Chapter 13 PDF

Schizophrenia 13
CHAPTER OUTLINE LEARNING OBJECTIVES

Schizophrenia Basics: Prevalence, Course, and Symptoms 13.1 Describe the prevalence of
Prevalence and Course of Schizophrenia schizophrenia and the time course
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Positive and Negative Symptoms of its development.
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LENS: Elyn Saks Describes Her Day-to-Day
13.2 Identify the positive
Experiences With Schizophrenia
and negative symptoms of
Positive Symptoms
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schizophrenia.
Negative Symptoms
Multilevel Process for Diagnosing Schizophrenia 13.3 Discuss the historical
Are There Subtypes of Schizophrenia? and evolutionary contexts of
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Understanding Changes in DSM–5: Schizophrenia schizophrenia.
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Historical and Evolutionary Perspectives on Schizophrenia 13.4 Identify genetic and
Historical Perspective environmental factors in the
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CASE OF JAMES STERN: Schizophrenia development of schizophrenia.
Evolutionary Perspective
13.5 Describe the brain
or
Factors in the Development of Schizophrenia changes seen in individuals with
Genetic Factors in Schizophrenia schizophrenia.
Endophenotypes Associated With Schizophrenia
13.6 Identify the treatments
t,
Causes and Effects: Neuroscience Findings About Schizophrenia available to individuals with
Schizophrenia and Brain Function schizophrenia.
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What Brain Changes Are Seen in Schizophrenia?
Ventricle Changes in Schizophrenia
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Schizophrenia and Brain Networks

Neurotransmitters Involved in Schizophrenia
How Are Cognitive Processes Changed in Schizophrenia?
Treating Individuals With Schizophrenia
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LENS: Mercy Bookings of Mental Patients

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Antipsychotic Medications
Psychosocial Interventions for Schizophrenia
LENS: Mental Health Networks of Those With Serious Mental Disorders
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Summary
Study Resources
Review Questions
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For Further Reading

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Key Terms and Concepts

SAGE edge
The voices arrived without warning on an October night in 1962, when I was
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fourteen years old. Kill yourself. . . . Set yourself afire, they said. Only moments
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before, I’d been listening to a musical group called Frankie Valli and the Four
Seasons singing “Walk like a man, fast as I can . . .” on the small radio that sat
on the night table beside my bed. But the terrible words that I heard now were
not the lyrics to that song. I stirred, thinking I was having a nightmare, but
I wasn’t asleep; and the voices—low and insistent, taunting and ridiculing—
© Alisha Marie Ragland
continued to speak to me from the radio. Hang yourself, they told me. The
world will be better off. You’re no good, no good at all.
—Steele and Berman, The Day the Voices Stopped. Copyright 2001. Reprinted
by permission of Basic Books, a member of the Perseus Books Group.
453
Copyright ©2017 by SAGE Publications, Inc.

This work may not be reproduced or distributed in any form or by any means without express written permission of the publisher.
454 Abnormal Psychology
After a time I began to hate work, and Bruce sometimes got on my nerves. I got
depressed and crashed out of an evening, staying up all night listening to Pink Floyd’s
“The Wall.” One day I was at work, Bruce was out and the phone rang. I picked it up. “We
are following your every move,” said a voice; then nothing. Instantly the PA system from
the next factory, which was quite loud, said, “Telephone for did-you-get-that? Telephone
call for we-know-you’re-listening.”
—From Richard McLean. (2003). Recovered, Not Cured:

A Journey Through Schizophrenia (p. 29). Australia: Allen Unwin.
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At the beginning of that summer, I felt well, a happy healthy girl—I thought—with a
normal head and heart. By summer’s end, I was sick, without any clear idea of what
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was happening to me or why. And as the Voices evolved into a full-scale illness, one
that I only later learned was called schizophrenia, it snatched from me my tranquility,
sometimes my self-possession, and very nearly my life.
t
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I spent my junior year abroad. While I was in Spain my first semester, the Voices were
softer, but I was so revved up, my motor seemed to be working overtime. When the
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Voices did speak to me, sometimes they did so in Spanish: “Puta! Puta!” they yelled.
“Vaya con el diablo.” Go to hell, whore.
or
Along the way I have lost many things: the career I might have pursued, the husband I
might have married, the children I might have had. During the years when my friends
t,
were marrying, having their babies and moving into houses I once dreamed of living in,
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I have been behind locked doors, battling the Voices who took over my life without even
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asking my permission.
Sometimes these Voices have been dormant. Sometimes they have been overwhelming.
At times over the years they have nearly destroyed me. Many times over the years I was
,
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ready to give up, believing they had won.
Today this illness, these Voices, are still part of my life. But it is I who have won,
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not they. A wonderful new drug, caring therapists, the support and love of my
family and my own fierce battle—that I know now will never end—have all
combined in a nearly miraculous way to enable me to master the illness that once
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mastered me.
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Today, nearly eighteen years after that terrifying summer, I have a job, a car, an
apartment of my own. I am making friends and dating. I am teaching classes at the very
hospital at which I was once a patient.
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—From The Quiet Room, by Lori Schiller and Amanda Bennett.

By permission of Grand Central Publishing. All rights reserved.
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s is made clear in these personal accounts from those living with it, schizophrenia is
one of the most debilitating of the mental disorders. In this chapter, I will introduce
you to the nature of schizophrenia and its prevalence around the world. As such, you
will learn about its symptoms and the time course of their development.

Chapter 13: Schizophrenia 455
Schizophrenia Basics: Prevalence, Course, and Symptoms

Schizophrenia is part of a broad category of disorders referred to as schizophrenia spectrum and schizophrenia: a debilitating
psychotic disorder in which
other psychotic disorders. Psychotic disorders (see Table 13.1) involve a loss of being in touch individuals may hear voices, see
with reality and are characterized by abnormal thinking and sensory processes. Individuals with images not seen by others, believe
a psychotic disorder may show delusions, hallucinations, disorganized thinking and speech, that others wish to harm or control
them, and have bizarre thoughts
abnormal motor behaviors, and negative symptoms. People with psychotic disorders other than
psychotic disorders: disorders
schizophrenia may show psychotic symptoms for a brief period of time or for a longer duration. that involve a loss of being
They may also show delusions, affective problems outside the normal range, or simply seem odd in touch with reality and are
characterized by abnormal
to those around them. Psychotic symptoms not part of schizophrenia can be induced through
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thinking and sensory processes
drugs, lack of sleep, and other medical conditions. Also, it should be noted that although the term
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delusions: beliefs without
schizophrenia comes from the Greek meaning to split the mind, it is a very different disorder from support for their occurrence
those of dissociation, such as dissociative identity disorder. The Diagnostic and Statistical Manual and which are at odds with the
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individual’s current environment
of Mental Disorders, Fifth Edition (DSM–5; American Psychiatric Association, 2013) describes
these conditions separately from schizophrenia. This chapter will focus on schizophrenia.
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TABLE 13.1 Table of DSM–5 Schizophrenia Spectrum and Other Psychotic Disorders
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DSM–5 DIAGNOSIS CHARACTERISTICS
or
Schizophrenia Symptoms such as delusions, hallucinations, disorganized thinking and speech,
abnormal motor behaviors, and negative symptoms, continuously present for at
least 6 months
t,
Brief Psychotic Disorder Symptoms such as delusions, hallucinations, disorganized thinking and speech,
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abnormal motor behaviors, and negative symptoms lasting for less than a month
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Schizophreniform Disorder Symptoms such as delusions, hallucinations, disorganized thinking and speech,
abnormal motor behaviors, and negative symptoms lasting for at least 1 month but
less than 6 months
Schizoaffective Disorder Symptoms such as delusions, hallucinations, disorganized thinking and speech,
,
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abnormal motor behaviors, and negative symptoms along with those of a major
mood disorder (major depressive or manic)
Substance/Medication-Induced Delusions or hallucinations related to drugs or medications

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Psychotic Disorder
Psychotic Disorder Due to Another Delusions or hallucinations related to a medical condition

Medical Condition
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Catatonic Disorder Due to Another Non-normal activity of the motor system such as stupor, holding of a posture,
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Medical Condition mutism, mannerisms, or grimacing
Unspecified Catatonia Non-normal activity of the motor system such as stupor, holding of a posture,
mutism, mannerisms, or grimacing
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Other Specified Schizophrenia Spectrum Symptoms such as delusions, hallucinations, disorganized thinking and speech,
and Other Psychotic Disorder abnormal motor behaviors, and negative symptoms that do not meet the criteria for
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other categories
Unspecific Schizophrenia Spectrum and Symptoms such as delusions, hallucinations, disorganized thinking and speech,
Other Psychotic Disorder abnormal motor behaviors, and negative symptoms that do not meet the criteria for
other categories
Delusional Disorder Presence of delusions for 1 month or longer without criteria for another
schizophrenia spectrum disorder

