the name adrenoleukodystrophy,
with “adreno” referring to adrenal insufficiency, “leuko” referring to the white matter of the
brain, and “dystrophy” referring to destruction of body tissues.) Adrenoleukodystrophy is a
highly variable disorder with major differences in prognosis from one person to the next.
Some people are completely asymptomatic, others show only signs of adrenal insufficiency,
and still others are profoundly impaired both cognitively and physically. Given the
widespread build-up of fatty acids throughout the white matter of the brain, intellectual
disability is often accompanied by a wide number of other cognitive and behavioral
problems including difficulties with speaking, listening, and understanding instructions that
can strongly resemble disorders like ADHD. Speci c neurologic signs including gait
disturbance, imbalance, and seizures are often seen as well.
As an X-linked disorder, adrenoleukodystrophy is more common in males. e age of
onset is also quite variable, with some (mostly boys) showing signs and symptoms as early as
5 years while others are not diagnosed until adulthood. Treatment of the disorder involves
hormone replacement to treat the adrenal insufficiency. For the neuropsychiatric symptoms,
stem cell transplants can be effective is used early enough in life. However, given the high
variability of the disorder and the fact that it is not currently possible to predict which
patients will go on to develop the neuropsychiatric symptoms, its use is controversial. Gene
therapy is an emerging area of research which has shown some promise but needs further
testing.
 

Adrenoleukodystrophy is an X-linked genetic

disorder resulting in intellectual disability,
behavioral problems, and adrenal insufficiency.
 

Split the name apart (“adreno-“ for adrenal and

“leuko-“ for white matter of the brain).
RETT SYNDROME

Rett syndrome is an X-linked genetic disorder characterized

by a sudden loss of developmental milestones, including both motor and speech skills.
Development is often normal until sometime between the ages of 1 and 4 when a sudden
and profound Retturn to previous developmental stages is seen. Rett syndrome is
characterized by signi cant intellectual disability and speci c movements including
stereotyped hand-wringing. A sudden decrease in head circumference (which is generally
normal for their age up until symptoms begin) can also be seen. Other conditions
commonly co-occur, including an elevated risk of seizures, scoliosis, and sleeping problems.

395
 Rett syndrome is caused by mutations in the MECP2 gene on the X chromosome.
e exact mechanism for how mutations in this gene lead to the characteristic signs and
symptoms of the disorder are unknown. Unlike most X-linked disorders, the majority of
people diagnosed with Rett syndrome are girls. ( is is because boys with this disorder
generally die either in utero or shortly after birth due to a lack of an additional X
chromosome containing a non-mutated form of the gene.) Rett syndrome is often confused
with autism due to the fact that both begin around the same age (1 to 4 years old) and
involve similar symptoms, including poor social skills, communication difficulties, and
repetitive movements. In contrast to autism, however, Rett syndrome is diagnosed primarily
in girls (rather than the male predominance seen in autism) and features prominent motor
symptoms (including gait abnormalities) that are not seen in autism. e real key, however,
is that Rett syndrome involves a Retturn to stages of development that had previously been
passed (in contrast to autism and other neurodevelopmental disorders where in most cases
these developmental milestones are never reached in the rst place).
 

Rett syndrome is an X-linked genetic disorder

characterized by a sudden and dramatic regression
in development to previous developmental stages.
 

Rett syndrome involves a Retturn to previous stages of

development.
 
LESCH-NYHAN SYNDROME
Lesch-Nyhan syndrome is an X-linked recessive genetic disorder that can cause severe
intellectual disability. ese cognitive de cits are accompanied by distinctive self-
mutilating behaviors (including frequent biting of the nails and lips) that appear around
the age of 2. ese self-mutilating behaviors are a telltale sign of Lesch-Nyhan syndrome
and are found in the majority of patients with the disorder. As an X-linked condition, the
majority of patients with the disorder are male.
 

Lesch-Nyhan syndrome is an X-linked recessive

disease that involves intellectual disability and
characteristic self-mutilating behaviors.
 

LeX-Nyhan is an X-linked disease that causes Nyhilistic

self-injurious behavior.
Lesch-Nyhan syndrome is caused by mutations in the gene coding for the
Hypoxanthine—Guanine PhosphoRibosylTransferase (HGPRT) enzyme. De ciencies in
this enzyme prevent cell breakdown products from being recycled back into DNA, so they
are instead shuttled into a different metabolic pathway which results in increased uric acid
production. Overproduction of uric acid leads to deposition of this compound into various

396
parts of the body, including joints (leading to in ammatory arthritis similar to gout) and the
urinary tract (causing kidney stones and urinary tract infections). You can remember the
association between Lesch-Nyhan syndrome and a mutated HGPRT enzyme by thinking
of it as He’s Got Purine Recycling Troubles.
 

Lesch-Nyhan syndrome is caused by a genetic

de ciency of the HGPRT enzyme.
 

HGPRT = He’s Got Purine Recycling Troubles.

 
MITH–MAGENIS SYNDROME
Smith–Magenis syndrome is an autosomal dominant genetic disorder involving a
microdeletion in the short arm of chromosome 17. It results in intellectual disability,
hyperactivity, and a distinctive appearance (including short stature, a ‘tented’ upper lip, a
depressed nasal bridge, a thick lower jaw, and a conjoined eyebrow in young adults).
However, what is most diagnostic of the condition is a characteristic behavioral pro le
involving severe self-injurious behavior (including hand-biting, head-banging, skin-
picking, insertion of foreign objects into bodily ori ces, and pulling out ngernails and
toenails) that is found in over 95% of people with the condition . A pattern of stereotyped
self-hugging is also observed and may be pathognomonic for the condition. Sleep is often
signi cantly impaired owing to a disruption of the circadian rhythm which may be offset by
giving melatonin supplements at night and beta-blockers (which suppress melatonin
production) in the morning. Social interaction is often impaired, though people with
Smith–Magenis syndrome still appear to desire the attention and affection of others. e
characteristic combination of signs and symptoms in Smith–Magenis syndrome can be
remembered using the mnemonic SMITH for Sleep disturbances, Manual injuries (from
biting of the hands and ngers), Intellectual disability, a Thick lower jaw, and self—
Hugging behaviors.
 

Smith–Magenis syndrome is a genetic disorder

resulting in intellectual disability, sleep
disturbance, and severe self-injurious behaviors.
 

SMITH: Sleep disturbances Manual injuries (from

biting of the hands) Intellectual disability Thick lower
jaw Self—Hugging

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CORNELIA DE LANGE SYNDROME
Cornelia de Lange syndrome is a complex genetic disorder that can be caused by mutations
in various genes. It can strongly resemble autism in its neuropsychiatric presentation, as
there is often poor social relatedness combined with a strong preference for structure and
routine. Behavioral problems such as aggression or self-injury are often observed as well,
and these appear to correlate directly with levels of pain or discomfort from related health
conditions such as gastroesophageal re ux. Speci c physical characteristics such as delayed
growth, excessive hair, and small head circumference are often seen, while hearing loss is
common (seen in 80% of people with the disorder). Cornelia de Lange syndrome can
resemble Smith–Magenis syndrome in some ways as both involve a combination of
intellectual disability and self-injurious behavior, but it can be identi ed by the absence of
desire for attention from caregivers (whereas people with Smith–Magenis syndrome tend to
show a desire for caregiver affection).

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DIFFERENTIAL DIAGNOSIS OF INTELLECTUAL
DISABILITY
Intellectual disabilities rarely tend to be confused with other psychiatric disorders due to
their onset in infancy or early childhood (unlike the majority of mental disorders which
begin in adolescence at the earliest). For this reason, missed diagnoses are more of a
problem than genuine misdiagnoses. While rates of psychiatric disorders are not necessarily
higher in people with intellectual disability compared to the population as a whole, clinicians
need to be vigilant not to assume that people with intellectual disability don’t have other
mental disorders as well. In fact, people with intellectual disabilities have signi cant rates of
mood disorders (5%), psychosis (4%), and anxiety (3%). Furthermore, people with
intellectual disabilities often have difficulty communicating effectively which can lead to
underreporting of symptoms. Because of this, care must be taken to investigate signs and
symptoms when they occur, and a greater emphasis may need to be placed on objectively
observed signs (such as the presence of psychomotor slowing, low appetite, and sleep
disruption arguing for a diagnosis of depression) compared to subjectively reported
symptoms.
 
NORMALCY
Like all of the syndromes we have talked about so far, intellectual disability occurs on a
spectrum. However, what is unique to intellectual disability is the fact that this spectrum is
directly embedded into the de nition of the condition, with the lowest performing 2.5%
of the population automatically given a diagnosis of an intellectual disability provided that
they also have de cits in adaptive functioning as well. It is important not to overpathologize
people who have intellectual disabilities, as many can lead healthy and full lives once
familial and societal expectations have been adjusted (such as the idea that everyone must
live independently, have a job, and get married). Indeed, there is as much of a danger from
expecting too little from someone with an intellectual disability as there is from expecting
too much, and clinicians working with people who have intellectual disabilities should keep
an eye towards maximizing adaptive functioning wherever possible.
LEARNING DISABILITIES
Intellectual disabilities must be carefully distinguished from learning disabilities as they are
mutually exclusive diagnoses. In contrast to intellectual disabilities (which affect adaptive
functioning in all areas of life), learning disabilities are limited to speci c domains such as
reading (dyslexia), writing (dysgraphia), and math (dyscalculia). erefore, diagnosing
someone who has an intellectual disability with a comorbid learning disability is redundant,
as their impairments in speci c areas would be considered to stem from a global intellectual
disability rather than representing a separate diagnosis in its own right.
People with learning disabilities differ from those with intellectual disabilities in that
they are generally able to bring their performance up to the level of their peers by learning
speci c adaptive skills. In contrast, people with intellectual disabilities can show
improvements in their adaptive functioning but are generally not able to catch up to their
peers due to inherent limitations in their cognitive abilities.
 
COMMUNICATION DISORDERS
Communication disorders are a large and heterogeneous group of conditions that all share
a core de cit in the ability to communicate effectively with others. ey can range in

399
severity from mildly impairing (such as stuttering) to profoundly disabling (such as the
complete inability to hear or speak). Communication disorders are often comorbid with
intellectual disabilities, although care should be taken to ensure that the signs and
symptoms of the communication disorder aren’t entirely accounted for by the intellectual
disability itself.
 
AUTISM
Autism is both a missed diagnosis and misdiagnosis for intellectual disability, as they are
often comorbid (indeed, as many as 70% of people with autism also meet criteria for an
intellectual disability, which goes counter to the “Rain Man” stereotype of all people with
autism having genius-level intellect). However, it is also possible for intellectual disability to
be misdiagnosed as autism (and vice versa) as both conditions present with failure to meet
developmental milestones. e key is to focus on the nature of de cits. If all of the observed
de cits fall within the domains of social communication and rigid adherence to structure
(the “aloneness” and “sameness” discussed in the next chapter), then a separate diagnosis of
intellectual disability is unnecessary. However, if the cognitive de cits exceed those domains
and spill into other areas as well, a comorbid diagnosis of intellectual disability is likely
warranted.
 

ATTENTION DEFICIT HYPERACTIVITY DISORDER

Similar to autism, ADHD can be confused for intellectual disability as they both have their
onset in early childhood and can both cause impairment in academic and adaptive
functioning. Just like with autism, the key is to determine whether the observed de cits are
found entirely within the core domains of ADHD (inattention and hyperactivity) or
whether they extend into other domains as well (such as learning, socialization, and
intellect). Another clue is that treatment of ADHD using stimulants often results in
dramatic improvement in symptoms whereas medications do not signi cantly improve the
de cits seen in intellectual disability. Keep in mind that it is absolutely possible for someone
to have both ADHD and an intellectual disability.
CEREBRAL PALSY

Cerebral palsy (roughly meaning “a movement disorder involving the

brain”) is a highly heterogeneous condition that involves poor coordination, muscle
weakness, and/or spasticity resulting from damage to the central nervous system. is often
results in pronounced postural abnormalities that often require the use of assistive devices
such as wheelchairs or braces to enable movement. e potential causes of cerebral palsy are
vast, although problems in pregnancy (such as pre-term birth and exposure to certain toxins
or infections) account for a large proportion. Cerebral palsy is often accompanied by
intellectual disability or learning disability, with up to half of all patients showing cognitive

400
problems. However, it is important to point out that it should never be assumed that all
patients with cerebral palsy are intellectually disabled! While cognitive de cits are common
in patients with cerebral palsy, they are not universal, and care should be taken not to allow
physical appearances to get in the way of promoting self-efficacy as much as possible.
 
ADDICTION
People with intellectual disabilities have rates of addiction and substance abuse that are
lower than the general population (likely re ecting decreased access to drugs). However, for
the small subset of people with an intellectual disability who manage to get their hands on
these substances, the risk of developing an addictive disorder is actually higher than average.
erefore, do not assume that people with intellectual disabilities are somehow “protected”
from developing substance use disorders, especially those in the mild range of disability.
 

DEMENTIA While both dementia and intellectual disability involve cognitive de cits, it
is easy to tell them apart by focusing on two things: onset and course. By de nition,
intellectual disabilities begin early in life and follows a stable course while dementia occurs
later (usually in one’s 50s or 60s at the earliest) and is marked by progressive deterioration.
It is possible for someone with an intellectual disability to develop dementia (in fact, many
people born with Down syndrome are also diagnosed with Alzheimer’s disease later in their
life).
 
SELF-HARM
Some forms of syndromic intellectual disabilities are characterized by frequent and
repetitive self-injurious behavior. It is important to keep in mind that the nature of self-
harm in intellectual disability differs signi cantly from both suicide as well as the non-
suicidal self-injurious behavior seen in some cases of borderline personality disorder. Self-
harm in intellectual disability is often related to decreased pain perception (as opposed to a
desire to die in suicide and a way of regulating painful emotions in borderline personality
disorder). In addition, people with intellectual disabilities can have difficulty
communicating pain verbally and may engage in self-harm as a way of distracting
themselves. erefore, always be vigilant to consider that self-injury can be a sign of an
unrecognized medical condition, especially if it is new or more severe than usual.

To aid in your memory, it can be helpful to recap the various

syndromic intellectual disabilities in which self-injury is a prominent clinical nding. Use
the mnemonic Corny CAPFULS to remember that self-injury is found in Cornelia de
Lange syndrome, Cri du chat, Autism, Prader-Willi syndrome, Fragile X syndrome,
Underlying pain, Lesch-Nyhan syndrome, and Smith-Magenis syndrome.
 

401
Self-injury in people with intellectual disabilities
can be a characteristic clinical nding of speci c
syndromes or be a sign of underlying pain or
distress.
 

Corny CAPFULS: Cornelia de Lange syndrome Cri

du chat Autism Prader-Willi syndrome Fragile X
syndrome Underlying pain Lesch-Nyhan syndrome
Smith-Magenis syndrome

402
PUTTING IT ALL TOGETHER
An intellectual disability is ultimately quite simple to diagnose, as it requires only two
things: intelligence scores in the lowest 2.5% of the population and evidence of impaired
adaptive functioning as a result. Nevertheless, in practice (and on test questions) things
quickly get more complicated. Much of this has to do with the fact that your ability to
diagnose intellectual disabilities relies upon an understanding of what is encompassed by
“normal” development. In addition, there are a large number of syndromic intellectual
disabilities that each present with unique physical, cognitive, and behavioral features
(making this probably the single densest chapter in the entire book). Unfortunately, there is
no easy way around this, and a large amount of information will simply need to be
memorized. As much as you can, study the most speci c features of each disorder (such as
an insatiable appetite in Prader–Willi syndrome, a loss of developmental milestones in Rett
syndrome, and stereotyped self-hugging in Smith–Magenis syndrome) to identify
syndromic cases when you see them.
Once an intellectual disability has been identi ed, switch your focus from the idea of
nding a “cure” to instead trying to enhance adaptive functioning both on the part of the
patient and their caregivers. ere is danger both in having expectations that are too high as
well as having expectations that are too low, and the treatment plan should be realistic about
what can reasonably be achieved while never settling for anything less than as full and
developed of a life as possible.

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REVIEW QUESTIONS
1. A 2 y/o M is brought to the pediatrician’s office by his parents on his birthday for
an annual check-up. He is quiet with the pediatrician but will speak to his parents
in short sentences consisting of no more than two or three words. He is able to
walk independently but still wears diapers due to a lack of consistent control over
both bowels and bladder. He continues to breastfeed but is able to eat solid foods
as well. When around other children his same age, he does not spontaneously
engage in conversation or do activities with them, preferring instead to play by
himself. Which of the following ndings is most concerning for abnormal
development?
A. Shyness around non-parent adults
B. Inability to speak in sentences more than a couple of words
C. Lack of bowel and bladder control
D. Continued breastfeeding
E. Playing by himself rather than with peers
F. None of the above
2. A 5 y/o F is referred for formal testing after her pre-school teacher mentions that
she seems “a little slow” compared to other children in her class. Her speech is
generally understandable, although she makes occasional grammatical errors
(“Your cookie is more bigger than my cookie.”). She is outgoing and social with
other children in her class. Her parents are unaware if has difficulty with tying her
own shoes as she wears shoes with Velcro straps. She can draw simple pictures but
cannot yet write a complete sentence involving both a noun and a verb. She needs
reminders from her parents at night to brush her teeth before going to bed. IQ
testing reveals that she is in the 2nd percentile for children her age. What is the
most likely diagnosis?
A. An idiopathic intellectual disability
B. A syndromic intellectual disability
C. A communication disorder
D. A learning disorder
E. None of the above
3. A 2 y/o M is brought to the emergency department of a local hospital after he was
found bleeding from his mouth. He was born at term after an uncomplicated
pregnancy. However, at the age of 4 months he began appearing “limp” and was
treated with physical therapy for generalized hypotonia. e boy’s parents report
that he is unable to walk and has been “essentially non-verbal” his entire life and
communicates primarily with grunting noises. Over the past month he has begun
aggressively biting his tongue and his lip. Immediately before coming to the
hospital, he bit off the entirety of his lower lip, leading to severe bleeding. Physical
examination reveals additional scarring on his thumb and ngers as seen below:
 

404
Which of the following is the most likely explanation for this patient’s behavior?
A. Nondisjunction of chromosomes resulting in additional copies
B. Inability to metabolize fatty acids
C. Deletion of a normally active maternal allele
D. Overproduction of uric acid
E. Exposure to toxic substances in utero
4. A 15 y/o M is seen by his ophthalmologist to evaluate a recent decrease in his
visual acuity. He is otherwise healthy and eats a normal diet. He is 6’5” tall and
appears to have longer than average limbs, ngers, and toes. While he is known to
have severe nearsightedness resulting in use of corrective eyeglasses, in the past
week he has noticed that his vision has become increasingly blurry.
Ophthalmologic exam reveals a lens that is displaced away from the midline.
Which of the following best describes this patient’s level of intelligence?
A. He is unlikely to have an intellectual disability (IQ 70 or above)
B. He likely has a mild intellectual disability (IQ 50-69)
C. He likely has a moderate intellectual disability (IQ 35-49)
D. He likely has a severe intellectual disability (IQ below 35)
E. It is impossible to tell whether he has an intellectual disability

405
4.
E.
1. e best answer is F. is 2-year-old child exhibits normal development in all
domains mentioned in the question stem. While stranger anxiety is unusual past
the age of 2, some degree of shyness around non-parent adults is completely
normal (answer A). Speech at this age generally consists of two or three word
sentences (answer B), while play is largely in parallel to, rather than directly with,
other children (answer E). Bowel and bladder control are often not achieved until
the age of 3 (answer C). Finally, stopping breastfeeding is not a developmental
milestone (answer D).
2. e best answer is E. is patient has received scores on an IQ test that are in the
range of intellectual disability (being in the lowest 2.5%). However, a diagnosis of
intellectual disability is based not only on tests of intelligence but also on whether
there are impairments in adaptive functioning as a result. Based on the case
presentation, she is within normal limits on all developmental milestones described
and shows no signs of signi cant impairment, effectively ruling out a diagnosis of
either a syndromic or idiopathic intellectual disability at this time (answers A and
B). It is possible that she will develop impairments in adaptive functioning in the
future as the tasks expected of her become more complex, but at this time there is
no basis for that diagnosis. Based on the description of her outgoing nature, she
may have Williams syndrome, but it is probably more likely that this is simply
within the range of normal personality. ere is no evidence at this time that she
has either a learning or a communication disorder (answers C and D).
3. e best answer is D. is boy likely has Lesch-Nyhan syndrome as evidenced by
signi cant delays in various milestones (including motor and speech) as well as the
presence of severe self-mutilating behaviors. While self-harm is seen in a variety of
syndromic intellectual disabilities including Smith-Magenis syndrome and
Cornelia de Lange syndrome, the early age of onset (2 years) and location of the
injuries (lips and ngers) strongly suggest Lesch-Nyhan syndrome, which is
associated with overproduction of uric acid. Nondisjunction of chromosomes
results in trisomies like Down syndrome (answer A), inability to metabolize fatty
acids suggests adrenoleukodystrophy (answer B), deletion of a normally active
maternal allele suggests Angelman syndrome (answer C), and exposure to toxic
substances in utero suggests fetal alcohol syndrome (answer E).
4. e best answer is A. is vignette describes a case of Marfan’s syndrome. While
commonly confused for homocystinuria due to a similar body habitus and the
presence of lens dislocation, the pattern described in this case (including the
outward dislocation of the lens and a lack of other medical history) contrasts with
the “down and in” lens dislocation, presence of medical comorbidities, and
requirement for a specialized low-sulfur diet seen with homocystinuria. While
homocystinuria is associated with intellectual disability, intelligence in Marfa
syndrome is often normal, so a lack of intellectual disability is the most likely
scenario.

406
18 AUTISM

Autism is a type of neurodevelopmental disorder

characterized by two primary features: difficulties in social communication and restricted
interests and activities. Like intellectual disability, it is often diagnosed during early
childhood based upon a failure to meet developmental milestones on time (particularly
those related to language). Autism is generally referred to as a spectrum disorder due to the
wide range in symptom severity and functional ability seen in people with this syndrome.
Despite these variations, however, abnormalities in the two core domains must be present
for all individuals diagnosed with this disorder, as these two traits (an “autistic aloneness”
and an “insistence on sameness”) have been associated with autism from the time it was rst
described in 1938.
Autism is de ned by impairments in social
communication and interaction as well as
restricted and repetitive interests and activities.
Autism Spectrum Disorder = ASD = Aloneness—
Sameness Disorder
Because difficulties in social communication are one of the core features of autism,
diagnosing the disorder requires an understanding of what is considered to be “normal”
development of language. For this reason, take some time to review the developmental
milestones in the previous chapter so that you can apply this information to the material
here.

407
SIGNS AND SYMPTOMS OF AUTISM
As mentioned before, a diagnosis of autism is based upon the presence of the two core
patterns of autism: de cits in social communication and interaction as well as rigid,
repetitive, and restricted interests and behaviors. We’ll go over each of these in turn.
 
DEFICITS IN SOCIAL COMMUNICATION AND INTERACTION
De cits in social communication and interaction can manifest themselves in various ways,
including both verbal and non-verbal aspects of language as well as difficulty
understanding and following the implicit rules of social interaction. ese de cits have a
tendency to directly impair one’s ability to make and maintain friendships.

De cits in verbal language often manifest as speech delays,

and failure to meet language milestones is perhaps the most common way that children with
autism come to clinical attention. For some people with severe autism, speech can be
entirely absent. However, speech delay is not required for a diagnosis of autism, and around
half of people with autism (generally those with less severe forms) have overall normal
speech abilities. For these individuals, de cits in social communication occur instead in
other domains, including difficulty with understanding and using non-verbal
communication such as body language and facial expressions. For example, most people
understand that when someone points at something you should look at the object they are
pointing to (rather than looking at the nger itself ). In contrast, someone with autism is
more likely to misunderstand what is being communicated and will look at the pointing
nger instead. People with autism are often overly literal and have difficulty understanding
things like sarcasm that rely so heavily on the non-verbal aspects of what is being said
including the context of the situation and the speaker’s vocal intonations. Some people with
autism have difficulty recognizing facial expressions (even seemingly basic ones like “happy”
or “sad”) and must be taught how to interpret these expressions explicitly. In this way,
people with autism can sometimes come across as “robotic” or machine-like in their
interactions.
De cits in social communication can also extend beyond language itself into difficulty
understanding the basic rules of social interaction. ese rules are so intuitive and ingrained
that most people follow them without even thinking about it. For example, most people
know even from a very young age that when you meet someone you should say a greeting
and introduce yourself by your name. Most people know that when you are talking with
someone, it is polite to speak sometimes—not so much that you dominate the entire
conversation but not so little that you come across as unengaged. Most people understand

408
basic principles of social engagement such as reciprocity (“If you give me something, I
should give you something back”), turn-taking (“I need to wait my turn in line”), and
sharing (“If there is not enough for everyone, I should share”). In contrast, people with
autism do not intuitively pick up on these rules and will often break them in subtle or not-
so-subtle ways. ey do not break these rules intentionally to be sel sh; instead, they have
difficulty understanding that they should behave this way to begin with. is lack of an
intuitive understanding of the rules of social engagement often makes people with autism
feel like “an anthropologist on Mars” trying to understand the laws of a society whose logic
they cannot intuitively grasp. Despite their difficulties interacting with other people, people
with autism often demonstrate a desire to be around others and often report loneliness or
isolation when they lack meaningful friendships.
 
RESTRICTED OR REPETITIVE INTERESTS AND ACTIVITIES

e other domain of autism involves restricted or

repetitive patterns of behavior, interests, and activities. e phrase “insistence on
sameness” captures the core pattern here very well, as people with autism often want (and
will demand of others) a strict adherence to speci c routines and patterns such as wanting
to eat the same food every day or needing to perform the same rituals before bed. Due to
the difficulties in social communication that often co-occur, a child with autism may be
unable to communicate their desires verbally and will instead act out, scream, or otherwise
show distress when these patterns are interrupted.

Restrictions in interests and activities may also

manifest through particular xations and fascinations such as studying the schedule for
each and every train at the local station or memorizing the weather patterns in certain parts
of the world. is may also manifest in stereotyped or repetitive movements that do not
necessarily make sense to an outside observer such as lining up objects in a speci c order,
apping their hands in the air repeatedly, or spinning the wheels on a toy car for hours on
end. For some individuals, this stereotyped behavior can include self-harm such as

409
repeatedly banging one’s head against the wall (although the nature and purpose of this
behavior differs signi cantly from that seen in borderline personality disorder and is more
similar to the patterns of self-injury seen in people with certain forms of intellectual
disability).
 
OTHER SIGNS AND SYMPTOMS
A large number of people with autism exhibit a variety of other signs and symptoms that,
while common, are not required for a diagnosis of autism. First, disturbances in sensory
perception are seen in up to 80% of children with autism. ese disturbances are often a
combination of hypersensitivity to certain stimuli (such as sounds or textures) and
hyposensitivity to other stimuli (such as pain or temperature). Second, a variety of motor
signs are often seen in autism including poor coordination, low muscle tone, and unusual
gait (such as walking on one’s tip toes). While these signs are common (occurring in 60 to
80% of cases), they are also not required for a diagnosis of autism.

410
AUTISM ACROSS THE LIFESPAN

e prevalence of autism varies signi cantly from

study to study, ranging from 0.01% to 1.5% depending on the diagnostic standard used
(reinforcing the idea that autism is a spectrum disorder that can encompass a wide range of
symptoms and severities). However, it can generally be thought of as a rare disorder with a
similar prevalence to schizophrenia or bipolar disorder. e prevalence of autism has
increased over the past several decades. It is unclear why, but changes in diagnostic
patterns (including more routine screening and increasing awareness of the disorder among
both healthcare providers and families) appears to explain the majority of the increase.
A signi cant gender gap exists with autism, as boys are diagnosed with autism more
than 4 times as often as girls. Despite popular misconceptions, there is no evidence that
autism is linked to vaccines, and the endurance of this theory likely comes from the fact that
the period of immunization occurs at the same age that symptoms of autism are rst
noticed (around 1 to 3 years old).
 
PROGNOSIS
As a developmental disorder, autism does not occur in discrete episodes but rather has a
chronic and persistent course. e functional prognosis for autism varies widely, as the
disorder can present in forms ranging from mild impairments in social interaction to severe
disability resulting in a complete lack of speech and total dependence upon caregivers for
survival. Even without treatment, there appears to be a natural lessening of social de cits
along with improvement in adaptive functioning over time as people with autism learn
speci c skills and ways of interacting with the world. However, some signs (such as
restricted interests) are nearly always present.
 
TREATMENT
At this time, no medications have been shown to be helpful for improving the core de cits
seen in autism. Treatment instead should primarily involve behavioral training to teach
speci c adaptive skills (such as providing positive reinforcement to encourage the use of
speech). Speech and language therapy can also be helpful for teaching skills to overcome
communication de cits, while interventions in the family and educational systems can
improve functional skills and decrease stress on caregivers. While treatment earlier in life is
associated with improved functional outcomes, the majority of individuals with autism
remain dependent on others for support during adulthood (although people with high-
functioning forms of autism are often be able to live, work, and maintain social relationships
independently).

411
MECHANISMS OF AUTISM
Efforts to explain the etiology of autism have been ongoing since the disorder was rst
described. While many of these theories have been discredited (such as an early attempt to
link autism to “refrigerator mothers” who used emotionless parenting styles), there are some
new explanations that are worth investigating.
A concept known as hierarchical organization suggests that, compared to those
without the disorder, people with autism have a neurobiologically ingrained tendency to
give the details of what they see (something’s “local” properties) an even greater level of
priority than they give the overall meaning or gist (its “global” properties). To illustrate this,

consider the following image:

e global image is the shape of the letter H. However, the local image is many copies of the
letter S. People without autism show a tendency to immediately interpret the shape as the
letter H due to a preference for global processing over local processing. However, people
with autism tend to focus on the local details more than the global gist of the image and are
more likely to say “the letter S” when asked to describe what the image is meant to
communicate.
is tendency towards local detail-oriented processing over global meaning-related
processing is observed in other ways as well, both bene cial and detrimental. Consider the
image on the following page:

412
 Now try to nd this triangle in the image. For people with autism, the ability
to break things down into their individual components makes this a relatively simple task
that they can pull off with ease. For someone without autism, however, the tendency to
focus on the overall message of the image (the shape of a baby carriage) makes it harder to
perform this task. Differences in sensory processing are also apparent in optical illusions

such as the following image:

Because they tend to focus exclusively on the individual parts, it is difficult for someone
with autism to get the overall “gist” of the image (the central white triangle), and studies
have found that only around 10% of individuals with this disorder can “see” the illusion.
is lack of hierarchical organization explains why individuals with autism show such
pro ciency with complex and detailed subjects such as mathematics or physics that people
without autism often struggle with. However, it also explains the de cits in verbal skills
and use of language that are core features of autism. For example, read the following
sentence out loud: A tear fell from his eye when he saw the tear in his mother’s quilt. Multiple
studies have shown that people autism fail to differentiate between the pronunciation of
each instance of the word “tear,” as this relies upon an ability to quickly understand the
overall meaning of the sentence (global processing) over and above the sound of each word
in isolation (local processing).

413
 ese difficulties are compounded further when it comes to non-verbal communication as
this requires integration of multiple stimuli at the same time (including not only the words
that are spoken but also the tone in which they are said, the context of the situation, and the
speaker’s body language and facial expressions). Because most people have a preference for
global processing, integrating all of this information at the same time is a simple and
automatic process. For someone with autism, however, the tendency to treat local details at
the same level as global impressions proves impairing. Facial expressions are another area
where the tendency to focus on details instead of the overall gist can produce difficulties.

Consider these two expressions:

Most people are able to look at these images and immediately say that the one on the left
represents a negative emotion like anger or fear while the one on the right is a more positive
emotion like happiness or surprise. However, by breaking down the image into its
individual components, one can see that the faces are ultimately quite alike, with only the
contour of the mouth differing between them. By focusing too much on the local details
(the eyebrows, eyes, and nose being similar) rather than the global gist, people with autism
can struggle to recognize and respond to facial expressions appropriately.
is innate preference for local over global processing also explains the restricted interests
and activities seen in autism which often involve subjects that are better suited for local
rather than global processing such as memorizing train schedules. is tendency is neither a
de cit nor a disability, as this cognitive style confers speci c advantages (like the ability to
attend to minute details) while eliminating others (like the ability to communicate easily
with others). It’s important also to keep in mind that this processing style is not
unchangeable, as people with autism can be taught (for example, using behavioral therapy)
to overcome their instinctive tendency to get lost in the details and instead look at the
overall meaning. In this way, the concept of hierarchical organization can help to assist in
con rming a diagnosis of autism as well as explain why behavioral training is effective in
managing the condition while medications, which cannot change processing style, are not.
(For anyone curious, the location of the triangle in the baby carriage can be found by turning to the last page of this chapter.)

414
DIAGNOSING AUTISM SPECTRUM DISORDERS

Because the speci c cause of autism is not known, diagnosis is

based primarily on observed behaviors. In particular, speech delay (de ned as a failure to
meet developmental milestones related to speech on time) is the most common reason for a
child to be referred for formal evaluation for autism. However, other causes for speech delay
must be ruled out. Use the mnemonic APHASIC (meaning “unable to speak”) to
remember some common causes of speech delay in a child, including Autism, Physical
de cits such as apraxia (difficulty in generating motor impulses to produce speech) and
dysarthria (the inability to form speech using vocal muscles), Hearing impairment, Abuse
or neglect (which can also present with failure to meet milestones), Selective mutism (an
anxiety disorder discussed in Chapter 9), Intellectual disability, and Cerebral palsy.
 

Speech delay is the most common initial symptom

of autism but can be a sign of other disorders as well.
 

APHASIC: Autism Physical de cits Hearing

impairments Abuse or neglect Selective mutism
Intellectual disability Cerebral palsy

Social communication de cits and restricted interests and activities must both be
observed in multiple settings and have begun during early childhood. Abnormalities in
behavior are often noticeable by the age of 2 and almost always by the age of 3 (even by
people not formally trained in diagnosing autism). Diagnoses of children younger than 2
years should be given cautiously, as diagnosing too early or on the basis of minimal
symptoms can lead to false positives (whereas diagnoses assigned later in life are more likely
to be lasting and durable). However, that shouldn’t deter you from referring these children
for further evaluation and possibly even treatment, as earlier intervention is often associated
with improved outcomes.
 
TYPES OF AUTISM
Historically, the DSM made a distinction between various types of autism. Individuals with
high-functioning forms of autism were said to have Asperger syndrome, a milder version of
the disorder which featured de cits in socialization and restricted interests and activities but

415
lacked speech impairment or any comorbid intellectual disability. Another diagnosis known
as “pervasive developmental disorder not otherwise speci ed” (sometimes called atypical
autism) was given to individuals who exhibited multiple traits associated with the disorder
but did not technically meet the core diagnostic criteria. However, in the interest of
integrating all cases of autism under a single diagnostic banner, these distinctions were
dropped in the DSM-5, and all of these cases would now be classi ed as an autism
spectrum disorder. (Given that Hans Asperger, the doctor after whom Asperger syndrome
was named, participated in euthanasia as part of a Nazi program, there is even more reason
to avoid using the name.) While there are no longer officially recognized subtypes of
autism, there are still some clinical features that may be relevant which we will explore next.
 
SAVANTISM

Savantism refers to cognitive abilities in speci c areas that

are astoundingly over and above what is known to be in the realm of normal human ability.
Individuals with savantism have incredible cognitive capabilities, often related to memory
(like being able to memorize endless amounts of seemingly trivial information) or
calculation (such as performing complex mathematical equations instantly in one’s head).
For example, someone might be able to tell you the day of the week and the weather for any
speci c date, even going back dozens of years (“April 2, 1933 was a Sunday. It was very
cold, with frost and ice in the morning and a dry wind in the afternoon.”). e relationship
of savantism to autism is well characterized, with “islets of ability as well as de cits” having
been described from the very rst reported cases of the disorder. While over half of all
savants show traits consistent with autism, the reverse is not true, and the majority of
people with autism are not savants. (Indeed, it is vastly more common for someone with
autism to have an intellectual disability than to be a savant.) Nevertheless, the higher than
average prevalence of savantism among people with autism suggests a link between the two
conditions (likely related to superior local processing enabling seemingly superhuman
mental feats). is serves as an important reminder that the features of autism are not
inherently pathological and likely act as a double-edged sword in many areas.
 

PRAGMATIC LANGUAGE IMPAIRMENT

Someone who presents with signi cant de cits in social communication but does not show
evidence of having restricted interests or activities would not be diagnosed with autism, as
impairments in both of these domains are required. However, these social communication
difficulties may still cause problems. For this reason, the DSM-5 introduced the concept of
pragmatic language impairment—officially called “social (pragmatic) communication
disorder”—to describe these cases. Because it is such a new diagnosis, it is unclear how

416
people diagnosed with this disorder will compare to those diagnosed with “textbook”
autism. However, given that prior to this diagnosis, a majority of autism diagnoses were
“not otherwise speci ed,” it is likely that it will be commonly on a clinical basis. A diagnosis
of pragmatic language impairment is mutually exclusive with a diagnosis of an autism
spectrum disorder, with the presence or absence of restricted or repetitive interests and
behaviors being the deciding factor.
 

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DIFFERENTIAL DIAGNOSIS OF AUTISM SPECTRUM
DISORDERS
As autism has become more prevalent, our understanding of how it relates to other
disorders has deepened. For example, for a long time it was commonly assumed that people
with autism did not become depressed, as the restricted affect seen in autism was seemingly
incompatible with such a severe mood disorder. However, we now know that autism can be
comorbid with nearly any psychiatric syndrome, making it important to be mindful of
missed diagnoses with this condition.
 

NORMALCY
Neither of the two domains of autism (social communication de cits and restricted interests
or activities) are inherently pathological, and decades of research shows that both of these
traits are on the spectrum of normalcy. Because of this, avoid knee-jerk diagnoses of autism
for anyone who has below-average social skills or above-average interest in their hobbies.
Instead, look for evidence that the process of these features is resulting in dysfunction. In
severe cases, this is not hard to see. In less severe cases, however, the line may not be so
clear. Review the advantages and disadvantages of diagnoses as outlined in Chapter 2 when
making a decision about diagnosis. In some cases, the advantages (such as increased access
to behavioral therapies or caregiving resources) may outweigh the downsides (including
increased stigma and lowered expectations for families), but this decision should be made
on a case-by-case basis.
Finally, it is worth mentioning that there is an ongoing debate over whether autism is a
neurodevelopmental disorder in need of treatment or a neurologic difference that has been
unnecessarily pathologized by the medical community. In fact, some people in the autism
community advocate for the idea that autism is not a disorder at all and instead should be
seen as a variation on normalcy. As with all psychiatric syndromes, however, at extremes the
quantitative becomes qualitative. For people with mild autistic traits, these differences can
and should be celebrated as a distinct way of looking at the world. However, for people who
have such a severe form of autism that they are completely unable to live independently or
care for themselves, it is much harder to make the case that autism is simply “neurodiversity
in action.” Nevertheless, it is an intriguing idea and an important reminder that autism
should only be diagnosed if there is evidence of dysfunction (even if someone has behaviors
or traits that are clearly “on the spectrum”).
 

INTELLECTUAL DISABILITY
e relationship between autism and intellectual disability is complex. e two disorders are
often comorbid, with around half of people with autism being intellectually disabled as well.
( is even applies to savants as well, as they often have signi cant disabilities even while
having speci c areas of extreme ability.) Diagnosing autism in the presence of intellectual
disability can be a challenge, as intellectual disability itself can be associated with social
dysfunction. Nevertheless, the social dysfunction must be clearly out of proportion to what
would be expected purely from the intellectual disability alone. In addition, there must be

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evidence of restricted and repetitive interests or activities to make a clear diagnosis of
autism.

PSYCHOSIS
e clinical features of schizophrenia and autism overlap in a few key ways which can lead
to confusion. In particular, the prodrome of schizophrenia tends to involve very similar
signs (such as social communication de cits and restrictions in affect) beginning around the
same time as autism. For this reason, it is possible that some people in the prodromal stage
of schizophrenia will instead be diagnosed with autism, although these cases will eventually
“declare themselves” when clear psychotic symptoms emerge.
 
CLUSTER A PERSONALITY DISORDERS
Autism may at times be confused for a personality disorder, as both are chronic and
enduring conditions. In fact, some studies have estimated that up to 50% of people with
autism meet criteria for a personality disorder. Out of the three clusters, cluster A
personality disorders are most likely to be misdiagnosed as autism due to several
overlapping features including social isolation in schizoid personality disorder and eccentric
interests in schizotypal personality disorder. It is notable that decreasing clinical interest in
cluster A personality disorders has coincided with an increase in rates of autism, and it is
possible (if not likely) that someone who would have previously been diagnosed with a
cluster A personality disorder would now receive a diagnosis of autism due to changes in
diagnostic trends. However, as a rule the clinical features of autism tend to be noticeable by
the age of 3 whereas those in cluster A personality disorders usually start in adolescence. In
addition, people with autism do not necessarily lack a desire to engage in social
relationships. Instead, they are often motivated to make friends but may come across as
socially “clumsy” in their attempts to engage with others.
 
CLUSTER B PERSONALITY DISORDERS
At rst glance, a diagnosis of autism seems unlikely to be confused with cluster B
personality disorders given the wide range of affect associated with them (in contrast to the
restricted affect seen in autism). However, both cluster B personality disorders and autism
share similar difficulties in mentalization that can give the appearance of poor social skills.
Don’t confuse these two conditions! In cluster B personality disorders, difficulties in
“reading” other people are more often related to hypermentalization (or the tendency to get
someone else’s emotional state wrong by overthinking social cues) whereas in autism this
appears to be connected to hypomentalization as a result of engaging in local processing of
facial expressions and social cues over global integration of complex contextual information.
 
CLUSTER C PERSONALITY DISORDERS
Finally, of the cluster C personality disorders, obsessive-compulsive personality disorder is
perhaps most likely to be misdiagnosed as autism as they share several features, including a
preference for rigid adherence to structure. In differentiating between the two, evaluate
whether the rigid patterns are the result of a desire for sameness (which would suggest
autism) or an ego-syntonic hyper-conscientiousness (which would suggest obsessive-
compulsive personality disorder). In addition, people with obsessive-compulsive personality

419
disorder do not necessarily have any problems with social communication, so if these are
present a diagnosis of autism is more likely.
ANXIETY DISORDERS
Individuals with autism appear to be at higher risk for anxiety, especially as they enter
adolescence and become more aware of how their differences set them apart from their
peers. Out of all the anxiety disorders, social anxiety disorder appears to have the most
overlap with autism, and up to a third of adolescents with autism may meet criteria for
social anxiety disorder. It is unclear how much of this co-occurrence has to do with the
signi cant overlap in symptoms (as both autism and social anxiety involve difficulties in
socializing) versus representing true comorbidity.
 
ATTENTION DEFICIT HYPERACTIVITY DISORDER
ADHD and autism should not be difficult to separate from each other, as ADHD primarily
involves difficulties in the domains of inattention and hyperactivity and does not necessarily
result in the “aloneness” and “sameness” that characterizes autism. However, diagnostic
confusion can happen (largely due to the fact that both occur more often in boys and begin
during early childhood).
 
OBSESSIVE-COMPULSIVE DISORDERS
Both autism and the obsessive-compulsive disorders feature the presence of rigid or
compulsive behaviors. Of note, these behaviors are ego-dystonic in people with OCD (who
are able to say why they are engaging in the behaviors even while they nd them to be
excessive or difficult to stop). In contrast, the restricted interests and behaviors of people
with autism are ego-syntonic, and there is often an inability to describe the reasons for
engaging in the behaviors (particularly in lower-functioning cases).
 
DEPRESSION
It should not be assumed that people with autism do not get depressed, as rates of
depression in these patients appear to match the 20% prevalence observed in the general
population. However, due to the restricted emotional expression that many people with
autism have, it can be difficult to assess this clearly. In particular, look for changes in the
patient’s baseline level of activity (such as less participation in hobbies or fewer attempts at
social interaction) that may be related to depression.
 

EATING DISORDERS
Patterns of eating are often abnormal in people with autism, which is often noticeable from
a very early age. Children with autism are often noted to be incredibly selective in what they
eat (they are often described as “picky eaters”), with some preferring to eat only a few foods
exclusively. In severe cases, this can even lead to nutritional de ciencies if not corrected. In
general, however, there is a normal amount of caloric intake (even if the food choices are
not diverse), and the eating patterns of autism lack the obsession with weight and body
image seen in both anorexia and bulimia.
 
SLEEP DISORDERS
Similar to eating habits, sleeping patterns in people with autism are often quite dysregulated
even from an early age. Speci c sleep difficulties can include difficulty falling asleep,

420
difficulty staying asleep, resistance to going to bed, and an out-of-sync circadian rhythm
(such as staying up all night or sleeping all day). Sleep difficulties often persist across the
lifespan. It is unclear why people with autism have abnormal sleep patterns, but when these
occur they are generally considered to be a part of the syndrome itself (rather than
necessitating a diagnosis of a separate sleep disorder).

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PUTTING IT ALL TOGETHER
By virtue of its onset in early childhood and persistent de cits across the lifespan, autism
can be among the most impairing of all psychiatric conditions. However, for every severely
disabled non-verbal person with autism there is an intellectually gifted individual who may
occasionally struggle with social communication but nevertheless remains functional and
independent in their daily life. is underscores the fact that autism is a spectrum disorder,
so do not expect two people with the same diagnosis to necessarily have the same prognosis.
To remember the two core features of autism, think of Autism Spectrum Disorder as
Aloneness—Sameness Disorder. e “aloneness” (or de cits in social communication) can
present as both language de cits as well as problems with understanding rules of social
engagement. While speech delay is a common reason for initial presentation, not all cases
of speech delay should be diagnosed as autism, so use the mnemonic APHASIC to
remember other possible causes of delayed speech. Finally, keep in mind that on a
mechanistic level autism appears to involve a preference for local processing over getting a
global “gist,” which can help to better identify cases of autism.
 

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REVIEW QUESTIONS
1. A 5 y/o M is brought into the pediatrician’s office by his parents. ey recently
immigrated to the United States, and this is their rst time visiting a doctor.
rough a translator, the parents report that the boy does not speak in full
sentences and communicates primarily by pointing at things and making loud
noises. He spends the majority of his time playing with a set of marbles that was
given to him by his grandparents one year ago. He will spend hours arranging
these marbles in a speci c order repeatedly, and if anyone moves or disturbs the
marbles, he will scream and cry for up to an hour. He refuses to eat the majority of
food placed in front of him and will only eat carrots, crackers, and a certain brand
of cookie. His parents report that there were no problems with either pregnancy or
childbirth. On exam, the boy does not respond to any questions that the
pediatrician asks through the interpreter. roughout the interview, his facial
expression registers no change in emotion when approached by either his parents
or any healthcare providers, and for the most part he appears indifferent to
whether anyone else is in the room. Which of the following developmental
milestones is this patient most likely to have missed?
A. Babbling at 6 months
B. Walking with assistance at 12 months
C. Two-word sentences at 24 months
D. Stacking 9 cubes at 36 months
E. Parallel play at 2 months
2. (Continued from previous question.) e parents are informed of the diagnosis
through the translator. ey nod quietly in response and ask, “We came here so
our son could have a better life. We want him to go to school and become
successful. What can we do to ensure this?” What is the best response?
A. “Your son will likely be very successful in life. He has been given
abilities most of us don’t have and will be able to memorize things
perfectly.”
B. “ e outlook for this condition is very good, and most cases resolve
within a few years. However, it is possible that symptoms will return
in the future.”
C. “As long as your son continues to take the medications he is
prescribed, he will do just ne.”
D. “It is too early to say for sure, but it is likely that your son will
struggle at least in some ways.”
E. “If your son had started treatment earlier, it may have been possible.
But now it is out of the question: your son will not nish school.”
3. A 16 y/o M is brought to a psychiatrist’s office by his mother. His mother asks to
speak with the psychiatrist separately. She says that the patient is “not normal” and
requests a full evaluation. In particular, she says that he has “a lot of trouble
reading people” and will often accuse his parents and others around him of being
upset or angry at him when they are not doing anything out of the ordinary. She
also says that he is “into some really weird things.” She knows this because she has
installed an internet monitoring device on his computer without his knowledge.
She says that he is part of an online message board for people who believe that

423
 they are animal spirits inhabiting human bodies (“He thinks he’s a platypus!”).
Because of these interests and his difficulties interacting with others, he restricts
his friendships to only two or three other students at school with whom he is very
close. He is otherwise doing well at school, with mostly As and Bs. He has no
medical conditions and saw a pediatrician yearly for check-ups throughout his life.
On interview, the patient denies that there is anything wrong and that he wants to
go home. He says atly that he frequently fantasizes about running away so that he
can “be with people who actually understand me.” What is the most likely
diagnosis?
A. Autism spectrum disorder with intellectual disability
B. Autism spectrum disorder without intellectual disability
C. An intellectual disability without autism
D. Pragmatic language impairment
E. Rett syndrome
F. None of the above
4. A 1 y/o F is brought by her parents to see a pediatrician. is is her rst visit with
a doctor. Upon entering the room, the pediatrician notices that the infant does not
turn her head to look at him and makes no attempts to imitate his vocalizations.
She does not attempt to speak or even babble. She instead largely points at objects
that she is interested in. Her developmental milestones are otherwise intact. When
taking a history from the family, they report that she is generally healthy other
than an episode three months ago when she developed a high fever and cried
inconsolably for several days. She experienced two seizures during this illness. ey
did not seek medical care at that time, and the fever resolved on its own within one
week. Which of the following is the best next step?
A. Inform the family of the diagnosis of autism and refer for speech and
behavioral therapy
B. Inform the family that autism is the most likely explanation but that
the patient is too young to say with complete certainty
C. Ask the parents to bring the patient back in one week after keeping a
vocalization journal
D. Refer the parents to an audiologist for evaluation
E. Determine whether there are other children in the home

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1. e best answer is C. is vignette describes a case of autism in a young boy as
evidenced by de cits in social communication (including lack of speech and
indifference to the presence of others) as well as restricted and repetitive activities
(such as a rigid adherence to playing with the same toys in the same ways). Autism
is most strongly associated with delays in speech-related milestones rather than
motor milestones (answers B and D). However, these de cits in speech often do
not begin until the age of 1 at the earliest, so de cits in babbling at 6 months are
unlikely to be apparent without speci cally looking for them (answer A). Parallel
play at 2 years is not pathological and is consistent with a diagnosis of autism
(answer E), although for this patient there was likely the absence of cooperative
play at age 4.
2. e best answer is D. e clinical course of autism is characterized by chronic
de cits in multiple domains rather than recurrent episodes of symptoms (answer
B). However, the prognosis for the condition is also highly variable, making it too
early to say for sure (although the lack of speech by age 5 is very concerning).
While the prognosis for autism is improved with earlier initiation of treatment,
most individuals still bene t from beginning treatment at the age of 5 (answer E).
While some cases of autism include savantism, this is the exception rather than the
rule, and most cases instead involve intellectual disability (answer A). Finally,
medications play no role in improving outcomes in autism (answer C).
3. e best answer is F. While this patient’s mother reports concerns in both the
patient’s social interaction and his interests, objectively there is little evidence of
actual impairment in either of these domains, so it would not be appropriate to
diagnose autism (answers And B). e fact that he has not been referred for
evaluation prior to adolescence argues further against a diagnosis of autism. In
addition, it is not clear that his difficulty with understanding the emotions of
others is related to hypomentalization as would be seen in autism; if anything, he
may engage in hypermentalization by assuming that others have negative emotions
that they may not have. He has an intact social support network which argues
against pragmatic language impairment (answer D), and he is performing well as a
student which argues against an intellectual disability (answer C). As a male, it is
unlikely that he would have survived into adolescence with Rett syndrome (answer
E).
4. e best answer is E. e patient has failed to meet her one-year language
milestones which is cause for immediate concern. While autism is one possible
explanation, there are many others that need to be ruled out as well (answers A
and B). In this case, there is clear evidence of medical neglect as the family did not
bring the child in for care despite a week-long fever with multiple seizures. As
with all cases of suspected abuse or neglect, ensuring that the patient and other
dependents in the home are safe is the highest priority, so it would not be
appropriate to send the infant home with her parents at this time (answer C).
While an auditory evaluation is likely necessary at some point to rule out hearing
loss (especially in the context of an undiagnosed fever), it is not the highest
priority at this time (answer D).

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19 INATTENTION AND HYPERACTIVITY

Attention de cit hyperactivity disorder (or ADHD) is a

syndrome that involves impairment in two domains: inattention and hyperactivity.
Handily, both of these domains are written right into the name (“attention de cit” and
“hyperactivity”), so no mnemonic is needed to remember them. ( e diagnosis was
previously called just “attention-de cit disorder,” so you may hear “ADD” used from time to
time.) Like intellectual disability and autism, ADHD is a neurodevelopmental disorder that
begins in childhood. However, unlike those disorders ADHD does not present with failure
to meet milestones. Instead, children with ADHD are most often brought to clinical
attention due to poor school performance, disruptive behavior, or both.
Diagnosing ADHD is tricky because there are signi cant downsides to both
undertreatment and overtreatment. On one hand, children with untreated ADHD often
have severe impairments in multiple areas of life as a direct consequence of this disorder
including poor academic achievement, unstable peer relationships, and frequent run-ins
with authority, some of which can have lasting consequences. For this reason, it seems cruel
to deprive these children of the bene ts of diagnosis (such as access to effective treatment).
On the other hand, overdiagnosis of ADHD can also be impairing by inappropriately
stigmatizing a child, communicating that there is something “wrong” with them, and taking
away their sense of self-efficacy if they begin to believe that they are unable to do things
without medications. ere is also the risk of “medicalizing” structural problems (such as a
child growing up in poverty who has trouble paying attention in school due to hunger, for
whom a diagnosis of ADHD is missing the real problem). Because the risks of both
overdiagnosis and underdiagnosis are so profound, taking the time to gain a good
understanding about how to evaluate the signs and symptoms of ADHD across the lifespan
is essential.

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SIGNS AND SYMPTOMS OF INATTENTION AND
HYPERACTIVITY
ADHD is a syndrome encompassing persistent de cits in two domains: inattention and
hyperactivity. Once symptoms appear, they are chronic and enduring (rather than episodic
or uctuating) which is consistent with the categorization of ADHD as a
neurodevelopmental disorder.
Inattention involves difficulties in focusing on a particular object or task over and
above other stimuli. While most people have a train of thought that is able to stay on track
for at least a few minutes at a time, in someone with ADHD the train of thought is easily
derailed. is leads to a high level of distractibility (“Oh look, a butter y!”) that can
manifest in difficulty completing tasks, frequent forgetfulness, a lack of attention to detail,
and general disorganization in daily life. Of note, many people with ADHD still show good
attention for subjects or tasks that they nd intrinsically interesting, suggesting that it is not
impossible for someone with ADHD to focus—it is just much harder for them than for most
people.

Hyperactivity involves a high level of energy that

makes it difficult to sit still or to refrain from acting impulsively. Hyperactive children may
squirm in their seats, talk constantly, interrupt others, make messes, have trouble waiting in
line, and generally come across as very impatient. ese children do not necessarily mean to
be disruptive, but they nd themselves unable to stop from engaging in these impulsive
behaviors. is can be a problem in everyday life, but it becomes a particular issue when
these children are placed in structured environments (such as school) that rely upon a
certain level of order and cooperation between the teacher and the students in class.
While the name “attention de cit hyperactivity disorder” suggests that both
inattention and hyperactivity are required for a diagnosis (similar to how a diagnosis of
autism requires both “aloneness” and “sameness”), the fact of the matter is that these two
symptom domains do not always co-exist. In fact, the most frequently diagnosed form of
ADHD involves only inattention without hyperactivity (accounting for over 60% of people
diagnosed with the disorder). is brings up an important question: if these two symptom
domains can occur in the absence of the other, why are they lumped together in the rst
place? ere are two reasons. First, inattention and hyperactivity co-occur in the same
person more often than would be predicted by chance. Second, both symptom domains
appear to respond to the same kinds of treatment. Together, these facts likely suggest a
shared neurobiological mechanism between inattention and hyperactivity.

427
 It’s important to remember that these symptoms are not problematic in and of
themselves. A certain level of inattention for tasks and subjects that we do not nd
interesting is completely normal, and hyperactivity is one of the perks of being a kid.
However, when these traits become persistent and in exible, a disorder can result. It’s not
a problem to be loud and hyperactive in places that can accommodate this (like a theme
park), but it can be disruptive in places that cannot (like school).

428
INATTENTION AND HYPERACTIVITY ACROSS THE
LIFESPAN
ADHD affects approximately 10% of children and 5% of adults, making it a common
condition with a high base rate in the population. e predominantly inattentive subtype
is the most common, accounting for over two-thirds of all cases of ADHD (with the
combined subtype making up around 20% and the hyperactive subtype accounting for the
other 10%). ADHD is more common in men compared to women, with a gender ratio of
over 2 to 1. However, this may be due at least in part to the fact that boys are slightly more
likely to have the hyperactive form of ADHD than girls (which is more likely to come to
clinical attention than the purely inattentive subtype).
ADHD is one of the most heritable psychiatric conditions, with studies showing that
genes account for about 75% of the variance between different people. However,
environmental factors are also believed to play a large role, with in utero tobacco exposure,
maternal stress, premature delivery, low birth weight, poverty, and (weirdly enough)
growing up in an English-speaking household all being risk factors for ADHD. Cultural
factors are likely involved, as rates of diagnosis vary from country to country.
e signs and symptoms of ADHD begin during childhood, with an age of onset around 3
to 8 years. e age of diagnosis varies by how severe the symptoms are, with children who
have severe symptoms often being diagnosed by the age of 5 while those with only mild
symptoms aren’t diagnosed until age 8 or even after. Despite some thought that there might
be an “adult onset” version of ADHD occurring in people with no history of the disorder
during childhood, evidence does not support this notion, as concurrent substance use
appears to explain the vast majority of supposedly “adult onset” cases. is solidi es
ADHD’s status as a neurodevelopmental disorder which necessarily has its roots in
childhood.
 
PROGNOSIS
e prognosis of ADHD varies depending from person to person. Interestingly, the two
domains of ADHD tend to follow different trajectories, as hyperactivity is often prominent
during childhood but then slowly decreases with age whereas inattention tends to persist at
roughly the same level throughout adolescence and adulthood. On the whole, however,
cases of ADHD tend to be enduring across the lifespan, and roughly two-thirds of people
diagnosed with ADHD as children will continue to show signs of the condition as adults
(either as a “full blown” disorder or in a subsyndromal form that falls short of diagnostic
criteria but still remains impairing to some degree). However, this also means that up to
one-third of children diagnosed with ADHD will show no signs of the disorder as adults,
so the diagnosis should not be assumed to be lifelong in every case. For unknown reasons,
cases of ADHD with a clear family history are most likely to “burn out” by adulthood while
those with a stronger environmental component are more likely to persist into adulthood.
Untreated ADHD can have profoundly impairing effects both during childhood and later
life. School-aged children with ADHD tend to have worse educational outcomes, greater
stress in family and peer relationships, and increased rates of other psychiatric disorders
(including anxiety and depression) compared to those without the disorder. For cases of
ADHD that persist into adulthood, there is an association with poorer long-term outcomes
in academic achievement, job performance, addictive behaviors, marital problems,
unwanted pregnancies, and car accidents.

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TREATMENT
Treatment of ADHD consists of therapy, medications, or both. e most commonly used
therapies consist of behavioral management and training, including CBT and family
therapy. In general, behavioral therapies for ADHD are associated with medium effect
sizes in the range of 0.6 to 0.7. Like most psychotherapies, the bene cial effects of
treatment last even after the treatment is discontinued.
Drug treatment of ADHD involves medications known as stimulants. Stimulants generally
work by increasing the levels of the neurotransmitters dopamine and norepinephrine
which results in improvement in both inattention and hyperactivity. e two most
commonly used stimulants are methylphenidate (commonly known as Ritalin) and
amphetamine salts (sold as Adderall). As a class, stimulants are associated with a very large
effect size above 1.0. In fact, stimulant medications are among the most effective treatments
for any psychiatric syndrome, with over 70% of people treated with these medications
showing signi cant improvement in the presenting symptoms. However, they are not
without risk, including the possibility of growth restriction (although these children often
“catch up” in height once the medication is stopped), appetite suppression, insomnia, and
the potential for addiction and abuse at higher doses. Given these risks, behavioral therapies
should generally be considered rst, especially for those who are younger or only have mild
symptoms.
A variety of non-stimulant medications are available as well (including atomoxetine,
guanfacine, and clonidine) which work by a variety of mechanisms. However, the effect
sizes for non-stimulants are lower (around 0.5), making them comparable to behavioral
therapies but without the bene t of long-lasting changes. For this reason, non-stimulants
are generally only used in cases where medication is necessary but a stimulant cannot be
used for a particular reason.

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MECHANISMS OF INATTENTION AND HYPERACTIVITY
While the precise mechanisms of ADHD are still unknown, one hypothesis suggests that
the inattention and hyperactivity seen in the disorder are both related to abnormal signal
processing in the central nervous system due to excessive neuronal background noise. To
understand this, let’s brie y review some neurophysiology.

Neurons work by generating an electrical signal (an action

potential) that then travels to speci c other neurons to communicate a message. For
example, if you were to accidentally hit your foot with a hammer, the neurons innervating
your foot would send action potentials to the primary somatosensory cortex in your brain to
register the sensation of pain. An action potential is meaningful because it represents a
distinct change from baseline. However, this also means that the ability of a neuron to
communicate information depends as much upon generating a signal when there is a
stimulus as it does upon not generating a signal when there isn’t a stimulus.
It is this latter process that appears to have broken down in ADHD, and studies have
shown that neurons in the central nervous system of people with this disorder are
signi cantly more likely to generate signals even when not exposed to any stimuli. is
creates a level of “background noise” that impairs the ability of these neurons to transmit
information about actual stimuli to the brain, making it difficult for these individuals to
focus on relevant stimuli. is is supported by studies showing that the noisiness of one’s
neuronal signals at baseline appears to correlate with the symptom severity of ADHD,
supporting a direct link to the pathophysiology of the disorder.

To understand how a noisy baseline signal leads

to inattention, imagine the mind as an old television set that receives video signals via an
antenna. e screen will stay on the same channel (equivalent to sustaining attention) as
long as it is receiving a clear signal. However, if the receiver loses the signal then it will
assume that the channel is off the air and attempt to switch over to another channel with a

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clearer signal. For most people, this automatic switch from a channel with a noisy degraded
signal to another channel with a clearer signal is helpful, as it prevents attention from being
wasted on irrelevant or extraneous information. For people with ADHD, however, the
signal is always noisy (like a busted television set that is overloaded with static). is static
interferes with the signal, causing the television set to “think” that there is no meaningful
information coming in. In response to this, the television set begins to constantly switch to
different channels in search of one with a cleaner signal. However, because the noise is
coming from the television set itself (not from the channels that it is tuned to) a cleaner
signal is never found, leading to frequent and unending attentional switches.
ere are a variety of ways to compensate for the perpetual neuronal “noise” that
people with ADHD experience. One is to boost levels of dopamine using stimulant
medications, which causes a general increase in the salience of information. is allows
incoming neuronal signals to stand out over the normal background “noise” (continuing the
previous analogy, the television set is better able to hold onto this boosted signal, leading to
less channel switching and more sustained attention). e salience of information can also
be boosted by novelty, as being in new or exciting situations appears to release dopamine in
a way similar to stimulants. Indeed, studies of brain metabolism in people with ADHD
have shown that they have abnormally strong responses to new objects and environments.
is could explain the hyperactive and impulsive behaviors that people with ADHD engage
in, as they help generate to novelty and thereby boost a signal that is noisy or degraded at
baseline.
e images on the following page can help to illustrate the concepts we have
discussed here, with the top image showing a signal with no noise (similar to someone
without ADHD) and the middle image showing a signal with an increased level of
background noise (representing someone with ADHD). e bottom image shows what
happens when the background image is “boosted,” demonstrating how stimulants and
novelty (which both increase the underlying signal) can help to provide a clearer picture
even when the signal is overlaid with noise.

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Image of a butter y without static noise.

Image of a butter y with static noise to mimic the degraded signal of an individual with ADHD.

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 Image of a butter y with same amount of static noise as above but with the
underlying signal “boosted” through enhanced contrast and brightness, leading to an increased ability to understand the image
despite the noise.

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DIAGNOSING ADHD
A diagnosis of ADHD is based upon the presence of inattention, hyperactivity, or both.
Despite the fact that the name includes both domains, it is possible to have inattention
without hyperactivity (known as the inattentive type) and hyperactivity without inattention
(known as the hyperactive-impulsive type). Individuals who have both inattention and
hyperactivity are considered to have the combined type. ADHD subtypes tend to be
unstable over time, and people may shift between them throughout their lives.
It would be a mistake to assume that every child who is inattentive or hyperactive quali es
for a diagnosis of ADHD. In many ways, ADHD is a diagnosis of exclusion because
medical, environmental, and social reasons for inattention and hyperactivity must be ruled
out rst. For example, a child who is stressed due to watching their parents ght every
evening will likely have difficulty sleeping at night, leading to fatigue and difficulty staying
awake during class. is may manifest as inattention, but it should not be automatically
assumed to be ADHD. While this is a rather obvious example, more subtle forms may exist
as well. For example, ADHD is diagnosed more frequently in the youngest children in each
class (likely due to their earlier stage of cognitive development compared to their peers),
illustrating how unconscious expectations play a large role in diagnosis as well.
To help control for situational differences in symptoms, signs of ADHD must be
present in at least two different settings (such as at school and at home) before assigning
the diagnosis. Nevertheless, as with any psychiatric syndrome, it is probably not possible to
completely remove diagnostic subjectivity from the equation.

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DIFFERENTIAL DIAGNOSIS OF ADHD
e vast majority (over 70%) of people with ADHD have at least one other comorbid
disorder, the most common being externalizing disorders like oppositional de ant disorder
and intermittent explosive disorder, internalizing disorders like depression and anxiety, and
neurodevelopmental disorders like intellectual disability and autism. For this reason, it is
important to evaluate for other psychiatric syndromes that can present with inattention
and/or hyperactivity.
 
NORMALCY

e inattention and hyperactivity seen in ADHD are not

inherently pathological. After all, isn’t some degree of not wanting to sit quietly in school
expected (even downright normal) during childhood? For this reason, ADHD remains a
controversial diagnosis. When considering a diagnosis of ADHD, it is worthwhile to keep
in mind that at extremes, the quantitative becomes qualitative. Many children lie somewhere
on a spectrum of severity in terms of inattention and hyperactivity. However, some children
have inattention and hyperactivity that is so pronounced that it leaves little doubt that these
characteristics impair their personal, social, and scholastic performance. In these cases,
diagnosing ADHD is not difficult.

ADHD must also be separated out from the normal effects

of abnormal circumstances. Because the symptoms of ADHD are so non-speci c, it is
important not to make a “knee-jerk” diagnosis when faced with a child who displays either
inattention or hyperactivity and instead take a close look at the wide variety of factors that
may be at play. To remember the various factors that can frequently mimic ADHD, use the
mnemonic PAN LID NOISE. (To link PAN LID NOISE to ADHD, imagine an
inattentive and hyperactive kid who is banging on pan lids and making lots of noise!)
PAN is for Parenting, Abuse, and Neglect. Parenting styles can profoundly alter a child’s
behavior depending on what actions are rewarded or punished, and this can have a major
impact on whether someone is diagnosed with ADHD. In more extreme cases, abuse and

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neglect can directly disrupt a child’s ability to behave in accordance with what is expected of
them (which can resemble the hyperactivity and impulsivity seen in ADHD).
 

LID is for Learning, Intellectual, and Developmental Disabilities. Poor performance in

school due to a learning disability can resemble ADHD, especially if the child becomes
frustrated with their lack of progress and begins acting out. While people with ADHD
often struggle in school environments, this is ultimately for a different reason than in
learning disabilities (which instead involve de cits in speci c cognitive domains such as
math, reading, and writing). In contrast to a learning disability, academic impairment
related to ADHD will resolve with medication treatment. Learning disorders and ADHD
can also co-occur, and in these cases both conditions must be treated separately (using
educational techniques for learning disorders and behavioral management and/or stimulants
for ADHD). ADHD must also be distinguished from autism and intellectual disabilities,
both of which can closely mimic (or are often comorbid with) this condition. One way to
distinguish ADHD from other neurodevelopmental disorders is that it rarely presents with
failure to reach speci c developmental milestones (whereas this is a diagnostic hallmark of
both autism and intellectual disability).
 

N is for Nutrition. Inadequate food can lead to persistent hunger that impairs one’s ability
to concentrate at school, making assessment of nutritional status an important part of the
diagnostic process.
 

O is for Other conditions. Be on the lookout for any unusual signs or symptoms that could
suggest an alternative medical or psychiatric explanation for the signs of ADHD. For
example, a child who develops type 1 diabetes mellitus may begin to show signs of
inattention, irritability, or hyperactivity when their blood sugar becomes abnormal. ere
will be other signs and symptoms of diabetes as well (such as excessive thirst or frequent
urination), but these would only be picked up if the clinician is careful to take a full medical
history.
 

I is for Intention. Children with ADHD engage in disruptive behaviors due to a general
inability to remain still. In contrast, a child may also misbehave intentionally in order to
complain, protest, or express anger about their situation. is should be considered within
the range of normal human behavior and not unnecessarily pathologized as a disorder.
(Some children who engage in intentional disruptive behavior may have an externalizing
disorder or callous-unemotional traits, which are not considered within the realm of
normalcy. ese are discussed next.)
S is for Sleep. Children who are unable to sleep at night will often have difficulty
concentrating or staying awake during the day, leading to persistent inattention and
irritability that can resemble the symptoms of ADHD. For this reason, assessing the
amount and quality of sleep for anyone presenting with ADHD-like symptoms is essential,

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and the presence of insomnia should lead to an investigation into possible causes of
disrupted sleep (such as bullying or stress).
 

E is for Environment. Finally, the signs and symptoms of ADHD must be seen in more
than one environment. Cases that are diagnosed based on only one environment likely
suggest an outside factor that is speci c to that place (rather than to the child).
 

A variety of medical and environmental factors

must be ruled out before assigning a diagnosis of
attention de cit hyperactivity disorder.
 

PAN LID NOISE: Parenting, Abuse, and Neglect

Learning, Intellectual, and Developmental disabilities
Nutrition Other conditions Intention Sleep
Environment
 
EXTERNALIZATION AND PSYCHOPATHY

While the majority of cases of ADHD involve inattention only,

those that involve hyperactivity (either alone or in combination with inattention) are the
ones that come to clinical attention most often as this hyperactivity results in frequent
disruptive behaviors. Because disruptive behaviors are one of the most common reasons
that a child is brought in for psychiatric evaluation (if not the most common reason), it is
worthwhile to establish a systematic framework for evaluating these patients. Many children
with disruptive behavior will t one of these three patterns: hyperactivity, externalization,
and callous-unemotional traits (known as psychopathy in adults). ese patterns are each
associated with vastly different prognostic and treatment considerations, so it is essential to
keep these distinctions in mind whenever you are evaluating a child with disruptive
behavior.
Patients with ADHD display disruptive behaviors as the result of persistent
hyperactivity. ey do not intend to misbehave and generally try to avoid annoying others,
but they often nd themselves unable to do so given their difficulty with sitting still.
Disruptive behaviors in these patients rarely involve agrant disregard for the rights of
others such as assault, bullying, or stealing.

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 In contrast, patients with externalizing disorders (discussed in the next chapter) often
engage in disruptive behaviors purposefully with a clear intention of infuriating or harming
others. ese children also experience overwhelming negative emotions most or all of the
time, and it is believed that their disruptive behaviors are a way of expressing these emotions
into the external environment.
e nal group of patients is characterized by antisocial behaviors that are done
purposefully with the intention of angering or hurting others. eir behaviors often exceed
those of the rst two groups in terms of harm and can involve overt violence towards people
or animals. In contrast to patients who externalize, these patients are characterized by a
distinct lack of emotionality that manifests as callousness and an absence of empathy.
Many of these children will grow up to have psychopathic traits as adults (discussed in
Chapter 21).
ese three patterns are reliable and have important implications for prognosis and
treatment. However, current diagnostic schemes (including the DSM) do not clearly
differentiate between these three groups. In fact, all three of these patterns are frequently
grouped together under the banner of “externalizing disorders” despite the lack of
externalization seen in either ADHD or psychopathy. For the purposes of clarity, this book
will refer to the rst group as having ADHD, the second group as having externalizing
disorders, and the third group as having callous-unemotional traits or psychopathy. ( is
is different than how some other books and research articles will refer to these diagnostic
entities, so please keep that in mind when reading about these conditions in other places. In
order to preserve the helpfulness of these distinctions, however, we will hold to them here.)
ABSENCE SEIZURES
A particular kind of seizure known as an absence or “petit mal” seizure is characterized by
sudden episodes of altered consciousness. Someone experiencing an absence seizure can
appear to an outside observer to be staring off blankly into space without paying attention
to what is going on around them. While this can sometimes present with accompanying
motor signs that make it obvious a seizure is occurring (like generalized body shaking), this
is not always the case. For this reason, it is not uncommon for absence seizures to be
initially misdiagnosed as ADHD. However, while children with absence seizures will
experience inattentive staring episodes, they will generally show good attention when not
having an episode (unlike the persistent inattention seen in ADHD). Absence seizures can
often be diagnosed clinically based on the history, although de nitive diagnosis requires
electroencephalography (which will show a pattern of 3 Hz generalized “spike and wave”
discharges that is practically pathognomonic for this disorder).
DEPRESSION
Given that depression and the inattentive subtype of ADHD can both present with
difficulty concentrating, each should be on the differential for the other. However, the
relationship between ADHD and depression goes deeper than that. For some people with
untreated ADHD, chronic underachievement and difficulty meeting goals can result in a
state of demoralization and lack of motivation that can strongly resemble depression. In
addition, symptoms of ADHD can often prevent people from forming social relationships,
with over 50% of children with ADHD reporting being lonely (which itself can lead to
depression). To distinguish between these two diagnoses, focus on the presence of other
symptoms of depression (the rest of SIGECAPS). In addition, in cases where someone’s
depressive symptoms stem entirely from the effects of ADHD, treatment of ADHD should

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itself improve depressive symptoms. In cases where these symptoms remain, consider
making a separate diagnosis.
 
ADDICTION
e impulsivity seen in hyperactive or combined subtypes of ADHD can predispose people
to developing addictions, and the rate of addictive disorders is signi cantly higher in people
with ADHD than without. In addition, the medications used to treat ADHD can
themselves be addictive (though typically at much higher doses than those used
therapeutically for ADHD), so be cautious if your patient begins asking for frequent or
early re lls. Finally, the effects of speci c substances (either during intoxication or
withdrawal) can easily mimic the inattention and hyperactivity seen in ADHD, so taking a
careful substance history (and possibly obtaining a urine drug screen) can be diagnostically
helpful.
 
ANXIETY
ADHD is frequently comorbid with anxiety in both children and adults. e anxiety
present in the disorder is often (though not always) related to speci c consequences of
ADHD such as worrying about being into trouble with parents and teachers, not getting
along well with peers, and doing poorly in school or at work. Treatment of ADHD will
often result in decreased anxiety in these cases, though in cases where anxiety persists even
after treatment, a separate diagnosis of an anxiety disorder (and treatment using CBT)
should be considered.
 

MANIA e hyperactivity and impulsivity of ADHD can be mistaken for mania, although
the timing of the two is completely different as these signs are episodic in mania and chronic
in ADHD. Differences in the age of onset (childhood in ADHD and adolescence or early
adulthood in bipolar disorder) can also differentiate between the two.
 
OBSESSIVE-COMPULSIVE DISORDERS
It may seem odd that ADHD and OCD would frequently be comorbid, as the impulsive
disinhibited behavior seen in ADHD seems to mix poorly with the compulsive risk-averse
patterns seen in OCD. Indeed, studies of the neuropsychological pro le of people with both
ADHD and OCD have found that the inattention seen in people with OCD may be (at
least in some cases) directly related to the obsessions themselves, which have become so
frequent and intrusive that they make it difficult to concentrate on anything else. Because of
this, consider whether inattentive symptoms in a patient with OCD can be attributed
entirely to obsessive thoughts (in which case treatment of OCD should improve both)
rather than to a separate diagnosis of ADHD.
 

TRAUMA A history of abuse or neglect during early childhood is associated with an

increased likelihood of developing ADHD. For this reason, it’s important not to let the
presence of hyperactivity and disruptive behaviors distract you from any trauma-related
internalizing disorders that may be present as well (including not only “textbook” PTSD
but also anxiety and depression as well). In fact, these internalizing disorders can often be

440
even more impairing and distressing to the patient than the disruptive behaviors that may
have “brought them in” for evaluation in the rst place.
 
PERSONALITY DISORDERS
e disinhibition and impulsivity of cluster B personality disorders can strongly resemble
ADHD, especially in those with a history of abuse or neglect. is association is
strengthened further by the fact that these traits are chronic and enduring in both ADHD
and personality disorders. In many cases, it is not always possible to tease out how much of
the impulsivity present is related to ADHD versus a personality disorder, but the age of
onset can often be a valuable clue (with ADHD generally beginning in childhood while
personality disorders tend to manifest during adolescence).
 
PSYCHOSIS
Schizophrenia can present with impairments in attention that can resemble ADHD. e
prodromal period is especially liable to misdiagnosis as the age range is roughly the same
while the dramatic positive symptoms of psychosis have yet to emerge. It is believed that
disruptions of the salience network underlie both of these conditions, although in
schizophrenia inattention is likely due to too much salience whereas in ADHD it is more
likely related to not enough salience.

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PUTTING IT ALL TOGETHER
ADHD is a neurodevelopmental disorder that begins in childhood and in many cases
continues on into adulthood. Signs and symptoms of ADHD involve the one or both
domains listed in the name of the disorder. While symptoms of ADHD can be incredibly
impairing, effective treatments are available, including both behavioral therapy and
medications. e availability of treatment underscores the need to carefully screen for the
condition, as untreated ADHD is associated with poor outcomes in various areas of life.
However, there are also signi cant downsides to diagnosing someone with ADHD,
including a risk of overtreatment and stigma. Always rule out other factors that can mimic
ADHD (as in the PAN LID NOISE mnemonic). Signs of ADHD must also have been
present since childhood and be seen in at least two different environments. Provided that
these conditions are met, however, working with someone who has ADHD can be a very
gratifying experience, as treatment often leads to improvements in functioning that are both
immediate and dramatic.
 

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443
REVIEW QUESTIONS
1. A 6 y/o M is brought to the pediatrician’s office by his mother. She says that he has
developed “severe school anxiety” and throws tantrums every morning on the way
to school. While at school, he is generally quiet and well-behaved. However, he
has not done well on his assignments, and during a parent-teacher conference his
mother was told that he often struggles to keep his focus on the subject at hand.
He often has difficulty sitting with his parents long enough to work on homework
at night, although he appears to have no difficulty sitting still to play video games
for hours at a time on weekends. Pregnancy and delivery were both uncomplicated,
and the patient has achieved all developmental milestones on time. He did well in
preschool and is well liked by his classmates. Which of the following is least
consistent with a diagnosis of ADHD as the primary explanation for this patient’s
behavior?
A. Onset of symptoms at age 6
B. Absence of hyperactivity at school
C. Presence of inattention in multiple settings
D. Being well-liked by his classmates
E. Ability to focus on activities he nds enjoyable
F. All of the above are consistent with a diagnosis of ADHD
2. (Continued from previous question.) e pediatrician places a referral for full
neurocognitive testing. Results from the test are strongly suggestive of ADHD. At
the next visit, the doctor discusses various treatment options and explains the risks
and bene ts of each. e mother says that she is hesitant about the idea of putting
her child on medications. What is the most appropriate response?
A. “ at is entirely your choice. Medications are an option, but they are
not the only one. Let’s look into other possibilities.”
B. “Medications have been scienti cally shown to be the single most
effective treatment for ADHD, so we really should look at starting
one right away.”
C. “A lot of parents have concerns about their children taking stimulants,
but these tend to go away with time. Here is the number for a group
of parents of children with ADHD who may be able to answer some
more of your questions.”
D. “If you aren’t interested in stimulants, there are a variety of non-
stimulant options available that are just as effective. Your child really
needs to be on some form of medication, though.”
E. “I agree. Children in this country are overmedicated, and even if you
wanted to start a stimulant I wouldn’t prescribe one.”
3. A teacher requests a parent-teacher conference regarding a 9 y/o F in her class.
During the conference, the teacher voices her concern that the girl frequently
appears inattentive during class and has been turning in incomplete schoolwork for
the past four weeks. e teacher notices several such episodes of “zoning out”
throughout the day, each of which last around 5 seconds. Prior to this, the girl had
been an “exceptional student” and was often seen reading at a level several years
higher than her age. e girl is otherwise healthy with no history of trauma, drug
exposure, or other medical conditions. e girl is referred to a child psychiatrist for

444
 further evaluation. e girl denies feelings of anxiety, depression, or irritability.
However, she is concerned about her school performance and says, “I don’t want to
disappoint my parents.” After a discussion with both the patient and her parents, a
decision is made to start treatment with methylphenidate. At the follow-up visit
two weeks later, her parents report no signi cant effect from the medication, so the
dose is doubled. is only appears to increase the severity of her inattention.
Which of the following best explains the patient’s unusual reaction to
methylphenidate?
A. Some people are simply non-responsive to methylphenidate and need
to be prescribed amphetamine salts instead
B. e patient is having an allergic reaction to stimulants and should be
prescribed a non-stimulant
C. It was inappropriate for the psychiatrist to have prescribed
medications for ADHD without attempting behavioral treatment
rst
D. It was inappropriate for the psychiatrist to have prescribed
medications for ADHD without completing a full work-up
E. is is a normal and expected reaction to methylphenidate
4. A 14 y/o M is brought to a child psychiatrist along with a note from his teacher
that reads “ADHD evaluation needed.” He recently transitioned into high school
where he has struggled both academically and socially. Prior to this, he went to a
private school that strongly emphasized accommodating different learning styles.
His learning style was determined to be “kinesthetic/tactile,” and he was
encouraged to build dioramas and art projects in place of taking written tests. He
did very well at this school and showed good attention even for projects that he did
not nd interesting. He was born two months premature and spent four weeks in
the neonatal intensive care unit but has otherwise been healthy during his life.
Testing performed at age 5 showed a slightly above average IQ of 114, but he has
not been retested since then. Both the patient’s parents and the teachers at his new
school con rm that he is well-behaved in class and shows no difficulty with
waiting in line for his turn. As part of his evaluation, he is given a self-evaluation
form to ll out. Despite taking an hour to look over the form, however, he hands it
in blank with a look of embarrassment on his face. Which of the following is the
most likely diagnosis at this time?
A. Attention de cit hyperactivity disorder, inattentive type
B. Attention de cit hyperactivity disorder, hyperactive type
C. Attention de cit hyperactivity disorder, combined type
D. An intellectual disability
E. A learning disorder

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1. e best answer is F. While other causes still need to be ruled out, the description
of this patient’s case is consistent with a diagnosis of ADHD. Cases of ADHD
often begin between the ages of 3 to 8 (answer A). While both inattention and
hyperactivity are found in the name, it is not necessary for both to be present for a
diagnosis to given, so the absence of hyperactivity does not rule out ADHD in this
case (answer B). e presence of symptoms in more than one setting is not only
consistent with a diagnosis of ADHD, it is required (answer C). It is not
uncommon for people with ADHD to be able to focus on activities they nd
intrinsically interesting or enjoyable (answer E). Finally, being well-liked by peers
is not related to a diagnosis of ADHD (answer D).
2. e best answer is A. Medications are one of the primary treatment options for
ADHD, but they are not the only option, as behavioral therapies have been shown
to be effective for ADHD as well. While stimulants are the single most effective
treatment, that does not mean that the mother should be pressured into starting
one for her child (answer B). Non-stimulants are available as well, although it is
incorrect to say that they are equally as effective as stimulants (answer D). Finally,
it would not be appropriate either to defer a discussion about medications to non-
professionals (answer C) or to refuse to prescribe stimulants for a clearly
documented case of ADHD even if the mother desired it (answer E).
3. e best answer is D. is describes a case of absence seizures as evidenced by the
fact that her inattention occurs in brief episodes lasting only a few seconds, which
is highly characteristic of an absence seizure. It is also unusual, though not entirely
outside the realm of possibility, for symptoms of ADHD to start suddenly in a girl
who previously had no difficulties. erefore, the psychiatrist should have
established the nature of her inattention more clearly and ordered an
electroencephalogram, which would show the 3 Hz “spike and wave” complexes
associated with absence seizures. While it is true that some patients respond better
to amphetamine salts than methylphenidate, a paradoxical worsening of
inattention in response to a stimulant of any kind is highly unusual (answers A and
E). is is not an allergic reaction to a stimulant, which would generally involve a
rash, itching, swelling, or difficulty breathing (answer B). Finally, in most cases of
ADHD it is reasonable to prescribe stimulants without rst attempting behavioral
therapy; however, in this case that would also have been ineffective as the
underlying condition would remain undiagnosed (answer C).
4. e best answer is E. is patient likely suffers from a learning disorder such as
dyslexia. While it is unusual for a learning disorder to suddenly “appear” during
adolescence, the style of the patient’s previous school likely allowed for difficulty
reading to remain undetected for longer than usual. It is highly unusual for
ADHD to spontaneously begin during adolescence or adulthood, and there are no
reports of either inattention or hyperactivity (answers A, B, and C). In addition, an
intellectual disability is absolutely ruled out by a lack of signs or symptoms
beginning in early childhood (answer D).

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20 EXTERNALIZATION

Externalization is the process by which negative

thoughts and emotions are expressed in the external environment through disruptive or
violent behavior. A number of psychiatric disorders are characterized by a consistent
pattern of externalizing behaviors in children and adolescents, including oppositional
de ant disorder, conduct disorder, intermittent explosive disorder, disruptive mood
dysregulation disorder, kleptomania, and pyromania. ese conditions are collectively
referred to as externalizing disorders. Externalization differs from the “normal”
misbehavior of childhood in that it is severe, recurrent, and accompanied by speci c
emotional or cognitive patterns that suggest a psychiatric etiology. is is an important
distinction to keep in mind as we discuss externalizing disorders, as not all children who
misbehave should be diagnosed with a mental condition.
Externalizing disorders stand in contrast to internalizing disorders (like anxiety or
depression) which involve negative thoughts and emotions that are directed inward towards
the self, leading to feelings of worthlessness, despair, and low self-esteem. Externalizing and
internalizing disorders are not mutually exclusive, and most people with an externalizing
disorder will also have an internalizing disorder (although the reverse is not necessarily true,
as only a minority of people with internalizing disorders also have an externalizing
disorder). In addition, some disorders have both internalizing and externalizing dimensions
(such as borderline personality disorder which features not only internalizing symptoms like
chronic dysphoria but also externalizing behaviors such as hostility and impulsivity). For the
rest of this chapter, however, we will focus primarily on disorders that have externalization
as a core clinical feature.

447
 SIGNS AND SYMPTOMS OF
EXTERNALIZATION
Externalization primarily takes the form of disruptive or inappropriate behaviors that
violate the rights of others or bring someone into con ict with other people. Speci c
examples include aggressive or violent acts like hitting or kicking, emotional outbursts,
vandalism, destroying property, engaging in theft, or bullying others through physical or
verbal threats. ese aggressive behaviors must be performed with some degree of intention
to cause frustration or harm. ( is separates externalization from the disruptive behaviors
found in ADHD or tic disorders such as cutting in line or yelling out profane words, which
are typically not done with the intention of harming or bothering others.) Episodes of
acting out are often impulsive as they are often associated with an emotional “thrill” or a
feeling of power that provides immediate positive reinforcement. However, in certain forms
of externalization (such as oppositional de ant disorder and conduct disorder) the
aggressive behaviors can also be premeditated and planned.
For disruptive behavior to be a form of externalization (rather than just “normal” bad
behavior), they must also be accompanied by speci c cognitive and emotional patterns.
Most commonly, this takes the form of intense and overwhelming feelings of anger,
sadness, or irritability that immediately precede the disruptive acts. ese emotions are
experienced quite strongly and are often considered to be signi cantly out of proportion to
the circumstances that provoked them by outside observers (such as parents, teachers, or
bystanders in the supermarket). For example, a girl who is grocery shopping with her father
asks him for a candy bar. When her father says no, she begins screaming loudly and
repeatedly kicking him in the legs—an emotional and behavioral response that most people
would nd to be an extreme overreaction. e negative emotions driving this behavior can
either be chronic (such as a child who has a persistent negative mood state that manifests
through daily sadness and irritability) or transient (in response to a speci c event or trigger
as in the above example).
While these behavioral excesses are the most notable, children who externalize often
have speci c behavioral de cits as well including profoundly poor social skills, lack of
impulse control, and difficulty understanding rule-based structures. is often leads them to
have few acquaintances and no close friends, resulting in a persistent sense of loneliness
and isolation that further drives the negative emotions underlying the aggressive behavior.