Schizophrenia affects one’s ability to express one-

self clearly, to have close social relationships, to express
positive emotions, and to plan for the future. Not every-
one with schizophrenia displays the same symptoms.
Individuals with schizophrenia may hear voices, see
images not seen by others, believe that others wish to
harm or control them, and have bizarre thoughts. The
most common set of symptoms seen in individuals with
© iStockphoto.com/Gawrav Sinha
schizophrenia over the past 100 years is a belief that oth-

ers are out to get them and the hearing of voices that
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others do not hear (Insel, 2010).
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Individuals with schizophrenia can display prob-
lems in terms of cognitive processes, emotional pro-
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cesses, and motor processes. Cognitive problems can
Individuals with psychotic disorder may experience delusions, be seen as a disorganization of thinking and behavior.
hallucinations, disorganized thinking and speech, abnormal motor In listening to a person with schizophrenia, you may
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behaviors, and negative symptoms.
note a speech style that although detailed does not seem
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to have a coherent focus and does seem to constantly
change themes. Technically, these are referred to as circumstantiality and tangentiality. In more
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severe cases, the speech is actually incoherent and contains a stream of words that are unrelated to
one another, which is referred to as word salad.
or
Mood symptoms include impairments in affective experience and expression. Depression is
a common experience with schizophrenia along with thoughts of suicide. A number of individu-
als with schizophrenia hear voices that tell them to kill themselves. Ken Steele’s voices told him
t,
“Hang yourself. The world will be better off. You’re no good, no good at all” (Steele & Berman,
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2001). Motor symptoms can range from repetitive behaviors such as rocking to total stiffness or
lack of change in posture referred to as catatonia.
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Prevalence and Course of Schizophrenia

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Schizophrenia affects about 1% of the population. It is seen throughout the world with simi-
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lar symptoms regardless of culture or geographical location. Onset of schizophrenia occurs

in the late teens or early twenties. Males show an earlier onset than females by about 5 years.
Some individuals with schizophrenia display the symptoms throughout their life. However,
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there is a subgroup of individuals who, a few years after the initial display of symptoms, show
a lack of symptoms even without treatment (Jobe &
Harrow, 2010). Even with symptoms, some people
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with schizophrenia are able to be part of the social and

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economic world experienced by healthy individuals.

In fact, two of the individuals whose self-reports are
included in this chapter work at major universities in
the United States.
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The symptoms of schizophrenia are not constantly

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present. There are examples of individuals with schizo-

phrenia who were able to finish college and main-
©iStockphoto.com/Nikada
tain jobs, even high-level jobs. Thus, individuals with

schizophrenia may show periods in which they are able
to function in terms of external realities. Symptoms
for some people tend to appear in times of change or
stress. Different individuals with schizophrenia may
Schizophrenia affects about 1% of the world’s population. show very different symptoms. For example, some

individuals may hear voices but never see

a visual hallucination. Others show a dif- FIGURE 13.1 Phases in the Development of Schizophrenia
ferent presentation of symptoms. This Schizophrenia has been described in terms of four phases: premorbid, prodromal,
has led some researchers to conclude that psychotic, and stable. This figure shows the natural history and course of schizophrenia.
there exists a variety of similar disorders Source: Tandon et al. (2009, p. 8), with permission from Elsevier.
that are currently described by the term
schizophrenia. This would suggest that Variable
degrees of
schizophrenia is not a single disorder but
recovery
a number of related disorders that are
described by this term.
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First psychotic episode
The course of schizophrenia gen- Prodromal
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erally first becomes evident in adoles- phase
Premorbid
cence or young adulthood (Tandon, phase Brief/ Psychotic Stable
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Nasrallah, & Keshavan, 2009). The attenuated phase phase
Cognitive positive
course of the disorder is shown in motor or Florid positive
symptoms symptoms Negative symptoms,
Figure 13.1. The initial phase is referred social and/or cognitive/
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deficits social deficits, functional
to as the premorbid phase. During functional
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decline decline
this phase, only subtle or nonspecific
Childhood Adolescence/young adulthood
problems with cognition, motor, or
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social functioning can be detected.
These are accompanied by poor academic achievement and social functioning. This is fol-
or
lowed by a prodromal phase in which initial positive symptoms, along with declining func-
tioning, can be seen. Based on prospective studies, this phase can last from a few months to
years, with the mean duration being about 5 years. Next is the psychotic phase, where posi-
t,
tive psychotic symptoms are apparent. For most individuals, this phase occurs at between
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15 and 45 years of age, with the onset being about 5 years earlier in males than females. This
phase is marked by repeated episodes of psychosis with remission in between. The great-
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est decline in functioning is generally seen during the first 5 years after the initial episode.
This phase is followed by a stable phase characterized by fewer positive symptoms and an
increase in negative ones (see definitions of positive and negative symptoms below). Stable
,
cognitive and social deficits also characterize this phase. The actual course of the disorder
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varies greatly across individuals.

Individuals with schizophrenia tend to die earlier than those their age in the general popula-
tion. These higher age-standardized mortality rates are approximately double those of the general
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population. The life span of individuals with schizophrenia is abbreviated by 15 to 20 years. Of

those with this abbreviated life span, approximately 25% can be attributed to suicide and 10% to
accidents. The remainder is related to medical conditions, particularly cardiovascular disease.
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Positive and Negative Symptoms

positive symptoms: in
Based on initial descriptions used by Hughlings Jackson in the 1800s, schizophrenia symptoms schizophrenia, the presence
are referred to as positive or negative. The more familiar positive symptoms are hallucina- of such characteristics as
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hallucinations, delusions,
tions, delusions, disorganized thinking, and disorganized behavior. The more familiar negative disorganized thinking, and
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symptoms include lack of affect in situations that call for it, poor motivation, and social with- disorganized behavior
drawal. Hughlings Jackson saw positive symptoms as reflecting a lack of high cortical control hallucinations: sensory
experiences that can involve any
over more primitive brain processes. Negative symptoms, on the other hand, were the result of of the senses and that are at
loss of function—what today we would refer to as a dysfunctional network of the brain. It should odds with the individual’s current
be noted that positive and negative are not evaluative terms when applied to symptoms of schizo- environment
phrenia. Instead, they indicate either the presence of something unusual such as hearing voices negative symptoms: in
schizophrenia, lack of affect in
or seeing hallucinations, which would be positive symptoms, or the lack of a normal human pro- situations that call for it, poor
cess, such as poor motivation or social withdrawal, which would be negative symptoms. motivation, and social withdrawal

LENS
Elyn Saks Describes Her Day-to-Day

Experiences With Schizophrenia
As you read about Is she trying to kill me? No, she’s a student. But what
schizophrenia, you about the others? The voices inside my head, the
generally learn of explosions. What do they want? Are they trying to
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the symptoms such interdict me, to hit me with the Kramer device? I went
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as hearing voices or to the store and they said “interdiction.” Interdiction,
feeling that others introduction, exposition, explosion. Voicemail is the
are out to get you. issue.
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AP Photo/Damian Dovarganes
What you don’t hear

about is the way those I knew not to say those thoughts out loud. Not
with the disorder are because they were crazy thoughts—they were every
bit as real as the students sitting right in front of
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successful. You also
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don’t often read about me—but I kept silent because others would think them
how an individual with crazy. People would think me as deranged as Billie
Boggs.
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schizophrenia lives
Elyn Saks her day-to-day life. In
the following essay, But I’m not crazy. I simply have greater access to the
or
Elyn Saks describes her experience of teaching a law truth.
school class.
“Good,” I replied. “But why isn’t it the case that your
sister has two selves, the sick one you see now and the
My students filled the room. They were interested
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healthy one you’ve known all your life? Why should
and eager, unusually so, given that they were second-
you get to pick which is real? Shouldn’t your sister
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and third-year law students for whom the fear and
make that choice?” Up shot more hands.
trembling that came with the first year had long since
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faded. The course was “Advanced Mental Health My brain is on fire! My head is going to explode right
Law.” The day’s topic: Billie Boggs. A street person here, right in front of my class!
who lived over a hot air vent in midtown Manhattan,
she threw food at people who wanted to help her “But isn’t health always preferred to illness?” a bright-
,
and chased them across the street. Her rantings and eyed young man countered. “We should prefer the
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ravings seemed crazy to most of the students, and healthy self.”

we were discussing whether she should be sent to a
psychiatric hospital. Mercifully, the class ended. A law-school dean spotted
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me as I walked back to my office. He said I looked as if

I heard myself speak, surprising myself by the steady I were in pain. “Just a lot on my mind,” I heard myself
sound of my voice as I tried to restore my attention to reply as I continued quickly down the hall. Keys out,
the group before me: “What if Billie Boggs were your door open, door shut. I crumpled into my chair and
sister—would you put her in a psychiatric hospital buried my face in my hands.
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then?” Up shot the hands.

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That was in September of 1991, and it was one of my

Concentrate. These are your students. You have worst such incidents. Ten years before, in my mid-
an obligation to them. Canceling class would be 20s, during my third psychiatric hospitalization,
admitting defeat. But there are explosions in my head. I had been given the diagnosis “chronic paranoid
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They’re testing nuclear devices on my brain. They’re schizophrenia with acute exacerbation.” My
very little and they can get inside. They are powerful. prognosis? “Grave.” I was, in other words, expected
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to be unable to live independently, let alone work.

I pulled myself together, enough to point to a young At best I would be in a board-and-care, holding a
woman who spoke often in class. “I couldn’t let minimum-wage job—perhaps flipping burgers—when
my sister live like that,” she said from across the my symptoms had become less severe.
classroom, which held the students in curved rows,
like a giant palm before me. “I know my sister. That That has not turned out to be my life. I am the Orrin
wouldn’t be her. There’s one and only one of her—and B. Evans professor of law, psychology, and psychiatry
that’s the one before she got sick.” and the behavioral sciences at the University of

Southern California’s law school; adjunct professor The same is true of a psychopharmacologist. Make
of psychiatry at the University of California at San friends and family members part of your team.
Diego’s medical school; and an assistant faculty
member at the New Center for Psychoanalysis, where Sometimes your team can see early warning signs
I am also a research clinical associate. before you can. For instance, my closest friend, Steve,
and my husband, Will, often identify when I am
My schizophrenia has not gone away. I still slipping. Will says I become quieter in a particular
become psychotic, as happened in class that way that signals all is not well. It’s a blessing to have
day in 1991. Today my symptoms, while not as such people in your life. Seek them out.
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severe, still recur and I struggle to stay in the world,
so to speak, doing my work. I have written about We also need to put a face on mental illness. Being
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my illness in a memoir and much of the narrative open about one’s own illness will probably do more
takes place after I had accepted a tenure-track good than all the laws we can pass.
appointment at USC.
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My own “outing” of myself was a bit of a risk, but has
turned out well. I am glad and relieved I no longer
Barring a medical breakthrough of Nobel-
have to hide. And my story seems to be meaningful
Prize-winning proportions, I will never fully
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to people—it has helped people understand mental
recover from schizophrenia. I will remain on
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illness more and perhaps has led to a decrease
antipsychotic medication and in talk therapy for
in the stigma. I was lucky in that my law school
the rest of my life. Yet I have learned to manage my
accommodated my teaching needs without my
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illness.
having to invoke the ADA. My colleagues are
supportive, and I no longer feel ashamed about
[There] are steps that everyone with mental
or
needing their help.
illness should take. First, learn about the illness
you have—the typical signs, symptoms, and course. Perhaps most important: Seek help when you need it.
Many excellent sources are available. You may Mental illness is a no-fault disease like any other, such
t,
want to start with the Diagnostic and Statistical as cancer or diabetes. Help is available, but you need
Manual of Mental Disorders, [DSM–5] Psychiatric to ask for it. Don’t let the threat of stigma deter you.
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textbooks, e.g., Kaplan and Sadock’s, can be helpful. You shouldn’t have to suffer.
I have also discovered excellent lay accounts of
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mental illness. And you shouldn’t allow mental illness to stand in the
way of the wonderful contributions you are poised to
Second, understand how your illness affects you. make to your students and to your field.
What are your triggers? What are your early warning
,
signs? What can you do to minimize your symptoms Thought Question: What are the important
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when they worsen—e.g., call your therapist, increase components of Elyn Saks’s treatment plan? How do
your medication, listen to music, exercise? Try to they apply to other psychological disorders?
devise some techniques for your own situation. Some
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colleagues and I are studying how a group of high- From “Mental Illness in Academe,” The Chronicle of Higher
functioning people with schizophrenia manage their Education, November 25, 2009 (edited part of a longer
article).
symptoms. You are in the best position to determine
what works for you. Elyn R. Saks is a professor of law, psychology, and psychiatry
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and the behavioral sciences at the University of Southern

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Put a good treatment team in place. You need a California’s law school. She is the author of a memoir, The
therapist you can trust and can turn to in times of Center Cannot Hold: My Journey Through Madness (Hyperion,
difficulty. Does he or she respond if you call in crisis? 2007).
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Positive Symptoms
Hallucinations are sensory experiences that can involve any of the senses, although auditory hal-
lucinations are the ones most commonly reported by individuals with schizophrenia. The two
examples of hallucinations presented at the beginning of this chapter illustrate the unusual expe-
riences that individuals with schizophrenia can have. Ken Steele, while listening to music on
the radio, heard it tell him to kill himself. Richard McLean picked up a phone to hear voices tell
him that they were following his every move. These auditory hallucinations were experienced as

coming from outside the person. Other individuals experience the voices or thoughts as com-
ing from within their head. Individuals with schizophrenia report that they may hear voices
throughout the day and on more than one day. Elyn Saks describes her experiences on a TED
Talk in which she explains her thoughts during a psychotic episode and aspects of her treatment
that helped her to improve (https://www.youtube.com/watch?v=f6CILJA110Y). Her experi-
ence of giving a lecture at law school is related in the LENS: Elyn Saks Describes Her Day-to-Day
Experiences With Schizophrenia.
Of course, all of us misinterpret our experiences once in a while. It is common for people to
mistakenly believe that they heard someone call their name or that the phone rang while they
were taking a shower. It is also common to mistake a stick on a path in the woods for a snake or
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to imagine an experience while falling asleep. These experiences are different from true hallu-
ut
cinations in that we check to see what the reality of the situation is or whether we are mistaken.
Individuals with schizophrenia treat their hallucinations as real. In hallucinations in which indi-
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viduals are instructed to perform an act, it is suggested that the instructions are obeyed by some
40% of people (Junginger, 1990). It should be noted that hallucinations can be produced by other
disorders, such as Charles Bonnet syndrome, or the medications used to treat Parkinson’s disease.
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In these situations, the person experiences the hallucination but generally knows that it is not real.
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Delusions are beliefs that have no support for their occurrence and are at odds with the
individual’s current environment. One hospitalized patient believed that the CIA had cam-
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eras in the drawer pulls of her dresser. Elyn Saks, whose story was presented in the previ-
ous LENS, believed that powerful individuals could put thoughts in her head. John Hinckley,
or
who tried to kill President Ronald Reagan, believed that Jodie Foster, the actress, would be
impressed by this event. Another patient believed that God spoke to her when the dogs out-
side her house barked.
t,
The most common delusions can be organized into categories. The first is persecution. This
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is the belief that other people or groups such as the CIA are plotting against the individual. John
Nash (introduced at the beginning of Chapter 1) wrote letters to the U.S. government describing
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attempts of others to take over the world. The second category is grandeur. This is the belief that
one is really a very famous person. The individual with schizophrenia may tell everyone that he
is Jesus or some other famous figure. The third delusion is control. As in the case of Elyn Saks, the
,
delusion is that someone or some entity such as aliens can put thoughts into one’s mind. A related
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delusion is that others can hear or understand one’s thoughts without being told what they are.
Finally, one common delusion is that one is special and that God or important individuals are
speaking directly to the person.
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Long-term delusional activity varies with the individual. In one study, 43 individuals with
schizophrenia were assessed six times over a 20-year period (Jobe & Harrow, 2010). Twenty-nine
percent of those individuals had no delusional activity
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over that time, another 26% displayed delusions at each

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of the six assessments, and the remaining individuals

had some delusions (see Figure 13.2).
Negative Symptoms
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Negative symptoms seen in schizophrenia tend to be

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more constant and stable than positive symptoms.

Several studies have linked negative symptoms with a
© iStockphoto.com/Gawrav Sinha
poorer prognosis (see Foussias & Remington, 2010, for

a review). Whereas it is usually the positive symptoms
that result in a diagnosis of schizophrenia, it is the nega-
tive symptoms that tend to persist over time. Many indi-
viduals with schizophrenia have little interest in doing
simple day-to-day activities such as taking a bath or

FIGURE 13.2 Variations in
Delusional Activity 60
66%
Not all individuals with schizophrenia show
% Pts. With Delusional

Activity Over 20 Years
long-term delusional activity. In this study,
47%
29% had no delusional activity over the 20 40
years, another 26% displayed delusions
at each of the six assessments, and the 29%28%
31%
remaining individuals had some delusions. 26% 26%
20
The figure shows the presence of delusional 19%
14%
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activity over a 20-year period for individuals
8%
with schizophrenia, other psychotic 0
5% 0%
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disorders, and others. No Delusional Some Delusional Frequent Delusional Delusional Activity
Activity Activity Activity at All Followups
Source: Martin Harrow and Thomas H. Jobe, n = 75 n = 55 n = 30 n = 12
“How Frequent Is Chronic Multiyear Delusional
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Activity and Recovery in Schizophrenia: A 20- Schizophrenia Patients Other Psychotic Disorders Nonpsychotic Patients
Year Multi–Follow-up,” Schizophrenia Bulletin
(2010) 36(1): 192–204, by permission of
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Oxford University Press.
d is
shopping for food. This lack of will or volition is technically referred to as avolition. Individuals avolition: lack of will or volition
with schizophrenia also show a lack of interest in talking with others or answering questions with
or
alogia: lack of interest in
more than a one- or two-word answer. This is referred to as alogia. They also show a flattening talking with others or answering
of affect or difficulty expressing emotion. Another symptom is referred to as anhedonia or the questions with more than a one- or
two-word answer
inability to experience pleasure.
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anhedonia: the inability to
experience pleasure
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Multilevel Process for
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Diagnosing Schizophrenia
The text revision of the fourth edition of the DSM (DSM–IV–TR) and DSM–5 set forth a multi-
level process for diagnosing schizophrenia.
,
The first level is symptoms, which includes delusions, hallucinations, or disorganized

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speech. At least one of these must be present. In addition, abnormal psychomotor behav-
iors, such as catatonia, and negative symptoms, such as a lack of volition or social process-
ing, may also be present. The second level is functioning. A reduction in functioning in the
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areas of work, interpersonal relations, and/or self-care should be present. The third level is
duration in which the presence of the positive or negative symptoms should have existed for
6 months with at least 1 month of positive symptoms. The final levels are designed to rule
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out psychotic-like symptoms found in other disorders such as mania or depression or those
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related to specific medical conditions such as drug abuse. The DSM–5 criteria are shown in
Table 13.2.
Are There Subtypes of Schizophrenia?