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EXTERNALIZATION ACROSS THE LIFESPAN
Externalizing behaviors in children are common, with up to 10% of youth showing a
consistent pattern of disruptive behavior. e prevalence is signi cantly higher in certain
areas such as the child welfare system where up to 25% of children living in orphanages or
foster care show signs of an externalizing disorder. Externalization is far more common in
males, with a gender ratio of 10 to 1. In nearly all cases, a pattern of externalizing behaviors
emerges during childhood and adolescence. However, whether the onset of disruptive
behavior occurred during childhood or adolescence has incredible implications for
prognosis, which we will discuss next.
 
PROGNOSIS
e prognosis of externalizing disorders varies considerably based upon the age at which the
disruptive behaviors emerged. People whose externalizing behaviors were apparent earlier in
life (during early childhood and school-age) are characterized by a signi cantly more severe
and persistent prognosis. ese life-course externalizers are almost always diagnosed with
antisocial personality disorder as adults, and many end up incarcerated or institutionalized
with limited social support.
In contrast to life-course externalizers, a second group of adolescence-limited externalizers
begin demonstrating disruptive behaviors only during their teenage years, with no earlier
signs of aggression during childhood. Externalizing behaviors by this group are often
disruptive (such as throwing tantrums, disobeying instructions, and vandalizing property)
but rarely reach the levels of overt violence and aggression that are seen in life-course
externalizers. Reassuringly, these behaviors often remit within a few years and do not
necessarily predict worse psychological or social outcomes as an adult. Interestingly, the
gender ratio for adolescence-limited externalization is more even (with 2 females for every 3
males).
 
TREATMENT
ere is a lack of high-quality studies on how to treat externalizing disorders. Most
evidence seems to suggest that the best outcomes are seen with use of speci c forms of
therapy, such as various forms of behavior modi cation (including applied behavior
analysis) and parent-child interaction therapy. ese treatments teach speci c skills to both
the child and their family unit with the goal of reducing the emotional dysregulation that
leads to disruptive behavior as well as providing behavioral alternatives to acting out (like
screaming into a pillow).
As a rule, medications have not been shown to be effective at treating externalizing
disorders. Nevertheless, they are frequently used, especially in under-resourced settings such
as group homes where money and time to appropriately address externalizing disorders are
often lacking. Stimulants are commonly used, as ADHD is frequently comorbid with the
majority of externalizing disorders (although it is unclear whether they have any effect in
the absence of comorbid ADHD). Antipsychotics are often used as well, with some studies
showing that risperidone has some efficacy. However, this must be balanced against the
clear evidence of long-term risks associated with antipsychotic use (including weight gain
and extrapyramidal symptoms). A number of small studies have suggested that speci c
medications may be helpful for managing speci c symptoms associated with particular
externalizing disorders (such as using SRIs to decrease emotional dysregulation in

449
intermittent explosive disorder or naltrexone to reduce impulsivity in kleptomania), but few
of these studies have been replicated enough times to be considered high-quality evidence.
In situations where there is a lack of resources available for either behavioral or family
therapy, it is likely that medications will continue to be used despite a lack of evidence.

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MECHANISMS OF EXTERNALIZATION
Externalization is a complex phenomenon for which no single explanation will likely ever be
found. is is because the core characteristics of externalization (misbehavior and emotional
dysregulation) are both multifactorial phenomena that can each be related to many
different things. Despite these variations, however, some patterns have begun to emerge.
Decades of research on childhood development have found that neglect (particularly
in the early years of life) produces a characteristic syndrome of impairments in attention,
impulse control, and social ability that accounts for the vast majority of children and
adolescents diagnosed with externalizing disorders. Just as a history of childhood abuse
predicts later development of the “abuse cluster” (including PTSD, personality disorders,
somatization, and dissociation), so too does neglect appear to predispose to a “neglect
cluster” comprised of externalizing disorders. While it is true that neglect increases the risk
of developing most mental disorders, its association with externalizing disorders is
particularly strong. Indeed, while disorders like depression and anxiety are 2 to 3 times
more common in impoverished settings, severe externalizing disorders like conduct disorder
are over 10 times as frequent.
e association of neglect to externalizing disorders appears to be fairly speci c as well.
For example, in children who were neglected but not abused, there does not appear to be a
signi cant increase in rates of trauma-related disorders like PTSD (while there is an
increased prevalence of externalizing disorders). Whether someone who experienced
childhood maltreatment ends up developing an externalizing disorder, an internalizing
disorder, or both appears to depend largely upon a few key factors, including the type of
maltreatment (with sexual abuse appearing to cause more internalizing disorders while
neglect and physical violence cause more externalizing disorders), age (with externalizing
disorders being more common with maltreatment in early childhood while internalizing
disorders are more common in older children), and gender (with boys more likely to
develop externalizing disorders than girls).

To understand why neglect is associated speci cally with the

development of externalizing disorders, consider the role that someone’s caretaker normally
provides. Infants and toddlers have a need for reciprocal interactions where the child and
caregiver are each engaged in both giving and receiving social interaction. ( e game
peekaboo is a perfect example of this, and tellingly it is found in nearly every society and
culture across the world.) ese sorts of interactions appear to play a key role in forming a
child’s concept of how one’s actions affect the feelings and emotions of others. For example,
while playing peekaboo it is common for the infant to laugh when the caretaker’s face is
revealed which in turn causes the caretaker to laugh. By engaging in this behavior, the

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infant can see that their actions have effects on others and that interacting with others can
be incredibly rewarding. is explains why social neglect is correlated with externalizing
behaviors much more than other forms of neglect such as physical or medical neglect.
is lack of opportunity to engage in reciprocal interactions appears to directly affect
the development of the central nervous system. In fact, studies have found that speci c
areas of the brain (in particular the prefrontal cortex) are noticeably smaller in people with
a history of early childhood neglect. ese brain regions are involved in attention, impulse
control, emotional regulation, and responses to stress—the exact cognitive domains that are
most dysregulated in externalizing disorders. De cits in these domains are noticeable as
early as childhood but persist throughout life, which mirrors the chronic life course
associated with externalizing disorders.

e environment outside of just the parent-child

relationship can play a large role as well. Unstable living arrangements, lack of access to
appropriate medical care, food insecurity, and exposure to violence in the community are all
known to be additional risk factors for externalizing behaviors in children. Indeed, you
should not walk away thinking that all children with externalizing disorders have “bad
parents.” Neglect comes in many forms, and not all of them are voluntary. Most parents
truly want to take good care of their children, but some are unable to due to factors outside
of their control. Societal racism, mass incarceration, and socio-economic disadvantage all
intersect here, creating a vicious cycle in which exposure to poverty and parental
institutionalization lead to externalizing behaviors on the part of the child, resulting in their
becoming institutionalized and impoverished and continuing the cycle further.
Despite the strong association between externalizing disorders and a history of
neglect, it is neither sufficiently sensitive nor speci c to be able to work backwards. (In
other words, you can never be sure that someone with an externalizing disorder was
neglected, nor can you be sure that someone who was neglected will develop an
externalizing disorder.) In addition, some neglected children develop internalizing disorders
(either instead of or in addition to externalizing disorders) while others are remarkably
resilient and develop no mental disorders at all. Consistent with the idea that it’s never just
one thing, you should never think that a history of neglect explains everything about
externalizing disorders. ere is likely a substantial genetic contribution as well, as parents
who neglect their children often have their own externalizing conditions (although studies
have found higher rates of antisocial behavior in children who have experienced neglect

452
even after controlling for genetic transmission of antisocial traits, supporting the idea that
neglect is an independent risk factor for externalization).
Overall, the association between neglect and externalization is a robust one that
provides an explanatory framework when working with patients whose behaviors we can
have difficulty understanding. It can be frustrating and emotionally draining to work with
patients who repeatedly engage in behaviors that hurt other people, especially when they
seem to have no desire to stop. However, by understanding that these patients often come
from backgrounds in which they were not afforded the same kinds of developmental
opportunities that are given to most people, we can be better equipped to approach their
care from a position of empathy and humility.

453
DIAGNOSING EXTERNALIZING DISORDERS
e concept of an externalizing disorder is not recognized in the DSM which instead
groups these disorders using the rather inelegant name of “Disruptive, Impulse-Control,
and Conduct Disorders.” However, despite a lack of official recognition, the concept of an
externalizing disorder has been found to be both valid and reliable.
While this was mentioned in the previous chapter, it is worth repeating that this book uses
the term “externalizing disorder” speci cally to refer to those cases where disruptive
behaviors are clearly associated with an excess of negative emotions. is places them in
contrast to disorders like ADHD and autism which (despite at times featuring disruptive
behavior) are not necessarily associated with negative emotions. is also places them in
contrast to psychopathy or callous-unemotional traits which is de ned by a distinct lack of
emotion. is may be confusing, as some clinicians and researchers will refer to both
ADHD and psychopathy as being externalizing disorders. However, for the purposes of
maintaining clarity within this book and to preserve the important prognostic differences
between these conditions, we will treat ADHD, externalization, and psychopathy as three
clinically distinct entities that all share a tendency towards disruptive behavior.
A variety of externalizing disorders are listed in the DSM-5, including oppositional de ant
disorder, conduct disorder, intermittent explosive disorder, disruptive mood dysregulation
disorder, kleptomania, and pyromania. It is unclear whether these syndromes (which the
DSM treats as separate disorders) are in fact distinct entities or if they instead represent
many possible variations on a core syndrome of externalization that is seen frequently in
children who experienced unstable upbringings. However, the high rates of comorbidity,
frequent overlap in symptoms, and unclear boundaries between “normal” and “abnormal”
misbehavior likely argue for the latter. We will now go over each of these diagnoses in turn.
 
OPPOSITIONAL DEFIANT DISORDER
Oppositional de ant disorder (with the unfortunate abbreviation of ODD) is de ned as a
pattern of consistent argumentativeness, vindictiveness, and/or de ance of parental or
authority gures that is excessive, destructive, and maladaptive to the point where it causes
harm to both the patient and those around them. Children and adolescents diagnosed with
oppositional de ant disorder frequently argue, refuse to follow rules, and purposefully do
things to annoy or upset others. However, these behaviors do not cross the line into
violation of others’ rights and stop short of overt violence, aggression, or theft (as occurs
with conduct disorder, discussed next).
ese patterns of disruptive behavior must be in excess of what is normally expected
for a child and must occur for at least 6 months. As with other externalizing disorders, there
is a signi cant mood component to oppositional de ant disorder, with persistent anger and
irritability being enduring emotional states. Treatment involves working with the family
both as a unit (as in family therapy) and individually (with psychotherapy and behavioral
training for the child and education on behavioral principles for the caregivers). Despite
being frequently used, there is little evidence that medications are effective for treating
oppositional de ant disorder.

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CONDUCT DISORDER

While oppositional de ant disorder and conduct disorder are both

characterized by disruptive behavior, conduct disorder takes this a step further to the point
where there is agrant disregard for the rights of others including violence, aggression,
theft, abuse, and assault. Conduct disorder is considered to be a more severe form of
oppositional de ant disorder, and in the majority of cases children are rst diagnosed with
oppositional de ant disorder before later “progressing” to conduct disorder. (However, it’s
worth pointing out that the majority of people diagnosed with oppositional de ant disorder
do not progress to conduct disorder.) Conduct disorder is itself conceptualized as a
precursor to antisocial personality disorder, with half of all children and adolescents
diagnosed with conduct disorder ultimately meeting criteria for antisocial personality
disorder as adults. Even those people who don’t technically meet criteria for a formal
diagnosis as adults often still struggle with occupational functioning and social
relationships, suggesting an overall poor prognosis for this condition, especially if left
untreated.
 
INTERMITTENT EXPLOSIVE DISODER
Intermittent explosive disorder (or IED, another unfortunate abbreviation) is de ned by a
consistent pattern of disruptive behaviors, including screaming, hitting, kicking, or
throwing tantrums. However, as highlighted by the word “intermittent” in the name, these
behaviors tend to happen in discrete episodes each lasting no more than an hour. ese
episodes often occur in response to an external event (such as being told “no”) and are
accompanied by intense feelings of anger, tension, or irritability that appear to be
signi cantly out of proportion to how most children would react. In between episodes,
however, mood returns to normal (which is in contrast to the persistent negative mood state
seen in oppositional de ant disorder and disruptive mood dysregulation disorder).
Intermittent explosive disorder can be conceptualized as a disorder of both emotion
regulation and impulse control, as the patient not only has difficulty regulating their
emotions in response to external stressors but also has trouble not acting out in a way that is
counterproductive and harmful towards others. Indeed, many children diagnosed with
intermittent explosive disorder express remorse about their actions once they have calmed
emotionally (in contrast to people with oppositional de ant disorder or conduct disorder
who are more likely to continue believing that they were justi ed in their actions). Like
other externalizing disorders, treatment is focused primarily on cognitive behavioral
interventions aimed at providing distress tolerance skills and impulse control. Family and

455
behavioral therapy can be incredibly helpful as well. Medications play more of a role in
treating intermittent explosive disorder compared to oppositional de ant disorder or
conduct disorder, with most evidence favoring use of SRIs. However, medications as a
whole are still quite limited in their effects, so behavioral and family therapy should be
offered as rst-line options whenever possible.
 
DISRUPTIVE MOOD DYSREGULATION DISORDER
Disruptive mood dysregulation disorder (DMDD) is similar to intermittent explosive
disorder in that the disruptive behaviors occur in intermittent episodes. However, it differs
from intermittent explosive disorder in that there is chronic irritability, sadness, or anger
even between outbursts. It further differs from oppositional de ant disorder and conduct
disorder in that children with this disorder show remorse for their behavior. As disruptive
mood dysregulation disorder is a relatively new diagnosis, data are not available on its
prognosis in relation to other externalizing disorders. However, it appears to be highly
associated with ADHD. In addition, most children who meet criteria for disruptive mood
dysregulation disorder will also meet criteria for oppositional de ant disorder, although the
reverse is not true.
 

KLEPTOMANIA Kleptomania is a condition in which

people regularly steal items that do not belong to them. Unlike “normal” theft, these items
are not stolen for personal or nancial gain. Rather, for someone with kleptomania the act
of stealing is experienced as intensely pleasurable and results in positive reinforcement
(often described as a “thrill” or “adrenaline rush”). For this reason, kleptomania is
considered a disorder of impulse control, placing it closer to addictive disorders than
compulsive disorders. Indeed, many of the treatments that are successful for kleptomania
resemble those used for treating addiction, including naltrexone. Kleptomania also appears
to be associated with other externalizing disorders that also feature a high degree of
impulsivity such as intermittent explosive disorder and disruptive mood dysregulation
disorder.
 

456
PYROMANIA Pyromania is a relatively rare condition
characterized by recurrent re setting leading to destruction of property. Similar to
kleptomania, re setting in pyromania is done not for any sort of external gain (in which
case it would be arson). Rather, for someone with pyromania the act of re setting is
experienced as being euphorically pleasurable. In contrast to people with kleptomania,
however, people with pyromania often describe a build-up of mental tension that can only
be relieved by starting res, making it appear that compulsivity likely plays as large of a role
in this disorder as impulsivity.
 

457
DIFFERENTIAL DIAGNOSIS OF EXTERNALIZING
DISORDERS
Externalizing disorders sit at a strange nexus of many different psychiatric diagnoses, with
certain elements of personality disorders, mood disorders, addictive disorders, traumatic
disorders, and neurodevelopmental disorders present in many of these conditions. For this
reason, it is important to pay close attention to the relationship between externalizing
disorders and other psychiatric conditions to avoid confusion.
 
NORMALCY
Diagnosing an externalizing disorder must be done with signi cant caution, as it usually
involves someone other than the identi ed patient saying that there is a problem (it’s usually
“My kid’s acting out again!” rather than “I’m acting out again”). is is in contrast to
something like depression where it is typically the identi ed patient who decides to seek
clinical attention because they themselves feel that something is wrong. In addition, the
tendency to characterize all disruptive or challenging behaviors as being indicative of
psychiatric pathology is concerning as it minimizes the contribution from other factors.
Indeed, disruptive behaviors have many possible sources, not the least of which is being a
logical (though not necessarily adaptive) response to stresses and injustices in one’s home,
school, or society as a whole. For example, over a quarter of all children living in foster care
or residential group homes have been diagnosed with either oppositional de ant disorder or
conduct disorder, yet a good number of these cases resolve when the child is placed into a
more stable living arrangement. By assigning a diagnosis, it is easy for someone to get the
impression that the “problem” lies entirely within the child when in reality they may simply
be the most vulnerable person in a complex system of inequality and dysfunction. For both
of these reasons, there is a higher risk of unjustly “labeling” or pathologizing behavior when
diagnosing externalizing disorders compared to most psychiatric conditions. erefore, it is
best to approach externalizing disorders from a place of clinical humility by always keeping
normalcy on the differential.
 
ANTISOCIAL PERSONALITY DISORDER
By de nition, antisocial personality disorder cannot be diagnosed in people younger than 18
years of age. However, this is a purely political construct, as nature doesn’t care one bit
whether someone with antisocial behavior is 17 ½ or 18 years of age. While the creators of
the DSM wanted to avoid giving such a stigmatizing diagnosis to children whose
development was not yet complete, this had the unfortunate effect of creating one
diagnostic scheme for adults and another for children, making it necessary to characterize
relationships between two disorders that are likely the exact same thing (at least as far as
biology is concerned). For children diagnosed with externalizing disorders, many (but not
all) will go on to “graduate” to antisocial personality disorder when they turn 18. e precise
graduation rate depends on the speci c diagnosis but is highest with conduct disorder (at a
little over 40%).
 
PSYCHOPATHY
A subset of children and adolescents who are diagnosed with an externalizing disorder
shows signs of callous-unemotional traits. As we will discuss further in the next chapter,
people with callous-unemotional traits engage in misbehavior not as a way of expressing

458
negative emotions but rather due to a temperamental lack of empathy that blinds them to
the pain and suffering that their behavior causes others. For the purposes of clarity, we will
not refer to people with misconduct related to callous-unemotional traits as having an
externalizing disorder as their behavior does not result from externalizing negative emotions
into the environment). Instead, we will refer to this pattern as its own thing (known as
psychopathy when it occurs in adults).
 
ATTENTION DEFICIT HYPERACTIVITY DISORDER
Given that externalizing disorders and ADHD (speci cally its hyperactive or combined
subtypes) are both characterized by persistent misbehavior, it is no wonder that there is
frequent confusion between the two. A key way to differentiate between these diagnostic
categories is to look at the intentionality of the behavior, as disruptive behaviors in “pure”
ADHD are rarely done with the intention of frustrating others (even if they end up having
that effect). e course of each disorder is important as well, as the hyperactivity from
ADHD tends to improve during the transition from childhood to adolescence in many cases
while the disruptive behaviors found in externalizing disorders often worsen as a teenager.
(Fortunately, disruptive behaviors related to both ADHD and externalizing disorders tend
to decrease as one enters adulthood.) However, even when careful diagnostic assessments
are made, there are many cases where people appear to have both ADHD and an
externalizing disorder. Indeed, the comorbidity of externalizing disorders with ADHD may
be as high as 40% even after conducting a thorough differential diagnosis. e presence of
both externalizing behavior and inattention predicts signi cantly poorer outcomes than
with either disorder alone. In addition, treatment using stimulants for children with
externalizing disorders appears to only result in positive improvements in behavior when
there is comorbid ADHD, further strengthening the concept that these are two separate
disorders with separate treatment considerations.
 
INTERNALIZING DISORDERS

Internalizing disorders like depression and anxiety and

externalizing disorders often co-occur, with the majority of children with externalizing
disorders also meeting criteria for an internalizing disorder (although the reverse is not
true). While externalizing behaviors are often the most pressing concern for the parents, it is

459
the internalizing symptoms that are more likely to be distressing to the child. erefore,
never let the presence of externalizing behaviors distract you from internalizing symptoms
as well. Children who struggle with depression and anxiety can occasionally externalize
their frustrations as well (such as yelling or punching a wall when they are upset). However,
a diagnosis of an externalizing disorder should be based upon disruptive behavior that is
frequent and persistent, so a single episode of misbehavior is not enough to warrant a
separate diagnosis of an externalizing disorder.
 
BIPOLAR DISORDER
ere is signi cant controversy surrounding bipolar disorder in children. is is because the
primary symptoms of pediatric bipolar disorder (such as irritability, rapid speech,
distractibility, and high energy) are all incredibly non-speci c and are found in a variety of
other disorders, including externalizing disorders and ADHD. In addition, longitudinal
studies have shown that pediatric cases of bipolar disorder rarely “graduate” to bipolar
disorder as adults, suggesting that the syndrome that is called “bipolar disorder” in children
is not the same as the one that is called “bipolar disorder” in adults. ere is reason to be
cautious, as incorrectly ascribing irritability, distractibility, or hyperactivity to bipolar
disorder has been shown to increase use of powerful and often harmful medications like
mood stabilizers and antipsychotics. As a general rule of thumb, avoid diagnosing pediatric
bipolar disorder unless there are speci c signs of mania (such as increased goal-directed
activity) and a high-degree of certainty that the symptoms cannot be attributed to any other
cause.
 
AUTISM
Children with autism may engage in violent behavior or otherwise act out due to the core
features of their disorder. For example, they may throw a tantrum when someone interferes
with their engaging in a restricted interest, or they may become upset if they are unable to
express their needs due to their communication de cits. Taking time to determine if either
of these are present when assessing children who are engaging in problematic behavior.
 

TRAUMA Many children with externalizing disorders have a history of trauma, with
neglect and exposure to violence being particularly common. However, because various
types of maltreatment tend to occur together, it is worthwhile to be on the lookout for signs
and symptoms of the “abuse cluster” for anyone diagnosed with a disorder from the “neglect
cluster.” Interestingly, “textbook” PTSD appears to be fairly rare following exposure to
trauma during childhood (with rates of less than 5% in children living in foster care or
residential group homes). Instead, cluster B personality disorders, somatization, and
dissociation appear to be much more common, with the age of trauma exposure seeming to
mediate much of this effect.
 
REACTIVE ATTACHMENT DISORDER
Reactive attachment disorder is a speci c form of traumatic disorder that is caused by severe
neglect during early childhood. Like PTSD, it presents with a characteristic constellation of
signs and symptoms, but the earlier and more pervasive nature of trauma in reactive
attachment disorder tends to manifest differently than someone with “textbook” PTSD.
Children with reactive attachment disorder rarely seek solace from caregivers when

460
distressed and are not calmed when an adult tries to comfort them. ey also tend to have
severely dysregulated mood, irritability, and difficulties with social interaction. Reactive
attachment disorder is rare in the general population but is found more commonly in
speci c settings (such as orphanages or group homes) where opportunities to engage in
infant-parent bonding are severely lacking.
In the DSM-5, a new diagnosis related to reactive attachment disorder was introduced
known as disinhibited social engagement disorder. Disinhibited social engagement disorder
and reactive attachment disorder both share an association with social neglect during early
childhood, but reactive attachment disorder is characterized more by internalizing
symptoms (such as sadness, irritability, and fearfulness) whereas disinhibited social
engagement disorder involves externalizing behavior (including an overly familiar way of
interacting with adults, wandering off with strangers without hesitation, and lacking
affection for any people in particular). Both of these disorders occupy a strange place in the
DSM, as no other disorders are diagnosed on the basis of attachment patterns alone.

461
PUTTING IT ALL TOGETHER
Misbehavior is perhaps the most common reason that children and adolescents are brought
in for psychiatric evaluation, yet psychiatry as a profession has little to offer patients or their
families in the way of explanation or treatment. is is because our understanding of these
disorders is incredibly limited and our diagnostic schemes for them a bit of a mess. It is not
uncommon for patients to have more than one externalizing disorder at a time or to switch
between different disorders from one clinic visit to the next. In addition, comorbidity is
common (both with externalizing disorders as a group and with other conditions like
depression and anxiety).
Nevertheless, the classi cation scheme for externalizing disorders in the DSM at least
attempts to provide some boundaries between different conditions (unlike antisocial
personality disorder, which places all adults with recurrent “bad behavior” into the same
diagnostic box). A core distinction between the different externalizing disorders involves the
intentionality of the behavior. While all externalizing disorders involve purposeful
destructive behaviors, intermittent explosive disorder and disruptive mood dysregulation
disorder are characterized by episodes of impulsive acting out for which the patient later
feels remorse whereas conduct disorder and oppositional de ant disorder instead involve
purposeful or planned actions. After making that initial distinction, you can separate
intermittent explosive disorder and disruptive mood dysregulation disorder by the presence
of a persistent negative mood state in disruptive mood dysregulation disorder (as opposed
to the generally normal mood state punctuated by episodes of intense negative affect seen in
intermittent explosive disorder). Oppositional de ant disorder and conduct disorder
themselves are separated by the severity of misbehavior (which escalates to involve overt
violence and abuse only in conduct disorder).
Many of these disorders are relatively new (having been introduced only in recent versions
of the DSM), so meaningful information on prognosis and treatment for these speci c
diagnoses will likely be lacking for a while. However, the underlying behavioral patterns
that they describe are anything but new, and many elds that overlap with but are
technically outside of psychiatry (such as behaviorism) can often give further guidance.
Nevertheless, the distinctions made by the DSM at least provide a framework for being able
to understand patients and families who struggle with these conditions and, through your
understanding, possibly provide some help.

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REVIEW QUESTIONS
1. A 7 y/o M is brought into a psychiatrist’s office by his adoptive mother who says
that she is “completely fed up.” He has been suspended from school for the third
time this year after he punched one of his classmates during an argument over
whose turn it was to use the handball court. In the past, he has gotten in trouble
for hitting the classroom rat after it bit him and throwing a classmate’s birthday
cake onto the oor after she refused to give him a piece before everyone else. e
patient has lived with his adoptive parents for just over one year, prior to which he
lived in various foster homes. He is not aware that his parents both died of a
heroin overdose when he was two years old. Which of the following questions to
the patient’s mother would best distinguish between intermittent explosive
disorder and disruptive mood dysregulation disorder?
A. “Has he ever done anything more violent like trying to rob someone
or attacking them with a weapon?”
B. “Has he ever hurt other people without being upset about something
rst?”
C. “What is his mood like most of the time?”
D. “Is he like this at home as well or only at school?”
E. “How does he feel about these actions after he has calmed down?”
2. A 13 y/o F meets with a psychiatrist at her group home for an appointment. A
complete psychiatric evaluation reveals that the patient meets diagnostic criteria
for panic disorder, kleptomania, the hyperactive subtype of ADHD, oppositional
de ant disorder, and a history of inhalant abuse. Which of these disorders should
the psychiatrist address rst in order to most improve the therapeutic relationship?
A. Panic disorder
B. Kleptomania
C. Attention de cit hyperactivity disorder
D. Oppositional de ant disorder
E. A history of inhalant use disorder
3. A 16 y/o F is brought to a psychiatrist’s office by her father who says that “she is
acting like a little shit these days.” Over the past year, she has begun skipping
school on multiple occasions and has seen her academic performance decline. She
has been arrested on two separate occasions: one for smoking cannabis in a public
place and another for spray-painting a billboard. Prior to one year ago, she was a
straight-A student and had plans to go to college on a softball scholarship. She
lives at home with her parents and younger sister. Although her parents are
married, they argue frequently and have threatened to divorce each other on
multiple occasions. e patient herself participates in the interview only minimally,
saying, “You’re just one of my dad’s lackeys. Why should I tell you anything?”
What is the most likely outcome for this patient’s behavior?
 

A. is behavior will only get worse, and she will likely be incarcerated
during her lifetime for a violent crime
B. is behavior will remain at the same level throughout her adult years

464
 C. is behavior will partially improve on its own, but she will continue to
engage in frequent disruptive behaviors throughout her life
D. is behavior will improve on its own within several years
E. e psychiatrist will be able to intervene immediately and resolve the
behavior today
4. A 17 y/o M drops out of school to support his mother who has recently been
diagnosed with metastatic breast cancer. His mother lacks health insurance, and
they have depleted their bank accounts paying for medical bills. He works over 14
hours per day between three different jobs in order to bring in enough income to
afford rent. On the way home from work one night, he fails to come to a complete
stop at a stop sign and is pulled over by a policeman. e policeman orders him to
step out of the car and put his hands above his head. Frustrated and angry, he yells,
“I’m not fucking doing that! I’ve had it! I’ve fucking had it!” and proceeds to honk
his car horn repeatedly. He is detained and taken to a local psychiatric emergency
room. During his initial assessment, the patient reports that he is “constantly
angry,” and he has yelled at both members of his family and several customers at
work in the past few weeks. He has one prior arrest for possession of cannabis but
says that he was selling drugs to “make ends meet.” At one point, he breaks down
crying in front of the psychiatrist and says that he wants to punch the face of
“every single person I see.” What is the most likely diagnosis?
A. Oppositional de ant disorder
B. Conduct disorder
C. Intermittent explosive disorder
D. Disruptive mood dysregulation disorder
E. Antisocial personality disorder
F. None of the above

465
1. e best answer is C. While all of these questions would provide helpful
information about this patient’s case, the key difference between intermittent
explosive disorder and disruptive mood dysregulation disorder involves whether
there are persistent mood symptoms such as sadness, anger, and irritability
between episodes of acting out (in which case a diagnosis of disruptive mood
dysregulation disorder would be more likely). Assessing the severity of the violent
acts can differentiate between oppositional de ant disorder and conduct disorder
(answer A), while asking about violence in the absence of emotional dysregulation
can help to rule callous-unemotional traits in or out (answer B). In addition,
assessing remorse can distinguish intermittent explosive disorder and disruptive
mood dysregulation disorder from oppositional de ant disorder and conduct
disorder (answer E). Finally, knowing whether the behaviors are present in
multiple settings is helpful diagnostically but does not distinguish between
intermittent explosive disorder and disruptive mood dysregulation disorder.
2. e best answer is A. Out of all the disorders listed, only panic disorder is
considered to be purely an internalizing disorder rather than an externalizing or
impulse control disorder. While externalizing disorders are often of the most
concern to others (such as parents, teachers, and supervisors), patients themselves
are most likely to want help with their internalizing disorders. erefore,
prioritizing treatment of the patient’s internalizing disorders is likely to result in a
better therapeutic relationship.
3. e best answer is D. is case describes a pattern of adolescence-limited
externalization as evidenced by onset at the age of 15 and no previous history of
signi cant externalizing behavior. In contrast to life-course externalization,
adolescence-limited externalization generally resolves on its own within several
years and does not necessarily predict worse psychological or social outcomes as an
adult (answers A, B, and C). It is rare that a psychiatrist will be able to change
behavior during a single visit, and externalization is no exception (answer E).
4. e best answer is F. is patient appears to be having a normal response to
extraordinarily abnormal circumstances. While there are some elements of
externalization present in how he is acting, a key feature of externalization is that
emotions and behaviors are considered to be signi cantly out of proportion to the
situation that provoked them. While the line between externalization and
normalcy is often ambiguous, there is at least some element of reasonableness to
how he is reacting, making a diagnosis of an externalizing disorder much less likely
(answers A through D). Based on the presentation, this patient is much more
likely to be suffering from an internalizing disorder such as depression or PTSD,
or to have no disorder at all. As a reminder, antisocial personality disorder cannot
officially be diagnosed in people less than 18 years of age (answer E).
 

466
21 PSYCHOPATHY

We now arrive at the nal stop on our three-chapter

tour of “psychiatric misbehavior.” Unlike externalization (which is characterized by extreme
emotionality) and hyperactivity (which does not speci cally relate to emotions and instead
stems from a neurodevelopmental process), psychopathy is characterized by a distinct lack of
emotion and empathy that results in frequent and persistent antisocial behaviors. ese
callous-unemotional traits form a highly reliable diagnostic construct which carries
important implications for both prognosis and treatment. For this reason, it is essential to
understand the concept of psychopathy when evaluating individuals with antisocial
behavior.
e terms psychopathy or sociopathy are often used as a quick shorthand for the presence
of callous-unemotional traits in adults diagnosed with antisocial personality disorder.
However, just like with antisocial personality disorder, these terms are not used to describe
someone under the age of 18 to avoid assigning a diagnosis viewed as “unchangeable” and
“untreatable” to someone who is still in the process of developing. Nevertheless, many
individuals with callous-unemotional traits begin to show signs during childhood which is
highly predictive of later development of psychopathy as an adult. Because “callous-
unemotional traits” and “psychopathy” refer to the same thing (except that the former is
used to refer to children and adolescents while the latter is not), we will use them
interchangeably throughout this book. When the term “antisocial personality disorder” is
used without a quali er, it should be assumed to mean non-psychopathic forms of the
disorder (even though, per DSM standards, psychopathic individuals would still be
diagnosed with antisocial personality disorder the same as people without callous-
unemotional traits).

467
SIGNS AND SYMPTOMS OF PSYCHOPATHY
e signs and symptoms of psychopathy are at least super cially very similar to those seen
in “garden variety” antisocial personality disorder and conduct disorder, as both are
characterized by behavior that infringes upon the rights of others. However, these behaviors
differ from those seen in non-psychopathic antisocial personality disorder by their severity
and purpose.
Individuals with callous-unemotional traits tend to engage in more severe behaviors,
such as assault, robbery, fraud, rape, and murder, compared to the petty theft, threats, and
battery that are more common in non-psychopathic forms of antisocial personality disorder.
e presence of psychopathy is also associated with a higher prevalence of sadism, with over
80% of psychopathic individuals who have committed sexual homicide having engaged in
some degree of sadistic behavior.

People with psychopathy are more likely to

engage in what is referred to as instrumental violence (also known as predatory or “cold-
blooded” violence). Acts of instrumental violence are performed not for the “rush” or “thrill”
of violence itself but rather to achieve a secondary gain (as in someone who murders a
wealthy-looking stranger walking home on the street just to steal their purse). Over 90% of
homicides committed by psychopathic individuals are instrumental in nature compared to
less than 50% for non-psychopathic individuals. In contrast, aggressive acts in “garden
variety” antisocial personality disorder are best characterized as reactive violence which is
impulsive and driven by extreme negative emotions in response to speci c threats or
provocations (such as someone who comes home to nd his wife in bed with another man
and proceeds to shoot both of them). e risk of reactive violence is increased by the
persistent irritability, affective instability, and extreme sensitivity to perceived insults (the
“cluster B-ness”), all of which are associated with non-psychopathic antisocial personality
disorder.
On a cognitive level, psychopathic behavior is accompanied by speci c ndings,
including the aforementioned callous-unemotional traits that are so characteristic of the
disorder. ese traits tend to manifest through three behavioral domains: boldness,
disinhibition, and meanness. Boldness refers to a high level of self-con dence, an above-
average tolerance of danger and unfamiliarity, and a general fearlessness in many areas of
life. Disinhibition involves poor impulse control and difficulty with foresight (a
characteristic that psychopathy shares with non-psychopathic antisocial personality
disorder). Finally, meanness encompasses a lack of empathy or caring for the feelings of
other people, both as individuals and on a societal level. is inability to understand the
feelings of others is pervasive, and imaging studies done on people with psychopathic

468
tendencies show a low level of activity in areas of the brain normally associated with
understanding the emotions of others. Indeed, psychopathy appears to prevent someone
from feeling the pain they cause others which explains why many of the most notorious
serial killers often have psychopathy rather than “simple” antisocial personality disorder.

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PSYCHOPATHY ACROSS THE LIFESPAN
Psychopathy is relatively rare, with estimates placing the prevalence at around 0.5% of the
population. However, it is signi cantly more common in incarcerated settings, with around
15% of all prisoners and 30% of violent prisoners showing signs of psychopathy. As with
other disorders featuring aggressive behavior, psychopathy is signi cantly more common in
men than women, with an even higher gender ratio (around 20 to 1) compared to non-
psychopathic antisocial personality disorder.
Psychopathy is a highly heritable condition (possibly the most heritable in all of
psychiatry), with over 90% of the variance between individuals in psychopathic traits being
attributable to genetic factors. is is even more pronounced than for non-psychopathic
antisocial personality disorder (which is around 60% heritable) and the adolescent-limited
form of externalization (which has very low heritability). However, even with a higher
contribution from “nature” over “nurture,” environment still matters a great deal as the
biological children of parents with psychopathy have lower rates of developing antisocial
behavior themselves when the adoptive parents have provided appropriate behavioral
reinforcement patterns.

By de nition, psychopathy is not diagnosed in someone

before the age of 18. However, the presence of callous-unemotional traits can be noted as
early as childhood. In fact, even as infants people with callous-unemotional traits are often
described as having a difficult temperament characterized by frequent and incessant crying,
irritability, lack of a social smile, and persistent hyperactivity. e speci c disruptive
behaviors that these individuals engage in varies by age, with mild physical aggression such
as biting and hitting seen during early childhood; stealing small objects, setting res, and
torturing animals during school age; bullying others and stealing larger objects during
adolescence; and progressing to robbery, fraud, assault, and rape as an adult.
 
PROGNOSIS
People with antisocial behavior related to callous-unemotional traits have a distinctly worse
prognosis than people with non-psychopathic antisocial behavior, with a higher severity of
aggressive acts and higher rates of recidivism after punishment. Callous-unemotional traits
show considerable stability over years and decades, even when assessed during childhood.
In other words, once someone is on the callous-unemotional trait “train,” it is exceptionally
hard to get off.
 
TREATMENT
Psychopathy is considered very difficult to treat using conventional psychiatric treatment
approaches (even more so than non-psychopathic forms of antisocial personality disorder).
ere are no medications that have proven effective at changing the core personality traits

470
associated with psychopathy or at reducing the frequency or severity of antisocial acts. Some
medications (like anticonvulsants) are used to reduce reactionary violence in non-
psychopathic antisocial personality disorder; however, because violent acts in psychopathy
are typically instrumental rather than reactive, they rarely work here.

Traditional psychological therapies fare little better, as

patients with psychopathic traits tend to be less engaged in therapy, show little motivation
for treatment, and demonstrate more limited improvement in almost all outcomes
compared to non-psychopathic antisocial personality disorder. A large part of this may be
attributed to poor compliance with treatment, as many people with psychopathic traits do
not believe that they have a problem (their actions are ego—syntonic) and are more often
compelled to engage in treatment by the legal system than they are intrinsically motivated
to get better on their own. Concerningly, people with psychopathic traits who appear to be
the most engaged in treatment are actually more likely to commit crime again in the future
(particularly violent or sexual crimes), suggesting that the appearance of treatment success
may in and of itself be a marker of a worse prognosis as it suggests a greater degree of
deceitfulness and manipulation. Despite incarceration and other legal punishments being
used frequently in this population, it is unclear whether any forms of punishment are
effective at treating psychopathy or reducing rates of violent behavior in this population.

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MECHANISMS OF PSYCHOPATHY
Psychopathy is a consistent and durable diagnostic construct which provides some level of
explanation for the “bad behavior” that is seen in some cases of conduct disorder and
antisocial personality disorder. On a mechanistic level, two primary neurobiological
differences have been noted in cases of psychopathy.
Research has consistently found that psychopathic individuals lack intrinsic
empathic ability and do not experience the same overwhelmingly aversive reactions to the
pain and distress of others that most people do. Consider the following image:
 

Most people looking at that picture will have an automatic negative emotional reaction that
is experienced as painful (it is even processed in the same parts of the brain that register
physical pain even though no actual injury has occurred). Someone with callous-
unemotional traits, however, will not automatically experience a negative emotional reaction
to seeing someone else in pain, and these parts of the brain stay turned “off ” when watching
other people in distress. is insensitivity appears to be related to structural and functional
differences in how the amygdala processes fear and facial expressions.

Interestingly, people with psychopathic traits are not

completely unable to empathize with the emotions of others, as the regions of the brain
associated with empathy “lit up” when subjects were speci cally asked to consider how
others felt. Instead, it appears that the empathic networks of the brain are turned off by
default but can be activated with enough effort. is explains why people with psychopathic

472
tendencies can often be very charming and manipulative as they can turn on their “empathic
switch” when it suits them and leave it off the rest of the time.
e other characteristic neurobiological difference that is seen in psychopathy is an inherent
trait of fearlessness which appears to separate psychopathy from “garden variety” conduct
disorder and antisocial personality disorder as reliably as an “off by default” empathic
switch. People with psychopathy do not experience fear in the same way that most people
do, with some evidence suggesting that there is reduced activity of the sympathetic nervous
system and HPA axis (which contrasts with the patterns seen in anxiety, depression, and
other internalizing disorders). is fearlessness accounts for the boldness and tolerance of
unfamiliarity that is frequently associated with psychopathy. Fearlessness also makes
psychopathy a particular challenge for the legal system, as most societies try to prevent
antisocial behavior like murder and theft through the fear of punishment (such as
imprisonment or the death penalty). If psychopaths lack fear, however, then these
punishments will not work, and that is exactly what we see: imprisonment and other
punishments appear to have little effect on preventing future crimes. is has led to the
widespread belief that psychopaths do not respond to rewards and punishments. However,
this is not true, as psychopaths clearly make decisions based on the relative rewards available
to them. Where they differ is in how they respond to rewards and punishments.
Let’s return to the example of a cookie jar that we rst brought up in the chapter on
addiction. e cookie serves as a positive reinforcer that most children would love to eat. To
prevent spoiling of the appetite, however, a parent will introduce the threat of punishment
(either a positive punishment like a slap on the hand or a negative punishment like taking
away a toy). Under this sort of threat, a child with a normal reward processing system will
experience signi cant anxiety and autonomic arousal while approaching the cookie jar. e
level of anxiety gets higher and higher as they approach the cookie jar, and for many
children this arousal reaches a critical point where it becomes aversive enough in and of itself
to make them walk away. For these children, the threat itself is enough of a positive
punishment to modify their behavior. In addition, by walking away from the cookie jar, this
anxiety rapidly dissipates (a negative reinforcement for the “good behavior” of not taking a
cookie).
In contrast, someone with trait-based fearlessness would not experience any sort of
anxiety as they approach the cookie jar, so there is no built-in positive punishment just for
thinking about it. In addition, for these children walking away from the cookie jar is
associated with more anxiety than walking towards it due to the feeling that they have lost
out on the opportunity to get the cookie. is makes “doing the right thing” for these
children associated with positive punishment rather than negative reinforcement! In contrast,
if they actually go through with it and take a cookie, then they are both positively reinforced
by the taste of the cookie as well as negatively reinforced by avoidance of “lost opportunity
anxiety.” In this way, trait-based fearlessness sets up the decisional calculus in such a way
that following the rules is actually punished while acting sel shly is rewarded. is
differential response to rewards and punishments can be seen at a very early age and is
predictive of future conduct problems as an adolescent and adult.

473
 To use a more real-world example, a “normal” adult
without psychopathic traits who is experiencing hard times may get the idea that they could
hold someone at gunpoint to steal their wallet. However, in deciding whether or not to do
this, they would balance the reward (money) against the punishment (including not only
anxiety about going to jail but also the extremely unpleasant physiologic and psychological
distress of seeing someone else in pain that would occur whether they got caught or not).
Based on this, a “normal” person would likely decide against robbing someone at gunpoint,
as the money is not worth the possibility of punishment plus the guaranteed aversive
emotional reaction. In contrast, someone with psychopathy would be more likely to choose
to go ahead with it as they are not aversively affected by the pain and distress of others. For
them, the only thing offsetting the prospect of a nancial reward is the chance of getting
caught (which is itself reduced or even negated by the trait-based fearlessness). With these
two physiological and psychological differences in play, it makes some sense why people
with psychopathic traits decide to engage in antisocial behavior.
is speci c neurocognitive pro le of both an “off by default” empathic switch and an
underlying trait of fearlessness results in the insensitivity to traditional punishments that is
seen in people with psychopathy which often prevents efforts at rehabilitating them to live
by the rules of “normal” society. is combination also provides a diagnostic focus that
differentiates people with psychopathy from other forms of misbehavior like non-psychotic
antisocial personality disorder and conduct disorder.
 

Psychopathy is characterized by callous-

unemotional traits that predict a higher risk of
violence and a greater propensity to reoffend.
 

Someone with Callous—Unemotional Traits is more

likely to CUT you.