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D
Individuals with schizophrenia have a variety of different symptoms and exhibit an inconsistent
picture of the disorder. This has led some to suggest that there is not a single schizophrenia disor-
der but rather a variety of syndromes. Historically, one approach to the variety of presentations
seen in individuals with schizophrenia was to look for subtypes. As noted previously, Kraepelin
suggested four subtypes. The fourth edition of the DSM divided schizophrenia into five subtypes.
These are paranoid, disorganized, catatonic, undifferentiated, and residual subtypes. Although
ICD-10 uses subtypes, DSM–5 removed the classification of subtypes but left the diagnostic crite-
ria for schizophrenia almost identical to DSM–IV–TR. DSM–5 also uses the subtype descriptions

TABLE 13.2 DSM–5 Diagnostic Criteria for Schizophrenia
A. Characteristic symptoms: Two (or more) of the following, each present for a
significant portion of time during a 1-month period (or less if successfully treated). At
least one of these should include 1–3.
1. Delusions.
2. Hallucinations.
3. Disorganized speech (e.g., frequent derailment or incoherence).
4. Grossly disorganized or catatonic behavior.
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5. Negative symptoms (i.e., diminished emotional expression or avolition).
ut
B. Social/occupational dysfunction: For a significant portion of the time since the onset
of the disturbance, levels of functioning in one or more major areas, such as work,
interpersonal relations, or self-care, is markedly below the level achieved prior to the
rib
onset (or when the onset is in childhood or adolescence, there is failure to achieve
expected level of interpersonal, academic, or occupational functioning).
C. Duration: Continuous signs of the disturbance persist for at least 6 months. This
t
6-month period must include at least 1 month of symptoms (or less if successfully
is
treated) that meet Criterion A (i.e., active-phase symptoms) and may include periods
of prodromal or residual symptoms. During these prodromal or residual periods, the
d
signs of the disturbance may be manifested by only negative symptoms or two or
more symptoms listed in Criterion A present in an attenuated form (e.g., odd beliefs,
unusual perceptual experiences).
or
D. Schizoaffective and Mood Disorder exclusion: Schizoaffective Disorder and Mood
Disorder With Psychotic Features have been ruled out because either (1) no Major
Depressive or Manic Episodes have occurred concurrently with the active phase
t,
symptoms; or (2) if mood episodes have occurred during active-phase symptoms,
s
their total duration has been brief relative to the duration of the active and residual
periods.
po
E. Substance/general medical condition exclusion: The disturbance is not due to the

direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a
general medical condition.
,
F. Relationship to a Pervasive Developmental Disorder: If there is a history of Autistic

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Disorder or another Pervasive Developmental Disorder or other communication

disorder of childhood onset, the additional diagnosis of Schizophrenia is made only if
prominent delusions or hallucinations are also present for at least a month (or less if
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successfully treated).
Source: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (Copyright 2013). Reprinted
with permission from the American Psychiatric Association. All rights reserved.
t
no
paranoid subtype: a type of in classifying other psychotic disorders. I include the subtypes in this section since they are of
schizophrenia characterized by
historical importance and are currently used in ICD-10.
o
delusions whose themes generally

center on ideas of grandiosity or The paranoid subtype is characterized by delusions whose themes generally center on
D
persecution
ideas of grandiosity or persecution. Individuals with this subtype might tell stories of how the
FBI or CIA is out to get them and they must be constantly vigilant. Normal everyday occur-
rences such as seeing a person with a camera or encountering problems running a computer
program would be interpreted as proof of the persecution. Others with the disorder might tell
of how they have special powers, such as the ability to read someone’s mind. The criterion for
being diagnosed with this subtype excludes disorganized speech, disorganized or catatonic
behavior, or flat or inappropriate affect. Overall, these individuals show the greatest possibility of
improvement.

The disorganized subtype, which was previously referred to as hebephrenic schizophre- disorganized subtype: a type
of schizophrenia characterized by
nia, is characterized by disorganized speech patterns and behavior. Individuals with this sub- disorganized speech patterns and
type display odd speech patterns often referred to as word salad in which a variety of words behavior
are put together in incoherent ways. Affective responses also appear odd to others in that
little affect is shown in response to what should be significant events. Instead, silly or child-
like responses are shown almost randomly. Whereas individuals with the paranoid subtype
tend to have a consistent theme to their delusions, individuals with the disorganized subtype
do not.
The catatonic subtype is characterized by non-normal activity of the motor system. One catatonic subtype: a type of
schizophrenia characterized by
classic symptom is referred to as waxy flexibility in that the individual will remain in a fixed
e
non-normal activity of the motor
position. If someone moves the individual’s arms or legs, he or she will then remain in this new system
ut
position. Motor movement can also be characterized by the opposite condition in which the
individual shows excessive, purposeless activity of his or her motor system. Other possible
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manifestations of this subtype include the repeating of someone else’s speech, referred to as
echolalia, and the repeating of someone else’s movements, referred to as echopraxia. Although
these individuals may copy the speech or movements of others, they may not follow instruc-
t
tions and even refuse to speak.
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Some researchers have suggested that catatonia should be considered a separate disorder and
not part of the schizophrenia group (Fink, Shorter, & Taylor, 2010). Part of the support for this
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position is that these individuals do not respond as frequently to antipsychotic medication, and
or
t,
Understanding Changes in DSM–5
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S C H I Z O PH R E N I A
Since the 1800s, there have been constant debates the paranoid and undifferentiated subtype, the
concerning the nature of schizophrenia. Most others are rarely used in diagnoses. Fourth, a
,
researchers do not consider schizophrenia to be dimensional approach was introduced to rate the
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a single disorder, but rather a number of different severity of the core symptoms of schizophrenia.
disorders (Tandon, 2012). From this perspective, This was established since different individuals with
there are problems in determining exact criteria for schizophrenia show different types of symptoms
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schizophrenia. such as auditory or visual hallucinations.
With this in mind, a number of changes were made Overall, there was less controversy with the change
in DSM–5. First, two of five key symptoms are now in the schizophrenia category in DSM–5 than
required in DSM–5, for a diagnosis of schizophrenia, with changes made in the diagnostic criteria for
t
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whereas DSM–IV required only one. These many other disorders. Some have been critical
symptoms include (1) delusions, (2) hallucinations, that DSM–5 did not rely more on neuroscience-
(3) disorganized speech, (4) disorganized or based criteria. However, as shown in this chapter,
catatonic behavior, and (5) negative symptoms. an exact one-to-one relationship has yet to be
Second, DSM–5 requires that the individual established between brain measures of function,
o
have at least one of the most blatant symptoms: connections, chemistry, or structure and the
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(1) delusions, (2) hallucinations, or (3) disorganized presence of schizophrenia. Others see DSM–5 as a
speech. Third, the subtypes such as paranoid, transition point toward the goal of basing criteria on
catatonic, undifferentiated, and so on, were removed. neuroscience perspectives (e.g., Nemeroff
The basic reason for dropping the subtypes from et al., 2013). Finally, DSM–5 is also seen as a step
DSM–5 was that research has shown that these toward bringing it and the newest version of
subtypes are not stable, and their differentiation ICD closer together on the criteria to be used in
is not supported by clinical evidence. Except for diagnosing schizophrenia (Tandon et al., 2013).

about 70% respond to the drug lorazepam alone. Lorazepam is a benzodiazepine associated with
relaxation and is often given for treatment of anxiety disorders.
If an individual shows signs of schizophrenia but does not fit in any of the three major sub-
types—paranoid, disorganized, or catatonic—then he or she would be diagnosed with an undif-
ferentiated subtype.
A final subtype is referred to as the residual subtype. Individuals with this subtype have had
schizophrenic episodes but no longer display the traditional positive symptoms of delusions and
hallucinations. They may still display strange ideas or odd behaviors.
There has been considerable debate as to the value of using the five subtypes for diagnosis
and treatment. Part of this debate involves a larger question of whether schizophrenia should be
e
considered in terms of discrete categories or existing along a dimension. If schizophrenia exists
ut
along a dimension, then it would be meaningless to consider categories or subtypes (Linscott,
Allardyce, & van Os, 2010). An additional question is whether the subtype information is actu-
rib
ally used in making diagnoses and designing treatment. As noted, DSM–5 dropped the use of
subtypes.
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is
CO N C E P T C H E CK
•• The symptoms of schizophrenia are characterized as positive symptoms
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and negative symptoms.
{{ What is the definition of each symptom type?
or
{{ What are primary examples of each type?
{{ What role does each type play in the course of schizophrenia?
•• How are the four stages of the course of schizophrenia defined, and when do they typically
t,
occur? Is the course the same for each individual? If not, how does it differ?
•• What can we say about the prevalence of schizophrenia across the life span? Across genders?
s
•• The DSM has set forth a multilevel process for diagnosing schizophrenia. What are the
po
characteristics of each of the levels?

•• What are the five subtypes of schizophrenia as defined by DSM–IV, and how are they
characterized? How are they used in the current edition, DSM–5, and what led to the change?
,
Historical and Evolutionary

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Perspectives on Schizophrenia
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As you will see in this section, schizophrenia has been described for thousands of years. As pro-
fessionals began to study the disorder through case studies in the 1800s, different aspects were
emphasized. As techniques from evolution and genetics were applied in the 1900s, it became
apparent that schizophrenia is a very old disorder. In fact, schizophrenia was probably present
t
no
when humans moved out of Africa some 100,000 years ago. As will be evident, genetics points to
schizophrenia as a complex disorder that cannot be explained by single genes. A current focus of
research is to discover underlying features of the disorder.
o
Historical Perspective
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Disorders with psychotic-like symptoms have been described for at least 4,000 years (Tandon, 2012;
Tandon et al., 2009; Woo & Keatinge, 2008). In addition, medical texts have been found through-
out the ancient world that suggest that psychosis was present in all cultures. By the 1800s, the pres-
ent-day terms of schizophrenia were being introduced. The German physician Ewald Hecker in
the 1870s referred to a silly, undisciplined mind as Hebephrenia, named after the Greek goddess of
youth and frivolity, Hebe. Figure 13.3 shows the evolution of the concept of schizophrenia.
In 1874, the German physician Karl Ludwig Kahlbaum used the terms paranoid and
catatonic. Paranoid referred to the idea that someone felt himself or herself to be in danger.

FIGURE 13.3 Evolution of the Concept of Schizophrenia

Source: Tandon et al. (2009, p. 3). Used with permission from Elsevier.
Historical influences Evolution of the Concept of Schizophrenia: A Historical Framework
Focus on validity
Existing treatments
Neurodegenerative Psychobiology Divergence between Focus on Minor found to be less
disease model Adolf Meyer ICD & DSM systems reliability changes diagnostically specific
Psychoanalytic “Schneider vs. Bleuler” Side effects of DSM-ICD Genetic & other neu-
e
model Advent of effective antipsychotics conver- robiological data
Expanding antipsychotic agents Advent of lithium gence suggest blurred
ut
neurodiagnostic International Pilot Response to diagnostic boundaries
methods Study of Schizophrenia Cooper Study How to explain
Hecker, heterogeneity?
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Kahlbaum
Author
Greisinger, Kraepelin Bleuler Schneider DSM-I DSM-II DSM-III DSM-III-R & DSM-IV DSM-5 & beyond
Morel ICD-1 ICD-6-7 ICD-8 ICD-9 ICD-10 ICD-11 & beyond
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is
VS. Unitary psychosis
Broad
Toward
d
schizo- Very
Mildly deconstructing
phrenia
Many psychoses
narrow schizophrenia
Concept
Schizo- Schizo- broadened

Dementia concept schizo-
phrenic schizophrenia/ OR psychosis:
praecox phrenia (latent,
or
reaction phrenia dimensions &
pseudo- psychosis concept
concept intermediate
neurotic
phenotypes
Secondary
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Manic schizophrenias,
Depressive e.g., Pellagra,
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Encephalitis
Timeframe
Insanity
Lethargica
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1850s 1900s 1950s 1960s 1970s 1980s 1990s 21st century

,
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Catatonic referred to the mannequin-like muscle stiffness associated with unusual postures.
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In 1878, Emil Kraepelin combined these various disorders into a single disease entity, which
he termed dementia praecox or dementia of early onset. The word early referred to the fact
that schizophrenia developed early in life rather than as part of a decline in mental functions
associated with the dementias of old age. Overall, Kraepelin established what we now refer
t
no
to as schizophrenia as a disorder with an onset in early adulthood that shows chronic and
deteriorating progression and results in pervasive impairments in mental functions over the
life span.
Kraepelin suggested there were four subtypes of dementia praecox. The first was the simple
© Science Source
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type, which was characterized by a slow decline along with social withdrawal and apathy. The
second type was paranoid, characterized by fear of persecution. The third type was hebephrenic,
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characterized by a mania-like presentation. The fourth type was catatonia, characterized by a lack
of movement. Kraepelin differentiated dementia praecox from what Falret in 1854 referred to as Emil Kraepelin
folie circulaire. Kraepelin referred to folie circulaire as manic–depressive insanity. Thus, Kraepelin
established manic depression, which we refer to today as bipolar disorder, as a separate category
from schizophrenia.
In 1911, Eugene Bleuler introduced the term schizophrenia, from the Greek meaning to split
the mind. Bleuler was critical of the term dementia praecox and suggested that there was not a sin-
gle schizophrenia but a number of different disorders or schizophrenias with different etiologies

and prognoses. There were, however, a series of characteristics described by Bleuler often referred
to as the four As.
1. Affect—Blunted or diminished emotional response

2. Associations—Loosening or inability to think in a logical manner
3. Ambivalence—Inability to make decisions
4. Autism—Social aloofness and an inability to remain in contact with the external
world
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Public domain
These four As were thought to be unique to schizophrenia and present in those with the
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condition.
In the 1950s, the DSM was introduced and described psychosis in broad terms as a disorder
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Eugene Bleuler resulting in serious functional impairment. Schizophrenia was differentiated from organic disor-
ders such as neurocognitive disorders (dementia), which may produce psychotic behaviors. By
DSM–III, schizophrenia was defined by more explicit criteria. In DSM–IV and DSM–IV–TR, the
t
criteria for schizophrenia were broadened. This made the diagnostic criteria used in the United
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States with DSM and Europe with the ICD system more similar, thus reducing the differential
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diagnosis rates.
Case of James Stern or

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S C H I Z O PH R E N I A
s
James Stern is a 20-year-old, single, Caucasian male usage because of his growing realization that the
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who is a full-time student at a nearby university where marijuana magnified feelings of paranoia that resulted
he also works part-time to offset living expenses. in isolating himself in his room for days amidst a
He resides off campus with three roommates, and growing suspiciousness that his roommates and
has been in an off-again, on-again relationship with classmates had been infiltrated by “dark forces” that
,
his girlfriend since high school. He first sought posed an increasing threat to mankind.
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treatment at a local student counseling center

for anxiety, depression, and general distress at Following his cessation of marijuana use, James
the urging of his family, but was then referred for continued to struggle with perceptions that his
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longer-term individual psychotherapy due to the professors were dropping surreptitious clues for him
increasing severity of symptoms that were described to decipher regarding the “dark forces” he still feared
by his therapist as paranoid ideation, ideas of were infiltrating society, and he began to believe that
reference, increasing distress, and dysphoric affect. those forces may have already “taken over” at least
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two of his roommates. At this point, his paranoia

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Mr. Stern confirmed that he had experienced and fears about “evil forces” escalated rapidly, and
symptoms that “others described as sounding he began to intermittently see “demons” moving
paranoid” since high school, although he also reported among people. His distress elevated to the point that
that throughout his developmental years, he felt a he refused to leave his apartment bedroom, which
lack of connection with his family and had few, if any, forced his withdrawal from school and termination
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close friends throughout his primary and secondary of employment. Mr. Stern has been diagnosed with
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school years. While he noted that he was always schizophrenia. Since beginning psychotherapy and
somewhat suspicious and guarded, he also reported pharmacotherapy, he has reported moderate to
that these feelings became much more intense after marked reductions in paranoia and distress, although
he relocated to the current local university from a he continues to report intermittent suspiciousness
much smaller college near his hometown. During this and ongoing uncertainty about his future in multiple
same time period, James also reported that he became domains (e.g., relationship, academic, and career
increasingly reliant on the daily use of marijuana to goals).
ease/cope with associated symptoms of anxiety and
distress. He was eventually “forced” to eliminate his Clinical vignette provided by Sandra Testa Michelson, PhD.

As noted earlier in this chapter, like DSM–IV–TR before it, DSM–5 includes a multilevel
process for making a diagnosis of schizophrenia: symptoms, functioning, and duration.
The case of James Stern (not his real name) illustrates difficulties in all three areas of
functioning.
Evolutionary Perspective
There is an evolutionary paradox with schizophrenia (Huxley, Mayr, Osmond, & Hoffer,
1964)—individuals with schizophrenia have fewer children than others, and males with schizo-
phrenia have even fewer children than females with schizophrenia. Given this situation, one
e
would expect that the disorder would disappear over evolutionary time, and the genes of indi-
ut
viduals with schizophrenia would not be passed on to the next generation. This, however, is not
the case. How can the disorder exist without a reproductive advantage? A number of sugges-
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tions have been made. One is that the genes associated with schizophrenia are also associated
with positive traits such as creativity, cognitive abilities, and language (Srinivasan et al., 2015).
It has been noted that many highly gifted and creative individuals manifest schizophrenic- schizotypal traits:
t
like traits, referred to as schizotypal traits, without having the disorder. However, it is not schizophrenic-like traits
is
uncommon for these individuals to have a first-degree relative with schizophrenia, suggesting a
genetic component. Andreasen (2005) suggested there may be a connection with scientific cre-
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ativity and schizophrenia within one’s family. She noted that a number of Nobel laureates had
family members who were thought to have schizophrenia, including Albert Einstein, Bertrand
or
Russell, and John Nash. (As mentioned earlier, John Nash’s story was described in the book and
film A Beautiful Mind.) But this still leaves open the question of how schizophrenia came about.
Two separate theories related to the evolutionary existence of schizophrenia were proposed
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by Tim Crow (2000) and Jonathan Burns (2004). Both of these theories note that schizophrenia is
found throughout the world in approximately the same prevalence across cultures, and it is found
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in populations that have been separate from one another for at least 50,000 years. Since similar
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rates are seen in both industrialized and agrarian societies, this suggests that schizophrenia has
existed as a part of the human experience since at least the time humans began migrations out of
Africa some 100,000 years ago. If it were a newer disorder, then one would expect to find different
,
rates in populations of humans in different parts of the world.