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DIAGNOSING PSYCHOPATHIC DISORDERS
Despite the fact that psychopathy as a clinical construct resembles a discrete disorder in
nearly every way, it is not recognized as a formal diagnosis in the DSM. is means that
nearly everyone above the age of 18 with psychopathic traits will receive a diagnosis of
antisocial personality disorder. However, the reverse is not true as only around 10% of those
who meet criteria for antisocial personality disorder will have psychopathic traits. While
this diagnostic scheme can be confusing, for the purposes of clarity it is helpful to think of
non-psychopathic antisocial personality disorder and psychopathy as two different
disorders that go by the same name. A speci c rating scale known as the Psychopathy
Checklist-Revised (PCL-R) is commonly used on a clinical basis to assess for the presence
of psychopathic traits.
 

475
DIFFERENTIAL DIAGNOSIS OF PSYCHOPATHIC
DISORDERS
Misdiagnoses for psychopathy are generally limited to the other diagnostic categories
characterized by bad behavior: externalizing disorders and ADHD. Missed diagnoses are
relatively rare, as the fearlessness seen in psychopathy appears to actually protect against the
majority of common mental disorders like depression and anxiety.
 
NORMALCY

It’s difficult to imagine that a condition characterized by

violent acts and a lack of empathy could be on the spectrum of normalcy. is is because
most people with psychopathic traits who come to clinical attention do so through the legal
system, which by de nition only captures those who have gotten in trouble with the law.
However, studies have found that a signi cant minority of people have callous-unemotional
traits but do not engage in violent or criminal behavior. ese people are seen to have the
same low levels of activity in parts of the brain linked to empathy, moral decision-making,
and impulse control seen in psychopathic criminals, yet many spend their days raising a
family and holding a job. (Indeed, some degree of fearlessness may actually be adaptive in
risky or competitive elds such as business and nance where boldness can give one a
competitive advantage.) rough this, we see once again that it’s never just one thing. Even
for someone with callous-unemotional traits, a stable and nurturing upbringing appears to
mitigate the potential for damage related to these traits and allows them to be funneled into
more pro-social activities.
 
ADHD AND EXTERNALIZING DISORDERS
Now that we have covered all three major psychiatric causes of disruptive behavior in more
detail, we can develop a framework for evaluating a patient who is brought in for evaluation
of “bad” or antisocial behavior. e mnemonic PIRATE can help you take a systematic

476
approach to this: P is for Purpose. What is the purpose of the
behavior? Instrumental violence involving some extrinsic reward is generally associated
with psychopathy while reactive violence involving a speci c emotional trigger is more
suggestive of an externalizing disorder or normalcy.
 

I is for Intentionality. How intentional is the behavior? A high degree of intentionality

argues for psychopathy, oppositional de ant disorder, or conduct disorder while a more
impulsive pattern suggests non-psychopathic antisocial personality disorder, intermittent
explosive disorder, and disruptive mood dysregulation disorder.
 

R is for Remorse. Whether the patient shows remorse for their actions can be a helpful clue
into whether the behavior is impulsive or not. Individuals with impulsive disorders like
intermittent explosive disorder or disruptive mood dysregulation disorder often say that they
regret having acted out while those with oppositional de ant disorder and conduct disorder
usually stick to their guns (so to speak).
 

A is for Activity. Disruptive behavior occurring in the context of elevated levels of activity
can be a helpful diagnostic clue. Persistent hyperactivity suggests ADHD while a sudden
change in level of activity would be more characteristic of mania. For this reason, knowing
the patient’s baseline level of activity and whether the disruptive behavior represents a
signi cant change from it is crucial.
 

T is for Timing. e timing of antisocial behaviors across the lifespan is important.

Misbehavior that begins at a younger age is more likely to suggest ADHD, callous-
unemotional traits, or life-course externalization. In contrast, bad behavior that is seen only
during certain periods of life (such as adolescence-limited externalization) is likely to have a
much better prognosis.
 

E is for Emotion. e nature of the emotions that a patient experiences around the time of
disruptive behavior contains important diagnostic clues. A high degree of intense negative

477
emotion is more consistent with an externalizing disorder or a cluster B personality disorder,
while a lack of emotion instead suggests psychopathy.
 

Disruptive behavior can be characterized by its

purpose, intention, remorse, timing, and the
associated level of activity and emotion.
 

PIRATE: Purpose Intention Remorse Activity Timing

Emotion
ADDICTION
Addiction is the primary exception to the idea that missed diagnoses are rare in
psychopathy, as up to two-thirds of all people with psychopathy have an addictive disorder.
It is likely that the fearlessness of psychopathy is directly responsible for this association, as
the anxiety about negative repercussions that holds many people back from using substances
is not at play here.
 
PSYCHOSIS
While people with schizophrenia are more likely to be the victims of violence than its
perpetrator, a small minority of people with schizophrenia do engage in violence. is can
occasionally be confused with psychopathy, as these violent acts can be premeditated and
planned (in contrast to the reactive aggression seen in non-psychopathic antisocial
personality disorder). e key difference is that premeditated violence in schizophrenia is
almost always related to a delusional belief system, whereas in psychopathy the primary
objective is often instrumental.
 

TRAUMA Histories of mistreatment during early childhood (including both abuse and
neglect) are frequently found in adults with psychopathic traits. However, this does not
necessarily result in higher rates of trauma-related disorders like PTSD in this population.
In fact, the fearlessness and hyporeactivity of the HPA axis seen in psychopathy may make
comorbidity with PTSD, which is often characterized by an overactive fear response and
HPA axis hyperreactivity, less likely.
 
OBSESSIVE-COMPULSIVE DISORDERS
Intrusive thoughts related to obsessive-compulsive disorder can often be of an intensely
aggressive nature (including thoughts of murder or sexual violence). However, it’s important
to point out that (consistent with the MURDER mnemonic) these thoughts are distinctly
ego-dystonic, and people with OCD rarely if ever actually act on the thoughts. (Many will
even go to great lengths to avoid situations that could possibly lead to this behavior such as
removing all knives or other sharp objects from their home.) People with violent thoughts
related to OCD often are quite motivated to seek help as well, which contrasts with the
poor treatment motivation seen in psychopathy.
 

478
MANIA People in a manic state may act in a way that harms others or infringes on their
rights either through impulsive recklessness (such as driving while under the in uence) or
by seeing other people as acceptable collateral damage in the service of a goal-oriented
activity. However, this behavior will be limited to the time of a mood episode (in contrast to
psychopathic traits which are relatively stable across the lifespan).

479
PUTTING IT ALL TOGETHER
Despite not being recognized as a discrete disorder in the DSM, psychopathy is a
consistent and enduring diagnostic construct with important implications for prognosis
and treatment. When evaluating anyone presenting with concerns about disruptive or
antisocial behavior, use the PIRATES mnemonic to systematically characterize the nature
of their behavior. While the presence of callous-unemotional traits is associated with an
incredibly poor prognosis, that does not mean that you should ever “give up” on a patient
with this condition. Indeed, the fact that some people with psychopathic traits appear to
function well in society suggests that there is always hope.
 

480
REVIEW QUESTIONS
1. A 25 y/o M is interviewed by a forensic psychiatrist in a maximum security prison.
He was sentenced to life in prison after DNA evidence linked him to the rapes
and murders of 5 women over a 7 year period. During the interview, the patient
gives simple and straightforward answers to the questions he is asked with no
perceptible change in affect even when describing details of his victims’ murders.
Electrophysiologic testing reveals a lack of perspiration when exposed to an
anxiety-provoking situation. Which of the following behaviors is this patient least
likely to have participated in?
A. Hitting a stranger in the head and stealing their hand bag
B. Slapping a signi cant other during a heated argument
C. Using a knife to intentionally in ict pain upon his victims
D. Memorizing a stranger’s credit card number to make a large purchase
E. All of the above are equally likely
2. (Continued from previous question.) Which of the following most likely describes
this patient’s pattern of neuroanatomical activity in response to situations involving
the pain and distress of others?
A. Decreased in both the amygdala and HPA axis
B. Decreased in the amygdala but increased in the HPA axis
C. Increased in the amygdala but decreased in the HPA axis
D. Increased in both the amygdala and HPA axis
E. None of the above
3. (Continued from previous question.) Which of the following statements about this
patient’s childhood is most likely true?
A. He exhibited no interpersonal or behavioral problems until the age of
18
B. He exhibited no interpersonal or behavioral problems until the age of
13
C. He exhibited no interpersonal or behavioral problems until the age of
8
D. At least one parent likely had callous-unemotional traits
E. None of the above are true
4. A 39 y/o M works as a stock trader at a large nancial investment company. He
has a reputation as a fearless trader who “never breaks a sweat” even when making
multi-million dollar transactions. He was orphaned as an infant and was raised by
adoptive parents from the age of 3. However, he has not seen them in over 20 years
since moving to the city and reports no feelings of closeness to them. He is single
and lives alone. He reports no interest in pursuing friendships or romantic
relationships. Hobbies include base jumping and playing poker. Which of the
following is the most likely diagnosis?
A. Psychopathic antisocial personality disorder
B. Non-psychopathic antisocial personality disorder
C. Narcissistic personality disorder
D. Avoidant personality disorder
E. None of the above

481
1. e best answer is B. People with psychopathy are more likely to engage in
antisocial behaviors characterized by instrumental violence with a clear secondary
gain (answers A and D). ey are also more likely than average to engage in
sadistic acts (answer C). In contrast, due to their lower emotional range they are
less likely to engage in reactive violence such as striking a partner during an
emotional argument.
2. e best answer is A. Studies on people with psychopathic traits have revealed key
differences in two functional areas of the brain: the amygdala, which is less
responsive to the pain and distress of others, and the hypothalamic–pituitary–
adrenal axis, which is less likely to activate in response to fear-inducing or stressful
situations. e combination of these differences leads to the boldness and
meanness that are commonly seen in people with this condition.
3. e best answer is D. Callous-unemotional traits are often apparent even from
early childhood although the nature and degree of antisocial behavior tends to
increase in severity as one ages (answers A, B, and C). ese traits are among the
most heritable of all traits seen in mental health settings, with over 90% of the
variance between individuals being explained by genetic differences. erefore, it is
likely that one or more parents showed evidence of having callous-unemotional
traits even if they did not necessarily meet criteria for a disorder.
4. e best answer is E. is person may have some degree of callous-unemotional
traits as evidenced by his fearlessness and boldness in both his work and his
hobbies. However, there is no indication of antisocial behavior of any kind, ruling
out a diagnosis of antisocial personality disorder even if callous-unemotional traits
are present (answers A and B). It is possible that he has narcissistic traits as well,
but this is not clear from the vignette (answer C). It is unlikely for him to have
avoidant personality disorder as people with this condition generally desire to have
relationships with others (answer D).
 

482
22 Dementia

Aging (also known as senescence) is a normal part of

development. Unlike childhood development, however, there are no speci c motor, speech,
or cognitive milestones for adults to meet as they enter old age. Instead, aging is often
accompanied by accumulating losses in functioning that gradually increase the risk of
mortality. Many of these changes (including some degree of memory loss) are considered to
be completely within the realm of normalcy. However, there are also a variety of conditions
associated with old age that cause distress and dysfunction not only for the patient
themselves but also for their family and caregivers.
For the rest of this chapter, we will focus primarily on a group of conditions known
formally as major neurocognitive disorders in the DSM-5 but generally called dementia.
Dementia is a broad category of diseases characterized by chronic and progressive loss of
memory and cognitive abilities. Like the word “cancer,” “dementia” does not refer to a
single disorder but rather to many diseases that all share commonalities. e main forms of
dementia are Alzheimer’s disease, dementia with Lewy bodies, frontotemporal dementia,
and vascular dementia. It is possible for multiple forms of dementia to be present at the
same time, known as mixed dementia. For example, someone with Alzheimer’s disease may
also have severe peripheral artery disease resulting in recurrent strokes that each reduce their
cognitive abilities. While we will spend the most time on Alzheimer’s disease, we will also
touch brie y on all forms of dementia with a speci c focus on identifying the clinical signs
and symptoms that are the most helpful in differentiating between these conditions.

483
NORMAL AGING

A number of physical and psychological changes are seen

during the process of aging. Most organ systems in the body slow down or become weaker.
Cardiac output decreases, air exchange in the lungs is slowed, and renal clearance is
reduced. e ability of the liver to metabolize substances is also impaired, requiring a more
cautious approach to drug dosing in the elderly. Osteoporosis and loss of muscle mass is
common, and skin starts to lose its elasticity and tone. e acuity of sight and hearing also
progressively diminishes while the immune system becomes less functional, leading to a
higher risk of infection.
Sleep also becomes an increasing concern in old age, with less than 20% of people
over the age of 65 feeling satis ed with the quality of their sleep. Frequent nighttime
awakenings can occur, leading to daytime fatigue. e amount of time spent in the most
restorative stages of sleep (known as slow wave sleep) also decreases with age and may be
completely absent by the age of 90.
e desire for social interaction is not signi cantly affected by aging, and social
contacts remain important throughout the entire lifespan. While the size of one’s social
network often decreases due to deaths and other losses, the quality of each relationship
often increases in proportion. Sudden changes in one’s patterns of socializing should
prompt a further assessment for any physical or psychological barriers that could be present
(such as social withdrawal due to depression). It is a myth that old people stop having sex,
and many remain sexually active late into their lives. In women, menopause occurs around
the age of 50 and is often accompanied by reduced vaginal lubrication and elasticity. In
men, there is no scienti cally recognized equivalent to menopause, and men remain fertile
into old age.

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 Some degree of cognitive impairment is
expected with aging. ese losses in speed and exibility occur primarily in the realm of
uid intelligence, which involves the ability to analyze and respond to new or novel
stimuli. In contrast, crystallized intelligence (which is the result of well-practiced skills,
abilities, and knowledge) is generally preserved and often even increases with old age. For
example, a blacksmith with decades of experience would likely be able to make tools even in
retirement due to preserved crystallized intelligence. However, if someone brought them a
new computer to work on, they may have more difficulty with this (even if step-by-step
instructions were available) due to reductions in uid intelligence.
 

Acquisition of new memories and retention of old memories are both impaired. e
type of memory most affected is explicit memory (also known as declarative memory)
which involves consciously recalling speci c facts or events (“Who was that person I ran
into at the store yesterday?”). In contrast, implicit memory (or non-declarative memory)
involving memories outside of one’s conscious awareness (“Can you sing the melody of
Happy Birthday?”) remains intact throughout life.
ere can also be de cits seen in some areas of language, including the ability to generate
lists of words (“Tell me all the words beginning with the letter F that you can think of ”).
ere can also be a small but noticeable loss of ability to speak and think abstractly, with a
more concrete thinking style noted in old age. In general, however, language and the
ability to communicate meaningfully with others are not signi cantly impacted by normal
aging.
Visual skills are often affected in a similar manner to intelligence: recognition of familiar
faces and situations remains intact, whereas working in new or unfamiliar situations (such as
assembling furniture from instructions) is more difficult.
Similar to knowing developmental milestones in childhood, understanding the cognitive
domains that are or are not commonly affected during normal aging can assist in identifying
when a more pathological process is going on. You can remember the cognitive domains
that are generally preserved during normal aging using the mnemonic Crystal CLIR which
stands for Crystallized intelligence, Concrete reasoning, Language, Implicit memory, and

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Recognition of faces and situations. In contrast, the speci c cognitive domains that are
affected by aging can be remembered using the mnemonic Not so FAST which stands for
Flexibility, Abstraction, Speed, and aTtention.
 

Crystallized intelligence, concrete reasoning,

language, implicit memory, and recognition are all
preserved in normal aging.
 

Crystal CLIR:
Crystallized intelligence Concrete thinking Language
Implicit memory Recognition

Normal aging is accompanied by decreases in

cognitive exibility, abstract reasoning, processing
speed, and attention.
 

Not so FAST: Flexibility Abstraction Speed aTtention

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SIGNS AND SYMPTOMS OF ALZHEIMER’S DISEASE
While normal aging can be associated with speci c de cits in health and cognition, the fact
that these changes are seen in the vast majority of the population argues against them being
a pathological state. In contrast, Alzheimer’s disease and other forms of dementia are
characterized by de cits that are not only uncommon but also result in signi cant
disability. In addition, dementia features not only the absence of normal functions but also
the presence of abnormal signs, symptoms, and behaviors such as confusion, restlessness, and
wandering. For these reasons, it seems rational to place dementia in the realm of pathology
rather than normalcy. Because Alzheimer’s disease is by far the most common form of
dementia , we will spend most of our time discussing this particular condition.
e primary clinical ndings in Alzheimer’s disease involve memory, cognition,
awareness, behavior, and neuropsychiatric phenomena. Memory de cits are similar in
nature to those observed in normal aging but are notably more frequent and pronounced.
Whereas an elderly person may have occasional moments of forgetfulness (such as blanking
on a speci c word, where they placed an object, or why they walked into a room), someone
with Alzheimer’s disease is likely to forget these things on a regular basis. Impaired
recognition of familiar faces (such as close friends and family members) is an exceptionally
sensitive marker of Alzheimer’s disease, as this tends to be spared in almost all healthy older
adults. Short-term memory (within the past several hours or days) is affected more severely
than long-term memory, although in later stages of the illness both forms of memory are
impacted. Explicit memory is involved more often than implicit memory, although with
time this distinction is erased as well.

Cognitive de cits in Alzheimer’s disease differ from the

normal FAST domains (Flexibility, Abstraction, Speed, and aTtention) into areas that are
not typically affected by old age, including concrete reasoning and language. Tasks that
require multiple cognitive abilities are often affected rst, as a breakdown at any step along
the way can derail the entire process. For example, someone going shing needs to have the
ability to make a list of everything that they’ll need to bring (executive functioning), ll out
the shing permit (language), use the map to nd the right location (visuospatial), know
whether they have already put bait on their line (short-term memory), and interpret what a
sudden pull on the line means (recognition), among many other things. If there is
impairment in any one of these domains, a shing trip may not be successful. Because of

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this, an inability to engage in complex processes that involve lots of planning is often an
early sign of Alzheimer’s disease.
Awareness is an important domain of Alzheimer’s disease, as it is progressively lost as the
disease becomes more severe. In elderly people without Alzheimer’s disease, episodes of
forgetfulness are often accompanied by a distinct sense that the information has been lost
(“I can never remember where I put my keys!”). A loss of awareness that something is
wrong is often indicative of dementia. In later stages of the disease, someone’s level of
orientation (their knowledge of who they are, where they are, what time it is, or why they
are there) is lost as well. is follows a temporal pattern similar to the orientation de cits in
delirium, with awareness of person, place, time, and purpose being lost in reverse order.

Behavioral manifestations of Alzheimer’s disease involve both

the loss of previously learned behaviors as well as the presence of new behaviors. Complex
skills such as reading and writing are among the rst to go, but in advanced stages of the
disease even more routine tasks such as walking, bathing, and speaking are lost. People with
Alzheimer’s disease often begin to show new patterns of behavior including frequent
wandering and agitation. e term “sundowning” is used to refer to a state of confused
restlessness that is more prominent in the evening. In the nal stages of the disease, many
people with Alzheimer’s disease are bed-bound and entirely dependent upon others for any
and all activities.
Finally, a variety of neuropsychiatric phenomena are frequently seen in Alzheimer’s disease.
As the disease progresses, mood often becomes more labile and inconsistent, with
increasing irritability and apathy. Around one-third of people with Alzheimer’s disease
develop delusions, including delusional misidenti cations (such as believing that their
daughter is an impostor who has come to rob them). ese neuropsychiatric signs and
symptoms are often a major barrier to quality of life, as they can interfere with the patient’s
ability to get the help that they need. For this reason, many people with Alzheimer’s disease
end up requiring help from professional caregivers who are skilled in managing confusion
and agitation.

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ALZHEIMER’S DISEASE ACROSS THE LIFESPAN

Alzheimer’s disease affects less than 1% of the total

population at any given time. However, because the primary risk factor for Alzheimer’s
disease is age, it is much more prevalent in the elderly. At the age of 65, the chance of
developing Alzheimer’s disease is around 3%. However, this risk doubles every 5 years after
that, meaning that over 20% of people above the age of 80 and 50% of people above the age
of 90 will develop this form of dementia. However, younger age does not rule out this
disorder entirely as early-onset forms of Alzheimer’s disease can begin in one’s 50s or 60s.
Women are affected more often than men, although this may have more to do with their
longer lifespan than it does with any risk factors that are inherent to their gender.
 
PROGNOSIS

Alzheimer’s disease is a progressive condition, with additional de cits

accumulating throughout the span of the illness and leading to pronounced decreases in
functional ability. People in advanced stages of the disease often require assistance with all
basic activities of daily living, including eating and bathing. Incontinence of urine and stool
is also seen in advanced stages of the disease and generally portends a poor prognosis.
Alzheimer’s disease is considered to be a highly lethal condition, as the risk of death is
increased signi cantly compared to people the same age without the diagnosis. e average
life expectancy from the time of diagnosis is around 5 years, with death almost always
occurring within 10 years. Alzheimer’s disease is rarely the direct cause of death. Instead,
the progressive functional decline leads to a lack of mobility which increases the risk of
infection (the most common cause of death in Alzheimer’s disease) and cardiovascular
disease.

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TREATMENT
Treatments for Alzheimer’s disease are available. However, on the whole they are quite
limited in their ability to make a meaningful impact on the condition. ere is no
medication or therapy that has been shown to halt or reverse the progression of Alzheimer’s
disease. Instead, the goal of treatment is limited to symptom reduction.
All but one of the medications used to treat Alzheimer’s disease are cholinesterase
inhibitors which increase the amount of acetylcholine in the brain. (As we will see in the
next section, destruction of acetylcholine-releasing neurons is a pathologic hallmark of
Alzheimer’s disease, and cholinesterase inhibitors help to temporarily offset this imbalance.)
e only other antidementia drug is memantine which works as an NMDA receptor
antagonist. Both cholinesterase inhibitors and memantine can be used to transiently
improve symptoms of Alzheimer’s disease, with a small effect size of around 0.2 to 0.3.
However, the effect of these drugs tends to be transient and lasts only a few months before
the normal course of the illness resumes. In addition, the primary metrics used to assess the
effectiveness of these medications are the patient’s scores on cognitive tests rather than their
functional ability or quality of life (which are likely the more clinically relevant outcomes).
It is not uncommon for antidepressants and antipsychotics to be used for treating
Alzheimer’s disease, especially in cases where there are pronounced mood or behavioral
features. ere is some evidence that antipsychotics can reduce levels of agitation, though
generally they have a very small effect size (around 0.1 to 0.2). However, antipsychotics
have also been associated with an increased risk of mortality in elderly patients with
dementia. Because of this, they should only be used after carefully weighing the possible
bene ts (a small chance of decreased agitation) against the known risks (increased
mortality).
Psychotherapy (at least in the traditional sense) is not effective for people with Alzheimer’s
disease, as their cognitive de cits prevent them from meaningfully engaging in this type of
treatment. In contrast, behavioral interventions are more effective and can improve quality
of life in speci c areas such as toileting abilities.
Because both medications and therapy are limited in their ability to treat Alzheimer’s
disease, the goal of treatment often shifts to social and environmental interventions. e
rst priority should be to take steps to protect the safety of the patient and those around
them, such as removing their driver’s license to prevent accidents. Working with families
and other caregivers during this process is also crucial. e speci c goals of care should be
outlined from the time of diagnosis, with education provided on whether the goals are
reasonable (“I want my father to be able to continue living at home as long as possible”) and
when they are not (“I want my father to go back to working as an engineer again”). As the
illness progresses, providing guidance with social interventions (such as arranging for
residential care or conservatorship) can be invaluable. Finally, be mindful of caregiver
burnout. Caring for people with Alzheimer’s disease (especially in advanced stages of the
disorder) can be physically, emotionally, and nancially draining, so encouraging family
members to engage in self-care and seek help when they need it can make a world of
difference.

490
MECHANISMS OF ALZHEIMER’S DISEASE
On a mechanistic level, Alzheimer’s disease is characterized by widespread atrophy in the
cerebral cortex with particular loss of cholinergic neurons. You can remember this
association by thinking that Alzheimer’s disease is caused when acetylcholine goes down.
is explains the symptomatic bene ts seen with use of cholinesterase inhibitors, which
increase the amount of acetylcholine that is active in the brain.
Alzheimer’s disease is characterized by loss of
cholinergic neurons.
Alzheimer’s disease is caused when acetylcholine goes
down.
However, this simplistic explanation does not tell us why these nerve cells are dying.
Current explanations for the neuronal destruction seen in Alzheimer’s disease suggest that it
results from an inability of the brain to remove two toxic waste products: senile plaques and
neuro brillary tangles.
Senile plaques, the rst type of toxic waste product, consist of extracellular proteins
known as amyloid beta that have clumped together. A certain amount of senile plaques is
normal and likely accounts for the cognitive changes seen in ordinary aging. However, when
too many amyloid beta proteins accumulate, they exert toxic effects in the brain by
damaging nearby nerve cells. To prevent this toxicity from occurring, the brain produces a
protein known as apolipoprotein E which functions as a “garbage truck” of sorts by
clearing away amyloid beta and thereby preventing senile plaques from forming. However,
some people have a gene variant (known as APOE4) that codes for a poorly functioning
version of apolipoprotein E. e defective apolipoprotein E is unable to clear away amyloid
beta which allows a high number of extracellular senile plaques to form. e number of
senile plaques has been found to correlate with the severity of Alzheimer’s disease,
suggesting a clear relationship between these plaques and the cognitive de cits seen in this
form of dementia. Because of this link, the APOE4 gene is a major risk factor for
developing Alzheimer’s disease (in fact, it is the single greatest risk factor for Alzheimer’s
disease aside from age). Compared to people with no copies of the APOE4 gene, people
with one copy have 3 times the risk of developing Alzheimer’s disease while those with two
copies have 15 times the risk.
e APOE4 gene encodes a poorly functioning
version of apolipoprotein E which allows amyloid
plaques to build-up, increasing the risk of
Alzheimer’s disease.
APOE4 causes Amyloid Plaques in the Old and Elderly
to FORm.
Neuro brillary tangles are another neuronal waste product that appear to be involved in
Alzheimer’s disease. Just as senile plaques are made up of amyloid beta proteins, these
neuro brillary tangles are made up of a protein called tau. Normally, tau is involved in
stabilizing structures known as microtubules which make up the cytoskeleton on the inside
of the cell. Microtubules act as tiny railroad tracks that transport nutrients and other
molecules across the cell. However, when tau undergoes certain chemical changes it
becomes misshapen, disrupting the cell’s ability to process nutrients. ese misshapen tau

491
proteins then accumulate and form intracellular neuro brillary tangles. Like senile plaques,
the number of neuro brillary tangles has been found to correlate with illness severity in
Alzheimer’s disease.

e precise mechanism by which amyloid beta and

tau work together to produce the speci c syndrome of memory loss and cognitive
impairment seen in Alzheimer’s disease is unclear. It is known that aggregations of amyloid
beta can induce neuron cell death, while it is hypothesized that the disrupted microtubule
transport network caused by neuro brillary tangles leads to ineffective metabolic processes
that then impair the ability of the cell to work properly. A variety of treatments that involve
either amyloid beta or tau are in the works, and it is possible that in the future treatment of
Alzheimer’s disease will look very different than it does now. For the time being, however, it
is sufficient to know that the pathogenesis of Alzheimer’s disease likely involves an inability
of the brain to take out its trash (speci cally its extracellular senile plaques and intracellular
neuro brillary tangles) effectively.
e number of extracellular senile plaques and
intracellular neuro brillary tangles both correlate
with behavioral symptoms in Alzheimer’s disease.
e neurons of people with Alzheimer’s disease are
SPeNT: Senile Plaques and Neuro brillary Tangles

492
DIAGNOSING DEMENTIA
Diagnosing dementia is a two-step process. First, you need to determine whether dementia
is present or not. If it is, the second step is to determine what type of dementia is present.
While Alzheimer’s disease is the most common form of dementia, it is not the only one.
Indeed, a variety of processes have been shown to result in the cognitive de cits that
characterize dementia, including dementia with Lewy bodies, frontotemporal dementia,
vascular dementia, and mixed dementia (which features elements of more than one type). It
is important to be knowledgeable about non-Alzheimer’s dementias, especially when it
comes to treatment (as attempting to treat every type of dementia like Alzheimer’s disease
can be ineffective at best and harmful at worst).
Answering the rst question (“Is dementia present?”) is largely accomplished using a
psychiatric interview and a physical examination. In addition, a variety of clinical tests such
as the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment
(MoCA) have been developed to be used as a standardized assessment of multiple cognitive
domains. ese tests provide a numerical score which is helpful not only for establishing the
diagnosis but also for tracking progression over time. For example, the MoCA involves
asking the patient to draw a clock from memory, a task that involves several cognitive
domains (including planning and visuospatial functioning). e ability to successfully
complete this tasks declines as dementia progresses, as seen below:

Normal Early stages Late stages

Once the presence of dementia has been established, the second task is to differentiate
between the different types of dementia. A clinical diagnosis can sometimes be determined
through a psychiatric interview and physical examination, as each form of dementia is
associated with speci c clinical features that can help to differentiate between them.
However, recognizing dementia subtypes on the basis of clinical ndings alone produces
inaccurate diagnoses around 25% of the time.
For this reason, it can be helpful to order neuroimaging for a de nitive diagnosis. In
particular, functional neuroimaging like positron emission tomography (or PET) scans
that reveal not only the shape of the brain but also its metabolic activity can help to
differentiate between the various forms of dementia. For example, the following brain scan
shows the brain activity of a normal person compared to someone with Alzheimer’s disease
(with brighter colors indicating a higher amount of metabolic activity). A global loss of
brain volume is apparent as well. While the senile plaques and neuro brillary tangles
mentioned earlier would be apparent on brain biopsy, the invasive nature of this procedure
(you’re literally taking a chunk of nerve cells out of someone’s brain) means that it is rarely
performed while the patient is alive. In contrast to most psychiatric disorders, the presence

493
of speci c anatomical and pathologic ndings in various forms of dementia means that they
can be classi ed as disease entities rather than merely subjective syndromes.
 

Normal brain Alzheimer’s disease

 
ALZHEIMER’S DISEASE
Because Alzheimer’s disease is the prototypical form of dementia, it is easily to fall into the
trap of seeing it as a diagnosis of exclusion (that is to say, if someone has dementia but
doesn’t have any of the signs, symptoms, or neuroimaging ndings suggestive of a different
subtype, then they should be given a diagnosis of Alzheimer’s disease). Don’t fall into this
trap. Try to think of Alzheimer’s disease as a speci c form of dementia with speci c
pathologic ndings (including both senile plaques and neuro brillary tangles) rather than
using the diagnosis as a dumping ground for unspeci ed cases of dementia.
 
EARLY-ONSET ALZHEIMER’S DISEASE
Early-onset Alzheimer’s disease refers to cases beginning before the age of 65. Early-onset
Alzheimer’s disease is thankfully uncommon, accounting for less than 10% of all cases. In
around a third of these cases (or 3% of the total population diagnosed with Alzheimer’s
disease) there is a clear familial pattern, with the disease inherited in an autosomal
dominant fashion. erefore, being below the age of 65 does not automatically rule out a
diagnosis of Alzheimer’s disease (especially if there is a positive family history).
 

VASCULAR DEMENTIA Vascular dementia is the second most common type of

dementia after Alzheimer’s disease (accounting for around 20% of all cases). It is
characterized by repeated minor strokes causing ischemic damage to brain tissue. Because
strokes can affect different parts of the brain to various extents, vascular dementia is not
associated with speci c signs or symptoms. Instead, the clinical hallmark of vascular
dementia is a series of stepwise decreases in cognition, with each drop in functional ability
representing another ischemic event. From a treatment standpoint, cholinesterase inhibitors
and memantine are used, although addressing the underlying risk factors for stroke (such
as high blood pressure) is the most important goal.
 
DEMENTIA WITH LEWY BODIES
Dementia with Lewy bodies (DLB) is the third most common type of dementia after
Alzheimer’s disease and vascular dementia. On a pathological level, it is characterized by the

494
accumulation of Lewy bodies, which are intracellular clumps of a protein known as alpha-
synuclein that accumulate and cause neuronal damage (a process that is roughly analogous
to the senile plaques seen in Alzheimer’s disease).

e hallmark symptom of dementia with Lewy bodies

is recurrent visual hallucinations which are found in over 80% of all cases (even during
early stages of the disease). ese visual hallucinations commonly are well-formed and
consist of people or animals that are moving across one’s eld of vision (“I see a bunch of
mice walking in a line across the oor”). To remember this hallmark symptom of dementia
with Lewy bodies, think of these patients as having visual hal-Lewy-cinations.
 

Dementia with Lewy bodies is characterized by

visual hallucinations.
 

Visual hal-Lewy-cinations are seen in dementia with

Lewy bodies.

Clinically, dementia with Lewy bodies can be differentiated from Alzheimer’s disease
by its rapid cognitive decline (with changes occurring in a matter of months instead of
years) and earlier onset in life (with the incidence increasing after the age of 50 instead of
65). Dementia with Lewy bodies also differs from other types of dementia in that its
progression is characterized by rapid uctuations in cognition (with patients alternating
between lucidity and confusion within the span of several hours) as well as motor de cits
including muscle rigidity and difficulty walking. ese motor de cits are often pronounced
enough that dementia with Lewy bodies is frequently misdiagnosed as Parkinson’s disease
(another condition involving both motor and cognitive signs which will be discussed in
more detail later in this chapter).
Like with Alzheimer’s disease, treatment of dementia with Lewy bodies is
symptomatic (rather than curative) and involves similar medications. Of note, people with
dementia with Lewy bodies are known to be exquisitely sensitive to antipsychotics
(especially typical antipsychotics) with severe side effects, confusion, or catatonia occurring
much more frequently in this patient population than others. For this reason, antipsychotics
should be strictly avoided when treating dementia with Lewy bodies.
 

FRONTOTEMPORAL DEMENTIA Frontotemporal dementia (or FTD) is

characterized by degeneration of the frontal and temporal lobes of the brain, resulting in
inappropriate behavior and a lack of impulse control. To understand why damage to the

495
frontal lobe lead to de cits in these speci c domains, it can be helpful to think of it as the
part of the brain that says “no” to other parts of the brain. When an action is deemed to be
morally or socially unacceptable, the frontal lobe sends signals to other brain areas (such as
those that govern voluntary movements) to inhibit their initial impulses. For example,
someone who arrives at a party and sees a delicious-looking birthday cake may be tempted
to immediately dig right in (even if only for a few milliseconds). However, the frontal lobe
would then kick in and remind them that it is not their birthday and that they will need to
wait until the guest of honor has arrived and “Happy Birthday” has been sung before eating
the cake. In this way, the frontal lobe has overridden the initial pleasure-seeking instinct in
favor of more socially acceptable behavior.

e degeneration of the frontal

lobe that occurs in frontotemporal dementia impairs the brain’s ability to override its baser
instincts, and as a result people with frontotemporal dementia often engage in actions that
provide immediate positive reinforcement without any regard for the potential
consequences. In particular, many people with frontotemporal dementia display
hyperorality and are often found putting things (particularly sweets and other
carbohydrate-rich foods) into their mouths. ey may also become hypersexual and end up
grabbing body parts or propositioning others at inappropriate times (such as asking a
relative for oral sex at a Family Thanksgiving Dinner). Use this uncomfortable situation to
remind you of the hyperorality and lack of impulse control seen in FrontoTemporal
Dementia.
 

Frontotemporal dementia is characterized by

hyperorality, hypersexuality, personality changes,
and a loss of impulse control.
 

FTD can result in asking a relative for oral sex at a

Family Thanksgiving Dinner (hyperorality and
hypersexuality).

In addition to the hyperorality and hypersexuality mentioned already, people with

frontotemporal dementia are afflicted by the same memory impairments and inability to
execute complex plans that are seen in other forms of dementia. People with frontotemporal

496
dementia also tend to have pronounced difficulty with both understanding and producing
speech (another symptom that largely involves the mouth). In early stages, frontotemporal
dementia is often characterized by mood symptoms like depression and anxiety, but as the
disease progresses the individual begins to display a profound apathy and emotionlessness
that can be very disconcerting.
As frontotemporal dementia involves the loss of neurons, a variety of clinical signs
suggestive of upper motor neuron damage are seen. ese include frontal release signs, or a
class of primitive re exes that are normally seen only in very young infants whose frontal
lobes have not yet fully developed. Speci c frontal release signs include the palmomental
re ex (where stroking the palm of the hand causes muscle contraction in the chin), the
palmar grasp re ex (where an object placed into the palm of the hand causes the ngers to
wrap around it instinctively without conscious effort), and the rooting re ex (where stroking
the cheek on one side causes the head to instinctively turn in that direction as in
breastfeeding).
Frontotemporal dementia is an uncommon cause of dementia and accounts for less than
10% of all cases. However, it tends to have an early-onset (between the ages of 45 and 65),
making it the second-most common cause of dementia before the age of 65. Like most
forms of dementia, frontotemporal dementia is progressive with a generally poor prognosis,
with treatment being primarily symptomatic rather than curative. Given that there is no loss
of cholinergic neurons (as occurs in Alzheimer’s disease or dementia with Lewy bodies),
cholinesterase inhibitors have little effect in frontotemporal dementia. Instead,
pharmacologic management of frontotemporal dementia typically involves an SRI (as some
evidence suggests that they are helpful for improving behavior), with atypical antipsychotics
used as a last resort.

497
DIFFERENTIAL DIAGNOSIS OF DEMENTIA
Dementia lies at the boundary between a psychiatric syndrome and a neurologic disease.
For this reason, the differential diagnosis for dementia must necessarily be very broad and
encompass not only the psychiatric conditions we have discussed so far but also quite a few
neurologic diseases that we haven’t. While a full discussion of all relevant neurologic
diseases is far outside the scope of this book, we will brie y make reference to some of the
most common neurologic conditions that should be on your differential diagnosis for
dementia.
 
NORMALCY
As discussed previously, a certain degree of cognitive decline and memory impairment is
completely normal and expected with aging, especially in the domains covered by the Not
so FAST mnemonic (including Flexibility, Abstraction, Speed, and aTtention). In contrast,
if there are signs of de cits in areas that are normally Crystal CLIR (such as Crystallized
intelligence, Concrete thinking, Language, Implicit memory, and Recognition), consider
initiating a full work-up for dementia.
 
MILD COGNITIVE IMPAIRMENT
Mild cognitive impairment (or MCI) is a halfway point between normal aging and
dementia where some level of cognitive de cit is present but hasn’t reached the level where
it results in signi cant dysfunction. Cognitive de cits tend to be exclusively related to
memory loss (with other cognitive functions such as planning generally remaining intact).
In a way, mild cognitive impairment can be thought of as the prodrome to dementia, as
people with the condition are up to 15 times more likely to develop Alzheimer’s disease
than those without any cognitive signs. Unfortunately, no medications or treatments have
been shown to prevent the progression to dementia, so management of mild cognitive
impairment largely involves educating both the patient and their family on what to expect
and providing guidance on necessary steps to take.
 

“REVERSIBLE DEMENTIA”
A variety of non-psychiatric, non-neurologic conditions can cause cognitive symptoms
which can strongly resemble dementia, including scoring poorly on tests like the MMSE or
MoCA. ese conditions are often referred to as reversible dementias, as treating the
underlying condition can effectively restore cognitive function back to its previous state. You
can remember the primary causes of reversible dementia using the mnemonic
DEMENTIA:
D is for Drugs and drinking. A variety of prescription medications drugs can be associated
with cognitive changes, including benzodiazepines, anticonvulsants, antihypertensives, and
anticholinergics. Look at the timing of symptom onset (especially if a new medication was
started in the past few weeks or months) and consider discontinuing any new medications
for a while to see if symptoms resolve. In addition, use of recreational substances can also
have a profound effect on cognition. By far the substance most commonly linked to
dementia-like symptoms is alcohol, as chronic use can lead to persistent cognitive de cits
that are indistinguishable from cases of “primary dementia” (in fact, it is estimated that up
to 10% of all cases of dementia are likely related directly to use of alcohol). Unlike

498
dementia, however, these cases can often (though unfortunately not always) be reversed
with cessation of alcohol intake.
 

E is for Eyes and ears. Sensory impairments such as vision or hearing loss can easily mimic
dementia, as not being able to see or hear can easily make someone appear more confused,
not remember what was said, or score poorly on cognitive tests. However, sensory
impairments have also been found to correlate with an increased chance of developing actual
dementia as well. Some evidence suggests that intervention (such as updating an eyeglass
prescription or providing hearing aids) can help to modify this risk, so be mindful to screen
for sensory impairments before diagnosing dementia.
 

M is for Metabolic. Conditions that alter metabolism (such as undiagnosed or poorly

treated diabetes mellitus) can be major risk factors for cognitive impairment.
 

E is for Endocrine. While a variety of endocrine disorders can have neuropsychiatric

symptoms, the one that most commonly resembles dementia is hypothyroidism due to its
slow onset, profound cognitive de cits, and presence of apathy. Hypothyroidism is easily
ruled out by ordering a thyroid stimulating hormone (TSH) and is rapidly treatable using
thyroid replacement.
 

N is for Nutrition. While malnutrition in general can itself be a risk factor for cognitive
dulling, speci c vitamin de ciencies have also been associated with cases of reversible
dementia. In particular, a de ciency of vitamin B12 can lead to fatigue, confusion,
irritability, and cognitive de cits that can be mistaken for dementia. A B12 level can quickly
rule this in or out.
 

T is for Tumor. Brain tumors (such as glioblastoma multiforme) or other space-occupying

central nervous system lesions have been associated with dementia-like symptoms in some
cases. While the signs and symptoms can mimic primary dementia, there are often clues
that something more is going on (such as the presence of speci c neurologic de cits, rapid
progression, and/or cognitive problems in some domains but not others depending on
where the lesion is located). When a tumor is suspected, head imaging is a good next step
for evaluating further.
 

I is for Infection. Certain infections can cause a state of impaired cognition that can be
hard to distinguish from dementia. For example, HIV-associated neurocognitive disorders
can occur in cases of uncontrolled retroviral infections. Another example is tertiary syphilis
(also known as neurosyphilis) which features the same insidious onset of profound cognitive
symptoms that “normal” dementia does. Due to the relative rarity of syphilis in the age of

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antibiotics, testing for it as part of a routine dementia work-up is no longer indicated, but in
particular cases (if there are signs of neurologic involvement such as ataxia or muscle
weakness) it should be considered.
 

A is for Autoimmune. An increasing number of autoimmune processes are being

recognized as causing dementia-like symptoms. While the evidence isn’t robust enough to
order a full “million dollar work-up” for all patients presenting with symptoms of dementia,
certain clues (such as a subacute onset of symptoms with a rapidly progressive course or
evidence of autoimmune signs in other organs) may raise your suspicion.
 

Common causes of reversible dementia include

neurosyphilis, hypothyroidism, B12 de ciency,
substances, sensory impairment, and metabolic
disease.
 

DEMENTIA: Drugs and drinking Eyes and ears

Metabolic Endocrine Nutrition Tumors Infection
Autoimmune

At a minimum, a CMP, CBC, B12 level, and TSH should be ordered for every patient
presenting with cognitive complaints suggestive of dementia. A rapid screen for vision or
hearing loss should also be performed. In cases where other symptoms are present,
additional tests (such as screening labs for HIV, syphilis, and autoimmune diseases or
neuroimaging for brain tumors) could be added.
PARKINSON’S DISEASE

Parkinson’s disease is a neurodegenerative disorder caused by

cell death in the basal ganglia which primarily affects motor functioning through the loss
of dopamine-releasing neurons. is creates a state of motor dysfunction known as
Parkinsonism that is characterized by a slowing of movements (known as bradykinesia), a
resting tremor, muscle rigidity, and poor balance. A highly speci c sign of Parkinson’s
disease is a pill-rolling tremor (so named because it looks like the patient is rubbing a pill

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between their index nger and thumb). A style of gait known as festination (which involves
short shuffling steps, a forward- exed posture, and a decrease in arm swing when walking)
is also highly speci c for Parkinson’s disease. Many of the signs of Parkinson’s disease
(including the pill-rolling tremor and decreased arm swing) are notably asymmetric in
nature and affect one side over the other, although they can sometimes become bilateral as
the disease progresses.
While motor signs are the most common clinical feature of Parkinson’s disease, a
signi cant minority of people with the condition experience profound cognitive and
emotional de cits that can closely resemble dementia, particularly in later stages of the
illness. People with Parkinson’s disease are often described as having a mask-like facial
expression that does not change or move, which is often accompanied by a slow and
monotonous voice. Psychiatric symptoms (including depression, anxiety, paranoia, and
visual hallucinations) are also common and can be even more impairing than the classic
motor abnormalities. While medications are available to reverse many of the motor
abnormalities of Parkinsonism, treatment of cognitive de cits remains symptom-driven
rather than curative.
 
PROGRESSIVE SUPRANUCLEAR PALSY

Progressive supranuclear palsy is a

neurodegenerative disease that speci cally targets regions of the brain involved in
movement and coordination such as the basal ganglia and brainstem. is results in motor
symptoms including abnormal gait, loss of balance, and frequently bumping into other
people or objects. Like with Parkinson’s disease, dementia-like de cits in memory and
cognition tend to occur later in the disease than the motor ndings. Uniquely, progressive
supranuclear palsy often involves a downward gaze palsy (in plain English: an inability to
look down). To remember the association of Progressive Supranuclear Palsy with a
downward gaze palsy, think of someone who is asked to Please Stop Peering. What is the
rst thing they do? Try to avert their gaze by looking down. However, if they had a
downward gaze palsy due to progressive supranuclear palsy, they wouldn’t be able to do this.

Progressive supranuclear palsy can result in

dementia but is generally diagnosed on the basis of
neurologic de cits, including downward gaze palsy.
 

Someone is who asked to Please Stop Peering may try to

look down but can’t.

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CORTICOBASAL DEGENERATION

Corticobasal degeneration is a neurodegenerative disease

affecting the cerebral cortex and basal ganglia. Given that the cerebral cortex is involved in
Alzheimer’s disease and the basal ganglia in Parkinson’s disease, it would make sense if
corticobasal degeneration had signs and symptoms similar to both of those conditions, and
that is exactly what we see (with both motor and cognitive de cits being common,
including slow movements, difficulty walking, memory loss, trouble speaking, and
depressed mood). However, because its symptoms overlap so much with other diseases,
diagnosis of corticobasal degeneration is difficult. One sign that is fairly speci c for
corticobasal degeneration is alien hand syndrome which occurs in around 60% of people
with the disorder. People with alien hand syndrome will fail to spontaneously move one of
their hands due to a sensation that their limbs are foreign to them. Notably, this is often
unilateral, affecting only one hand.
 
TRAUMATIC BRAIN INJURY

Traumatic brain injury (or TBI) is a catch-all term for

the wide variety of medical abnormalities and cognitive de cits that can be seen following a
physical injury to the head. Because the nature of physical injuries can vary so much in
extent and severity (from something as minor as hitting one’s head on a low doorway to as
major as being in a coma for several weeks following a car crash), there is no characteristic
syndrome associated with traumatic brain injury. Instead, signs and symptoms following a
traumatic brain injury can mimic nearly every other neurologic and psychiatric syndrome
including depression, anxiety, mania, psychosis, impulsive control disorders, and OCD. Out
of all the clinical features, however, memory loss is perhaps the most common, with up to
80% of all people experiencing some form of memory loss following a head injury. Repeated
injury to the head is even more closely associated with a dementia-like neurodegenerative
process known as chronic traumatic encephalopathy (also called dementia pugilistica or

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“boxer’s dementia”). Interestingly, chronic traumatic encephalopathy involves deposition of
tau protein throughout the brain, suggesting it has a similar mechanism to Alzheimer’s
disease.
 
NORMAL PRESSURE HYDROCEPHALUS
Normal pressure hydrocephalus is a condition in which the cerebrospinal uid- lled
ventricles of the brain expand, raising intracranial pressure and causing dysfunction in
adjacent regions of the brain. Classically, normal pressure hydrocephalus presents with a
characteristic triad of dementia, incontinence, and gait instability (DIG). Treatment
involves neurosurgical placement of a shunt to drain the excess uid, which effectively
reverses symptoms of dementia in most (though not all) patients.
 

Normal pressure hydrocephalus is characterized by

the clinical triad of dementia, urinary
incontinence, and gait instability.
 

DIG = Dementia, Incontinence, and Gait.

 
WERNICKE-KORSAKOFF SYNDROME
While chronic alcohol use can result in symptoms that are largely indistinguishable from
cases of primary dementia, a speci c condition known as Wernicke-Korsakoff syndrome
warrants separate discussion from “normal” cases of alcohol-related dementia. Wernicke-
Korsakoff syndrome is actually a combination of two different conditions: Wernicke
encephalopathy (a state of confusion accompanied by an unsteady gait and difficulties with
eye movement) and Korsakoff syndrome (involving profound anterograde amnesia, or an
inability to form new memories). Due to the lack of ability to form new memories, people
with Wernicke-Korsakoff syndrome often confabulate or make up information when asked
questions (“What did you do for a living?” “I was… a sailor!” “Your wife says you were an
accountant.”).

Wernicke-Korsakoff syndrome is caused by a de ciency of thiamine

(or vitamin B1) which is itself related to chronic alcohol use. On an anatomic level,
Wernicke–Korsakoff syndrome is associated with damage to the mammillary bodies, a pair

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of structures in the brain that are involved in memory and recall. To remember these
associations, think of a man who is so drunk that he begins inappropriately staring at a
nearby statue’s breasts (mammillary being Latin for “resembling a breast”). When someone
asks him what he is doing, he responds by slurring the phrase, “I’m thorry, th1amine (I am
in) a drunken thtupor.” is story can help you make associations between alcohol,
mammillary bodies, inappropriate behavior, and th1amine (or vitamin B1) de ciency.
 

Wernicke-Korsakoff syndrome is a syndrome of

confusion, ataxia, and amnesia caused by thiamine
de ciency related to chronic alcohol use.
It is associated with damage to the mammillary
bodies.
 

ink of a drunk disinhibited man looking at a statue’s

mammillary bodies and saying, “I’m thorry, th1amine
a drunken sthupor.”

PRION DISEASE
Prion diseases are a group of rapidly progressive neurodegenerative diseases caused by the
presence of abnormally folded proteins known as prions. ese misshapen proteins then
develop the capability of inducing other proteins to misfold as well, setting off a chain
reaction that leads to a rapid virus-like spread throughout the brain and other neural tissues.
ese misfolded proteins directly cause degeneration of nerve tissue, a process that quite
literally punches holes in the brain and leads to a characteristic spongiform (or sponge-like)
appearance under the microscope. On a clinical level, prion diseases cause profound
memory loss, changes in behavior and personality, movement problems, and sensory loss.
While the highly variable presentation of the illness ensures that there are no
pathognomonic signs or symptoms, cases of prion disease can often be recognized by their
rapid progression involving multiple cognitive domains. Prion diseases are uniformly fatal,
with almost all patients with the diagnosis dying within one year of symptom onset. e
initial misfolded protein that starts the cascade can be acquired by being exposed to prions
from other people (such as through cannibalism or brain surgery). In a minority of cases,
prion disease is caused by a mutation in a gene known as PRNP.
 
DELIRIUM
Dementia must be distinguished from delirium (discussed in Chapter 4) which is a
transient and reversible state (unlike the chronic and progressive nature of dementia). By
far the most reliable indicator of delirium is the timing of symptoms, as memory loss,
disorientation, and other cognitive de cits tend to come on rapidly (often within a few days
or weeks) compared to the insidious onset of dementia occurring over several months or
years. In addition, delirium often uctuates from hour to hour which contrasts to dementia’s

504
persistent de cits. Delirium is generally associated with other medical conditions (such as
an infection), so the presence of any vital sign abnormalities or speci c ndings on physical
exam should also raise your suspicion for delirium. It is entirely possible for someone to
have both dementia and delirium (indeed, dementia is itself a signi cant risk factor for
developing delirium), so in these cases look for a level of confusion that is an acute change
from baseline.
 
DEPRESSION
Certain symptoms of depression (including fatigue, apathy, poor concentration, and reduced
interest in activities) can strongly resemble dementia. In addition, people with severe
depression can even score poorly on tests like the MMSE or MoCA (although this is
usually due to low motivation to complete the test rather than genuine cognitive de cits).
is phenomenon is common enough that the term “pseudodementia” has been coined to
describe these cases. It is imperative to distinguish between these two conditions, as
depression is episodic and reversible while dementia is not. Depression can be differentiated
from dementia by its more rapid onset (often over weeks rather than the months or years
seen in dementia) and presence of speci c thought patterns (like negative affective biases).
In addition, someone who is having memory lapses as a result of being in a state of
depression is more likely to say that they are concerned by these changes (as opposed to
someone with dementia who is unlikely to have awareness that memory loss is occurring).
 
PSYCHOSIS
Paranoia, delusions, and hallucinations are often found in dementia, particularly in certain
forms of dementia (such as dementia with Lewy bodies) or in advanced stages of the
disease. Differentiating between them on the basis of age of onset can be helpful (as
schizophrenia often begins earlier in life), but this cannot be followed as a rule due to the
fact that both late-onset schizophrenia and early-onset dementia exist. Further clues towards
dementia rather than psychosis include a lack of prior psychiatric history, generally intact
socio-occupational functioning prior to disease onset, and the presence of generalized
de cits on cognitive testing.
 
INTELLECTUAL DISABILITY
e cognitive de cits seen in intellectual disability can mimic those in dementia is nearly
every way. However, by de nition intellectual disability must be present from early
childhood (whereas dementia begins later in life). ese two processes appear to be distinct,
as people with intellectual disability can develop further memory impairment and other
signs of dementia later in their lives (such as the increased risk of Alzheimer’s disease seen
in Down syndrome).
 
DISSOCIATION
Both dementia and dissociation involve memory loss. However, dissociative amnesia tends
to involve a speci c (and often very traumatic) time of one’s life and generally reverses with
time (the memory is later “recovered”). In contrast, memory loss in dementia is pervasive
and enduring, and these memories cannot be regained. Dissociation can further be
distinguished from dementia in that people with dissociative amnesia generally show an
awareness that they are afflicted by memory loss (“I can’t remember anything from last

505
summer”) and will not show signi cant impairments in executive functioning in life or on
cognitive testing.
 
SOMATIZATION AND MALINGERING
Memory loss can sometimes be the presenting complaint for someone who is somatizing or
wants to feign an illness, as it is both entirely subjective and profoundly distressing. As with
depression and dissociation, however, there is often concern about memory loss (which is
highly unusual for dementia due to the lack of symptom awareness seen in most
neurocognitive disorders). In addition, when performing cognitive tests, people who are
malingering will often “overplay their hand” by trying to perform poorly on all cognitive
tests, including those that are so simple that even people with dementia would be able to do
them (“Can you tell me your name?” “You know I can’t do that, doc…”). Your clinical
suspicion for somatization or malingering should be higher in cases where there is evidence
of either primary or secondary gain (such as someone presenting for a disability evaluation).

506
PUTTING IT ALL TOGETHER
Dementia is a deeply disabling condition involving de cits in memory, cognition,
awareness, and behavior that is associated with a high disease burden not only for the
patients themselves but also for their families and the societies in which they live. To avoid
overdiagnosing the changes seen in normal aging as a pathological process, use the
mnemonics Crystal CLIR and Not so FAST to remember which changes are expected and
which are more suggestive of disease. Once the presence of dementia has been established,
use what you know about the speci c signs and symptoms associated with each form of
dementia (such as the stepwise progression associated with vascular dementia or the “visual
hal-Lewy-cinations” seen in dementia with Lewy bodies) to determine the speci c type you
are working with. While current treatments are symptomatic rather than curative,
diagnosing dementia still has the bene t of providing clarity to patients and their families
on the nature of what they are experiencing as well as knowledge about what to expect in
the future. Given the rate at which our knowledge about Alzheimer’s disease and other
forms is dementia is expanding, it is likely that in the future we will be able to do more to
combat this progressive and lethal disease. In the meantime, do the best you can to
maximize function for the patient and minimize burden for their caregivers.
 

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REVIEW QUESTIONS
1. A 76 y/o F goes to her primary care provider for an annual visit. When asked
about her memory, the patient says that she has occasional episodes of entering a
room and not being able to remember why she entered. She also has noticed that
she will often not be able to recall the name of a friend that she encountered earlier
that same day. She has called the police two times in the past month to report an
intruder after not recognizing that the person entering her house was her home
care nurse. While she used to be able to sit and read the Bible for hours on end,
she nds that now she has trouble keeping track of what she is reading for more
than 30 minutes at a time. Which of the following features is most concerning for
a diagnosis of dementia?
A. Being unable to remember why she entered a room
B. Being unable to recall the name of a friend whom she saw the same
day
C. Being unable to recognize her home care nurse
D. Being unable to focus on reading for more than 30 minutes at a time
E. None of the above are concerning for dementia
2. (Continued from previous question.) e primary care provider performs a MoCA
(a cognitive screening test with a normal score of 25 and above), and the patient
scores 19/30. Observed de cits include delayed recall, executive functioning, and
abstraction. e patient denies use of alcohol, cigarettes, or any other drugs (“I’ve
been a churchgoer all my life.”). She denies visual hallucinations. According to her
home care nurse, she has not had any changes in her eating or speaking habits. e
nurse describes the patient as having experienced a “progressive decline” rather
than one characterized by sudden decreases in cognitive and functional abilities.
Physical exam, including a complete neurologic exam, is generally normal. Her
blood pressure is 128/78, and she has never had a stroke. Which of the following
diagnoses can be given with certainty at this time?
A. Alzheimer’s disease
B. Frontotemporal dementia
C. Dementia with Lewy bodies
D. Vascular dementia
E. Mixed dementia
F. None of the above
3. (Continued from previous question.) On the way to her next appointment, the
patient is involved in a motor vehicle accident for which she is at fault. She is
admitted to the hospital for a broken femur. Which of the following could have
prevented this outcome had it been done at the rst visit?
A. Prescribing a cholinesterase inhibitor
B. Ordering positron emission tomography
C. Inquiring about the presence of osteoporosis
D. Performing a test of auditory and visual acuity
E. None of the above
4. (Continued from previous question.) e patient is discharged from the hospital.
Over the next 4 years, she experiences progressive loss of cognitive ability and soon
is dependent upon others for all activities of daily living including eating and

508
 bathing. She is admitted to the hospital for pneumonia and dies several days later.
Which of the following ndings is least likely to be seen on a post-mortem
autopsy?
A. Widespread cortical atrophy
B. Selective loss of cholinergic neurons
C. Spongiform appearance of brain tissues under the microscope
D. Intracellular neuro brillary tangles
E. Extracellular senile plaques
F. All of these are likely to be observed
5. A 66 y/o M is brought to see his primary care provider by his daughter who is
concerned about him. According to his daughter, the patient experienced the death
of his wife 6 months ago and since then has had a “major decline” in his ability to
function. His daughter now feels the need to stop by his house at least once per
day to ensure that there are meals available for him to eat “or else he would
probably just starve.” He scores a 19/30 on the MoCA, with points lost primarily
for several tasks which he declines to attempt (“ at sounds like a lot of work.
What’s the point of all this? I want to go home.”). When asked about his memory,
he says, “Yeah I forget things all the time. Phone numbers, names, dates—they’re
all gone.” He reports difficulty sleeping at night and says that sometimes he hears
the voice of his wife “calling out my name.” Which of the following most strongly
argues against a diagnosis of Alzheimer’s disease for this patient?
A. Age of onset of symptoms
B. Presence of auditory hallucinations
C. Recent death of his wife
D. Awareness of memory loss
E. Score on the MoCA

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1. e best answer is C. Normal aging is accompanied by a variety of cognitive
changes, including de cits in short-term memory (answer A), declarative memory
(answer B), and attention (answer D). However, recognition of familiar faces is
often spared. erefore, changes in one’s ability to recognize faces and objects is
concerning and should be accompanied by a thorough evaluation.
2. e best answer is F. While this patient is likely suffering from some form of
dementia, the speci c subtype remains unclear. e lack of changes in oral habits
argues against frontotemporal dementia (answer B), the absence of visual
hallucinations argues against dementia with Lewy bodies (answer C), and the lack
of a stepwise progression argues against vascular dementia (answer D). is makes
Alzheimer’s disease the most likely diagnosis. However, it is important to keep in
mind that Alzheimer’s disease is not a diagnosis of exclusion and that diagnoses of
dementia subtypes based only on clinical examination are incorrect 25% of the
time. erefore, it is not possible to diagnose Alzheimer’s disease with any degree
of certainty in the absence of further testing (answer A).
3. e best answer is E. Patients with a clinical suspicion for dementia should not be
permitted to drive or operate complex machinery that could potentially put their
own lives or the lives of others at risk. Medication treatments for dementia have
only a mild bene t at best and would not necessarily prevent accidents (answer A).
Aiding the diagnosis through neuroimaging (answer B) or ruling out sensory
impairments (answer D) could have been helpful but would also not have
necessarily prevented this outcome. Finally, assessing for osteoporosis would not
have prevented the proximal cause of the broken femur—the accident itself
(answer C). is outcome could have been prevented by removing her license and
arranging alternate transportation.
4. e best answer is C. A spongiform appearance is seen in prion diseases. However,
the fact that the patient lived for 4 years following her initial diagnosis strongly
argues against prion diseases being the cause of her cognitive decline. Instead, the
clinical picture suggests that Alzheimer’s disease is the most likely explanation.
Widespread cortical atrophy, selective loss of cholinergic neurons, intracellular
neuro brillary tangles, and extracellular senile plaques (answers A, B, D, and E)
are all likely to be observed in a patient with Alzheimer’s disease.
5. e best answer is D. is patient’s recent decline in function appears to be most
consistent with a diagnosis of depression, which can resemble dementia in elderly
patients (including scoring poorly on cognitive tests). Awareness of memory loss
strongly argues against a diagnosis of dementia, as people in all but the earliest
stages of dementia often lack an awareness that their cognition is decreasing. His
age is consistent with a diagnosis of Alzheimer’s disease (answer A). Psychotic
symptoms can occur in dementia, including auditory hallucinations and delusional
misidenti cations (answer B). e recent death of his wife can be consistent with a
diagnosis of Alzheimer’s disease, especially if she was previously taking care of his
activities of daily living (answer C). His score on the MoCA is abnormal, although
this appears to be due to low motivation (answer E).

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23 SLEEP

Sleep needs no introduction. Every person on earth has had

the experience of being asleep at least once, and most people spend up to a third of their
lives in this state. However, for the purposes of clarity, let’s de ne exactly what we mean by
it. Sleep is a temporary state of decreased consciousness characterized by reduced
wakefulness, inhibition of incoming sensory information, and lowered muscle activity. Sleep
allows the body to regenerate its energy and restore muscle tissues used during the day. On
a cognitive level, sleep promotes memory through the consolidation of recently learned
information.
Most people already grasp on an intuitive level that sleep is incredibly important for
maintaining not just physical health but mental health as well. However, while the fact that
there is a relationship between sleep and mental health is obvious, the exact nature of the
relationship is not quite so simple. While psychiatric disorders are often associated with
changes in the amount and quality of sleep, it is not always clear whether the disruption in
sleep preceded the mental distress or is an aftereffect of it. For example, international travel
across multiple time zones is a well-known trigger for manic episodes, suggesting that
dysregulation of sleep itself may prompt a sudden change in mood. However, the reverse
can also be true, as depression itself is known to induce changes in one’s sleep cycle but only
after someone has already started exhibiting symptoms of depression. It is likely that most
interactions between sleep and mental health are two-way streets where each impacts the
other in a reciprocal manner. Because understanding sleep is central to maintaining mental
health, we will spend our nal chapter discussing sleep physiology, insomnia, and other
disorders related to sleep.

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SLEEP PHYSIOLOGY

e daily cycle of alternating between periods of sleep and

wakefulness is known as the circadian rhythm. is cycle is regulated by the hormone
melatonin, which is secreted by the pineal gland at night in response to low light in the
environment. Melatonin acts to decrease wakefulness and promote sleep induction.
Melatonin secretion stops in the morning, at which time the hormone cortisol (which
forms part of the HPA axis) is at its peak. is daily alternation between both melatonin
and cortisol correlates with the subjective feelings of being “awake” or “sleepy” throughout a
24-hour period.
Sleep itself is a dynamic process that ebbs and ows throughout the night even if we are
not necessarily conscious of this. Sleep generally occurs in sleep cycles that last 90 minutes
on average (meaning that most people will have 4-6 sleep cycles in a single night). Sleep
cycles involve a regular progression through various stages of sleep as seen in the following
gure:

Schematic diagram of sleep cycles over a single night of sleep, with hours of sleep on the x-axis and stage of sleep on the y-axis.

Each stage of sleep is characterized not only by speci c signs (mostly involving levels of
muscle activity) but also by a speci c pattern of electrical activity in the brain which can be

512
seen using an electroencephalogram (EEG). A sleep cycle proceeds in a fairly regular order
from lighter phases of sleep (stages I and II) down towards deeper phases of sleep (stages III
and IV) which are associated with slower and less frequent activity on EEG. e order of
the sleep cycle can be memorized using the mnemonic BATS Drink Red Blood:
B is for Beta waves. Beta waves are the patterns of electrical brain activity that occurs
during waking consciousness.
 

A is for Alpha waves. On average, people take around 15 minutes to fall asleep from the
time they go to bed. Between wakefulness and sleep is an in-between state where one feels
drowsy but remains conscious. is state is characterized by alpha waves on EEG, which
re ects slowed brain activity compared to the beta waves seen during wakefulness.
 

T is for eta waves. eta waves mark the time when someone crosses over from
wakefulness into stage I sleep. Stage I sleep is also known as light sleep, as someone is just
barely asleep and is easily arousable by various stimuli (such as the sound of the television in
the other room). Sudden muscle twitches known as hypnic jerks can occur, although in
general muscle tone is reduced.
 

S is for Spindles and K complexes. Stage II sleep is characterized by the absence of

consciousness and a further decrease in muscle tone. On EEG, this appears in the form of
speci c forms of electrical activity known as sleep spindles and K complexes.
 

D is for Delta waves. e presence of low frequency delta waves characterizes deep sleep.
is is considered to be the most restorative phase of sleep both physically and mentally. In
this state, someone becomes unaware of all but the most intrusive external stimuli. For
example, traffic noise or the sound of a television are typically blocked out, although louder
noises (like the sound of an alarm clock going off ) may break someone out of this stage of
sleep.
 

e deepest stages of sleep are characterized by

delta waves on EEG.
 

Slow frequency delta waves indicate deep sleep.

R is for Rapid eye movement. Rapid eye movement (or REM) sleep is a paradoxical stage
of sleep in which the brain’s level of activity is increased to levels similar to wakefulness but
the person as a whole feels most deeply asleep. e name of REM sleep comes from the fact
that the eyes are noted to move rapidly during this time even though the eyelids remain

513
closed. Consistent with the high levels of brain activity observed during this stage, REM
sleep is when the most dramatic dreaming occurs. (Dreaming can occur during non-REM
sleep as well, but it tends to be less vivid and is less likely to be remembered compared to
dreams occurring in REM sleep). REM sleep is also characterized by muscle paralysis,
with no movement of voluntary muscles occurring during this stage.
 

Vivid dreaming most often occurs during REM

sleep.
 

You’re more likely to REMember your dREMs during

REM sleep.

B is for Back again. Following REM sleep, the person returns to a previous stage of sleep to
begin another sleep cycle (or, if they have had enough sleep, to wake up).
 

Sleep cycles between REM and non-REM phases

several times per night. While sleep progresses through its various stages in a speci c order
(as captured in the BATS Drink Red Blood mnemonic), this progression tends to become
more erratic and less consistent as the night goes on, with less deep sleep and more REM
sleep occurring in each cycle. After enough time, the person spontaneously wakes up.
Someone waking up from a lighter stage of sleep often feels more well rested than if they
had woken up directly from deeper sleep. At this point, someone’s level of melatonin
secretion is minimal to non-existent while their levels of cortisol are near the highest levels
for the day, creating a sensation of alertness (and even a mild sense of stress) to prepare for
the day ahead.
 

e sleep cycle proceeds in a relatively consistent

order, with each stage characterized by different
clinical and electroencephalographic ndings.
 

BATS Drink Red Blood: Beta waves (awake) Alpha

waves (drowsy) Theta waves (Stage I sleep) Spindles

514
and K complexes (Stage II sleep) Delta waves (Stage III
and IV sleep) REM sleep Back again

515
INSOMNIA

Sleep is critical for health, with most experts

recommending at least 7 to 8 hours of sleep per night for most adults. Lack of sleep is
associated with a host of physical and mental consequences, including an increased risk of
obesity, hypertension, heart disease, diabetes, and infection. Because of the consequences of
inadequate sleep, anything that threatens someone’s ability to consistently get enough sleep
is cause for concern. ese abnormalities or impairments in sleep are known as sleep
disorders. By far the most common form of sleep disorder is insomnia, de ned as difficulty
with sleeping. However, there are other conditions that lead to a reduced quality of sleep or
to episodes of falling asleep at inappropriate times which can be equally impairing (these
will be discussed later in this chapter).
Insomnia can involve difficulty sleeping in multiple ways, including trouble falling
asleep, frequent awakenings throughout the night, or waking up long before desired.
Insomnia is not inherently pathological, and occasional nights of bad sleep are completely
normal. However, if the inability to sleep continues for too long or becomes severe, it can be
the source of signi cant stress and dysfunction. On a symptomatic level, people with
chronic insomnia often struggle with fatigue, poor mood, irritability, and inattention
throughout the day. ese symptoms are often accompanied by some level of distress about
their lack of sleep.
Insomnia can occur as a result of a variety of factors, including stress, lifestyle, drugs,
medical conditions, and psychiatric comorbidity. However, it can also occur on its own
without a clear etiology, sometimes called idiopathic or “primary” insomnia. Insomnia is
common, with around 30% of the population reporting problems with sleep on at least an
occasional basis. For this reason, insomnia should not be considered a disorder until it
becomes frequent and severe. e majority of cases involve secondary causes of insomnia;
once these have been excluded, the prevalence of primary insomnia falls to around 5% of the
general population.
Age and gender are the largest risk factors for insomnia, with older adults and women
both being at higher risk compared to the rest of the population. e presence of a
comorbid psychiatric disorder is also a major risk factor, with studies showing that around
40% of all people with insomnia meet criteria for at least one mental disorder (compared to

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only 15% of people without sleep complaints). Of these, depression is by far the most
common, although anxiety is a close second.

As a general rule, insomnia tends to be

persistent, although it may come and go in an episodic fashion across one’s lifespan.
Chronic insomnia is associated with worse outcomes in nearly all areas of one’s life,
including physical health, mental well-being, pain perception, and levels of social support.
Physical and cognitive performance decreases as well, with people who miss even one night
of sleep driving just as badly (if not worse) than someone who is under the in uence of
alcohol. In fact, people who are chronically sleep deprived have a rate of accidents that is up
to 4.5 times higher than the average. All of these together predict a greatly increased risk of
mortality, with severe insomnia (sleeping less than 4 hours a night) being associated with a
15% higher mortality rate.
Treatment of insomnia involves therapy, medications, or both. e rst-line treatment
should be a variant of CBT known as cognitive behavioral therapy for insomnia (or
CBTi). CBTi involves practicing good sleep hygiene combined with addressing and
correcting any dysfunctional beliefs that may be contributing to sleep-relaxed anxiety (“If I
don’t get enough sleep tonight, I’m going to have a terrible day tomorrow and everything
will be ruined!”). CBTi has been associated with signi cant reductions in both subjective
sleep-related distress (with a large effect size as high as 1.0) as well as objective
improvements in the amount and quality of sleep (albeit with a smaller effect size around
0.1 to 0.3). In addition, the bene cial effects of CBTi tend to persist even after treatment
has ended.
 

Medications used to treat insomnia are known as hypnotics and consist of a wide
variety of drugs with different mechanisms of action, including antihistamines,
benzodiazepines, and “Z-drugs” like zolpidem (Ambien). While the efficacy of these drugs
varies depending on the class, as a whole their effects tend to be limited to the time in
which they are taken, and people tend to develop tolerance to their sedative effects after
only a few nights of regular use. Finally, hypnotics can cause daytime sedation and poor
balance, leading to an increased risk of falls (especially in the elderly). For this reason,
hypnotic drugs should generally be recommended only after other interventions (such as
CBTi) have been tried, and even then only for as short a period of time as possible.
 

SECONDARY CAUSES OF INSOMNIA e prognosis of insomnia varies considerably

depending on whether it is primary or secondary. Some causes of secondary insomnia (such
as obstructive sleep apnea) will resolve immediately with treatment while others (like
restless leg syndrome) are more difficult to treat. erefore, appropriate diagnosis and
treatment of insomnia rests upon having looked at the most common underlying causes of

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insomnia. Because the range of possible causes of insomnia is so wide, it can be helpful to
have a systematic way of evaluating someone who presents with complaints about sleep. You
can use the mnemonic SOUR DREAMS to remember those factors that commonly
contribute to insomnia:
S is for Stress. Stress is well known to make both falling and staying asleep more difficult,
so someone who comes in saying that they are not sleeping well should be asked about
particular circumstances in their life that may be a source of stress.
 

O is for Obstructive sleep apnea. Obstructive sleep apnea

(or OSA) is a condition in which people suffer from brief but recurrent episodes of apnea
(or pauses in breathing) throughout the night. is occurs as a result of anatomical
blockage of the airways due to both the muscle relaxation that occurs during sleep as well
as the recumbent position that most people sleep in. ese hypoxic episodes lead to
transient “micro-awakenings” that occur throughout the night and prevent the person from
entering into deep sleep, resulting in sleep that is not restorative. is leads to persistent
daytime fatigue and other symptoms such as headaches. While intuitively it would seem
like the poor quality sleep associated with obstructive sleep apnea would make people more
able to fall asleep at night, studies have shown that as many as half of all people with
obstructive sleep apnea still struggle with bedtime insomnia.
It’s important to ask about obstructive sleep apnea for anyone presenting with chronic
fatigue, as patients are not always aware that they are waking up frequently at night. You
can use the mnemonic STOP BANG to remember the speci c factors that are predictive of
obstructive sleep apnea, including Snoring loudly, feeling Tired all the time, apneic episodes
that have been directly Observed by someone else, high blood Pressure, high Body mass
index, older Age, a large Neck circumference, and male Gender . Sleep apnea is a major
threat to health, as untreated sleep apnea is associated with a higher risk of heart attack and
stroke. Treatment for obstructive sleep apnea involves using a continuous positive airway
pressure (or CPAP) machine that provides a steady stream of air to keep the airway from
getting compressed.
 

Risk factors for obstructive sleep apnea include

snoring, chronic fatigue, hypertension, obesity,
older age, a large neck, and male gender.
 

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 STOP BANG: Snoring Feeling Tired all the time
Observed apneic episodes High blood Pressure High Body
mass index Older Age Large Neck circumference Male
Gender

U is for Urination. Frequent urination at nighttime (known as nocturia) can cause chronic
sleep deprivation, which is especially common in the elderly. Treatment of underlying
causes can provide signi cant improvements in sleep quality.

R is for Restless legs. Restless legs syndrome (or RLS) is a condition in which a person
experiences recurrent feelings of internal energy or restlessness while at rest. is
restlessness is temporarily alleviated by moving one’s legs, leading to frequent leg
movements when trying to fall sleep. is can often impair both the length and quality of
sleep, leading to symptoms of sleep deprivation. Around half of all cases of restless legs
syndrome are idiopathic, with genetics playing a large role. However, it can also occur as the
result of other medical or psychiatric conditions, with common culprits being iron
de ciency (seen in 20% of all cases), renal failure, diabetes, and Parkinson’s disease. In these
cases, treatment of the underlying condition (such as giving iron supplementation) takes
priority. For idiopathic cases, no curative treatments are available. Instead, a variety of
symptomatic treatments can help to improve sleep duration and quality of life. Medications
that boost dopamine such as pramipexole are often effective. However, their bene ts must
be balanced against the potential downsides including a risk of rebound symptoms (where
restlessness becomes even more severe than it initially was when the drug is stopped).
 

D is for Drugs. A wide variety of prescription and recreational drugs can interfere with
sleep. By far the most common culprit is caffeine, which is widely available and consumed
by the majority of the population. People tend to underestimate the amount of caffeine that
they drink, so ask your patients with insomnia to keep track of their intake so they can tell
whether their insomnia is likely related to caffeine intake. Another common culprit is
alcohol which can help to induce sleep through its sedative effects but often leads to
nighttime awakenings several hours later when a mild state of withdrawal occurs.
 

R is for Routine. Asking about daytime and nighttime routine can help to reveal particular
habits that may be contributing to difficulty falling asleep, including frequent afternoon
naps, exercising too close to bed, or exposure to bright lights at night (which can suppress

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melatonin secretion and throw off one’s circadian rhythm). Having a bedtime routine like
making a cup of decaffeinated tea or going to bed at the same time each night can also
improve sleep quantity and quality.
 

E is for Environment. Sleeping should be done in a space that is quiet, peaceful, and cool.
e bed should be used only for sleeping and sex, as other activities (including eating,
watching television, or using the phone) can undo the association of your bed as being a
place where you go to sleep.
 

A is for Anxiety. Anxiety is associated with difficulty both falling and staying asleep, so
assessing for the presence of anxiety disorders is critical. Often, anxiety about not getting
enough sleep can itself perpetuate a cycle of sleeplessness. In addition, someone may have
anxiety about falling asleep if they have frequent nightmares (as can occur after trauma) or
experience night terrors or sleep paralysis.
 

M is for Mood. Mood disorders such as depression and bipolar disorder have disruptions in
sleep as core clinical features (remember SIGECAPS and DIG FAST). Depression is often
associated with impaired ability to fall asleep at night and early morning awakenings while
mania presents with decreased need for sleep.
 

S is for Subjective. A number of people report a feeling that they aren’t getting enough
sleep, but a sleep study then reveals that their sleep patterns are adequate. Always consider
the possibility that the amount of sleep that someone gets may be greater than they sense,
and if this appears to be the case, consider educating on ways of reducing sleep-related
anxiety.
 

Insomnia can be idiopathic but is more likely

secondary to a number of other medical and
psychological factors.
 

SOUR DREAMS: Stress Obstructive sleep apnea

Urination Restless legs Drugs Routine Environment
Anxiety Mood Subjective

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MECHANISMS OF PRIMARY INSOMNIA
Mechanistically, cases of insomnia that are attributable to any secondary causes often
involve overactivation of the HPA axis, as the severity of insomnia appears to correlate with
measurable differences in levels of corticotropin-releasing factor and cortisol. is overactive
HPA axis leads to a state of persistent hyperarousal during the day. On a cognitive level,
this hyperarousal manifests as anxious thoughts about particular life stresses. ese thoughts
begin to persist at night, which interferes with the ability to fall asleep and worsens one’s
quality of sleep. After a few nights of bad sleep, the focus of worry often shifts to include
not only whatever someone was stressed about in the rst place but also the detrimental
effect of poor sleep itself. is results in hypervigilance about falling asleep, leading to an
increase in anxiety around bedtime which further prevents someone from entering the state
of relaxation necessary for sleep and creating a vicious cycle. e involvement of the HPA
axis appears to explain the common comorbidity of insomnia with both depression and
anxiety disorders, as they all likely share a common mechanism. It also explains the
effectiveness of CBT in breaking the cycle of insomnia, as anxious thought patterns about
sleep are replaced by healthier thought processes and habits.

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OTHER SLEEP DISORDERS
In addition to insomnia, there are a variety of other sleep disorders that you should be aware
of. While a full discussion of sleep disorders would take an entire book on its own, this
section can serve as a brief introduction to each major type of sleep disorder to help you
recognize them when they occur clinically.
 

CIRCADIAN RHYTHM DISORDERS

People who are not able to consistently follow a set daily schedule (such as those who work
night shifts or travel across time zones regularly) are at risk for circadian rhythm disorders.
ese disorders are characterized by excessive sleepiness during the daytime (when they
should be awake) and involuntary wakefulness at night (when they should be asleep).
Providing education on sleep hygiene (such as avoidance of naps and caffeine prior to sleep)
can be an initial rst step. For those with excessive difficulty falling asleep at night,
melatonin supplements can be incredibly helpful. For those with difficulty staying awake
during the day, exposure to bright lights can be effective, as can the medication moda nil
which helps to promote wakefulness.
 

SLEEPWALKING
Sleepwalking (also called somnambulism) is when an individual performs activities as if
they are awake despite being in a state of deep sleep. is most commonly involves walking
around, although other activities (such as going to the bathroom, cooking, and even driving)
have been reported. Sleepwalking is a type of parasomnia, a category of sleep disorders
characterized by abnormal movements or behaviors during sleep. Parasomnias like
SLeepwalking occurs during SLow-wave sleep when muscles are not paralyzed as they are
during REM sleep. Most cases of sleepwalking are idiopathic, with no clear cause ever
being found. However, in some cases they may be related to use of Z-drugs like zolpidem.
 

REM SLEEP BEHAVIOR DISORDER

REM sleep behavior disorder is characterized by abnormal movements during REM sleep.
Recall that REM is the stage of sleep when dreaming is most vivid but one’s muscles are
paralyzed. For someone with REM sleep behavior disorder, however, a lack of muscle
paralysis during REM sleep leads to their acting out their dreams. is can be very
disruptive to others sharing the bed, and people with REM sleep behavior disorder can

522
sometimes even unintentionally injure themselves or their partners if they are experiencing a
particularly violent dream. Compared to sleepwalking, REM sleep behavior disorder is
more often related to another disorder (such as dementia with Lewy bodies or Parkinson’s
disease) than it is idiopathic.
 
NIGHTMARE DISORDER
Nightmares are unpleasant or terrifying dreams that occur during REM sleep. Most
people have nightmares from time to time, but a minority of people are afflicted by
nightmares that are frequent or severe enough to qualify as a disorder. People with
nightmare disorder are more likely to have a history of trauma (recall that nightmares are
one of the common symptoms of PTSD). If treatment is desired, the use of stress
reduction techniques such as mindfulness can be helpful as can the medication prazosin
which has been shown to reduce the frequency and severity of nightmares.
 

SLEEP TERRORS

Sleep terrors (also called night terrors) differ from

nightmares in that they occur during non-REM sleep. As is typical of dreams during non-
REM sleep, the person its typically unable to remember what they were dreaming about.
However, upon awakening they are clearly distressed, often crying out or sitting upright
with eyes wide open. Physiologic signs can resemble a panic attack, with tachycardia and
hyperventilation being common. Sleep terrors are most common during childhood, and the
vast majority of cases do not persist into adulthood (with less than 1% of adults
experiencing sleep terrors on a regular basis). For this reason, reassurance is typically
sufficient for children who suffer from sleep terrors (as well as their parents).
SLEEP PARALYSIS

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 Capping off the trio of conditions involving terrifying
experiences while asleep is sleep paralysis. Sleep paralysis occurs when someone wakes up
from REM sleep and gains consciousness of the world but remains unable to move. is
sensation is often accompanied by a feeling of fear or panic. In addition, many people
report a distinct sensation of being watched and can even hallucinate a malevolent gure in
the room. Episodes of sleep paralysis can be highly disturbing, especially if they are so
regular or severe that someone develops anxiety about going to bed. Up to half of all adults
have experienced at least one episode of sleep paralysis, although less than 5% have them on
a regular basis. Education on the nature of sleep paralysis and teaching of relaxation
techniques can often be treatment enough, although in more severe cases CBT or
medications (typically SRIs) can been used.
 
NARCOLEPSY
Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness that in
some cases leads to people having episodes where they suddenly fall asleep without
intending to. While these sudden “sleep attacks” are the most dramatic and memorable
symptom, there are a variety of clinical features found in narcolepsy that can inform your
diagnosis. e mnemonic CHAP will help you remember these:
C is for Cataplexy. Cataplexy refers to sudden episodes of muscle paralysis during
wakefulness. is can manifest as subtle signs such as slight weakness in the limbs all the
way up to someone collapsing on the ground due to a complete loss of muscle tone.
Cataplexy is often triggered by strong emotional states, but it can occur “out of the blue” as
well. Cataplexy is likely related to activation of the same state of muscle paralysis seen in
REM sleep but without the accompanying loss of consciousness (it is only half of the REM
sleep state). Cataplexy is believed to be unique to narcolepsy, making it a very speci c sign.
Of note, cataplexy should be differentiated from catalepsy which is associated with catatonia.
You can remember this by thinking that catalepsy is found in psychiatric conditions whereas
cataplexy is related to the bedroom (as you use a bed for both sleep and sexy time).
 

Cataplexy, or sudden episodes of muscle paralysis

during wakefulness, is a core feature of narcolepsy.
 

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 Catalepsy is found in psychiatric conditions while
cataplexy is related to narcolepsy (use a bed for both sleep
and sexy time).

H is for Hypnagogic and hypnopompic hallucinations. e term hypnagogic refers to the

transition from wakefulness to sleep (the feeling of “just drifting off ”), while hypnopompic
refers to the transition from sleep to wakefulness. Accordingly, hypnagogic and
hypnopompic hallucinations are speci c sensations (usually vivid images, although sounds
can be heard as well) that one experiences when falling asleep or waking up. is imagery
can range from random lights or “speckles” all the way to fully formed images of people and
places. In contrast to the hallucinations seen in dreaming, it is rare for hypnagogic or
hypnopompic hallucinations to involve any sort of narrative or story. As a bonus mnemonic,
you can remember the difference between hypnagogic and hypnopompic hallucinations by
thinking that hypno—grog-ic hallucinations occur when you are grog-gy, while hypno—
pump-ic hallucinations occur when you need to pump yourself up in the morning.
 

Hypnagogic and hypnopompic hallucinations are

sensory experiences that occur during the transition
between sleep and wakefulness.
 

Hypno—grog-ic hallucinations occur at night when you

are grog-gy, while hypno—pump-ic hallucinations occur
when you need to pump yourself up in the morning.

A is for Attacks of sleep. Sudden episodes of sleep are perhaps

the most dramatic and well-known sign of narcolepsy. ese “sleep attacks” (which are
distinct from the “dream attacks” seen in dissociative episodes) typically last only a few
seconds or minutes, but due to their unpredictable nature they can be incredibly distressing
and impairing. Not all people with narcolepsy experience such sudden “attacks” of sleep,
with some people primarily experiencing excessive daytime sleepiness (even when they get
adequate sleep).
 

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P is for Paralysis. Sleep paralysis is common in narcolepsy and represents another
manifestation of the tendency towards experiencing only half of the REM sleep state
(muscle paralysis without the sleepiness, only this time occurring at night instead of during
the day as occurs during cataplexy).
 

Narcolepsy is characterized by the tetrad of

cataplexy, hypnagogic and hypnopompic
hallucinations, sleep attacks, and sleep paralysis.
 

CHAP: Cataplexy Hypnagogic and hypnopompic

hallucinations Sleep Attacks Sleep Paralysis

While diagnosing narcolepsy is easy when someone has all four of these clinical features, not
everyone with narcolepsy does. Sleep studies can help to detect the speci c abnormalities
(such as rapid transitions between wakefulness and REM sleep) that characterize
narcolepsy.
Narcolepsy is a rare diagnosis, affecting less than 0.1% of the population (although it
may be underdiagnosed, especially in people who do not have all four of the characteristic
symptoms). It tends to have its onset during adolescence and early adulthood, with men
and women being affected equally. Treatment is symptomatic rather than curative. Sodium
oxybate (perhaps better known by its street name gamma-hydroxybutyric acid or GHB)
appears to be effective at reducing the severity of multiple symptoms of narcolepsy,
including excessive daytime sleepiness, episodes of cataplexy, and altered sleep architecture.
In addition, the wakefulness-enhancing drug moda nil appears to be effective at reducing
daytime sleepiness and sleep attacks but does not signi cantly affect episodes of cataplexy.
Careful maintenance of sleep hygiene and avoidance of sleep-impairing substances such as
caffeine and alcohol are crucial as well. Behavioral and lifestyle changes such as scheduling
naps and exercise sessions can be bene cial as well.
 

FATAL INSOMNIA Fatal insomnia is a type of prion disease that begins in adulthood
(typically around the age of 50) and manifests as an absolute inability to enter any sleep
stages deeper than stage I. is complete sleeplessness is typically accompanied by a variety
of neuropsychiatric symptoms including extreme anxiety, panic attacks, paranoia, and
hallucinations. Like other prion diseases, fatal insomnia is rapidly progressive, with
increasing cognitive de cits that resemble dementia leading to a state of mutism and non-
responsiveness. Death typically occurs within one or two years of initial diagnosis. Luckily,
fatal insomnia is an extremely rare disease with less than 100 cases being documented. e
majority are related to a mutation in the gene encoding prion protein PrPC, although a few
idiopathic cases have been documented as well.