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GL Archive/Alamy
Tim Crow (2000) suggested that the development of language and the genetic changes
required for producing and understanding speech were associated with the development of
schizophrenia. Since the time of both Broca and Hughlings Jackson in the 1800s, it has been
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known that the brain is lateralized, with linguistic functions associated with left hemispheric net-
works. In 1879, Crichton-Browne suggested that since language processes evolved more recently A number of Nobel laureates
had family members who were
than many other brain processes, these might be the first involved with mental disorders. Crow thought to have schizophrenia,
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noted how one common positive symptom in schizophrenia around the world is the experience including Albert Einstein.
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of hearing voices, which are experienced as separate from one’s normal thought processes. This
suggests a disruption in normal language processes resulting from incomplete differentiation of
the hemispheres, leading to a loss of the ability to differentiate thought and speech. Crow and his
colleagues (Angrilli et al., 2009), using electroencephalography (EEG), showed that individuals
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with schizophrenia compared with normal controls failed to show a left hemispheric dominance
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when processing language.

Jonathan Burns (2004) suggested that schizophrenia is better understood as a disorder of
the social brain rather than of language ability. For Burns, schizophrenia results from disordered
connections from the frontal to temporal areas and the frontal to parietal areas, which are critical
brain connections related to social functioning. Historically, schizophrenia for Burns exists as the
result of a trade-off at two separate stages of cognitive evolution in humans.
The first trade-off occurred between 2 and 16 million years ago. It was during this period that
our species evolved specialized neural processing and complex interconnections of the brain
required to respond to group living. To perform the tasks required for social living, a higher level

of cognitive functioning was required. In order for the brain to develop the circuits required,
brain maturation was lengthened. That is, given the physical constraints of the developing brain
in the human fetus, brain development time needed to be lengthened. This trade-off meant that
the developing brain experienced a long period of time in which complex gene interactions or
accidents could happen.
The second trade-off for Burns (2004) happened more recently, about 100,000 to 150,000
years ago. This date is important. Since schizophrenia is seen in all cultures with similar symp-
toms, it is assumed that the genes involved in its manifestation would have evolved before human
groups began migrations out of Africa. What happened at this point was that some individu-
als experienced non-normal connections in the frontal areas of the brain. These connections
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resulted in some individuals being especially creative and thinking in different ways. These indi-
ut
viduals may have been able to make important contributions to culture, much as our present-day
artists and creative thinkers do. However, some individuals demonstrated a more severe version
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of these connections, which resulted in psychopathological experiences. Burns further suggested
that this different way of experiencing the world in either its mild or severe form did not have any
reproductive advantage. However, since the genes that controlled these experiences evolved as a
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part of the larger cortical networks needed for the cognitive and intellectual demands of social
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life, these genes continued to be passed on through their connections with adaptive mechanisms.
Thus, according to Burns, schizophrenia represents one of the prices paid for evolving complex
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cognitive and social abilities. Further, it should be noted that ancient burial sites have bones of
older individuals with various deformities. Since these individuals could not have survived with-
or
out care from others, this suggests to some that individuals with schizophrenia-like symptoms
may also have been cared for and made part of the community.
t,
s
•• What can we say about the prevalence of schizophrenia across history? Across the world?
po
•• “Disorders with psychotic-like symptoms have been described for at least 4,000 years.”
Describe four important advancements in the development of the concept of schizophrenia
since 1850.
,
•• Describe the evolutionary paradox that schizophrenia presents. What different theories did Crow
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and Burns present to explain the paradox?
Factors in the Development of Schizophrenia

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Schizophrenia typically is first noted during the transition from late adolescence to adulthood.
However, theories related to its development generally see its onset at this time as the manifestation
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of a process that may have begun before the individual was born (Uhlhaas, 2011). In a review of
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birth cohort studies in which individuals are followed from birth, there is evidence to suggest that
children who later develop schizophrenia show different profiles from those who do not (Welham,
Isohanni, Jones, & McGrath, 2009). These data from seven different countries show subtle deficits
in terms of behavioral disturbances, intellectual and language deficits, and early motor delays.
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The current research literature suggests that schizophrenia is a disorder that begins early in
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life. This has led some researchers to suggest that we consider schizophrenia as a neurodevel-
opmental disorder (Insel, 2010). A variety of negative events can happen to a fetus including
infections and malnutrition. It has been shown, for example, that vitamin D deficiency during
pregnancy can be a risk for developing schizophrenia (McGrath, Burne, Féron, Mackay-Sim, &
Eyles, 2010). Likewise, maternal infection is now regarded as a potential risk factor for schizo-
phrenia (A. Brown & Patterson, 2011).
Overall, the theory that development of schizophrenia involves events experienced during
pregnancy is referred to as the neurodevelopmental hypothesis. The basic idea is that during the
time the fetus is in utero, an insult happens that influences the changes to the brain that later take
place during adolescence.

Weinberger (1987) was one of the originators of the neurodevelopmen-

tal view and suggested that problems during the second trimester lead to an
incomplete development of frontal lobe networks in the brain during adoles-
cence. Currently, the neurodevelopmental hypothesis itself is not completely
developed. However, the second trimester has clearly been noted as an impor-
tant period in brain development.
What can be described about the reorganization of brain processes during
adolescence in relation to schizophrenia? We know that adolescence is a time
of great reorganization of cortical networks. Gogtay, Vyas, Testa, Wood, and
Pantelis (2011) reviewed two longitudinal studies with this question in mind.
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The first data set was composed of individuals who developed schizophre-
ut
nia before puberty and has been studied at the National Institute of Mental
Health (NIMH). The second data set was from Melbourne, Australia, and
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included adolescents who are ultra-high risk for schizophrenia. Imaging stud-
ies showed larger ventricles and greater gray matter loss in the parietal and
frontal areas in children who developed schizophrenia before puberty as com-
Bubbles Photolibrary/Alamy
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pared with those who developed schizophrenia in adulthood. The data set
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from Australia indicated that those adolescents who developed schizophrenia
showed greater gray matter loss, especially in the prefrontal cortex (PFC), as
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compared with those who did not develop the disorder.
Environmental factors can also play a role in the development of schizo-
or
phrenia (van Os, Kenis, & Rutten, 2010). The basic idea is that environmental factors can influence Adopted children from families
the developing social brain and lead to the development of schizophrenia in those at risk. Such with schizophrenia show a
similar rate of schizophrenia
factors as early life adversity, growing up in an urban environment, and cannabis use have been
t,
development to those raised
associated with the development of schizophrenia. Being part of a particular ethnic group is not with their natural families.
s
This implies that the manner
associated with schizophrenia per se, if the ethnic group lives together, but if one is a minority in a in which individuals are reared
larger ethnic group, then there is an association. Also, if one moves from an urban environment to
po
is not directly related to the

a rural one, then the chance of having schizophrenia goes down. Overall, greater amounts of stress development of schizophrenia.
are associated with greater chances of developing schizophrenia. However, environmental factors
continue to reflect an interaction with genetic influences and are not a sole condition in themselves
,
for developing schizophrenia (Sariaslan et al., 2016).

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Genetic Factors in Schizophrenia

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Since schizophrenia tends to run in families and is seen throughout the world, it is assumed to
have a genetic component. That is to say, the risk of developing schizophrenia is much higher if
someone else in your family also has the disorder. As can be seen in Figure 13.4, schizophrenia
t
indeed has a strong genetic component. The more similar the genes between two individuals, one
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of whom has schizophrenia, the more likely the other person will also develop its characteristics.
However, the genetic underpinnings of schizophrenia are not simple. It is clearly not the result of
a single gene as with some other neurological disorders such as Huntington’s disease.
Research suggests that the number of genetic variants seen in individuals with schizophrenia
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is very large. There may be 1,000 different genes contributing to the disorder, which also include
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rare genetic variants (T. D. Cannon, 2015; E. Walker, Shapiro, Esterberg, & Trotman, 2010; Wray
& Visscher, 2010). These genes may act in an additive or interactive manner to produce the dis-
order. In other words, there may be a variety of genetic combinations that are associated with
schizophrenia. For example, heritable traits such as white matter connections and the thickness
of gray matter in the brain are reduced in individuals with schizophrenia.
Those with schizophrenia show both fewer connections that link different parts of the brain
and a reduction of dendrite connections at the level of the neuron. Adolescence and early adult-
hood bring extensive elimination of synapses in distributed association regions of the cerebral
cortex, such as the prefrontal cortex. An impairment of this process takes place in those with
schizophrenia. Research suggests that this is related to variations in the HMC locus, particularly

the genetic allele called component 4 (C4) (Sekar et al., 2016). This suggests that schizophre-
nia should be viewed as a developmental disorder that takes place as the brain is reorganized in
adolescence.
Further, the genetic factors that influence the correlation between schizophrenia and white
matter measures were found to be different from the genetic factors that influence the correlation
between schizophrenia and reduced gray matter thickness (Bohlken et al., 2015). That is, there
are different genetic pathways for each type of deficit.
In addition, individuals with schizophrenia compared with healthy controls show more
abnormalities in their deoxyribonucleic acid (DNA) in the form of deletions or duplications of
DNA sequences. Surprisingly, these gene abnormalities are even seen in the monozygotic (MZ)
e
twin who does not develop schizophrenia as compared with the one who does. This suggests that
ut
these abnormalities are the result of both inherited and non-inherited factors.
If schizophrenia were a totally inherited disorder, then if one MZ twin developed the disorder,
rib
the other would also. However, this is not the case. There are three factors that may be playing a role
in this situation. First, as genes are reproduced during fetal and later development, there may be
slight changes in one twin as compared with the other. These are referred to as copy number varia-
t
tions. Maiti, Kumar, Castellani, O’Reilly, and Singh (2011) studied copy number variations in MZ
is
twins from families with schizophrenia and found genetic differences in the twins. Thus, even iden-
tical twins can show differences in their total genetic makeup. Second, differences in twins may not
d
result from differences in the DNA itself but from the results of epigenetic factors in which genes of
an affected individual may be turned on differently from those of a non-affected individual, suggest-
or
ing that internal and external environmental factors play a role (S. King, St-Hilaire, & Heidkamp,
2010). And third, environmental factors may play a role that does not involve genetic changes.
A number of studies over the years have shown that there is a higher concordance rate for
t,
MZ twins than for DZ twins. However, because of differences in how these studies were con-
s
ducted in terms of diagnostic characteristics of schizophrenia, the concordance rates differ. Yet,
in every study, MZ twins show a higher rate than DZ twins, supporting the importance of genet-
po
ics. The initial studies of the 1990s show a 48% concordance rate for MZ twins. This suggests that
the environment plays an important role. Although environmental stress is known to exacerbate
the disorder, there is little evidence that psychological stress can actually cause schizophrenia.
,
Further, adopted children from families with schizophrenia show a similar rate to those raised
py
with their natural families. This implies that the manner in which individuals are reared is not
directly related to the development of schizophrenia.
Other work has suggested a role for poor maternal nutrition or infections during fetal peri-
co
ods. However, this work is also inconclusive. A more recent review of the genetics of schizophre-
nia indicates a higher concordance rate for MZ twins and schizophrenia—82% (Rutter, 2006).
Recent speculation suggests that epigenetics (see Chapter 2) may offer a more viable mechanism
t
for the development of schizophrenia (Petronis, 2004).

no
Another way to examine the genetic factor is to look at adolescents whose parents had schizo-
phrenia. When compared with healthy controls, adolescents who did not have schizophrenia
but whose parents did were shown to have dysfunctional interactions within cortical networks
involved in emotional processing (Diwadkar et al., 2012). This suggests an endophenotype could
o
be connected with schizophrenia.

D
Endophenotypes Associated With Schizophrenia

Presently there is no one biomarker that can identify a person with schizophrenia. A num-
ber of researchers have sought to find endophenotypes related to schizophrenia (see Miller &
Rockstroh, in press, for an overview). As described in Chapter 2, an endophenotype is a pattern
of processes that lies between the gene (the genotype) and the manifestations of the gene in the
external environment (the phenotype). These processes can be biological, such as white and gray
matter integrity or patterns of EEG activity. They can also be a higher-level psychological process

such as difficulties with memory or difficulties in recognizing emotional changes or empathy. The
only requirement is that there is a pathway from the gene to the endophenotype to the phenotype.
In the case of psychopathology, the phenotype is typically the clinical expression of a disorder.
These stable internal physiological or psychological markers associated with schizophrenia
have been found in a variety of areas. In one review of the literature, which compared individuals
with schizophrenia, their relatives, and healthy control individuals, endophenotypes were found
in five major areas (A. J. Allen, Griss, Folley, Hawkins, & Pearlson, 2009).
•• The first area is minor physical anomalies, which include differences in head or body
size or motor movements.
e
•• The second area of physiologic abnormalities is based on the membrane theory of
ut
schizophrenia. This theory suggests that normal metabolism in the brain is dis-
turbed in individuals with schizophrenia.
rib
•• The third area is neuropsychological measures. Studies reviewed in this area include
such measures as the Wisconsin Card Sorting Test (WCST), in which the person
must respond to changing demands, and the Continuous Performance Task, which
t
measures attentional abilities.
is
•• The fourth area involves neuromotor abnormalities. One task has to do with smooth
pursuit eye movement. Individuals with schizophrenia show a different pattern of
d
eye movement if asked to follow a person’s finger moving from right to left in front
of them. Rather than showing a smooth motion of eye movement, they show peri-
or
ods of quick pursuit in which they attempt to catch up with the finger movement.
•• The fifth area is sensory processing and event-related potentials. Numerous studies
have shown EEG differences between individuals with schizophrenia and others. In
t,
response to cognitive tasks, the evoked potential waveforms of P50, P300, and N400
were noted as important.
s
po
As can be seen in Figure 13.4, individuals with schizophrenia and their first-degree
relatives without schizophrenia show similar responses to tasks in the five areas. This sug-
gests an endophenotype related to schizophrenia but not a definitive biomarker of the
disorder.
,
py
co
FIGURE 13.4 Endophenotype Percent Abnormal Averages

Anomalies and Schizophrenia
Minor Physical
In terms of endophenotype anomalies, Anomalies
t
those with schizophrenia show the most,

no
followed by their relatives, and the least

Endophenotype Category
Physiologic
are shown by healthy controls. This figure Abnormalities
shows the average percentage abnormal
for each endophenotype category for Neuropsychological
Measures
o
those with schizophrenia (SC), their

relative (REL), and healthy controls (HC).
D
Neuromotor
Source: Allen et al. (2009, p. 31). Used
Abnormalities
with permission from Elsevier.
Sensory Processing
and Event−Related
Potential Measures
0.0 60.0
Percentage Abnormal
HC REL SCZ

Recent reviews of the literature suggest that cognitive deficits are among the most impor-
tant symptom of schizophrenia, especially in terms of their impact on society and quality of
life (G. Miller & Rockstroh, in press). Factor analyses by Seidman et al. (2015) of data from 83
schizophrenia patients, 151 unaffected siblings, and 209 community comparison participants
yielded five distinct cognitive factors. These factors are episodic memory, working memory,
perceptual vigilance, inhibitory processing, and visual abstraction. Each of these factors was
shown to be significantly heritable. Another review emphasizes the importance of social cog-
nition in schizophrenia (Green, Horan, & Lee, 2015). Deficits in the ability to perceive social
cues, regulate social emotions, and share with others are seen as potential endophenotypes
related to schizophrenia. At this point, research studies are focused on determining appropri-
e
ate biological and psychological endophenotypes related to schizophrenia, although a final list
ut
has yet to be determined.
In a series of papers, Rajiv Tandon and his colleagues (Tandon, 2012; Tandon et al., 2009;
rib
Tandon et al., 2013) reviewed the literature to determine what aspects of schizophrenia have been
shown to be stable through a number of replications. These are presented in Table 13.3. These
researchers also suggested that a dimensional approach including the study of endophenotypes
t
will be important in future conceptualizations of schizophrenia.
d is
or
TABLE 13.3 Clinical “Facts” of Schizophrenia
•• Schizophrenia is generally diagnosed on the basis of the presence of positive

symptoms in conjunction with impaired social function in the absence of significant
t,
mood symptoms, other recognizable neurological illness, or substance use that can
s
account for the psychotic symptoms.
•• The nosological boundaries between schizophrenia and other psychiatric disorders
po
are indistinct.
•• There is significant heterogeneity in neurobiology, clinical manifestations, course, and
treatment response across patients.
•• Schizophrenia is characterized by an admixture of positive, negative, disorganization,
,
cognitive, psychomotor, and mood symptoms.

py
•• The severity of different symptom clusters varies across patients and through the
course of the illness.
•• There is a generalized but highly variable cognitive impairment.
co
•• There may be additional specific impairment in a range of cognitive functions (such

as executive functions, memory, psychomotor speed, attention, and social cognition).
•• Cognitive impairments are present prior to onset of psychosis and persist during the
course of the illness.
t
•• There is a higher occurrence of obesity and cardiovascular disease.

no
•• There is increased prevalence of cigarette smoking and other substance use

disorders.
•• There is increased suicidality.
•• There is some phase-specific increase in violent behavior.
•• There are significant premorbid impairments in a substantial proportion of patients.
o
•• Onset of psychotic symptoms is usually during adolescence or early adulthood.

D
•• The age of onset is earlier in males.

•• There is an approximate doubling of age-standardized mortality.
•• Schizophrenia is frequently a chronic and relapsing disorder with generally incomplete
remissions.
•• Social outcomes include reduced rates of employment and financial independence,
and increased likelihood of homelessness and incarceration.
•• Poor outcome is predicted by male gender, early age of onset, prolonged period of
untreated illness, and severity of cognitive and negative symptoms.
Source: Adapted from Tandon et al. (2009). With permission from Elsevier.