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PUTTING IT ALL TOGETHER
Sleep is a vital part of life that is essential not only for living but for living well. In the eld
of psychiatry, impaired sleep has been associated with nearly all forms of mental illness in a
bidirectional fashion (with disturbances in sleep increasing the risk for developing a
psychiatric disorder as well as psychiatric disorders themselves increasing the risk of
impaired sleep). Because of the close relationship of sleep to mental health, you should
consider assessing sleep patterns as part of every psychiatric evaluation.
Understanding the physiology of normal sleep can help with identifying the exact stages in
the process where things have gone awry. Use BATS Drink Red Blood to remind yourself
of the stages of sleep. From there, evaluate where in the process the dysfunction is
occurring, then use the SOUR DREAMS mnemonic to evaluate for common causes of
insomnia dysfunction. Once these have been ruled out, consider a referral to CBTi or
another evidence-based form of therapy, with medications used sparingly if at all.

527
REVIEW QUESTIONS
1. A 29 y/o F awakens suddenly at 2:53 in the morning and experiences an “electrical
sensation” running down her entire body from head to toe. She has a distinct sense
that someone has broken into her house and is standing in the doorway, but she
nds that she is unable to roll over in bed to look and know for sure. She feels her
heart begin beating loudly in her ears and feels short of breath. A few seconds later
she is able to turn over and sees that there is no one in the doorway. Which of the
following best describes this episode?
A. Nightmare
B. Hypnagogic hallucination
C. Cataplexy
D. Sleep paralysis
E. Sleep terror
F. None of the above
2. (Continued from previous question.) Which of the following statements is true
about this condition?
A. Taking prazosin regularly will help to prevent these episodes
B. It is likely to recur frequently once it has started
C. It is common in children but rare in adults
D. It is less likely to occur while taking medications to treat depression
E. It is almost invariably fatal within one or two years
F. None of these statements are true
3. A 25 y/o M sees her primary care provider complaining of insomnia. He says that
for the past 2 months he has had severe difficulty falling asleep and will often feel
the need to move his legs for up to 2 hours before nally falling asleep. He says, “I
just can’t seem to get comfortable. It’s like I just drank coffee except I don’t drink
anything.” Asking about additional sources of caffeine, including chocolate and
tea, con rms the absence of caffeine intake. He also denies drinking alcohol or
using other psychoactive substances. He denies having speci c thoughts going
through his head while falling asleep, saying, “I’m not worried about anything. I
mean, since this started I have begun to get worried about it, but otherwise my life
is going ne.” He denies daytime fatigue, saying, “I only get 5 or 6 hours which is
enough to function, although I’d like to get more.” Which of the following is the
best next step?
A. Prescribe an antidepressant
B. Prescribe a hypnotic
C. Refer for a sleep study
D. Refer to a specialist in cognitive behavioral therapy for insomnia
E. Order laboratory tests
 

4. A 13 y/o F is brought to see a neurologist for recurrent “fainting spells” that she
has been experiencing for the past two months. She reports feeling “super tired all
day, every day” and often falls asleep during class. She has been sent to the
principal’s office several times who has encouraged her to “go to bed earlier and
stop drinking so much coffee at night.” At a surprise birthday party that her family

528
arranged for her over the weekend, she suddenly collapsed several seconds after the
guests yelled, “Surprise!” She denies losing consciousness at that time and has full
memory of the event. However, she also has experienced other episodes when she
will fall down for several minutes and wake up with no memory of the experience.
She recently has begun waking up from nightmares but nds herself unable to
move. She denies hearing or seeing things as she is falling asleep. She otherwise
has no medical or psychiatric history. Which of the following is the most
appropriate statement for the neurologist to make at this time?
A. “ is is likely a dissociative disorder. You need to see a psychiatrist
who can help you with this more than I can.”
B. “ is sounds like narcolepsy, but without the presence of hypnagogic
hallucinations we cannot diagnose it as such.”
C. “Your principal is right: you need to get more sleep and drink less
coffee in the evenings.”
D. “I can see what you are trying to do here, but there are better ways of
getting out of class than this.”
E. “I wish I could do more to help, but this is a completely untreatable
condition.”
F. None of the above would be appropriate statements to make

529
1. e best answer is D. is vignette describes a case of sleep paralysis which
involves becoming conscious while in a state of muscle paralysis related to REM
sleep. Panic-like psychological and physiologic symptoms as well as a feeling that
someone or something else is present in the room are common. Nightmares also
occur during REM sleep, but the hallucinated objects and paralysis do not persist
after awakening (answer A). Hypnagogic hallucinations refer to seeing or hearing
things while falling asleep, not while waking up from sleep (answer B). Cataplexy
is a state of sudden muscle paralysis during daytime wakefulness, not sleep (answer
C). Sleep terrors occur during deep sleep and are not accompanied by muscle
paralysis (answer E).
2. e best answer is D. Antidepressants like SRIs are sometimes used to treat
recurrent sleep paralysis, so someone taking them to treat depression is likely to
experience these episodes less often. Sleep paralysis is rarely recurrent, although for
a minority of people they can be (answer B). Prazosin helps reduce the frequency
and severity of nightmares, not sleep paralysis (answer A). Sleep terrors are
common in children but rare in adults (answer C). Fatal insomnia, not sleep
paralysis, is invariably fatal (answer E).
3. e best answer is E. is vignette describes a case of restless legs syndrome.
Restless legs syndrome can be idiopathic, but in many cases it is related to a
medical condition. Of these, iron de ciency is the most common, so this should be
ruled out immediately. If no cause is found, drugs that increase dopamine such as
pramipexole can be used. Antidepressants have not been shown to help in cases of
restless legs syndrome (answer A). Prescribing a hypnotic, ordering a sleep study,
or referring to a specialist in CBT for insomnia may be helpful but should not be
done before the most obvious underlying causes are ruled out rst (answers B, C,
and D).
4. e best answer is F. is describes a case of narcolepsy involving cataplexy, sleep
attacks, and sleep paralysis. While hypnagogic hallucinations are also found
commonly in narcolepsy, most cases of narcolepsy do not involve all four
symptoms (answer B). Narcolepsy is a treatable condition (answer E) but requires
more than just telling someone to get more sleep and drink less caffeine (answer
C). Narcolepsy should be differentiated from dissociation which involves “dream
attacks” rather than the “sleep attacks” (answer A). Diagnosing malingering is
inappropriate as this clinical case matches what is known about the
phenomenology of narcolepsy almost exactly (answer D).

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 4.

24 FINAL REVIEW

Hey, you made it! Congratulations. Learning about an entire

eld of medicine over a few hundred pages is no easy task, so kudos to you for your hard
work and determination. While psychiatric diagnosis is neither simple nor easy, hopefully
you have gained some of the skills and knowledge required to approach this task with a clear
mind. Psychiatric diagnosis is a powerful tool, but like any tool it must be used responsibly
to avoid being unintentionally turned into a weapon. Despite the inherent shortcomings of
the process, we cannot sidestep diagnosis entirely as it remains the cornerstone of our ability
to bring understanding and hope to the people struggling with these syndromes. To avoid
the downsides of diagnosis, remember to always keep normalcy on the differential, as sadness
is not depression, happiness is not mania, hearing voices is not schizophrenia, worrying is
not an anxiety disorder, being orderly is not OCD, experiencing trauma is not PTSD,
having emotions is not a personality disorder, and so on. Keep this crucial distinction in
mind as you prepare to help a world of people who need your knowledge, guidance, and
compassion more than ever.
While each chapter so far has made references to topics in other chapters, these nal
review questions are intended to supercharge your learning by helping you draw additional
comparisons between the various disorders we have studied. is will also help to
consolidate the information that you have learned so far and better prepare you for real-
world clinical situations where patients can come in with any possible problem (rather than
just the one from the chapter you happened to be studying at the time).
Good luck!

531
FINAL REVIEW QUESTIONS
1. A 28 y/o F brings her 1-month-old baby girl to her pediatrician’s office for a well-
child check. She has been raising the baby alone after her boyfriend left upon
discovering that the girl had Down syndrome. Examination of the baby reveals
that she is at the 4th percentile in weight for her age. Upon entering the room, the
pediatrician notices that the baby is crying and that the mother is wearing large
amounts of makeup. e mother says, “ ank you doctor for seeing my baby. She’s
a tiny little girl now, but she’s going to grow up to be a star. She’s already singing
right now, and it’s beautiful, beautiful, absolutely booty-full.” When the
pediatrician tries to pick up the infant for examination, her mother pulls her back
suddenly, yelling, “Oh no you don’t! She’s mine! If you think you’re getting rich off
me and my baby, you’re dead wrong!” e baby continues crying throughout this
exchange. What is the next best step?
A. Prescribe an antipsychotic
B. Prescribe a mood stabilizer
C. Prescribe an antidepressant
D. Arrange for transfer to the hospital
E. Provide reassurance and conclude the appointment
2. A 7 y/o M is brought to see a child psychiatrist by his mother for “problems at
school.” Pregnancy, birth, and early childhood were non-eventful, and he met all
developmental milestones on time. However, halfway through the school year, the
patient began having difficulty sitting still. He previously was completing his
schoolwork without any problem, but he suddenly started showing no interest in
school. His mother is concerned because he appears to have forgotten things that
he has previously learned, including the alphabet and how to do arithmetic. He
lives with both of his parents and an older sister. ere is no history of medical or
psychiatric problems in the family. Which of the following is the most likely
diagnosis?
A. Attention de cit hyperactivity disorder, inattentive type
B. Attention de cit hyperactivity disorder, hyperactive type
C. Attention de cit hyperactivity disorder, combined type
D. Rett syndrome
E. Disruptive mood dysregulation disorder
F. Oppositional de ant disorder
G. Autism spectrum disorder
H. None of the above
3. (Continued from previous question.) e patient is referred for neuropsychiatric
testing. Five days after the initial evaluation, he experiences a tonic-clonic seizure
lasting for approximately one minute. He is sent by ambulance to the emergency
department. Vitals signs are HR 108, BP 84/58, RR 22, and T 100.7°F.
Laboratory studies show severe hyponatremia. An MRI of the brain is conducted
which reveals white matter changes in the posterior periventricular area. Physical
examination of his mouth shows the following :

532
Which of the following is true of this condition?
A. It is untreatable
B. It is equally common in males and female
C. It was previously known as Asperger’s syndrome
D. Some people with this condition are completely asymptomatic
E. It tends to respond to stimulant medications
F. None of the above are true
4. A 25 y/o M comes to a psychiatrist’s office for an initial evaluation. He says that he
has always been “a bit of an introvert” but has generally been successful in his life.
He graduated from college with a degree in geological engineering several years
ago and has a well-paying job. He is currently single but has dated in the past. He
has never seen a psychiatrist or taken psychotropic medications prior to this visit
but did see a therapist for two months around the time of his parents’ divorce at
the age of 12. His primary concerns today are trouble sleeping, daytime fatigue,
and difficulty concentrating at work. He often cannot fall asleep for several hours
and has been averaging only 4 hours of sleep per night. Once he falls asleep, he is
generally able to sleep through the rest of the night. He has noticed these
symptoms for the past 3 months over which time they have been slowly getting
worse. He denies any major stresses or changes in his life. His mood is generally
“good” and he nds that he still enjoys his favorite activities such as going
mountain biking (although he does not do it as often due to fatigue). He denies
feelings of hopelessness or thoughts of suicide. He feels that sometimes he is
moving more slowly but is unsure (he looks confused when asked the question).
Which of the following is the most likely diagnosis?
A. Unipolar depression
B. Bipolar depression
C. Dysthymia
D. Adjustment disorder
E. Generalized anxiety disorder
F. None of the above
 

5. An 18 y/o F with a history of the hyperactive subtype of ADHD undergoes

extensive neuropsychiatric testing which reveals very high levels of impulsivity (in
the 92nd percentile for adults her age) and very low levels of compulsive behavior.
Which of the following behaviors is she least likely to engage in?
A. Eating lots of food in a single sitting and then vomiting them up

533
 B. Using a razor to make super cial cuts on her wrist following a break-
up
C. Pulling out small patches of hair from her head until it bleeds
D. Going to a friend’s party to drink despite having had her driver’s
license revoked after a DUI one month ago
E. rowing a plate against the wall during an argument with her
parents
6. A 20 y/o M is brought to the psychiatrist’s office by his mother who says that she
“doesn’t know what to do with him anymore.” On interview, the patient declines to
speak with the psychiatrist because “he will steal my energy,” so the mother
provides the majority of the history. Per the mother, the patient rarely showers or
changes clothing until his parents tell him to. He worked at a local fast food
restaurant until he was red for coming into work “looking like he lost a ght with
a homeless person.” He now spends most of his free time on various online
message boards. He previously did very well in school and graduated with straight
As. However, he declined several scholarships at prestigious colleges. When asked
why, he says, “Colleges are like banks for your mind, and I want to keep mine
stuffed under the bed.” e psychiatrist tries again to ask him questions, and this
time he responds. He says he prefers not to shower because it “replaces my internal
aura with something more arti cial.” He denies feeling depressed or anxious. He
has no trouble sleeping and says he does not hear voices. He wants nothing from
the psychiatrist at this time, describing himself as “happy.” When asked if he has
friends, he says, “Mostly people online who also enjoy the wonders of the jade
stone arts.” His mental status exam is unremarkable except for an affect that is
sometimes inappropriate to the topic at hand. After nishing the session, the
psychiatrist asks to speak with the patient’s mother separately. She begins crying
and says, “I want answers. My brother is schizophrenic. Will my son be too?”
Which of the following is the most appropriate response?
A. “Your son has schizophrenia. Let’s talk about treatment.”
B. “Your son does not have schizophrenia, but he may develop it later.”
C. “I can say de nitively that your son will not develop schizophrenia.”
D. “Your son won’t develop schizophrenia, but he has a related condition
known as schizoid personality disorder.”
E. “ ese beliefs may come across as being related to schizophrenia, but
they are caused by something called paranoid personality disorder.”
F. “Your son is completely normal. I’d like to see you alone next time.”
7. A 15 y/o F is hospitalized after a second suicide attempt. While speaking with the
patient’s parents, the psychiatrist says, “We need to work together to come up with
a comprehensive plan, as the next few years won’t be easy. Your daughter’s
condition has the highest chance of death of any psychiatric condition, so we really
need all hands on deck.” What is the patient’s most likely diagnosis?
A. Major depressive disorder
B. Bipolar disorder
C. Schizophrenia
D. Panic disorder
E. Obsessive-compulsive disorder
F. Post-traumatic stress disorder

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 G. Factitious disorder
H. Borderline personality disorder
I. Anorexia nervosa
J. Bulimia nervosa
8. A 53 y/o M is seen for the rst time by a neurologist specializing in memory loss.
He says that he worked in construction for many years and recently found out that
he was exposed to “some kind of toxic chemical, I don’t remember the name but
apparently it’s pretty bad” on a regular basis. He believes that exposure to this
chemical is related to some “annoying brain problems” he has been having and
desires a full evaluation. He has contacted other people that he worked with in the
past who are planning on ling a class action lawsuit against their previous
employer. In regards to speci c complaints, the patient says that his ability to
remember letters and numbers has “basically evaporated” in the past 5 years.
While he is able to read, he says that he cannot recall phone numbers, addresses,
or other pieces of information that involve combinations of letters and numbers.
When asked to spell his own name, he says, “ at’s one of those things, I can’t do
it anymore.” His MoCA score today is 5/30 (normal range of 25 and above).
When asked about his driving, he says, “ at I can do—driving, going to the store,
putting on my shoes—that’s all ne.” Which of the following would be the best
next step?
A. Writing a report that suggests the patient is suffering from a severe
neurocognitive disorder
B. Conducting a thorough physical and neurologic examination
C. Ordering a CT scan of the brain
D. Telling the patient to “stop lying and get out of my office”
E. Taking a non-confrontational approach and politely reassuring the
patient that there is nothing wrong with him
9. An 18 y/o F is admitted to the hospital after telling her therapist that she is
“hearing voices telling me to kill myself.” She began hearing these voices 2 weeks
ago and describes them as originating from inside her head. She has been
hospitalized over 10 times since the age of 14 and has multiple diagnoses in her
chart, including depression, bipolar II disorder, an unspeci ed anxiety disorder,
PTSD, and irritable bowel syndrome. At her most recent hospitalization, she was
told by a frustrated nurse, “Don’t come back here until you are really sick like the
other people here!” after which she became incredibly agitated. During rounds
with her team on the morning after admission, she describes feeling depressed “for
as long as I can remember” and denies periods of normal or balanced mood. She
says that she feels unloved by her mother at home and desires to go to a residential
treatment program after discharge. When told by the social worker that her
insurance doesn’t cover this, her affect rapidly darkens and she tells the social
worker, “ e voices say you’re stupid and worthless.” Which of the following is
true of this patient’s condition?
A. She is unusually young for a female to develop this condition
B. It is a rare diagnosis that bridges psychotic and mood disorders
C. It responds well to a combination of antidepressants and
antipsychotics

535
 D. It is a lifelong condition, and her symptoms will continue to worsen
over the next several decades
E. It is correlated with a history of abuse
10. An 18 y/o M is brought to the hospital by his parents who found him making cuts
to his wrist while sitting in his room. A picture of his injuries is seen below:

e injuries are determined by the triage nurse to be non-life-threatening, and given

that it is a busy Saturday night in the emergency department, he ends up waiting to be
evaluated by a physician for over 8 hours. When seen by the physician, he complains of
bilateral headache, nausea, and dizziness beginning one hour ago. Vitals signs are HR
74, BP 120/76, RR 16, and T 98.2°F. He appears somewhat lethargic and is slurring
his words. However, there are no other abnormalities on physical exam. He continues
to report suicidal ideation, so a plan is made to admit him to the psychiatric unit. On
the unit, he tells one of the nurses that he is having severe pain in his right upper
abdominal. At this time he is alert and oriented to person only. A rapid response is
called, and he is quickly transferred to the intensive care unit where he is diagnosed as
being in fulminant hepatic failure. Which of the following could have prevented this
outcome?
A. Being seen by the physician within one hour of arriving at the hospital
B. Taking a complete substance history including the time of last drink
C. Having a high index of suspicion for occult overdoses
D. Ensuring that the patient had access to adequate hydration while waiting
in the emergency department
E. Nothing could have prevented this outcome
 

11. (Continued from previous question.) e patient is determined to need an urgent

liver transplant to survive. However, his mental status continues to uctuate, and
he is unable to answer questions about his condition other than saying his name
and “it hurts” repeatedly. Which of the following is the best next step?
A. Ask the patient if he understands the risks and bene ts of the
procedure
B. Ask the parents what they would like to do based on their belief
system

536
 C. Call the outpatient psychiatrist to determine the psychiatric diagnosis
D. Cancel plans for transplantation
E. None of the above
12. A 20 y/o F nursing student with no prior medical or psychiatric history is
attending a learning session on how to perform an intradermal injection. She is
paired with another student to practice inserting a needle into each other’s skin.
Her partner follows the instructions including proper sterile technique and begins
to insert the needle as seen below:

Upon insertion of the needle, the girl suddenly feels faint. Her heart begins racing and
she feels lightheaded. She experiences a distinct sense that the world is not real, and
she feels that she is controlling herself in the same way she would control a puppet or
doll. She begins screaming, and an ambulance is called. Which of the following is the
most likely diagnosis?
A. Acute stress disorder
B. Post-traumatic stress disorder
C. Obsessive-compulsive disorder
D. Panic disorder
E. Dissociative amnesia
F. Depersonalization-derealization disorder
G. None of the above
13. A 31 y/o F makes an appointment to see her primary care provider to discuss her
weight. She has been mildly obese for much of her life. However, over the past 6
months she has gained 25 pounds. She acknowledges eating too much, including
a strong preference for fatty and carbohydrate-rich foods like snack cakes. She
denies episodes of binge eating, saying, “Recently I eat this way all the time.” She
notes that her increase in food intake coincided with her boyfriend of 11 years
breaking off their engagement. She has felt “pretty down” since then, but then
says, “But that’s life, you know? Life is a shit sandwich sometimes.” She denies a
persistent depressed mood, saying, “When I see friends I still have a good time,
but on an average day I feel like crap.” She is worried about the effect that her
recent weight gain will have on her ability to nd a new romantic partner, saying,
“Who wants to date a whale?” She has cried frequently over the past few weeks,
often in response to a friend making a comment that she perceives as making fun
of her weight (“He said my cookies were ‘almost too good’! What’s that supposed

537
 to mean?”). She then asks for a prescription for Adderall, saying, “It’s supposed to
help you lose weight, right? And I could use the energy boost. I feel like I’m
spending all day in bed.” Which of the following is the best response?
A. “Based on what you’re telling me, an antidepressant will likely help
even more than Adderall.”
B. “Medications won’t do anything to help you. e only thing that will
help is a type of therapy known as dialectical behavior therapy.”
C. “ is sounds like you have social anxiety. Let me refer you to
someone who can do cognitive behavioral therapy.”
D. “It’s not uncommon for people with bulimia to get depressed, but we
need to focus on treating the bulimia rst.”
E. “Adderall sounds like a good option for you. I’ll write you a script.”
F. None of the above
14. A 9 y/o F comes to school wearing a turtleneck sweater. It is the end of August,
with temperatures outside approaching 100°F. An observant lunch lady pulls the
girl aside to ask her if she isn’t too warm and wouldn’t prefer to take her sweater
off. However, the girl resists this suggestion, so she is sent to the nurse’s office. e
nurse conducts a full physical examination and observes the ndings below:

e girl refuses to answer any of the nurse’s questions. Later, when the girl’s father
comes to pick her up, the nurse asks about her neck. e father replies, “It’s nothing.
She plays a lot. She probably just fell.” When the nurse continues to ask him
questions, he says, “Look, I told you it’s nothing. She was clumsy this morning and
knocked herself in the neck while getting out of bed. Can I go now?” Which of the
following conditions is this girl most likely to have at this time?
A. Social anxiety disorder
B. Post-traumatic stress disorder
C. Oppositional de ant disorder
D. Borderline personality disorder
E. Dissociative identity disorder
15. (Continued from previous question.) e girl is referred to a child and adolescent
psychiatrist whom she sees at least twice yearly for the next decade. At the age of
18, she is working at a local daycare and going to school in the evenings to study
early childhood education. However, she often nds herself unable to fully
concentrate on either her job or her studies. She suffers from muscle tension and is
unable to relax even when at home on the weekends or around friends. She
frequently worries about how she will do at school and frequently visualizes her
boss ring her. ese thoughts often come to her head as she goes to bed, leading

538
 to frequent nights of poor sleep with resultant daytime fatigue. Which of these
conditions is she least likely to develop over her lifetime?
A. Anxiety about most things most of the time
B. Episodes of depressed mood
C. Persistent depressed mood
D. Nightmares more often than average
E. Flirtatious attention-seeking behaviors which come across as shallow
16. A 21 y/o M is pulled over for driving 40 miles per hour above the speed limit. He
greets the police officer with a smile and says, “Hiya fuckface! How about you quit
being such a do-gooder choad and let me go?” e officer arrests him. Urine
toxicology reveals the presence of opioids, cannabis, amphetamines, and alcohol.
Seven days later, he is seen by a psychiatrist. Chart review reveals that the patient
has been arrested under similar circumstances on one previous occasion. ere is
no history of violent crime or interactions with the legal system prior to the age of
20. However, he was hospitalized at age 19 after a suicide attempt. e patient has
spent most of the previous week pacing around his room and talking endlessly to
neighbors in adjacent cells. On multiple occasions, he has disrobed and begun to
masturbate before being stopped by guards. When this happens he becomes very
upset and punches the walls of the cell. On interview, the patient describes himself
as “the magni cent Mr. Miyagi” and asks the psychiatrist to observe his “karate
judo moves.” He says that he plans to “synthesize all martial arts into a single
discipline” that he will teach to school children “so that no one will ever be afraid
again.” He laughs frequently during the interview and attempts to leave several
times before being asked to sit back down by the guard. Which of the following is
the most likely primary diagnosis?
A. Narcissistic personality disorder
B. Psychopathic antisocial personality disorder
C. Non-psychopathic antisocial personality disorder
D. Schizophrenia
E. Bipolar I disorder
F. Multiple substance use disorders
G. Attention de cit hyperactivity disorder
17. An 8 y/o M is admitted to the hospital while on vacation with his family for
severe abdominal pain and vomiting. While staying at an all-inclusive resort, the
patient unlocked his door and walked to the all-you-can-eat buffet where he
proceeded to eat until he began crying and vomiting. He speaks slowly and is
unable to understand most questions asked of him, though his parents say that
this is his baseline behavior. A picture of the patient taken before the incident is
below:

539
 e patient subsequently undergoes an exploratory laparotomy which reveals gastric
rupture and necrosis. Which of the following diagnoses most likely explains this
patient’s behavior?
A. Binge eating disorder
B. Bulimia nervosa
C. Down syndrome
D. Prader-Willi syndrome
E. Angelman syndrome
F. William syndrome
G. None of the above
18. A 58 y/o F comes into the psychiatrist’s office complaining of depression after
realizing “what a complete and utter failure my life has been.” She voices a desire
to both engage in psychotherapy and start taking medications for depression. She
denies an episodic pattern to her depression and instead says that she has been
“constantly depressed” for several decades. She denies changes in sleep, appetite,
or energy levels. She denies having close friends, saying, “My whole world has
been at home.” She lives with her husband who previously worked as a car
salesman. However, they are now living on disability payments since her husband
hurt his back while working in the garage (although she says, “Sometimes I
wonder if he’s really as hurt as he says he is.”). Financially, they frequently struggle
to make ends meet, but he has refused to discuss the possibility of her returning to
work to bring in additional income. Earlier in life, she was accepted into law
school but declined the offer after her husband disapproved of her going to school.
He has recently begun to bring additional sexual partners into their bedroom so
that they can have threesomes (“and sometimes foursomes,” she says sheepishly).
When asked if she enjoys these sexual encounters, she says, “No! I hate them. I
want him to look at me the way he looks at these random strangers he brings
home.” She has never told him of her dislike of these sexual encounters and says
that she “plays along” to make him happy. During times when he is away, she feels
“a physical pain deep down in my body” that only goes away when he returns. e
patient is provided with a referral for a psychotherapist who takes her insurance.

540
 However, she then asks for “at least 5 referrals” as “I want to make sure that my
husband is okay with them.” Which of the following is true of this patient’s
condition?
A. It is unlikely to change
B. It is likely to resolve on its own without treatment
C. It is likely to resolve with use of an antidepressant
D. It is known to respond well to cognitive behavioral therapy
E. It is likely related to dysregulation of the sympathetic nervous system
19. A 56 y/o M comes to a psychiatric clinic with his wife. He is observed to walk
very slowly and requires assistance from his wife when turning to walk through the
clinic door. When asked how the clinic can help, the wife immediately breaks
down crying and says, “He doesn't love me anymore.” As his wife is crying, the
patient shows no change in affect and continues to stare straight ahead. His wife
soon stops crying and composes herself. She then says, “ ings haven’t been the
same for the past year. I don’t think he loves me anymore. He doesn’t say more
than a few words each day. But he also doesn’t let me go anywhere. If I leave him
for even a few minutes to go to the store, he’ll call me on my phone and ask where
I am. He doesn’t do anything for himself. I cook for him, and if I don’t remind
him he won’t shower or change his clothes.” e patient was started on an
antidepressant by his primary care provider three months ago. When asked if he is
depressed, he atly answers, “No.” When asked if he has any concerns, he again
answers, “No.” His voice is notable for a complete absence of prosody. A resting
tremor is noted in his left hand but not his right. A MoCA is performed, and the
patient scores an 18/30 with signi cant de cits in executive functioning and
delayed recall. ere are no abnormalities in cranial nerve function. Which of the
following is the most likely diagnosis at this time?
A. Alzheimer’s disease
B. Early-onset Alzheimer’s disease
C. Frontotemporal dementia
D. Dementia with Lewy bodies
E. Vascular dementia
F. Mixed dementia
G. Parkinson’s disease
H. Corticobasal degeneration
I. Progressive supranuclear palsy
J. Prion disease
K. None of the above
20. A 6 y/o M is brought to see his pediatrician after he begins refusing dinner. He
spends dinnertime arranging his food in such a way that no different foods are
touching each other. If someone tries to get him to eat, he screams and runs away
from the table. He now refuses to eat any foods that are not individually wrapped.
While there is no evidence of either weight loss or weight gain, the patient’s
mother is concerned about the effect that eating only pre-packaged foods will have
on his health. She says that this behavior started after he was gifted a children’s
book on microbiology by his grandmother. Since then, he has spent several hours
each day reading about different forms of bacteria on the internet. When the
pediatrician asks him why he does this, he says, “Bacteria friends!” When asked

541
 what the consequences of eating bacteria would be, he cannot think of any. He
makes poor eye contact with the pediatrician and often looks around the room.
Which of the following is the most likely explanation for his behavior?
A. Obsessive-compulsive disorder
B. Obsessive-compulsive personality disorder
C. Autism spectrum disorder
D. Intellectual disability
E. Anorexia nervosa
F. None of the above
21. A 14 y/o F is brought to see a doctor by her parents who say that she is “out of
control” the past 3 days. Per their report, she has been incredibly irritable and has
frequently yelled not only at her parents but also her friends, classmates, and
teachers at school. ey say that “a lot of the time what she says makes no sense”
and play a video they took of her arguing with a friend and accusing her of being
“a witch with broom booms.” At times, she has needed to be restrained by others
out of fear that she may attack someone else. She also sometimes has “ ts of
crying” that do not appear to be related to any speci c events or circumstances.
ey also note that she has stopped sleeping regularly and returned home this
morning at 6:00 appearing as if she had been outside wandering all night. ere is
no prior medical or psychiatric history, and the patient was previously doing very
well in school. ere are no recent psychosocial stressors that the parents are aware
of, although they note that the patient appeared to have “the u” about one week
ago. On exam, the patient herself is entirely mute but will direct her eyes to the
person asking her questions. She makes a repetitive chewing-like motion with her
lips. ere are beads of sweat on her brow, and she appears to have urinated on
herself. Which of the following is most likely to result in a change in behavior?
A. Gentle reassurance that the behavior is normal
B. Starting an antidepressant
C. Starting a mood stabilizer
D. Starting an antipsychotic
E. Referring to cognitive behavioral therapy
F. Referring to dialectical behavior therapy
G. Surgical intervention
 

22. A 44 y/o M with a history of binge eating disorder in remission for the past year
comes in to see his psychiatrist for a follow-up visit. Despite no longer engaging in
episodes of binge eating, the patient remains overweight with a BMI of 34.9. He
describes feeling tired all of the time. While he often falls asleep during the day,
he frequently has difficulty falling asleep at night and asks to be started on a
medication to help with sleep. All of the following should be part of his initial
evaluation except:
A. A substance intake history
B. A sleep study
C. A physical examination
D. A review of systems
E. Taking vital signs

542
 F. All of these should be part of his initial assessment
23. (Continued from previous question.) His psychiatrist starts him on zolpidem. At
the next visit one month later, the patient has gained 10 pounds. He says that he
still is not binge eating but often wakes up in the morning to nd food stains on
his shirt and empty cartons of food that he does not remember eating in his trash
can. He lives alone. What is the most likely explanation for this behavior?
A. e patient has returned to binge eating but does not remember
them
B. e patient has returned to binge eating but does not want to tell his
doctor
C. e patient is experiencing an idiopathic parasomnia
D. e patient is experiencing a substance-induced parasomnia
E. None of the above
24. A 51 y/o M with Down syndrome is brought to see his primary care provider by a
sister who acts as his caretaker. His sister reports that over the past year she has
noticed that he does not appear to recognize her anymore. He has also had several
episodes of wetting the bed over the past few months which he normally does not
do. He also previously enjoyed painting but has not engaged in this activity
recently, even with her direct prompting. She says, “Over the past month in
particular, he has seemed to be more irritable than usual, which isn’t the sweet boy
I’ve known my whole life.” His vital signs and recent labs are all within normal
limits. Which of the following is the most appropriate response?
A. “ is is typical behavior for someone with Down syndrome. How
long have you been his caretaker?”
B. “His lack of painting is likely a sign of depression. He can’t do
therapy so we should start an antidepressant.”
C. “ is is likely the result of a urinary tract infection. We should take
him to the hospital for further evaluation.”
D. “I’m concerned about this, but we need to perform cognitive testing
before we can be certain of a cause.”
E. “I know this can be hard to hear, but what you’re telling me suggests
that your brother’s condition will likely continue to get worse.”
 

25. A 39 y/o M is brought to the hospital by ambulance after he collapsed at work.

He was in the middle of cleaning out his desk after being red from his job for
repeatedly looking at pornography on his company computer. He did not appear
to lose consciousness when he fell as his co-workers reported that his eyes
remained open. However, he has not responded to any questions asked of him. He
appears to be unable to walk and needs to be lifted by the paramedics into the
ambulance. When interviewed by the emergency medicine physician, he still does
not respond to questions asked of him. All vital signs are within normal limits. A
complete physical exam reveals no abnormalities. He does not respond to requests
to cooperate with a neurologic exam. A CT of the head is ordered and shows no
evidence of pathology. A psychiatric consultation is ordered. e patient continues
to not respond to questions, although he is noted to become tearful when the
psychiatrist asks him, “What happened at work today?” Chart review reveals that

543
 he was admitted to the psychiatric hospital once ve years ago for transient
suicidal ideation that resolved within one day of admission. Which of the
following is the most likely diagnosis at this time?
A. Catatonia
B. Selective mutism
C. Hypochondriasis
D. Conversion disorder
E. Somatic symptom disorder
F. Factitious disorder
G. Malingering
H. None of the above
26. (Continued from previous question.) e patient’s wife arrives and asks to know
more about this condition. Which of the following statements could be made?
A. “ is condition has a good prognosis, and he will likely be back to
normal by the time he leaves the hospital.”
B. “It’s not really up to us. He’ll get better when he decides to get
better.”
C. “Based on what we know, we are quite certain about his diagnosis.”
D. “Once he is discharged, he will likely need to see a neurologist for the
rest of his life.”
E. None of the above
27. A 33 y/o F is seen by her psychiatrist for a yearly follow-up visit. She has a history
of treatment-resistant depression that was treated with electroconvulsive therapy
three years ago. Since then, she has been generally euthymic. At today’s visit,
however, she says that she is “not good.” She reports that over the past month she
has felt herself “slide back into the abyss” and has begun to feel hopeless about her
future and believes that she will never nd a full-time job or have a stable
relationship. She works as a freelance journalist and has begun staying up until late
at night to write more articles because “the more you write, the more likely you are
to get picked up.” She has also joined a dating website and has started to go on “a
lot of dates, I try for one a day but last week I met three guys on a single day.” In
spite of these efforts, she has not yet found a steady job or a stable relationship,
and she now feels like “it’s probably pointless to keep trying.” She feels that she
has “brought this on myself ” and that she should have “gone to podiatry school
like my parents wanted.” She feels anxious and restless most of the day and reports
only sleeping 2 or 3 hours most nights. She denies use of caffeine, alcohol, or
other substances. Which of the following is the most likely diagnosis given her
current symptoms?
A. Major depressive disorder
B. Bipolar disorder
C. Schizoaffective disorder, depressive type
D. Schizoaffective disorder, bipolar type
E. Dysthymia
F. Cyclothymia
G. Borderline personality disorder
H. None of the above

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28. A 29 y/o F is brought to the psychiatrist’s office by her sister. She has a history of
schizophrenia beginning at age 25 resulting in two hospitalizations, the last being
over one year ago. Her psychotic symptoms are currently well controlled on
risperidone at night. However, her sister is concerned because she “appears
depressed.” Her sister reports that the patient used to love playing the violin but
has stopped playing entirely in the past several years. On interview, the patient
reports feeling lonely and isolated. She denies a history of major depressive
episodes prior to the age of 25. She denies thoughts of hopelessness, guilt, or
suicide. She sleeps several hours per night and eats three full meals per day. Her
affect is dysthymic with a restricted range. What is the most likely diagnosis?
A. Schizophrenia
B. Schizoaffective disorder, depressive type
C. Major depressive disorder
D. Major depressive disorder with psychotic features
E. Both schizophrenia and major depressive disorder
29. A 24 y/o M who works in food delivery comes to the county clinic requesting an
evaluation. He says that over the past year he has developed a distinct sensation
that he cannot feel his own body. He reports feeling “hollow, like a kick drum” on
a daily basis and describes a sensation that “my skin is just covering a sack of
meat.” He describes being socially isolated due to intense anxiety regarding social
encounters. When he does attempt to make contact with old friends, he feels
“dead inside, even though I try to smile so that the other person doesn’t feel all
awkward and weird.” is sensation tends to come and go over a period of weeks,
but recently it has lasted for a month straight. e patient reports a history of
childhood abuse at the age of 8 by his older stepbrother (“I think that’s probably
where I actually died, now this feeling is just con rmation”). He says, “I realize
that these thoughts are strange, and that’s why I’m here.” He suffers from chronic
feelings of depression and reports thoughts of suicide most days. He denies
compulsive behaviors, auditory hallucinations, or feelings that others are out to
harm him. Which of the following diagnoses best accounts for this patient’s
presentation?
A. Schizophrenia
B. Schizoaffective disorder
C. Social anxiety disorder
D. Primarily obsessional obsessive-compulsive disorder
E. Depersonalization-derealization disorder
F. Schizotypal personality disorder
G. Schizoid personality disorder
H. None of the above
30. A 28 y/o F comes to a psychiatrist’s office for an evaluation. She reports a history
of “depression and bipolar” going back for “as long as I can remember.” After
taking a thorough history, the psychiatrist diagnoses her with major depressive
disorder, borderline personality disorder, opioid use disorder, social anxiety
disorder, binge eating disorder, and post-traumatic stress disorder. Which of these
conditions should be the initial focus of treatment?
A. Major depressive disorder
B. Borderline personality disorder

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 C. Opioid use disorder
D. Social anxiety disorder
E. Post-traumatic stress disorder
F. All of these conditions should be treated concurrently
31. A 29 y/o M is brought to the hospital by his sister after he stopped returning her
phone calls for three days. When she arrived, she found him sitting motionless on
the bed in a pool of dark yellow urine. e trash at his home was empty, and the
refrigerator is completely empty except for moldy bread and a few pieces of rotten
fruit. He normally works a full-time job. However, upon calling a co-worker, his
sister nds out that the patient has not been seen at work for over one week. On
interview, he is entirely mute and responds to questions by making small nods or
shakes of the head. His affect is at. e psychiatrist is unable to assess his mood,
thought content, thought process, perception, insight, or judgment. When
nishing the interview, the consulting psychiatrist offers to shake his hand. e
patient raises his hand in response to the psychiatrist’s offered hand but does not
actually make contact with it. When the psychiatrist puts her hand down, the
patient’s hand remains in the air as seen below:

Which of the following is the most likely diagnosis?

A. Major depressive disorder
B. Bipolar disorder
C. Schizophrenia
D. Conversion disorder
E. Factitious disorder
F. Malingering
G. None of the above
32. A 50 y/o M is brought in to the psychiatrist’s office by his wife after he was red
from his job as an accountant. He says that he has been “unjustly let go” and plans
to hire a lawyer. When asked why he was red, he says that he discovered that his
boss was “bilking our customers” by transferring “black money” and engaging in
tax evasion. His wife looks upset when he starts talking, saying, “ is again! He
never stops talking about this, and I’m sick of it!” She threatens to divorce him if
he ever brings this up again, to which he responds, “I’m going to take those
bastards down if it’s the last thing I do.” His wife throws her hands up and walks
out of the room, saying, “ ere’s something wrong with him. He’s never been like
this before. I can’t take it anymore.” When asked, the patient denies auditory
hallucinations, visual hallucinations, or suicidal ideation. He describes his mood as
“good,” and he averages 7 hours of sleep per night. His thought process is linear

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 and logical. Despite losing his job, he has been able to support himself, saying that
he is a “big saver.” However, he is planning on using up most of his savings to hire
a lawyer. What is the most likely diagnosis?
A. Schizophrenia
B. Delusional disorder
C. Paranoid personality disorder
D. Depression with psychotic features
E. Bipolar disorder with psychotic features
F. None of the above
33. A 42 y/o F is playing basketball with a friend when she suddenly experiences a
sensation that her heart is beating incredibly fast in her ears along with shortness
of breath and dizziness. She feels incredibly scared that something bad is going to
happen and tells her friend who drives her to the closest hospital. By the time they
arrive in the hospital 15 minutes later, her symptoms have resolved, and she
decides not to go in to avoid having to pay for the medical expenses. One year
later, she experiences the same symptoms while having sex with her husband. is
time the symptoms last over 30 minutes, so she calls an ambulance. Again the
symptoms resolve by the time she reaches the emergency room, so no work-up is
performed and she is immediately discharged with a referral to see her primary
care provider. In the next few days, she experiences episodes of palpitations lasting
no more than a few seconds each. ey are so brief that she is unsure if she is
merely imagining them. She experiences life as less enjoyable, as she is constantly
worried about whether her palpitations will return. She has stopped having sex or
playing sports, and she is considering whether or not she feels that she can
continue driving (“What if this happened while I was on the freeway?”). Which of
the following is the most likely diagnosis?
A. Panic attacks
B. Panic disorder
C. Generalized anxiety disorder
D. Somatic symptom disorder
E. Hypochondriasis
F. None of the above
34. (Continued from previous question.) Which of the following regions of the brain
is most likely initially involved in recognizing the sensation of her heart beating
rapidly in her ears?
A. e insula
B. e anterior cingulate cortex
C. e orbitofrontal cortex
D. e medial prefrontal cortex
E. e hippocampus
F. None of the above
35. A 74 y/o M is brought to see a psychiatrist by his wife for “delusions.” e patient
recently has begun to become more paranoid and has rejected food and water from
his wife on several occasions, saying, “Don’t try to poison me.” Over the past
week, he has been seen arguing with houseplants and empty tables. e patient’s
wife says that he seems to “come and go” mentally, as sometimes he seems
completely confused and disoriented while at other times he is “the same old Jim.”

547
 She denies any prior psychiatric history or substance use that she is aware of. He is
diagnosed with late-onset schizophrenia and prescribed risperidone, an
antipsychotic. At the follow-up visit one week later, the patient’s wife says that
he’s “completely worse” and now “walks like a statue.” His confusion has also
become persistent rather than transient over the past week, and he has forgotten
the names of people around him. One morning, his wife became scared that he
had died in his sleep when it took several minutes to awaken him in the morning.
e patient is oriented to person and place only. His MoCA score is 20/30.
Which of the following is the best next step?
A. Discontinue risperidone
B. Continue risperidone at its current dose
C. Increase the dose of risperidone
D. Add a cholinesterase inhibitor
E. None of the above
 

36. A 51 y/o M Army veteran makes an appointment to see a psychiatrist. On

interview, he says that he is suffering from “bad, bad PTSD” from his time in the
military and requests an evaluation to see if he is entitled to bene ts as a result.
Which of the following would be the best question to ask if the interviewer is
concerned about malingering?
A. “Tell me about what you are experiencing.”
B. “What was the nature of the traumatic event?”
C. “Do you nd yourself avoiding places that remind you of the
trauma?”
D. “Do you nd yourself easily startled?”
E. “Do you experience frequent nightmares?”
F. “How long has this been going on?”
37. A 15 y/o M is brought to the hospital after he engaged in self-injurious behavior.
On interview, he denies thoughts of suicide or any desire to die. Which of the
following patterns of self-injurious behavior would be most consistent with a
diagnosis of autism?
A. Cutting his abdomen with a kitchen knife with the stated purpose of
“destroying the alien evil within”
B. Hitting himself in the head repeatedly and not giving a verbal
response when asked why he is doing this
C. Banging his head against a wall while repeatedly yelling “I’m stupid,
I’m bad, I’m stupid, I’m bad” after hitting his sister during an
argument
D. Making repeated super cial cuts to his wrists after being told that he
is “ugly and worthless” by an ex-girlfriend
E. Using bleach to wash his hands after touching a bathroom door
handle
F. Injecting himself with a syringe containing water mixed with his own
feces and then calling 911
G. None of the above

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38. A 56 y/o M is arrested while following a young girl on her way home from school.
When he attempted to grab her by the arm on several occasions, she screamed. A
neighbor heard her cry and called the police. When the police arrived, he opened
his coat and exposed his naked body to them. When interviewed by the detective
assigned to the case, the patient acknowledges that his actions were wrong but
expresses no remorse for them. e patient’s wife arrives. She reports that over the
past year he has had multiple incidents, including being red from his work as an
office supplies salesman after he continued to take inventory home with him
despite multiple reprimands. Since he has been home, she has noticed him eating
out of the garbage can on several occasions. She denies any prior psychiatric
history or interactions with the legal system. Which of the following regions of his
brain is most likely to demonstrate pathology?
A. e amygdala
B. e temporal lobe
C. e anterior cingulate cortex
D. e endogenous opioid system
E. e pituitary gland
39. A 59 y/o F makes an appointment with a therapist to address feelings of
depression and loneliness. She reports a history of depression beginning in her
teenage years but has not been in any form of treatment for over 20 years. She says
that she regularly went to therapy in her 20s and 30s for “anger towards myself
and my family.” She has tried various medications for depression, none of which
had any positive effects. While she says that she’s not the “burning ball of rage”
that she was in her youth, she is still “angry at my family for betraying me, at my
friends for abandoning me, and at God for letting this all happen.” Her depression
is described as “this dull feeling, like I’m an empty shell of a person without a
purpose.” She denies changes in appetite or weight. She suffers from regular
periods of insomnia but generally gets 6 or 7 hours of sleep per night. She has had
three marriages, the longest of which lasted 3 years. She describes being in
“constant pain” from a variety of medical symptoms for which she has not found a
diagnosis. Her current list of specialists includes a rheumatologist and a
gastroenterologist. Which of the following is true of this patient’s condition?
A. It is likely to respond to electroconvulsive therapy
B. Psychotherapy is unlikely to help unless it is paired with medications
C. Medication treatment should consists of more than one drug at a
time
D. Cognitive behavioral therapy is the most helpful form of therapy
E. It has a high suicide rate
40. A 19 y/o M comes to see a psychiatrist requesting to be “put on antidepressants so
I don’t do anything bad.” He tells the psychiatrist that since graduating from high
school last year he has started to regularly see mental imagery of young girls. He
nds this imagery incredibly disturbing and says, “It doesn’t even make sense! I’m
not attracted to children!” Recently he has begun hearing voices whispering,
“Touch them!” when he sees a young girl. He also has begun only showering at
the gym, as when he showers at home he constantly worries that there is a naked
girl standing behind him. When told that this is impossible, he replies, “Well yes,
duh, I know that. But it’s still terrifying as hell.” He has done extensive reading

549
 online about the dulling effects that antidepressants have on sex drive and says, “I
need to start one right away at the highest dose. If I don’t start one, I don’t know
what I would do. I’ve thought about killing myself. It would be better than
molesting a child!” He denies spending time engaging in behavior related to these
thoughts “unless if you count doing everything I can to not be anywhere near a
school or daycare.” Which of the following interventions is most likely to reduce
his distress over the long-term?
A. Prescribing a serotonin reuptake inhibitor
B. Prescribing an antipsychotic
C. Prescribing both a serotonin reuptake inhibitor and an antipsychotic
D. Asking him to imagine being near young girls during a therapy
session
E. Asking him to look up pictures of young girls on the internet
F. None of the above
41. A 16 y/o M comes with his mother to a family therapy session. He is slightly
overweight for his age. His mother is concerned because he has started refusing to
eat dinner for the past two weeks. When asked, he says, “I don’t know, I’m not
hungry. And my stomach hurts a lot.” His mother responds, “Maybe it’s because
of all that crap you’re eating!” Turning to the therapist, she says, “Did I tell you he
ate both tubs of ice cream I brought home for the school social? ey weren’t even
in the house 24 hours and then I see them in the trash!” He yells, “Mom, shut
up!” e therapist asks to speak with the patient and his mother separately. When
speaking with the therapist alone, the mother says, “Recently I saw him sneaking
into my bathroom and looking through my medicine cabinet. Now all my laxatives
are missing.” When interviewed alone, the patient denies self-induced vomiting.
He says, “I told you. My stomach just hurts a lot so I don’t want to eat.” e
therapist notices the following marks on the patient’s right hand:

Which of the following is the most likely cause of his decreased food intake?
A. Oppositional de ant disorder
B. Bulimia nervosa
C. Binge eating disorder
D. Anorexia nervosa
E. Depression
F. Somatic symptom disorder
G. None of the above

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42. A 40 y/o M is seen by his primary care doctor for an annual physical. He is found
to be in good health with the exception of mildly elevated cholesterol levels. He is
in a long-term relationship and has two children. He works as a salesman at a
local sporting goods store. ere is no history of legal trouble. During the
interview, the doctor asks about substance use. He reports use of alcohol on a
weekly basis when with friends and cocaine around 2 or 3 times per year. He
denies a history of depression but reports difficulty falling asleep for an hour
around once per week. Family history is positive for alcohol abuse in his father
who died from liver failure in his 50s. Which of the following is the most likely
diagnosis?
A. Major depressive disorder
B. A substance-induced mood disorder
C. Alcohol addiction
D. Cocaine addiction
E. Addiction to both alcohol and cocaine
F. Idiopathic (primary) insomnia
G. None of the above
43. (Continued from previous question.) One month later, the patient is brought to
the hospital on a Saturday night by ambulance at around 2:00 in the morning. He
was at a night club when a re broke out and spread rapidly. He evacuated within
several minutes, but after leaving the building he began coughing continuously
and reporting shortness of breath, palpitations, and extreme dizziness. He stated,
“I feel like I’m going to die” several times on the way to the hospital. Upon
arriving at the hospital, he is very agitated and talks continuously. Laboratory tests
show a positive urine toxicology screen for cocaine and an elevated blood alcohol
level. Which of the following is the most likely diagnosis at this time?
A. Alcohol and cocaine use disorders
B. Post-traumatic stress disorder
C. Acute stress disorder
D. Substance-induced psychotic disorder
E. Panic attack
F. Panic disorder
G. None of the above
44. A 35 y/o F makes an appointment with a psychiatrist complaining of depression
for the past 6 months. She was encouraged to seek treatment by her sister who
recently started an antidepressant that “worked wonders” for her. e patient
initially went to see her primary care provider for this prescription but was told
that she was “not depressed” and that she would not be prescribed an
antidepressant. When asked, the patient reports that she has difficulty sleeping
several times per week, has not enjoyed being around friends as she usually does,
and often feels tired during the day. She denies feelings of guilt or hopelessness,
difficulty concentrating, changes in appetite, or thoughts of suicide. Her mental
status exam is notable for a dysthymic affect with a restricted range and lack of
prosody in her voice. No psychomotor retardation is noted. She denies use of
alcohol or other substances. She reports one prior episode of depression in her
early 30s which lasted 9 months; she saw a therapist at that time but did not nd
it very helpful and is not interested in therapy at this time. She says that normally

551
 she is a “fun, outgoing person.” She asks, “So I’m really hoping to get started on
something, as things have been really bad for me recently.” Which of the
following is the most appropriate response?
A. “You very likely have depression. Let’s talk about different treatment
options.”
B. “Your primary care provider is right: you don’t actually meet criteria
for major depressive disorder, so there is no role for treatment right
now.”
C. “You technically have adjustment disorder. I know you’re not keen on
therapy, but it’s really the best treatment for what you have.”
D. “I’m worried that you have bipolar disorder, so antidepressants are
more likely to harm than help in your case.”
E. “You have what is known as dysthymia. Let’s start an antidepressant.”
F. None of the above
45. A 30 y/o M is brought to the hospital by his wife who reports that he has been
“acting bizarrely” for the past week, including telling others that he is “covered in
all-seeing eyes” and that he is being followed by “the eye holders” who want to
capture and enslave him for his abilities. He has no prior psychiatric or medical
history and works at an art gallery downtown. He reports that for the past year he
has been smoking cannabis around 2 times per week “to enhance my artistic
abilities.” When using cannabis, he nds that colors are “brighter,” and recently
colors have started to “talk to me and tell me how they would like be used in a
painting.” During the interview, a nurse enters and tells the patient that he will
need to change into a hospital gown. He immediately becomes furious and yells,
“Shows don’t wear clothes!” and begins pounding on the walls of the room.
Security is called, and the patient is given an intramuscular antipsychotic. He is
hospitalized for four weeks and then referred to a psychiatrist for long-term
follow-up. Six months after his initial presentation, he has remained abstinent
from cannabis. However, he continues to state that “the walls talk to me” and that
he is being watched. Which of the following are the most accurate diagnoses at
the time of admission and discharge, respectively?
A. Brief psychotic disorder and schizophreniform disorder
B. Cannabis use disorder and schizophrenia
C. Substance-induced psychotic disorder and schizophrenia
D. Substance-induced mood disorder and bipolar disorder
E. Schizophrenia at both admission and discharge
F. None of the above
46. A 28 y/o M is brought to the hospital after he attempted to rob a bank using a
rearm. Security camera footage shows him repeatedly threatening a teller with
the gun before accidentally dropping it, at which point the gun res a bullet into
his foot, as seen below:

552
 e patient is taken to the operating room for surgical repair. Upon awakening from
anesthesia, he appears startled and attempts to nd ways of leaving the hospital.
However, police officers have been stationed outside of his room to place him under
arrest as soon as he is medically stabile. e on-call psychiatrist is asked to evaluate his
condition and determine whether he needs psychiatric hospitalization. On interview,
the patient expresses remorse for his actions but says that he “had no choice.” He says
that he needed to rob the bank to pay people who will “kill me without a second
thought if I don’t get them their money.” However, he refuses to identify these
individuals. e patient claims to have no prior medical, psychiatric, or criminal record
which is con rmed both by the police outside and later by the patient’s wife. His
mental status exam is generally within normal limits with the exception of an anxious
affect and an exaggerated startle response. His speech, thought content, thought
process, perceptions, and cognition are otherwise intact. Which of the following is the
most likely diagnosis?
A. A psychotic disorder
B. A psychopathic disorder
C. An externalizing disorder
D. An addictive disorder
E. A neurodevelopmental disorder
47. A 20 y/o F is brought to the hospital by her college roommate saying that she is
“acting completely crazy.” e patient is incredibly hostile and attempts to bite the
nurse bringing in her food tray. e on-call psychiatrist is consulted but is unable
to interview the patient, as she is sedated from the intramuscular medications that
were administered after the attempted attack. e psychiatrist instead speaks with
the patient’s roommate who has lived with her for the past two years. On
interview, the roommate describes that she is “a totally different person” from time
to time. She says further that the patient has “like three or four different
personalities—sometimes she’s super fun and outgoing, but other times she’s really
moody and hostile.” She says that she has looked into switching roommates on
multiple occasions, but due to a housing shortage on campus she has not been able
to. Which of the following questions would best discriminate between dissociative
identity disorder and bipolar disorder for this patient?
A. “How long do each of these personalities last?”

553
 B. “Is she ever seemingly both happy and sad at the same time?”
C. “Has she ever become so moody that she has attempted suicide?”
D. “Do you know if your roommate drinks alcohol, smokes marijuana,
or uses any other substances on a regular basis?”
E. “Do you know what medications your roommate takes?”
F. None of the above
48. An 81 y/o M is seen by his primary care provider. During the pre-visit assessment,
the patient registers a high score on the PHQ-9, a depression screening tool.
During the interview, the patient indicates that he has been drinking half a bottle
of wine each night for the past 5 years. When asked, the patient indicates that he
has felt depressed for several years. He denies a history of depression prior to the
age of 75 but says that “after my wife died, it’s like the oor fell out from under
me.” He is unaware of whether he began drinking before his mood symptoms
appeared or if his mood worsened after he began drinking. e patient also
indicates that he has difficulty sleeping through the night and often wakes up
feeling “very awake and anxious” around 3:00 in the morning. He is generally
unable to return to sleep, leaving him feeling tired most of the next day. As part of
routine screening for older adults, the primary care provider administers a
screening test for dementia on which the patient scores below the cut-off for
normal cognition. Which of the following is the best next step for management at
this time?
A. Prescribe a cholinesterase inhibitor to enhance memory
B. Prescribe uoxetine, an antidepressant that is highly energizing, to be
taken in the morning
C. Prescribe trazodone, an antidepressant that is highly sedating, to be
taken at night
D. Prescribe a benzodiazepine to help with sleep
E. Prescribe naltrexone to reduce the pleasurable effects of drinking
F. Refer to cognitive behavioral therapy for depression
G. Refer to cognitive behavioral therapy for insomnia
H. Refer to a substance rehabilitation program
I. Assess the patient’s readiness to change his pattern of drinking
J. Instruct the patient that his driver’s license will need to be revoked
49. (Continued from previous question.) e patient is very concerned after being told
that his driver’s license will be revoked, saying, “I can’t survive without my car.
How will I get around? I need to get my license back. I don’t care about anything
else. at’s my highest priority.” Which of the following is the next best step in
management?
A. Prescribe a cholinesterase inhibitor to enhance memory
B. Prescribe uoxetine, an antidepressant that is highly energizing, to be
taken in the morning
C. Prescribe trazodone, an antidepressant that is highly sedating, to be
taken at night
D. Prescribe a benzodiazepine to help with sleep
E. Prescribe naltrexone to reduce the pleasurable effects of drinking
F. Refer to cognitive behavioral therapy for depression
G. Refer to cognitive behavioral therapy for insomnia

554
 H. Refer to a substance rehabilitation program
I. Assess the patient’s readiness to change his pattern of drinking
50. A 31 y/o M makes an appointment with a psychiatrist but asks to be seen on the
ground oor of the building rather than in the psychiatrist’s usual office on the
third story. On interview, the patient thanks the psychiatrist for meeting him on
the ground oor, saying, “I don’t do elevators.” e patient denies a history of
panic-like responses around elevators. Instead, he says, “I just don’t trust things
like that, you know? So many ways for things to go badly in an elevator.” He
reports similar fears of vehicles and cooking appliances. He is currently living in
his parents’ house as he has been unable to nd a job, saying, “I want to do
something meaningful with my life, but I’m pretty sure I’ll screw it up if I’m
actually given something important to do.” He desires a romantic relationship as
well but is fearful that any girl is “only going to break my heart.” He describes a
constant sensation of being “on edge” and says that he has never been able to relax,
even when on vacation or spending time with friends. He says that this is a big
part of the reason that he feels socially isolated, as he was “always harassing my
friends about whether we should buy plane tickets now or wait until they come
down in price later or whether we should take that trip to San Francisco if a big
earthquake is probably going to hit soon.” Which of the following biological
markers is most likely to show abnormalities in this patient?
A. Levels of serotonin in the brain
B. Metabolism of the frontal and temporal lobes
C. Release of cortisol from the adrenal glands
D. Reactivity of the amygdala to fear-inducing stimuli
E. Resting signal-generating activity in the retinas
F. Receptivity of the insula to afferent nerve signals
51. A 30 y/o M is brought to the police station after he was found attempting to
break into the headquarters of the Central Intelligence Agency. He reports that he
is being followed by North Korean spies and needs to enter the building to “gather
splintelligence” so that he can ght back. He describes himself as “the only thing
standing between this country and all-out nuclear war” and demands to be let go.
He reports having “radio implants” in his ears that allow him to listen in on the
North Korean spies who “constantly talk about me.” He becomes incredibly
irritable when told that he cannot leave, yelling, “You bastards don’t get it! I’m the
key! Just put me in the lock and you’ll see!” He lacks identi cation of any kind,
and he appears disheveled and unkempt. Which of the following features
de nitively rules out a diagnosis of bipolar disorder with psychotic features in this
case?
A. His disheveled and unkempt appearance
B. His use of the word “splintelligence”
C. His rhyme between “key” and “see”
D. His belief that he is the only one who can save the world
E. His belief that he is being followed by spies
F. His irritability when he is blocked from his goals
G. His belief that he can listen in on North Korean spy communications
H. None of the above

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52. A 66 y/o F is diagnosed with multiple myeloma after experiencing several months
of bone pain in her spine and ribs. She is started on chemotherapy but still
experiences signi cant pain, so her oncologist prescribes her oxycodone (an
opioid). While this is initially effective at managing her pain, she now nds that
she is “sneaking” additional doses throughout the day to achieve the same level of
pain control. She often experiences a great deal of pain getting out of bed in the
morning and will often take an additional pill within 5 minutes of waking up. She
feels very guilty about this and has taken to hiding her prescriptions from her
daughter who normally helps with her medical care. Her oncologist notices that
she has been requesting early re lls from the pharmacy and calls her in for an
appointment. Which of the following is the best next step at this time?
 

A. Increase the dose of oxycodone

B. Maintain the same dose of oxycodone
C. Decrease the dose of oxycodone
D. Discontinue oxycodone
E. Refer to an addiction medicine clinic
F. More than one of the above
53. A 41 y/o M sees his psychiatrist for an evaluation. He has previously been
diagnosed with depression and is taking both uoxetine (an antidepressant) and
clonazepam (a benzodiazepine) prescribed by his primary medical doctor. Given
the risks of long-term benzodiazepine use, his psychiatrist discontinues
clonazepam. At a follow-up appointment one month later, the patient reports
persistent irritability, restlessness, insomnia, palpitations, and anxiety about most
things for the past month. He denies recent stressors or an episodic pattern to his
anxiety. Which of the following is the most likely diagnosis?
A. Generalized anxiety disorder
B. Panic disorder
C. Social anxiety disorder
D. Anxiety related to major depressive disorder
E. None of the above

556
1. e best answer is D. is mother is likely suffering from postpartum psychosis as
evidenced by her grandiose thought patterns and erratic behavior. Postpartum
psychosis often begins during the rst two weeks following delivery and is
considered to be a psychiatric emergency warranting immediate hospitalization
and treatment to protect both the mother and the child. Postpartum psychosis is
not a normal reaction to childbirth (answer E), and while medications will likely
be needed for treatment (answers A, B, and C), the immediate priority is to ensure
that both the patient and the child are in a safe and monitored environment.
(Chapter 6—Diagnosing Bipolar Disorders)
2. e best answer is H. is boy is presenting with symptoms of inattention and
hyperactivity that suggest a diagnosis of ADHD. However, it is very unusual for
ADHD to present with sudden onset or with the loss of previously learned
cognitive abilities like doing math (answers A, B, and C). Rett syndrome does
present with a loss of developmental milestones but is diagnosed almost exclusively
in girls (answer D). is patient has shown no behavior that is consistent with an
externalizing disorder (answers E and F) or the de cits in social communication
and restricted interests seen in autism (answer G). erefore, the best answer is
none of the above. (Chapter 19—Inattention and Hyperactivity Across the Lifespan)
3. e best answer is D. e presence of seizures, hyponatremia, white matter
changes on MRI, and hyperpigmentation of the oral mucosa are highly suggestive
of adrenoleukodystrophy, a condition that can sometimes be mistaken for ADHD
due to the presence of similar clinical features. Adrenoleukodystrophy is a highly
variable condition, with some people being completely asymptomatic and others
having very severe symptoms. It is an X-linked genetic disorder that is more
common in males (answer B). It is treatable, though not curable (answer A).
Unlike ADHD, it does not respond to stimulants (answer E). Asperger’s syndrome
was used to describe high-functioning cases of autism (answer C). (Chapter 17—
Intellectual Disability)
4. e best answer is F. While this patient shows some signs of depression (including
sleep changes, fatigue, poor concentration, and possibly psychomotor slowing), it
is notable that all of these symptoms are consistent with the effects of sleep
deprivation. In addition, the two most sensitive symptoms of depression
(depressed mood and anhedonia) are both absent. For this reason, a diagnosis of
either unipolar or bipolar depression is unlikely (answers A and B). While
dysthymia can similarly present with subsyndromal depressive symptoms, the lack
of cognitive features such as hopelessness or low self-esteem both argue against
this disorder (answer C). Adjustment disorder could be a reasonable diagnosis, but
there is no major recent change or stressor (answer D). Generalized anxiety
disorder can similarly present with difficulty sleeping, but there should be evidence
of excessive worrying in multiple areas of life (answer E). In the absence of any
other information, a primary sleep disorder such as idiopathic insomnia could be
entertained, although other causes of poor sleep such as obstructive sleep apnea
should be ruled out as well. (Chapter 23—Insomnia)
5. e best answer is C. Trichotillomania is considered to be a compulsive behavior
that is similar to obsessive-compulsive disorder in nature. In contrast, the other
behaviors listed are generally more impulsive in nature, including binge eating

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 (answer A), self-injurious behavior (answer B), addiction (answer D), and
externalization (answer E), which would all be more common in someone with
high impulsivity. (Chapter 10—Diagnosing Obsessive-Compulsive Disorders)
6. e best answer is B. is patient shows signs of having unusual beliefs and makes
odd associations between thoughts and ideas. However, he does not show signs of
psychosis as evidenced by a lack of delusions, auditory hallucinations, and
disorganized behavior or speech which together argue against a diagnosis of
schizophrenia at this time (answer A). e most likely diagnosis is schizotypal
personality disorder which is considered to be on a similar spectrum to
schizophrenia, as people with the disorder are at higher risk of developing it
(answer C). e presence of these unusual beliefs as well as a desire for social
companionship both argue against schizoid personality disorder (answer D).
While there is an element of paranoia to some of what he says, someone with
paranoid personality disorder would likely be more mistrustful and wouldn’t have
the same degree of odd beliefs present (answer E). Finally, it is worth considering
whether the patient has a disorder at all as he appears generally satis ed with his
life; however, the fact that he has been red from jobs and appears to not be living
up to his potential due to his beliefs argues against complete normalcy (answer F).
(Chapter 12—Cluster A Personality Disorders)
7. e best answer is I. Anorexia nervosa has the highest mortality rate of any single
psychiatric condition at 20%. (Chapter 16—Anorexia Nervosa)
8. e best answer is B. ere are many signs that point to malingering in this case,
including a presentation that does not match known causes of memory loss,
reported de cits that are severely out of proportion to what is normally seen in
similar cases, the possibility of nancial gain from having a more severe illness, and
resistance to considering other consequences of having the disorder such as one’s
license being taken away. However, even in cases where there is a high degree of
suspicion for malingering, it remains a diagnosis of exclusion. erefore, it would
be inappropriate to respond as if the patient were de nitively malingering until a
complete work-up had been completed (answers D and E). However, ordering a
CT scan is likely unnecessary at this time and risks exposing the patient to
unnecessary ionizing radiation (remember to “Do no harm”) (answer C). Finally,
diagnosing a neurocognitive disorder should not be done until there is additional
evidence of a primary neurologic cause, especially with such a high chance of
malingering in this case (answer A). (Chapter 15—Diagnosing Somatoform
Disorders and Chapter 22—Differential Diagnosis of Dementia)
9. e best answer is E. is case describes a typical presentation of psychotic
symptoms in a patient with borderline personality disorder as evidenced by the
presence of affective instability, hostility, chronic dysphoria (rather than episodic
depression), somatoform complaints, and dysfunction beginning in adolescence.
ere is possibly an element of factitious disorder as well, as the patient may be
fabricating psychotic symptoms to appear more ill and therefore warrant
hospitalization. Cases of borderline personality disorder are more common in
people with a history of abuse. While she would be unusually young to develop
schizophrenia, the phenomenology of her auditory hallucinations is inconsistent
with primary psychosis (answer A). Schizoaffective disorder is a rare diagnosis that
bridges psychotic and mood disorders, but it is unlikely to be the diagnosis here

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 (answer B). Depression with psychotic features responds well to a combination of
antidepressants and antipsychotics, but the non-episodic pattern of her mood
symptoms argues against this diagnosis (answer C). Finally, while some degree of
dysfunction related to borderline personality disorder is likely to persist across the
lifespan, it is generally considered to have a good prognosis after early adulthood
with a gradual lessening of symptoms (answer D). (Chapter 7—Differential
Diagnosis of Psychotic Disorders and Chapter 13—Differential Diagnosis of Borderline
Personality)
10. e best answer is C. is vignette describes a case of acetaminophen poisoning
in a patient with suicidal ideation. Acetaminophen is often used for intentional
overdoses due to its easy availability as an over-the-counter drug. Cases of
acetaminophen poisoning are not always immediately obvious, as signs and
symptoms are often not seen for up to 72 hours after ingestion. at is why it is
essential to have a high index of suspicion for occult overdoses in patients
presenting with suicidal ideation. It is tempting to think that alcohol withdrawal
could account for his symptoms, especially considering that alcohol can cause liver
damage and a withdrawal state that begins in the same time period (24 to 72
hours after ingestion). However, it is rare for alcohol withdrawal to cause
fulminant hepatic failure, especially in a young patient (answer B). Being seen by
the physician within one hour of arriving at the hospital would not have made a
difference here as the physician did not screen for this (answer A), although
having seen a different physician may have. Adequate hydration is unrelated to
treatment for acetaminophen overdose (answer D). (Chapter 4—Suicide)
11. e best answer is E. For major medical and surgical interventions like a liver
transplantation, a capacity evaluation is warranted. However, it is clear from the
vignette that this patient is not able to meaningfully communicate, so it is already
impossible to determine his level of capacity (answer A). In cases where a patient
lacks capacity, the next step is to locate a surrogate decision maker, which in this
case would likely be the parents. However, the parents should be asked to make a
decision as the patient would have, not based on their own belief systems (answer
B). Determining the psychiatric diagnosis is not a priority in an emergent
situation like this (answer C). A liver transplantation is often required for survival,
and canceling it on the basis of the patient lacking capacity would be grossly
unethical (answer D). (Chapter 4—Delirium)
12. e best answer is G. is patient is experiencing a panic attack in response to a
speci c stimulus. However, a single panic attack is insufficient for a diagnosis of
panic disorder, as panic disorder involves sudden, unexpected, repeated panic
attacks that give rise to dysfunction in one’s life (answer D). It is more likely that
this girl has a speci c phobia of needles. She would not be diagnosed with a
traumatic disorder as the stimulus was not a life-threatening or extremely violent
event (answers A or B). While she experienced distinct sensations of both
depersonalization and derealization, the fact that these have only occurred in the
setting of a panic attack rules out depersonalization-derealization disorder, as the
dissociative symptoms must be severe and persistent (answer F). ere is no
evidence of either obsessions or compulsions (answer C), nor is there evidence of
amnesia at this time (answer E). (Chapter 9—Diagnosing Anxiety Disorders and
Chapter 14—Diagnosing Dissociative Disorders)

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13. e best answer is A. is patient has many features consistent with a diagnosis of
atypical depression, including the presence of depressed mood with preserved
mood reactivity, high interpersonal rejection sensitivity, hypersomnia, and
hyperphagia. She is also in her early 30s which is around the average age of onset
for episodic depression. erefore, the best treatment at this time would be an
antidepressant and/or psychotherapy. A stimulant would likely only help with
symptoms rather than treating the underlying cause (answer E). While atypical
depression has many features that overlap with borderline personality disorder, the
later age of onset and lack of other features of the disorder argue against that
diagnosis (answer B). e interpersonal rejection sensitivity seen in atypical
depression can also resemble social anxiety, but the presence of additional features
such as hyperphagia and hypersomnia are unaccounted for by a diagnosis of only
social anxiety disorder (answer C). Finally, bulimia is ruled out by the lack of
binge eating episodes which are a prerequisite for this diagnosis (answer D).
(Chapter 5—Diagnosing Depressive Disorders)
14. e best answer is A. is is a case of probable child abuse as evidenced by the
appearance of bruising in an unexposed area that is unlikely to be injured on
accident as well as the father’s denial and inconsistent responses. e effect of
trauma on children is different compared to adults, with children under the age of
10 being very unlikely to develop the same signs and symptoms of PTSD that are
seen in adults (answer B). Instead, the most common immediate response to
childhood trauma is an internalizing disorder such as social anxiety disorder. e
fact that anxiety disorders generally begin during childhood and are the single
most common form of psychiatric condition (giving them a high base rate in the
general population) also argue for social anxiety disorder being the most likely
diagnosis (although it’s important to keep in mind that it is very possible that,
despite her exposure to abuse, she has not developed any form of psychiatric
pathology). Externalizing disorders are associated with neglect more than abuse
and are more common in boys than girls (answer C). Borderline personality
disorder and dissociative identity disorder are both associated with a history of
trauma as a child. However, these disorders do not tend to develop until
adolescence or young adulthood, making them unlikely to be present at this time
(answers D and E). (Chapter 11—Traumatic Disorders Across e Lifespan)
15. e best answer is E. e symptoms described in this case, including muscle
tension, restlessness, fatigue, insomnia, and inattention, are consistent with
overactivation of the HPA axis which is commonly seen in people who have
experienced childhood abuse. Abnormalities of the HPA axis are seen in a variety
of psychiatric disorders, all of which this patient is at increased risk for including
generalized anxiety disorder (answer A), depression (answer B), dysthymia
(answer C), and nightmare disorder (answer D). In contrast, histrionic personality
disorder does not have this same association with an abnormal HPA axis and is
notably the only cluster B personality disorder that does not have an association
with a history of abuse. (Chapter 9—Signs and Symptoms of Anxiety and Chapter 12
—Cluster B Personality Disorders)
16. e best answer is E. is case describes a patient with classic symptoms of mania
including increased goal-directed activity, distractibility, impulsivity, grandiosity,
and talkativeness. In addition, a previous suicide attempt suggests a history of

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 depression which is commonly seen in people with bipolar I disorder. is case is
complicated by the presence of substance abuse, and it is possible that his initial
presenting symptoms were at least partially related to substance use. However, the
persistence of these symptoms long after the effects of these drugs would have
worn off argues against substance use disorders being a primary (rather than
secondary) cause of his condition (answer F). While there are narcissistic elements
to his goals, it is unclear that these would persist in the absence of this mood
episode, so narcissistic personality disorder should not be diagnosed at this time
(answer A). While there is a high degree of recklessness to his behavior that could
endanger others, this does not appear to be his primary goal; in combination with
a lack of previous violent crimes, this argues against antisocial personality disorder
(answers B and C). Hyperactivity must be demonstrated outside of a current
mood episode for a diagnosis of ADHD (answer G). Finally, while he has
grandiose delusions and some degree of disorganized behavior, he lacks other
symptoms of a primary psychotic disorder like schizophrenia (answer D). (Chapter
6—Differential Diagnosis of Bipolar Disorders and Chapter 8—Differential Diagnosis
of Addictive Disorders)
17. e best answer is D. is describes a case of Prader-Willi syndrome, a genetic
condition characterized by an insatiable sense of hunger that leads to excessive
food intake. In severe cases, this behavior can directly lead to gastric rupture and
necrosis, as occurred here. Prader-Willi syndrome is caused by the deletion of a
normally active paternal allele. Angelman syndrome is caused by a similar deletion
of a maternal allele but presents with completely different symptoms (answer E).
e early onset of symptoms and the co-occurrence of receptive and expressive
language de cits both argue against binge eating disorder or bulimia, and it is rare
for binges related to an eating disorder to be so excessive that they cause gastric
perforation (answers A and B). Neither Down syndrome nor William syndrome
are related to excessive food intake (answers C and F). (Chapter 17—Intellectual
Disability)
 

18. e best answer is A. is describes a case of dependent personality disorder as

evidenced by her extremely deferential nature towards her husband in multiple
areas of life which directly results in distress and dysfunction. Dependent
personality disorder involves an extreme and in exible level of agreeableness,
which is a core personality trait that may not change over time (answer B) even
with use of medications or psychotherapy (answers C and D). ere is no evidence
that dependent personality disorder is related to dysregulation of the sympathetic
nervous system (answer E). (Chapter 12—Cluster C Personality Disorders)
19. e best answer is G. is patient presents with several changes in personality,
cognition, and level of functioning that are immediately concerning for some form
of dementia. However, the presence of speci c neurologic ndings including an
abnormal gait, a at affect (the highly characteristic “mask-like” face), absent
prosody, and a unilateral resting tremor all strongly suggest Parkinson’s disease
over and above other causes of dementia (answers A through F, H, I, and J).
(Chapter 22—Differential Diagnosis of Dementia)

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20. e best answer is C. Rigid behaviors can be seen in a variety of psychiatric
conditions, including OCD, obsessive-compulsive personality disorder, autism,
and anorexia. In this case, the patient’s rigid behavior involves limited food
preferences occurring in the context of restricted interests in microbiology and
bacteria. ere is also evidence of poor language structure, minimal eye contact,
and abnormal social interactions with the pediatrician, all of which together argue
for a diagnosis of autism. While it would be unusual for OCD to start so young, it
is not unheard of. However, the patient does not report any obsessional thoughts
that directly lead to his behaviors which makes OCD less likely (although his
verbal de cits it is hard to say with certainty). In addition, the belief appears to be
ego-syntonic rather than ego-dystonic (answer A). Obsessive-compulsive
personality disorder would result in rigid behaviors done because it is more moral
or ethically correct (answer B). ere is no evidence that the patient is avoiding
food due to a distorted body image, and his caloric intake appears to remain the
same (answer E). Finally, there is no evidence of intellectual disability, as the
patient’s de cient grammar is more likely explained by a diagnosis of autism
(answer D). (Chapter 18—Signs and Symptoms of Autism)
21. e best answer is G. is patient is presenting with externalizing behaviors and
psychotic symptoms that have begun in the past 3 days. While this sudden onset
is itself unusual, there are a variety of signs and symptoms that are highly
concerning for a medical etiology of her condition, including a recent u-like
illness, the presence of tardive dyskinesia in a patient who has no prior psychiatric
history, and signs of autonomic dysfunction including sweating and urinating on
herself. is combination is highly suggestive of anti-NMDA receptor
encephalitis, a condition that can strongly mimic cases of primary psychosis. In
some cases, the condition is associated with ovarian teratomas in which case
surgical removal of the tumor will result in rapid improvement of symptoms.
While it is not yet certain that she has an ovarian teratoma, compared to the other
treatment options (all of which have virtually zero chance of working) surgical
intervention is the most likely to result in a change in her behavior even if we
cannot yet say that it will de nitively do so. Remember to consider anti-NMDA
receptor encephalitis when a young patient presents with sudden onset of
psychotic symptoms with no prior psychiatric history, especially when features of
autonomic or neurologic dysfunction are present. (Chapter 7—Differential
Diagnosis of Psychotic Disorders)
22. e best answer is F. A substance history, physical exam, and review of systems
should be part of every psychiatric evaluation (answers A, C, and D). A substance
history in particular can elucidate patterns of caffeine and/or alcohol intake that
could be interfering with a normal sleep schedule. Vital signs are not required for
every psychiatric evaluation. However, in the context of someone with an eating
disorder and possible obstructive sleep apnea, they can help to diagnose comorbid
conditions (such as hypertension) that may be related to the problem (answer E).
A sleep study is not required at every psychiatric evaluation, but for someone who
is obese, male, and complains of feeling tired all the time, the clinical suspicion is
high enough to warrant one (answer B). (Chapter 3— e Psychiatric Interview and
Chapter 23—Insomnia)

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23. e best answer is D. Parasomnias (including “sleep-eating”) are a known side
effect of Z-drugs like zolpidem, and the emergence of this behavior soon after
starting this medication strongly argues for a substance-induced parasomnia.
While most parasomnias are idiopathic, the timing argues against that in this case
(answer C). It is possible that the patient has experienced a recurrence of binge
eating disorder, but in the context of the behavior only happening at night this is
less likely (answers A and B). (Chapter 23—Other Sleep Disorders)
24. e best answer is E. It can be difficult to detect cases of dementia in someone
with an existing intellectual disability due to the presence of cognitive de cits at
baseline. However, it can usually be detected based on reports of changes in
personality and ability to do things that one normally could (in this case, things
like recognizing his sister or painting pictures). Over half of people with Down
syndrome will develop Alzheimer’s disease during their lifetime. As with all cases
of Alzheimer’s disease, the onset of the disorder portends a poor prognosis. While
not engaging in one’s usual hobbies can be a sign of depression, in the context of
other signs such as urinary incontinence it is less likely (answer B). An infection
could account for the incontinence, but it is unlikely to have persisted for several
months without other signs of infection (answer C). Cognitive testing is helpful
for diagnosing cases of dementia in an otherwise healthy population, but for
someone with an intellectual disability it is unlikely to be revealing (answer D).
Finally, dismissing a caregiver’s observations is completely unwarranted and risks
ignoring the most important source of information available (answer A). (Chapter
17—Intellectual Disability and Chapter 22—Alzheimer’s Disease Across the Lifespan)
25. e best answer is D. is patient is showing signs of multiple neurologic de cits
(including mutism and bilateral extremity weakness) following a major
psychosocial stressor, which is strongly suggestive of conversion disorder. In
addition, thus far all objective tests of neurologic disease are negative, further
supporting the diagnosis. e patient’s mutism could be related to catatonia, but
in the absence of other signs such as muscular rigidity, waxy exibility, or
negativism, this is less likely (answer A). Selective mutism is an extreme variant of
social anxiety disorder and is typically chronic rather than sudden onset (answer
B). Both hypochondriasis and somatic symptom disorder present with concern
about symptoms rather than neurologic signs (answers C and E). Finally, there is no
evidence that the patient is intentionally fabricating these de cits as would be seen
in factitious disorder and malingering, although these cannot be ruled out
de nitively (answer F and G). (Chapter 15—Diagnosing Somatoform Disorders)
26. e best answer is A. Conversion disorder is a diagnosis with a relatively good
prognosis, with most patients showing resolution of their neurologic de cits by
the time of discharge (although a quarter will have a recurrence within one year).
However, because conversion disorder is a diagnosis of exclusion, it should never
be given to anyone with absolute certainty, as a medical or neurologic cause is
eventually found in up to a third of all cases (answer C). Long-term care will
likely involve a psychiatrist, not a neurologist (answer D). Finally, it is
inappropriate to assume that the patient is fabricating his condition or to imply
that to others (answer B). (Chapter 15—Diagnosing Somatoform Disorders)
27. e best answer is B. is patient is experiencing a mixed state. While she
endorses depressive symptoms including guilt, hopelessness, and depressed mood,

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 she also reports symptoms of mania including increased goal-directed activity and
a lack of need for sleep. is combination of both depressive and manic symptoms
simultaneously should be re-diagnosed as bipolar disorder rather than continuing
her previous diagnosis of unipolar depression (answer A). ere is no evidence of
psychotic symptoms, ruling out schizoaffective disorder (answers C and D). A
mixed state is a very high-risk time and rules out subsyndromal disorders such as
dysthymia and cyclothymia (answers E and F). Finally, there is no evidence of
affective lability or a strong interpersonal aspect to her current presentation,
arguing against borderline personality disorder (answer G). (Chapter 6—
Diagnosing Bipolar Disorders)
28. e best answer is A. While this patient reports depressive symptoms including
anhedonia, all of them overlap with the standard symptoms of schizophrenia,
making a separate diagnosis of major depressive disorder (with or without
psychotic features) unnecessary (answers C, D, and E). ere is no history of
depressive symptoms prior to the onset of schizophrenia, making the depressive
type of schizoaffective disorder an unlikely diagnosis (answer B). (Chapter 7—
Differential Diagnosis of Psychotic Disorders)
29. e best answer is E. is patient is describing chronic and severe feelings of
depersonalization which along with a history of trauma best t a diagnosis of
depersonalization-derealization disorder. While the patient’s reported beliefs may
sound odd to most people, they are notably ego-dystonic as he recognizes that
they sound strange, which argues against a diagnosis of a primary psychotic
disorder (answers A and B) or schizotypal personality disorder (answer F). A
recurrent ego-dystonic belief brings to mind OCD, although there is no pattern of
overactive error recognition to his beliefs (answer D). While the patient reports
some degree of social anxiety, his symptoms are pronounced enough that they
extend far beyond “just” social anxiety disorder (answer C). While the patient
avoids others, he appears to desire companionship on some level as evidenced by
the fact that he continues to reach out to old friends (answer G). (Chapter 14—
Diagnosing Dissociative Disorders)
30. e best answer is C. People with borderline personality disorder often have
multiple psychiatric comorbidities. is makes prioritizing an essential part of
treatment for these patients as it is generally not possible to meaningfully engage
in treatment for all of these disorders at the same time (answer F). As a general
rule of thumb, treatment of borderline personality disorder should take priority
over other conditions such as depression, anxiety disorders, and PTSD (answers
A, D, and E), as leaving borderline personality disorder unaddressed tends to
worsen treatment outcomes for the other disorders. e primary exceptions to this
are active substance use, severe mania, and a severe eating disorder all of which
either represent a more immediate threat to health or would interfere with their
ability to be treated for their other disorders (answer B). Out of these, this patient
only has a current opioid use disorder, so this should be addressed rst. (Chapter
13—Borderline Personality Across the Lifespan)
31. e best answer is B. is patient is exhibiting classic signs of catatonia including
mutism, echopraxia, and catalepsy. While no additional history is available, in any
given population bipolar disorder is the most common cause of catatonia and
accounts for over half of all cases, with depression and schizophrenia accounting

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 for a third and 15%, respectively (answers A and C). While there are some
neurologic de cits observed including mutism, it is not clear that the patient is
suffering from conversion disorder, and the presence of signs speci c to catatonia
argues for this as the better explanation (answer D). Both factitious disorder and
malingering are diagnoses of exclusion and should not be diagnosed in the
presence of clear signs of another disorder (answers E and F). (Chapter 4—
Catatonia)
32. e best answer is F. is patient lacks evidence of signi cant pathology on
mental status exam. e lack of auditory hallucinations or disorganized thought
process makes schizophrenia unlikely (answer A), while his intact mood and sleep
patterns argue against a diagnosis of a mood disorder (answers D and E). His
wife’s comment that “he has never been like this before” strongly suggest against a
diagnosis of paranoid personality disorder which is characterized by a life-long
pattern of paranoia resulting in dysfunction (answer C). is leaves delusional
disorder (answer B) as the most likely diagnosis. However, while the patient is
experiencing occupational dysfunction as a result of his belief, it is not clear that
his belief is a delusion, as it is notably non-bizarre and cannot be assumed to be
false. In fact, there have been cases similar to this where whistleblowers have been
accused of being psychiatrically ill when attempting to call attention to unfair
practices. While it is certainly possible that this patient’s beliefs are false, there is
insufficient evidence to diagnose a delusional disorder at this time. (Chapter 7—
Diagnosing Psychotic Disorders)
33. e best answer is F. is vignette describes a case of an arrhythmia (in this case,
supraventricular tachycardia) whose symptoms strongly resemble those of a panic
attack. It is notable that at no point in this vignette does the patient receive a
medical work-up for her symptoms. If she had, her doctors may have discovered
speci c abnormalities on electrocardiogram that would have alerted them to the
presence of an arrhythmia. is reinforces the fact that panic attacks are a
diagnosis of exclusion, as a medical cause for the symptoms must be ruled out
(answers A and B). e patient’s symptoms of anxiety are episodic rather than
persistent, ruling out generalized anxiety disorder (answer C). While she shows
concern about her symptoms, this is a normal and reasonable response to her
experiences (answers D and E). (Chapter 9—Differential Diagnosis of Anxiety
Disorders)
34. e best answer is A. Palpitations, or the sense that one can hear their own
heartbeat, is a form of interoception which is largely processed in the insula.
While hyperactive signaling in the insula is believed to underlie psychiatric
disorders related to somatization, interoception is ultimately a helpful function (in
this case, it has allowed this person to recognize that there is a problem and seek
medical help). e anterior cingulate cortex is involved in interpreting an
interoceptive signal as representing an error, not in recognizing it initially (answer
B). e orbitofrontal cortex is most implicated in mood disorders while the medial
prefrontal cortex and hippocampus are implicated in PTSD (answers C, D, and
E). (Chapter 15—Mechanisms of Somatization)
35. e best answer is A. is patient is most likely suffering from dementia with
Lewy bodies as evidenced by the uctuating pattern of his cognitive impairments,
his sensitivity to antipsychotic medications, and his likely visual hallucinations as

565
 he has been observed talking to unseen objects. Antipsychotics should generally be
avoided for people with dementia with Lewy bodies, so continuing or increasing
the dose of risperidone would not be appropriate (answers B and C). Simply
adding a cholinesterase inhibitor without stopping risperidone would also not
resolve the problem (answer D). (Chapter 22—Diagnosing Dementia)
36. e best answer is A. When concerned about malingering, the best approach is to
use open-ended questions whenever possible. Asking questions about speci c
symptoms may inadvertently provide information on what symptoms are most
salient to the interviewer (answers B, C, D, and E). Asking about the duration of
symptoms does not necessarily do this, but in general closed-ended questions are
less preferable than open-ended ones (answer F). (Chapter 3— e Psychiatric
Interview and Chapter 11—Differential Diagnosis of Traumatic Disorders)
37. e best answer is B. While non-suicidal self-injurious behavior is most often
associated with borderline personality disorder, it is found across many different
psychiatric conditions and is not speci c to any one disorder. People with autism
or intellectual disabilities will often engage in self-injurious behavior without a
discernable purpose, especially in cases where the patient is non-verbal. Cutting
one’s abdomen in response to a bizarre delusion is more consistent with
schizophrenia (answer A), punishing one’s self after impulsive misbehavior is more
consistent with an externalizing disorder (answer C), making super cial cuts after
an interpersonal rejection is more consistent with borderline personality disorder
(answer D), using bleach to calm a contamination obsession is more consistent
with OCD (answer E), and intentionally inducing an illness is more consistent
with factitious disorder (answer F). (Chapter 18—Signs and Symptoms of Autism)
38. e best answer is B. is patient has likely developed frontotemporal dementia
as evidenced by his disinhibited sexual behavior, change in eating habits, and poor
impulse control. e onset of symptoms in his late 50s is also highly suggestive of
this disease. As the name implies, frontotemporal dementia is associated with
hypometabolism in both the frontal and temporal lobes of the brain. Abnormal
emotional processing in the amygdala is associated with psychopathic traits.
However, despite his recent remorseless antisocial behavior, the lack of any prior
history strongly argues against this diagnosis (answer A). e anterior cingulate
cortex is involved in processing error recognition in OCD and somatization and
would not be expected to be involved here (answer C). e endogenous opioid
system is likely dysregulated in borderline personality disorder and other cluster B
disorders, not frontotemporal dementia (answer D). Finally, the pituitary gland is
part of the HPA axis which is implicated in a variety of internalizing disorders; it
is also unlikely to be involved in this case (answer E). (Chapter 22—Diagnosing
Dementia)
39. e best answer is E. is vignette describes a case of borderline personality
disorder in an older adult as evidenced by the presence of chronic dysphoria,
persistent anger, relationship dysfunction, likely somatization, and a poor sense of
identity. While she denies the dramatic symptoms of borderline personality
disorder such as self-harm, impulsivity, and psychosis-like symptoms, this is
consistent with the idea that these symptoms often remit with age while these
other symptoms tend to remain. Borderline personality disorder is associated with
a high suicide rate on par with mood disorders like depression and bipolar

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 disorder. While ECT is an effective treatment for treatment-refractory depression,
there is no evidence that it is helpful for chronic dysphoria related to borderline
personality disorder (answer A). Medications should play a limited role in treating
borderline personality disorder due to a lack of efficacy (answers B and C). ere
is little evidence supporting the use of CBT in borderline personality disorder
(answer D). Instead, other forms of therapy such as dialectical behavior therapy
and mentalization-based treatment have the most evidence. (Chapter 13—
Borderline Personality Across the Lifespan)
40. e best answer is D. is vignette describes a case of purely obsessional OCD as
evidenced by this patient’s recurrent, distressing, and intrusive ego-dystonic
thoughts about wanting to molest young girls. Purely obsessional OCD is notably
harder to treat compared to “textbook” OCD. However, for both forms of OCD,
exposure and response prevention remains the gold standard of treatment. In cases
like this where exposure to the feared stimulus is immoral or illegal, asking the
patient to imagine scenarios during therapy allows them to be exposed to
situations that cannot be experienced through traditional exposure and response
prevention. While antidepressants are also effective at treating OCD, they are less
effective than exposure and response prevention, so they should not be the rst-
line treatment if only one can be pursued (answer A). Despite the presence of
psychotic-sounding symptoms including auditory hallucinations, these thoughts
are notably ego-dystonic and are recognized as coming from within the patient’s
own mind, making them more consistent with OCD than with any kind of
psychotic disorder that would warrant use of an antipsychotic (answers B and C).
Asking the patient to do an illegal and immoral activity is not appropriate (answer
E). (Chapter 10—Obsessions and Compulsions Across the Lifespan)
41. e best answer is B. is patient’s food intake appears to follow the pattern of
bulimia, including binge eating episodes and purging with the use of laxatives.
While bulimia is uncommon in males, it is not unheard of. It is likely that he is
self-inducing vomiting as well given the lacerations on his knuckles which can be
caused by the skin brushing against the teeth when activating the gag re ex
(sometimes known as Russell's sign). If the patient were not engaging in purging
efforts, he would instead likely be diagnosed with binge eating disorder (answer
C). As he is overweight, it is impossible to determine whether he suffers from
anorexia which relies upon the presence of a distorted body image (answer D).
While it is possible that the patient’s stomach pain is related to either a
somatoform disorder (answer F) or a medical condition (answer G), the presence
of both bingeing and purging behaviors provides a better explanation. If the pain
persists after these behaviors have stopped, then these disorders should be
considered. While decreased food intake can often be seen in depression, there is
not enough additional evidence of this disorder for it to be diagnosed (answer E).
Finally, arguing with one’s parents as a teenager is not evidence of oppositional
de ant disorder (answer A). (Chapter 16—Bulimia Nervosa)
42. e best answer is G. Based on the vignette, there is no evidence of psychiatric
pathology in this patient. While he admits to use of alcohol, this appears to be
culturally normal (answers C and E). While cocaine use is illegal, he does not
appear to have suffered signi cant personal consequences as a result of use, and
having negative repercussions is a required component for diagnosing addiction

567
 (answer D). He denies depression or any mood symptoms (answers A and B).
Finally, while he reports difficulty sleeping once per week, this is also common in
the general population and should not be diagnosed as pathological (answer F).
(Chapter 2—Normal Versus Abnormal, Chapter 8—Signs and Symptoms of Addiction,
and Chapter 23—Insomnia)
43. e best answer is G. As before, there is no evidence of psychiatric pathology in
this case, as the patient’s reaction to a life-threatening situation is completely
within the realm of normalcy, ruling out both acute stress disorder and PTSD
(answers B and C). While he reports symptoms consistent with a panic attack,
these same symptoms could also be accounted for by smoke inhalation (answers E
and F). While he was using substances at the time of the incident, they do not
appear to have directly resulted in negative repercussions, as he would have been
exposed to this event whether he was using substances or not (answer A). Finally,
there is no evidence of psychotic symptoms at this time (answer D). (Chapter 2—
Normal Versus Abnormal, Chapter 8—Signs and Symptoms of Addiction, and Chapter
11—Differential Diagnosis of Traumatic Disorders)
44. e best answer is A. is case illustrates the pitfalls of relying too strictly on
diagnostic criteria when approaching patient care. While this patient technically
does not meet DSM-5 criteria for major depressive disorder (she has only 4
symptoms instead of the required 5), she ts the pattern of depression in every
other way. She should therefore be offered treatment in the form that she desires,
as not offering treatment based on a rigid reliance upon diagnostic criteria is
confusing the criteria for the actual disorder (akin to mistaking the map of an area
for the terrain itself ) (answer B). It may be tempting to diagnose a different
disorder that also features subsyndromal symptoms of depression such as
adjustment disorder or dysthymia, but the lack of a major life stressor rules out the
former (answer C) while the presence of euthymia between episodes rules out the
latter (answer E). While we cannot say for sure that the patient does not have
bipolar disorder, there is no evidence of it at this time (answer D). (Chapter 2— e
DSM and Chapter 5—Diagnosing Depressive Disorders)
45. e best answer is C. At the time of initial presentation, this patient is best
classi ed as having a substance-induced psychotic disorder related to cannabis, as
diagnostically it is impossible to tell whether he has a primary psychotic disorder
until he has been abstinent from cannabis and other substances long enough for
their effects to have worn off. However, after six months it is clear that his
psychotic symptoms have remained even in the absence of cannabis use, so a
diagnosis of schizophrenia is more appropriate. It would not be appropriate to
diagnose a primary psychotic disorder at the time of admission in the context of
using a substance that can induce psychosis in some people who take it (answers A
and E). While the patient is experiencing negative repercussions as a result of
cannabis use, he was able to stop his use of the substance. Only if he had been
unable to quit using cannabis despite having experienced negative repercussions
would cannabis addiction be diagnosed (answer B). Finally, the symptoms
described in this case are more consistent with a psychotic disorder than a mood
disorder (answer D). (Chapter 7—Differential Diagnosis of Psychotic Disorders and
Chapter 8—Signs and Symptoms of Addiction)

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46. e best answer is D. is patient presents to the hospital after attempting to
engage in instrumental violence. Instrumental violence is more often associated
with psychopathy than an externalizing disorder, which is instead characterized by
reactive violence in response to negative emotions (answer C). However, the
patient’s stated remorse and his lack of psychiatric or legal history prior to this
incident strongly argue against psychopathy (answer B). It is notable that the
patient’s mental status exam is almost entirely normal which strongly argues
against a psychotic disorder (answer A). ere is no evidence of either autism or
intellectual disability for this patient. While ADHD is also a neurodevelopmental
disorder, misbehavior associated with this condition is generally impulsive rather
than instrumental as was the case here (answer E). erefore, the most likely
explanation is that what the patient is saying is true, which may be related to an
addictive disorder such as gambling disorder. Addictive disorders should be
considered whenever there is no evidence of overt pathology on the mental status
exam. (Chapter 8—Diagnostic Addictive Disorders)
47. e best answer is A. e mood states seen in bipolar disorder can sometimes be
so extreme that it appears to others that one’s core personality has changed to a
completely different person. A key differentiating factor is the frequency at which
these changes occur, as the mood states seen in bipolar disorder tend to last for
weeks or months while the identity states in dissociative identity disorder can
change in a matter of minutes, hours, or days. Suicide is found in both bipolar
disorder and dissociative identity disorder and does not reliably distinguish
between them (answer C). Features of both happiness and sadness at the same
time can either represent a mixed state due to bipolar disorder or the extreme
affective instability seen in many cases of borderline personality disorder, which is
frequently comorbid with dissociative identity disorder (answer B). While
knowing the substance history is incredibly helpful for assessment, it would not
distinguish between bipolar disorder and dissociative identity disorder in this case
(answer D). Finally, because both bipolar disorder and dissociative identity
disorder are frequently misdiagnosed and improperly treated, it would be unwise
to rely too strongly on the medication history for differentiating between these
two conditions (answer E). (Chapter 14—Differential Diagnosis of Dissociative
Disorders)
48. e best answer is J. is is a complicated case of an elderly man with multiple
problems including cognition de cits, depression, alcohol abuse, and insomnia, so
deciding on a treatment strategy should involve prioritizing these various
conditions. As with any case, the highest priority should be given to keeping both
the patient and others safe. In this case, that will involve revoking the patient’s
license to drive, as this has the greatest potential to result in immediate harm to
either the patient or others. (Chapter 22—Alzheimer’s Disease Across the Lifespan)
49. e best answer is I. Once the immediate threat to safety is addressed, deciding
which of the patient’s conditions to prioritize becomes more challenging. In
looking at the patient’s complaints, it becomes clear that all of them may be
related at least in some way to alcohol. Alcohol use can exacerbate depression or
even cause it entirely by itself; it can directly cause cognitive de cits which often
resolve with alcohol cessation; and it can often disrupt sleep signi cantly which
can directly cause the kinds of nighttime awakenings that the patient is

569
 experiencing. For this reason, addressing the patient’s alcohol use should take
priority over treatment of dementia (answer A), treatment of depression (answers
B, C, and F), or treatment of insomnia (answers C, D, and G). To treat his
alcohol addiction, a variety of treatment options are available, including
medications like naltrexone and referrals to substance rehabilitation programs.
However, neither of these interventions will be effective if the patient is not
committed to change (answers E and H). erefore, assessing the patient’s current
readiness to change as directed by the principles of motivational interviewing is
the best next step for managing this patient’s concerns. (Chapter 8—Addiction
Across the Lifespan)
50. e best answer is C. is vignette describes a stereotypical case of generalized
anxiety disorder as evidenced by persistent worries in multiple domains of his life
directly leading to impairment. Generalized anxiety disorder is most correlated
with dysregulation of the HPA axis which manifests through abnormalities in the
release of cortisol from the adrenal glands. Abnormal metabolism in the frontal
and temporal lobes is associated with frontotemporal dementia (answer B),
hyperreactivity of the amygdala is seen in PTSD (answer D), high resting
neuronal activity in the retina has been demonstrated in ADHD (answer E), and
high receptivity of the insula to afferent signals is seen in somatization (answer F).
No conditions have been reliably associated with abnormal serotonin levels in the
brain (answer A). (Chapter 9—Diagnosing Anxiety Disorders)
51. e best answer is H. Bipolar disorder with psychotic features shares many signs
and symptoms with primary psychotic disorders such as schizophrenia, with a lack
of self-care (answer A), grandiose delusions (answer D), paranoid delusions
(answer E), and auditory hallucinations (answer G) being found commonly in
both conditions. is makes distinguishing between the two a clinical challenge.
Some signs and symptoms are more often associated with one of these conditions
than the other, such as disorganized speech (answers B and C) being more
common in schizophrenia while irritability when blocked from reaching one’s
goals is more consistent with bipolar disorder (answer F). However, none of these
are absolutely diagnostic of either condition, and it is impossible to de nitively
rule out bipolar disorder based on the information provided. Knowing how the
patient has functioned across his lifespan would be much more helpful, with
preserved functioning in between episodes being highly characteristic of bipolar
disorder while a progressive decline in functioning is much more consistent with
schizophrenia. (Chapter 6—Diagnosing Bipolar Disorders and Chapter 7—Signs and
Symptoms of Psychosis)
52. e best answer is A. is patient has poorly controlled pain related to a severe
medical condition that warrants additional treatment, such as increasing the
analgesic dose or switching to another drug that offers better coverage.
Maintaining, reducing, or discontinuing her current level of pain management
would not be appropriate (answers B, C, and D). While some of the features of
this case (including a pattern of escalating use and feelings of guilt related to
substance use) are found in addictive disorders as well, they can also be seen as a
result of physiologic tolerance and societal stigma. In addition, there is no
evidence that this patient is using opioids for their positively reinforcing effects.
Rather, she appears to use them appropriately to remove pain (a negative

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 reinforcement). erefore, referring to an addiction medicine clinic would not be
appropriate as she is not suffering from an addiction (answer E). You could
consider using non-pharmacologic pain reduction techniques such as mindfulness
meditation in addition to pain medications for greater effect. (Chapter 8—
Differential Diagnosis of Addictive Disorders)
53. e best answer is E. is patient is experiencing the effects of benzodiazepine
withdrawal which is characterized by both psychological and physiologic arousal
that can manifest in feelings of severe anxiety. In this context, it would be
inappropriate to diagnose a new anxiety disorder (answers A, B, and C) or to
attribute his anxiety to his depressive disorder (answer D). is is a common
clinical scenario when lowering the dose of or discontinuing a benzodiazepine,
and patients should be counseled on what to expect prior to beginning this
process. Slowly tapering the dose of the benzodiazepine can also help to reduce
the chances of a severe withdrawal state, although it cannot always be avoided
entirely. (Chapter 8—Intoxication and Withdrawal and Chapter 9—Differential
Diagnosis of Anxiety Disorders)
 

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RECOMMENDED READING
e following articles are intended to provide those who are interested with directions for
further reading on many of the subjects we have discussed so far. is list is not meant to be
a comprehensive catalog of references for the information in this book. For any questions
about the sources of speci c data, please contact the author at
[email protected].
CHAPTER 2 | DIAGNOSIS
Prince et al. “No health without mental health.” Lancet. 2007 Sep
8;370(9590):859-77.
Kindler KS. “Explanatory models for psychiatric illness.” Am J Psychiatry.
2008;165:695-702
Rosenhan. “On being sane in insane places.” Science. 1973;179:250-258
Croskerry. “ e importance of cognitive errors in diagnosis and strategies to
minimize them.” Acad Med. 2003 Aug;78(8):775-80.
Crumlish et al. “How psychiatrists think.” Advances in Psychiatric Treatment.
2009;15(1):72-79.
Aboraya et al. “ e Reliability of Psychiatric Diagnosis Revisited: e Clinician's
Guide to Improve the Reliability of Psychiatric Diagnosis .” Psychiatry (Edgmont).
2006 Jan;3(1):41-50.
CHAPTER 3 | EVALUATION
Warner. “Clinicians’ guide to evaluating diagnostic and screening tests in
psychiatry.” Advances in Psychiatric Treatment. 2004;10:446–454.
McGough et al. “Estimating the Size of Treatment Effects: Moving Beyond P
Values.” Psychiatry (Edgmont). 2009 Oct;6(10):21–29.
Pewsner et al. “Ruling a diagnosis in or out with ‘SpPIn’ and ‘SnNOut’: a note of
caution.” BMJ. 2004;329(7459):209-213.
Grimes et al. “Re ning clinical diagnosis with likelihood ratios.” Lancet. 2005 Apr
23-29;365(9469):1500-5.
CHAPTER 4 | PSYCHIATRIC EMERGENCIES
Hawton et al. “Suicide.” Lancet. 2009 Apr 18;373(9672):1372-81.
Harris et al. “Suicide as an outcome for mental disorders. A meta-analysis.” Br J
Psychiatry. 1997;170:205-228.
Skegg. “Self-harm.” Lancet. 2005 Oct 22-28;366(9495):1471-83.
Klonsky. “ e functions of deliberate self-injury: a review of the evidence.” Clin
Psychol Rev. 2007 Mar;27(2):226-39.
Elbogen et al. “ e intricate link between violence and mental disorder: results
from the National Epidemiologic Survey on Alcohol and Related Conditions.”
Arch Gen Psychiatry. 2009 Feb;66(2):152-61.
Stowell et al. “Psychiatric Evaluation of the Agitated Patient: Consensus Statement
of the American Association for Emergency Psychiatry Project BETA Psychiatric
Evaluation Workgroup.” Western Journal of Emergency Medicine. 2012;13(1):11-
16.
Petit. “Management of the Acutely Violent Patient.” Psychiatric Clinics;28(3):701-
711.
Legano et al. “Child abuse and neglect.” Curr Probl Pediatr Adolesc Health Care.
2009 Feb;39(2):31.e1-26.

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 Christian et al. “ e evaluation of suspected child physical abuse.” Pediatrics. 2015
May;135(5):e1337-54.
Inouye. “Delirium in older persons.” N Engl J Med. 2006;354:1157-1165.
Appelbaum. “Assessment of patients’ competence to consent to treatment.” N Engl
J Med. 2007;357:1834-1840.
Bhati et al. “Clinical Manifestations, Diagnosis, and Empirical Treatments for
Catatonia.” Psychiatry (Edgmont). 2007;4(3):46-52.
CHAPTER 5 | DEPRESSION
Kendler. “ e Phenomenology of Major Depression and the Representativeness
and Nature of DSM Criteria.” Am J Psychiatry 2016 Aug 1;173(8):771-80.
Burcusa et al. “Risk for Recurrence in Depression.” Clinical psychology review.
2007;27(8):959-985.
Paykel et al. “Life events and depression. A controlled study.” Arch Gen Psychiatry.
1969 Dec;21(6):753-60.
Harmer et al. “Why do antidepressants take so long to work? A cognitive
neuropsychological model of antidepressant drug action.” Br J Psychiatry 2009;
195:102-108.
Nelson et al. “Childhood maltreatment and characteristics of adult depression:
meta-analysis.” Br J Psychiatry. 2017 Feb;210(2):96-104.
Cipriani et al. “Comparative efficacy and acceptability of 21 antidepressant drugs
for the acute treatment of adults with major depressive disorder: a systematic
review and network meta-analysis.” Lancet 2018 Apr 7;391(10128):1357-1366.
Bostwick et al. "Recognizing mimics of depression: e ‘8 Ds’." Current Psychiatry.
2012 Jun;11(6):30-36.
CHAPTER 6 | MANIA
Kendler. “ e clinical features of mania and their representation in modern
diagnostic criteria.” Psychol Med. 2017 Apr;47(6):1013-1029.
Ghouse et al. “Overdiagnosis of Bipolar Disorder: A Critical Analysis of the
Literature.” e Scienti c World Journal. 2013;2013:297087.
Joffe et al. “A prospective, longitudinal study of percentage of time spent ill in
patients with bipolar I or bipolar II disorders.” Bipolar Disord. 2004 Feb;6(1):62-
6.
Cuellar et al. “Distinctions between bipolar and unipolar depression.” Clinical
psychology review. 2005;25(3):307-339.
Geddes et al “Treatment of bipolar disorder”. Lancet.
2013;381(9878):10.1016/S0140-6736(13)60857-0.
Cipriani et al. “Comparative efficacy and acceptability of antimanic drugs in acute
mania: a multiple-treatments meta-analysis.” Lancet. 2011; 378:1306-1315
Nusslock et al. “Elevated reward-related neural activation as a unique biological
marker of bipolar disorder: assessment and treatment implications.” Behav Res
er. 2014 Nov;62:74-87.
Paris et al. “Borderline personality disorder and bipolar disorder: what is the
difference and why does it matter?” J Nerv Ment Dis. 2015 Jan;203(1):3-7.
CHAPTER 7 | PSYCHOSIS
Picchioni et al. “Schizophrenia.” British Medical Journal. 2007;335(7610):91-95.
Kendler. “Phenomenology of Schizophrenia and the Representativeness of
Modern Diagnostic Criteria.” JAMA Psychiatry. 2016 Oct 1;73(10):1082-1092.

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 Fusar-Poli et al. “ e psychosis high-risk state: a comprehensive state-of-the-art
review.” JAMA Psychiatry. 2013;70:107-120.
Kapur. “Psychosis as a state of aberrant salience: a framework linking biology,
phenomenology, and pharmacology in schizophrenia.” Am J Psychiatry.
2003;160:13-23.
Emsley et al. “ e nature of relapse in schizophrenia.” BMC Psychiatry.
2013;13:50.
Schwartz et al. “Congruence of diagnoses 2 years after a rst-admission diagnosis
of psychosis.” Arch Gen Psychiatry. 2000 Jun;57(6):593-600.
Kendler. “Psychosis within vs outside of major mood episodes: a key prognostic
and diagnostic criterion.” JAMA Psychiatry. 2013 Dec;70(12):1263-4.
Leucht et al. “Comparative efficacy and tolerability of 15 antipsychotic drugs in
schizophrenia: a multiple treatments meta-analysis.” Lancet. 2013;382:951-962.
Resnick et al. “Faking it: How to detect malingered psychosis.” Current Psychiatry.
2005 Nov;4(11):12-25.
CHAPTER 8 | ADDICTION
Lüscher et al. “ e mechanistic classi cation of addictive drugs.” PLoS Med. 2006
Nov;3(11):e437.
Koston et al. “Management of drug and alcohol withdrawal.” N Engl J Med. 2003;
348:1786-1795.
Nestler et al.” DeltaFosB: a sustained molecular switch for addiction.” Proc Natl
Acad Sci U S A. 2001 Sep 25;98(20):11042-6.
Lopez-Quintero et al. “Probability and predictors of remission from lifetime
nicotine, alcohol, cannabis, or cocaine dependence: Results from the National
Epidemiologic Survey on Alcohol and Related Conditions” Addiction. 2011
March;106(3):657–669.
Berlin et al. “Understanding the Differences Between Impulsivity and
Compulsivity.” Psychiatric Times. 2008 Jul;25(8):58-61.
Olsen. “Natural Rewards, Neuroplasticity, and Non-Drug Addictions.
Neuropharmacology.” 2011;61(7):1109-1122.
Grant et al. “Introduction to Behavioral Addictions.” e American journal of
drug and alcohol abuse. 2010;36(5):233-241.
CHAPTER 9 | ANXIETY
Craske et al. “Anxiety.” Lancet. 2016 Dec 17;388(10063):3048-3059.
Bystritsky et al. “Current Diagnosis and Treatment of Anxiety Disorders.”
Pharmacy and erapeutics. 2013;38(1):30-57.
Steimer. “ e biology of fear-and anxiety-related behaviors.” Dialogues in Clinical
Neuroscience. 2002;4(3):231-249.
Faravelli et al. “Childhood stressful events, HPA axis and anxiety disorders.” World
Journal of Psychiatry. 2012;2(1):13-25.
Zorn et al. “Cortisol stress reactivity across psychiatric disorders: A systematic
review and meta-analysis.” Psychoneuroendocrinology. 2017 Mar;77:25-36.
Stein et al. “Social anxiety disorder.” Lancet. 2008 Mar 29;371(9618):1115-25.
Roy-Byrne et al. “Panic disorder.” Lancet. 2006; 368:1023-1032.
Aronson et al. “Phenomenology of panic attacks: a descriptive study of panic
disorder patients' self-reports.” J Clin Psychiatry. 1988 Jan;49(1):8-13.

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 Bystritsky et al. “Acute responses of anxiety disorder patients after a natural
disaster.” Depress Anxiety. 2000;11(1):43-4.
CHAPTER 10 | OBSESSIONS AND COMPULSIONS
Abramowitz et al. “Obsessive-compulsive disorder.” Lancet. 2009; 374:491-499.
Hollander. “Obsessive-compulsive disorder and spectrum across the life span.” Int
J Psychiatry Clin Pract. 2005;9(2):79-86.
Huey et al. “A psychological and neuroanatomical model of obsessive-compulsive
disorder.” J Neuropsychiatry Clin Neurosci. 2008 Fall;20(4):390-408.
Bjornsson et al. “Body dysmorphic disorder.” Dialogues Clin Neurosci.
2010;12(2):221-32.
Scarella et al. “ e Relationship of Hypochondriasis to Anxiety, Depressive, and
Somatoform Disorders.” Psychosomatics. 2016;57(2):200-207.
Leckman. “Phenomenology of tics and natural history of tic disorders.” Brain Dev.
2003 Dec;25 Suppl 1:S24-8.
Woods et al. “Diagnosis, Evaluation, and Management of Trichotillomania.” e
Psychiatric clinics of North America. 2014;37(3):301-317.
CHAPTER 11 | TRAUMA
Bisson et al. “Posttraumatic stress disorder.” e BMJ. 2015;351:h6161.
Ehlers et al. “A cognitive model of posttraumatic stress disorder.” Behav Res
erapy 2000;38:319-345.
Brewin et al. “Meta-analysis of risk factors for posttraumatic stress disorder in
trauma-exposed adults.” J Consult Clin Psychol. 2000 Oct;68(5):748-66.
Santiago et al. “A Systematic Review of PTSD Prevalence and Trajectories in
DSM-5 De ned Trauma Exposed Populations: Intentional and Non-Intentional
Traumatic Events.” PLoS ONE. 2013;8(4):e59236.
Creamer et al. “ e relationship between acute stress disorder and posttraumatic
stress disorder in severely injured trauma survivors.” Behav Res er. 2004
Mar;42(3):315-28.
Sullivan et al. “Pharmacotherapy in posttraumatic stress disorder: evidence from
randomized controlled trials.” Curr Opin Investig Drugs. 2009 Jan;10(1):35-45.
Flory et al. “Comorbidity between posttraumatic stress disorder and major
depressive disorder: alternative explanations and treatment considerations.”
Dialogues in Clinical Neuroscience. 2015;17(2):141-150.
CHAPTER 12 | PERSONALITY
Tyrer et al. “Classi cation, assessment, prevalence, and effect of personality
disorder.” Lancet. 2015 Feb 21;385(9969):717-26.
Newton-Howes et al. “Personality disorder across the life course.” Lancet. 2015
Feb 21;385(9969):727-34.
Bateman et al. “Treatment of personality disorder.” Lancet. 2015 Feb
21;385(9969):735-43.
Trull et al. “Dimensional models of personality: the ve-factor model and the
DSM-5.” Dialogues in Clinical Neuroscience. 2013;15(2):135-146.
Lynam et al. “Using the Five-Factor Model to Represent the DSM-IV Personality
Disorders: An Expert Consensus Approach.” Journal of Abnormal Psychology.
2001;110(3):401-412.
Bierer et al. “Abuse and neglect in childhood: relationship to personality disorder
diagnoses.” CNS Spectr. 2003 Oct;8(10):737-54.

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 Esterberg et al. “A Personality Disorders: Schizotypal, Schizoid and Paranoid
Personality Disorders in Childhood and Adolescence.” Journal of psychopathology
and behavioral assessment. 2010;32(4):515-528.
Caligor et al. “Narcissistic personality disorder: diagnostic and clinical challenges.”
Am J Psychiatry. 2015 May;172(5):415-22.
Disney. “Dependent personality disorder: a critical review.” Clin Psychol Rev. 2013
Dec;33(8):1184-96.
Mancebo et al. “Obsessive compulsive personality disorder and obsessive
compulsive disorder: clinical characteristics, diagnostic difficulties, and treatment.”
Ann Clin Psychiatry. 2005 Oct-Dec;17(4):197-204.
Weinbrecht et al. “Avoidant Personality Disorder: a Current Review.” Curr
Psychiatry Rep. 2016 Mar;18(3):29. doi: 10.1007/s11920-016-0665-6.
CHAPTER 13 | BORDERLINE
Leichsenring et al. “Borderline personality disorder.” Lancet. 2011; 377:74-84.
Paris. “Why Psychiatrists are Reluctant to Diagnose: Borderline Personality
Disorder.” Psychiatry (Edgmont). 2007;4(1):35-39.
Zanarini et al. “Fluidity of the Subsyndromal Phenomenology of Borderline
Personality Disorder Over 16 Years of Prospective Follow-Up” Am J Psychiatry.
2016 Jul 1;173(7):688-94.
Gunderson et al. “Ten-Year Course of Borderline Personality Disorder:
Psychopathology and Function From the Collaborative Longitudinal Personality
Disorders Study.” Archives of general psychiatry. 2011;68(8):827-837.
Stanley et al. “ e Interpersonal Dimension of Borderline Personality Disorder:
Toward a Neuropeptide Model.” e American Journal of Psychiatry.
2010;167(1):24-39.
Fonagy et al. “Borderline personality disorder, mentalization, and the neurobiology
of attachment.” Infant Ment Health J. 2011 Jan;32(1):47-69.
Lieb et al. “Pharmacotherapy for borderline personality disorder: Cochrane
systematic review of randomised trials.” Br J Psychiatry. 2010 Jan;196(1):4-12.
Chapman. “Dialectical Behavior erapy: Current Indications and Unique
Elements.” Psychiatry (Edgmont). 2006;3(9):62-68.
CHAPTER 14 | DISSOCIATION
Lyssenko et al. “Dissociation in Psychiatric Disorders: A Meta-Analysis of Studies
Using the Dissociative Experiences Scale.” Am J Psychiatry. 2018 Jan 1;175(1):37-
46.
Lynn et al. “Dissociation and Dissociative Disorders Challenging Conventional
Wisdom.” Current Directions in Psychological Science. 2012 Jan;21(1):48-53.
van der Kloet et al. “Fragmented Sleep, Fragmented Mind: e Role of Sleep in
Dissociative Symptoms.” Perspect Psychol Sci. 2012 Mar;7(2):159-75.
Simeon et al. “Feeling unreal: a depersonalization disorder update of 117 cases.” J
Clin Psychiatry. 2003 Sep;64(9):990-7.
Brand et al. “A review of dissociative disorders treatment studies.” J Nerv Ment
Dis. 2009 Sep;197(9):646-54.
Brand et al. “Dispelling myths about dissociative identity disorder treatment: an
empirically based approach.” Psychiatry. 2014 Summer;77(2):169-89.
CHAPTER 15 | SOMATIZATION

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 Fink. “Physical complaints and symptoms of somatizing patients.” J Psychosom
Res. 1992 Feb;36(2):125-36.
Smith. “ e course of somatization and its effects on utilization of health care
resources.” Psychosomatics. 1994 May-Jun;35(3):263-7.
olde Hartman et al. “Medically unexplained symptoms, somatisation disorder and
hypochondriasis: course and prognosis. A systematic review.” J Psychosom Res.
2009 May;66(5):363-77.
Boeckle et al. “Neural correlates of somatoform disorders from a meta-analytic
perspective on neuroimaging studies.” Neuroimage Clin. 2016 Apr 10;11:606-13.
Harvey et al. “Conversion disorder: towards a neurobiological understanding.”
Neuropsychiatric Disease and Treatment. 2006;2(1):13-20.
Eastwood et al. “Management of factitious disorders: a systematic review.”
Psychother Psychosom. 2008;77:209-218.
Lebourgeois. “Malingering: Key Points in Assessment.” Psychiatric Times. 2007
Apri;24(4).
Mellers. “ e approach to patients with ‘non-epileptic seizures.’” Postgraduate
Medical Journal. 2005;81(958):498-504.
CHAPTER 16 | EATING DISORDERS
Treasure et al. “Eating disorders.” Lancet. 2010;375:583-93.
Yager et al. “Anorexia nervosa.” N Engl J Med. 2005;353:1481-1488.
Eddy et al. “Diagnostic crossover in anorexia nervosa and bulimia nervosa:
implications for DSM-V.” Am J Psychiatry. 2008 Feb;165(2):245-50.
Hadad et al. “Addicted to Palatable Foods: Comparing the Neurobiology of
Bulimia Nervosa to that of Drug Addiction.” Psychopharmacology.
2014;231(9):1897-1912.
Morgan et al. “ e SCOFF questionnaire: a new screening tool for eating
disorders.” Western Journal of Medicine. 2000;172(3):164-165.
CHAPTER 17 | DEVELOPMENT
McLaughlin. “Speech and Language Delay in Children.” American Family
Physician. 2011 May;83(10):1183-88.
Noritz et al. “Motor delays: early identi cation and evaluation.” Pediatrics. 2013
Jun;131(6):e2016-27.
Daily et al. “Identi cation and evaluation of mental retardation.” Am Fam
Physician. 2000 Feb 15;61(4):1059-67,1070.
Kendall et al. “Intellectual disability and psychiatric comorbidity: Challenges and
clinical issues.” Psychiatric Times. 2015 May;32(5).
Summers et al. “Self-Injury in Autism Spectrum Disorder and Intellectual
Disability: Exploring the Role of Reactivity to Pain and Sensory Input.” Brain
Sciences. 2017;7(11):140.
CHAPTER 18 | AUTISM
Levy et al. “Autism.” Lancet. 2009;374(9701):1627-1638.
Kanner. “Autistic disturbances of affective contact.” Acta Paedopsychiatr.
1968;35(4):100-36.
Constantino et al. “Diagnosis of autism spectrum disorder: reconciling the
syndrome, its diverse origins, and variation in expression.” Lancet Neurol. 2016
Mar;15(3):279-91.

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 Grodberg et al. “ e Autism Mental Status Exam: Sensitivity and Speci city
Using DSM-5 Criteria for Autism Spectrum Disorder in Verbally Fluent Adults.”
Journal of autism and developmental disorders. 2014;44(3):609-614.
Landa et al. “Developmental Trajectories in Children With and Without Autism
Spectrum Disorders: e First 3 Years.” Child development. 2013;84(2):429-442.
Rajendran et al. “Cognitive eories of Autism.” Developmental Review. 2007
Jun;27(2):224-260.
CHAPTER 19 | INATTENTION AND HYPERACTIVITY
Cherkasova et al. “Developmental course of attention de cit hyperactivity disorder
and its predictors.” J Can Acad Child Adolesc Psychiatry. 2013 Feb;22(1):47-54.
Elder. “ e importance of relative standards in ADHD diagnoses: evidence based
on exact birth dates.” J Health Econ. 2010 Sep;29(5):641-56.
Bubl et al. “Elevated background noise in adult attention de cit hyperactivity
disorder is associated with inattention.” PLoS One. 2015 Feb 18;10(2):e0118271.
Faraone. “Using Meta-analysis to Compare the Efficacy of Medications for
Attention-De cit/Hyperactivity Disorder in Youths.” P&T. 2009 Dec;34(12):678-
94.
Fabiano et al. “A meta-analysis of behavioral treatments for attention-
de cit/hyperactivity disorder.” Clin Psychol Rev. 2009 Mar;29(2):129-40.
CHAPTER 20 | EXTERNALIZATION
Jenson et al. “Externalizing Disorders in Children and Adolescents: Behavioral
Excess and Behavioral De cits.” Oxford Handbook of School Psychology. 2011.
Zoccolillo et al. “ e outcome of childhood conduct disorder: implications for
de ning adult personality disorder and conduct disorder.” Psychol Med. 1992
Nov;22(4):971-86.
Guttmann-Steinmetz et al. “Attachment and Externalizing Disorders: A
Developmental Psychopathology Perspective.” J Am Acad Child & Adolescent
Psychiatry;45(4):440-451.
Bronsard et al. “ e Prevalence of Mental Disorders Among Children and
Adolescents in the Child Welfare System: A Systematic Review and Meta-
Analysis.” Medicine. 2016;95(7):e2622.
Sala et al. “Phenomenology, longitudinal course and outcome of children and
adolescents with bipolar spectrum disorders.” Child and adolescent psychiatric
clinics of North America. 2009;18(2):273-vii.
Grant et al. “Choosing a treatment for disruptive, impulse-control, and conduct
disorders.” Current Psychiatry. 2015 Jan;14(1):28-36.
CHAPTER 21 | PSYCHOPATHY
Gregory et al. “ e antisocial brain: psychopathy matters.” Arch Gen Psychiatry.
2012 Sep;69(9):962-72.
Ogloff. “Psychopathy/antisocial personality disorder conundrum.” Aust N Z J
Psychiatry. 2006 Jun-Jul;40(6-7):519-28.
Gregory et al. “Punishment and psychopathy: a case-control functional MRI
investigation of reinforcement learning in violent antisocial personality disordered
men.” Lancet Psychiatry. 2015 Feb;2(2):153-60.
CHAPTER 22 | DEMENTIA
Harada et al. “Normal Cognitive Aging.” Clinics in geriatric medicine.
2013;29(4):737-752.

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 Burns et al. “Dementia.” BMJ. 2009 Feb 5;338:b75.
Blennow. “Alzheimer's disease.” Lancet. 2006 Jul 29;368(9533):387-403.
Carlesimo et al. “Memory de cits in Alzheimer's patients: a comprehensive
review.” Neuropsychol Rev. 1992 Jun;3(2):119-69.
Velayudhan et al. “Review of brief cognitive tests for patients with suspected
dementia.” International Psychogeriatrics / Ipa. 2014;26(8):1247-1262.
Mortimer et al. “Neuroimaging in dementia: a practical guide.” Pract Neurol. 2013
Apr;13(2):92-103.
Sabbagh et al. “Increasing Precision of Clinical Diagnosis of Alzheimer's Disease
Using a Combined Algorithm Incorporating Clinical and Novel Biomarker Data.”
Neurol er. 2017 Jul;6(Suppl 1):83-95.
McKeith et al. “Diagnosis and management of dementia with Lewy bodies.”
Neurology. 2005;12:1863-1872.
Warren et al. “Frontotemporal dementia.” e BMJ. 2013;347:f4827.
Jorge. “Neuropsychiatric consequences of traumatic brain injury: a review of recent
ndings.” Curr Opin Psychiatry. 2005 May;18(3):289-99.
CHAPTER 23 | SLEEP
Roth. “Insomnia: De nition, Prevalence, Etiology, and Consequences.” Journal of
Clinical Sleep Medicine. 2007;3(5 Suppl):S7-S10.
Irish et al. “ e Role of Sleep Hygiene in Promoting Public Health: A Review of
Empirical Evidence.” Sleep medicine reviews. 2015;22:23-36.
Abad et al. “Diagnosis and treatment of sleep disorders: a brief review for
clinicians.” Dialogues in Clinical Neuroscience. 2003;5(4):371-388.
Williams et al. “Cognitive behavioral treatment of insomnia.” Chest. 2013 Feb
1;143(2):554-565.
Edinger et al. “Subtyping primary insomnia: is sleep state misperception a distinct
clinical entity?” Sleep Med Rev. 2003 Jun;7(3):203-14.

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ATTRIBUTIONS
e fonts Oswald and Source Sans Pro were used for the cover and inside text,
respectively. ey were accessed from Google Fonts under an open-source license.
All images displayed in this book are under the public domain, with the following
exceptions. Use of this content does not suggest that the content’s original creator(s)
endorse this book or its author in any way.
COVER AND BACK
Cover and back design by Stephen Sauer (SingleFinDesign.com).
Images and icons designed by Freepik.
CHAPTER 2 | DIAGNOSIS
“A patient consulting his friendly doctor.” Credit: Wellcome Images (Creative
Commons Attribution 4.0 International license).
“Doctor talking with pregnant woman.” Credit: P.S.Art-Design-Studio
(Shutterstock.com).
CHAPTER 8 | ADDICTION
“Cookie jar.” Credit: LHF Graphics (Shutterstock.com).
“Hand sanitizer pump dispenser.” Credit: Zern Liew (Shutterstock.com).
“Injecting drugs.” Credit: KUCO (Shutterstock.com).
“Chairs arranged in a circle.” Credit: Eugenia Petrovskaya (Shutterstock.com).
“S’mores.” Credit: pimlena (Shutterstock.com).
CHAPTER 9 | ANXIETY
“Scary clown.” Credit: Danny PiG (Creative Commons Attribution 2.0 Generic
license).
CHAPTER 10 | OBSESSIONS AND COMPULSIONS
“Man putting toilet paper up to his mouth.” Credit: txking (Shutterstock.com).
“OCD Letter Blocks.” Credit: amenclinicsphotos ac (Creative Commons
Attribution-ShareAlike 2.0 Generic license).
CHAPTER 12 | PERSONALITY
“Man standing in a courtroom dock putting his case forward to the magistrate.”
Credit: Wellcome Images (Creative Commons Attribution 4.0 International
license).
CHAPTER 15 | SOMATIZATION
“Male torso, revealing internal organs and system. Credit: Wellcome Images
(Creative Commons Attribution 4.0 International license).
CHAPTER 16 | EATING DISORDERS
“Pods and sliced pieces of okra.” Credit: Olga_Zaripova (Shutterstock.com).
“Cartoon teen boy sick in the toilet.” Credit: Anton Brand (Shutterstock.com).
CHAPTER 17 | DEVELOPMENT
“Sketch of skateboarder.” Credit: Olga Tropinina (Shutterstock.com).
“Boy with Down syndrome.” Credit: Wellcome Images (Creative Commons
Attribution 4.0 International license).
“Silencing of the FMR1 Gene in Fragile X Mental Retardation Syndrome.”
Credit: Dr. Marian L. Miller ( Journal-Cover-Art.com) (Creative Commons
Attribution-Share Alike 3.0 Unported license).
“Baby with fetal alcohol syndrome.” Credit: Teresa Kellerman (Creative Commons
Attribution-Share Alike 3.0 Unported license).

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 “Distinctive facial appearance of person with Williams syndrome.” Credit: E. A.
Nikitina, A. V. Medvedeva, G. A. Zakharov, and E. V. Savvateeva-Popova, 2014
Park-media Ltd (Creative Commons Attribution 3.0 Unported license).
“Dermatophagia.” Credit: 6th Happiness (Creative Commons Attribution 3.0
Unported license).
CHAPTER 22 | DEMENTIA
“ e progressive deterioration of pattern processing ability in a subject as they
progress from mild cognitive impairment (MCI) to severe Alzheimer's disease
(AD).” Credit: Mattson M (Creative Commons Attribution 3.0 Unported license).
CHAPTER 24 | FINAL REVIEW
“Intradermal injection.” Credit: British Columbia Institute of Technology
(Creative Commons Attribution 4.0 International license).
“Love bite.” Credit: Janek B. (Creative Commons Attribution-Share Alike 3.0
Unported license).
“8 year-old patient with Prader-Willi syndrome.” Credit: Fanny Cortés M1, M.
Angélica Alliende R1,a, Andrés Barrios R1,2, Bianca Curotto L1,b, Lorena Santa
María V1,c, Ximena Barraza O3, Ledia Troncoso A2, Cecilia Mellado S4,6, Rosa
Pardo V (Creative Commons Attribution 4.0 International license).
“Dare to reach out your hand into the darkness, to pull another hand into the
light.” Credit: Sundaram Ramaswamy (Creative Commons Attribution 2.0
Generic license).
“X-ray of a foot, showing a bullet.” Credit: Wellcome Images (Creative Commons
Attribution 4.0 International license).

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Get Memorable Psychopharmacology and Memorable Neurology, both available now from
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584
 Memorable Psychopharmacology
Now that you have the information needed to approach psychiatric diagnosis, take your
learning to the next step by understanding the evidence behind the treatment of these
disorders. Memorable Psychopharmacology uses a conversational tone, catchy mnemonics,
visual aids, and practice questions to ensure that you not only learn the material but retain it
far into the future.
For anyone preparing to meet the mental health needs of their patients, Memorable
Psychopharmacology is an indispensable review.
 

585
 Memorable Neurology
e nervous system can be a scary place to explore without a guide! Memorable Neurology
gives you the tools you need to understand the structure, function, and potential
dysfunction of the most complex organ system in the body. Memorable Neurology combines
a solid foundation in neuroanatomy with a focus on clinical diseases to give you a leg up in
the eld of neurology. A generous helpful of mnemonics, visuals, and practice questions
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586
ABOUT THE AUTHOR
Jonathan Heldt is currently on faculty at the UCLA Semel Institute for Neuroscience &
Human Behavior. He completed his Bachelor’s degree in Biochemistry at Paci c Union
College, his medical degree at the Loma Linda University School of Medicine, and his
residency at the UCLA Psychiatry Residency Training Program. He is interested in both
mental health and medical education and hopes that this book will inspire these interests in
others. He has no con icts of interest to disclose.
For questions, comments, and updates, please visit memorablepsych.com or email
[email protected].

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