CO N CE P T C H E CK
R E S E A R C H T E R M S TO K N OW
•• Schizophrenia typically is first noted during the transition from late
adolescence to adulthood, but current research suggests that the
Factor Analysis
disorder begins early in life. What evidence from research into genetic and Factor analysis is a statistical technique
environmental factors points to this characterization? that allows us to know which variables
•• “Schizophrenia has a strong genetic component.” But it’s not simple and go together. Typically, a factor analysis
straightforward. What three factors that we’ve learned from research with MZ study will collect a large number of
twins help to explain this genetic component? variables on a group of individuals. The
•• There is currently no one biomarker to identify an individual with statistical technique creates factors
e
schizophrenia. However, what five internal physiological or psychological that describe which of these variables
markers associated with schizophrenia suggest a potential endophenotype are responded to in a similar way. For
ut
related to schizophrenia? example, if a number of individuals
were given a variety of cognitive tests,
rib
it is possible to see that those who
Causes and Effects: Neuroscience do well on one type of problem also
Findings About Schizophrenia do well on another. One study found
t
five factors related to intelligence.
is
In this section, I will discuss structural and functional changes in the brain that These were reasoning, spatial ability,
are related to schizophrenia. This will include the manner in which chemical memory, processing speed, and
d
and electrical information moves throughout the brain. The section ends with vocabulary (Deary, Penke, & Johnson,
a look at the cognitive changes found in schizophrenia. One of the more inter- 2010). Another study examined
or
esting phenomena seen in schizophrenia, which I will discuss at the end of this psychopathology over 20 years in
section, is the Charlie Chaplin illusion in which those with schizophrenia see a terms of personality functioning,
mask from an opposite perspective in comparison to those individuals without life impairment, family histories and
developmental histories of psychiatric
schizophrenia.
t,
disorders, and measures of brain
s
integrity (Caspi et al., 2014). These
Schizophrenia and Brain Function researchers reported three factors.
po
These were an internalizing liability

Schizophrenia manifests on a variety of levels including abnormal sensory expe-
related to depression and anxiety,
riences such as hallucinations, problems in cognitive processes such as delusions an externalizing liability related to
and disordered thought, changes in affect such as lack of expression, and in some antisocial and substance-use disorders,
,
cases problems with language and future directed planning. This presents a chal-
py
and a thought disorder liability related

lenge to describe the manner in which brain processes relate to the disorder. to symptoms of psychosis.
Current research examining individuals with schizophrenia has emphasized
five different neuroscience measurements. The first is anatomical changes such
co
as the loss of brain volume in particular areas. The sec-

ond is functional processes such as the manner in which
cortical areas and networks process information as seen
t
in brain imaging. The third is neural oscillations that

no
underlie the cortical networks. The fourth is changes in

neurotransmitters such as dopamine, GABA, glycine,
and glutamate. And the fifth is the development of corti-
o
cal processes beginning in utero.

A variety of studies have shown that individuals
D
with schizophrenia have emphasized differential activ-

ity in the dorsolateral prefrontal cortex (DLPFC), the
ACC, and the thalamus (see Minzenberg, Laird, Thelen,
Peter Beck/Corbis/Getty Images
Carter, & Glahn, 2009, for a meta-analysis). Due to its

involvement with executive function tasks such as plan-
ning and social tasks, the frontal lobes have been exten-
sively studied. When examining the entire brain and
schizophrenia, other reviews point to enlargement of
the ventricles and abnormalities of the medial temporal

FIGURE 13.5 Differential
Activity in the Brain Related to
Symptoms of Schizophrenia
The ventrolateral prefrontal cortex
(VLPFC) is associated with negative
symptoms (red) and medial prefrontal
activity with positive symptoms
(yellow). The figure shows differential
brain activity exhibited in schizophrenia
e
by positive symptoms, negative
symptoms, and disorganization.
ut
Source: Goghari et al. (2010, p. 481).
Used with permission from Elsevier.
rib
lobe structures, including the amygdala, hippocampus, and neocortical temporal lobe func-
tions (Shenton, Dickey, Frumin, & McCarley, 2001). More recent reviews point to a connection
t
is
between the DLPFC and disorganized symptoms (Goghari, Sponheim, & MacDonald, 2010). In
addition, the ventrolateral prefrontal cortex (VLPFC) was found to be associated with negative
d
symptoms and the medial prefrontal activity with positive symptoms (see Figure 13.5).
The EEG reflects the electrical activity of the brain at the level of the synapse (Nunez &
or
Srinivasan, 2006). It is the product of the changing excitatory and inhibitory currents at the syn-
apse. The neural oscillations seen in the EEG offer a window for understanding how brain pro-
cesses influence cortical networks, which can reflect normal cognitive, emotional, and motor
processes. More low-frequency oscillations seen in the theta (4–7 Hz) and alpha (8–12 Hz)
t,
ranges reflect longer distant relationships in the brain, whereas higher frequency oscillations
s
in the beta (13–30 Hz) and gamma (30–200 Hz) ranges reflect more local cortical networks
po
(Uhlhaas & Singer, 2011, 2012).

Activity in the four frequency bands has been associated with a variety of cognitive processes
in normal functioning. Since individuals with schizophrenia may show deficits in these cognitive
processes, the study of cortical oscillations offers important insights into how schizophrenic pro-
,
cesses affect the brain.

py
Cortical networks in the brain begin in utero and the period following birth. However, the
development of these networks is not perfectly continuous. There is also a fundamental reorga-
co
nization of these networks in adolescence (Uhlhaas et al., 2009; Uhlhaas & Singer, 2011, 2012).
The reorganization during adolescence is reflected in both cognitive performance and EEG
synchrony (Uhlhaas et al., 2009). Prior to adolescence, there is a period of increase over the
years in both cognitive performance and EEG synchrony. This synchrony is reflected in similar
t
EEG activity displayed in a variety of sites throughout the brain. However, during adolescence
no
there is a decrease in both. After this period, there is a reorganization of EEG activity such that
the synchrony is more focused at specific EEG sites, especially parietal and occipital electrodes.
Figure 13.6 depicts three critical periods in which changes in the physiology and anatomy
o
of cortical processes would show changes consistent with the neurodevelopmental hypothesis
of schizophrenia. The first period is fetal development in which genetic and epigenetic factors
D
impair the electrical activity of the brain and with that the rhythmical activity associated with the
formation of cortical circuits. Adverse experiences during fetal development are associated with
the development of schizophrenia (Debnath, Venkatasubramanian, & Berk, 2015). The second
stage involves the reorganization of cortical networks seen in adolescence. Along with this come
changes in white and gray matter as well as neurotransmitters. Although all adolescents show
gray matter declines in the PFC during this period of synaptic pruning, declines are higher in
individuals with schizophrenia (Karlsgodt, Sun, & Cannon, 2010). The third stage describes
the situation in which individuals with schizophrenia fail to develop the coordinated networks
necessary for normal cognitive processes.

FIGURE 13.6 Critical Periods Related to the Brain and Schizophrenia

As schizophrenia develops, cortical networks cease to work as large-scale networks. This figure shows the three critical periods
and key changes in the physiology and anatomy of these cortical processes.
Source: From Peter J. Uhlhaas and Wolf Singer. “The Development of Neural Synchrony and Large-Scale Cortical Networks During Adolescence:
Relevance for the Pathophysiology of Schizophrenia and Neurodevelopmental Hypothesis.” Schizophrenia Bulletin, 2011 May; 37(3): 514–523,
by permission of Oxford University Press.
Large-Scale Disintegration Leads

Reorganization of Cortical to Emergence of Psychosis
Networks Confers Vulnerability
e
Pre-/Perinatal Insult
ut
t rib
d is
0 15 20 Age (years)
Genetic and epigenetic factors Increase in high-frequency oscillations In schizophrenia, late maturational processes
or
impair electric, rhythmic activity and long-range synchrony during late are aberrant and networks fail to express
and lead to the malformation of adolescence is associated with a transient precisely coordinated network oscillations.
cortical circuits destablization of network functions. Psychotic symptoms emerge as the result of
the large-scale disintegration of network activity.
Physiological and anatomical correlates:
t,
myelination, synaptic pruning, maturation
of GABAergic and dopaminergic
s
neurotransmission
po
CO N CE P T C H E CK
,
•• According to current research, what are the five different neuroscience measurements related to
py
individuals with schizophrenia?

•• What are the three critical periods of neurological changes in the development of schizophrenia?
co
What Brain Changes Are Seen in Schizophrenia?

Exactly when brain changes take place in those with schizophrenia is an important question.
In order to better understand the role of timing in terms of brain structure, John Gilmore and
t
his colleagues (2010) performed imaging studies before and after birth. These researchers used
no
ultrasound scans prior to birth and magnetic resonance imaging (MRI) scans after birth while
the babies slept. They compared children whose mothers had schizophrenia with a matched
control group whose mothers did not have the disorder. Using ultrasound prior to birth, they
o
found no differences between the two groups. After birth, males whose mothers had schizophre-
nia showed more gray matter in the brain, increased cerebrospinal fluid, and larger ventricles.
D
Female infants did not show any differences. This suggests that at least the endophenotype for
schizophrenia in males can be seen early in life.
Neuroimaging studies of those with schizophrenia have included both structural and func-
tional approaches (Karlsgodt et al., 2010; Shenton & Turetsky, 2011). Structural approaches have
focused on gray matter and white matter differences as well as the size of the ventricles (T. D.
Cannon, 2015; Thompson et al., 2001). In a variety of reviews, both general and specific reduc-
tions in gray matter have been reported for individuals with schizophrenia. Specifically, reduc-
tions have been noted in the temporal cortex, especially the hippocampus, the frontal lobe, and
the parietal lobe. In addition, the striatum part of the basal ganglia has been shown to be reduced

FIGURE 13.7 Gray Matter

Reductions in Schizophrenia
Even if they are identical (monozygotic, or MZ)
twins, if one has schizophrenia there are gray
matter reductions. This figure shows average gray
matter deficit between identical twins. One twin has
schizophrenia and the other does not. Note: Color
represents the difference in gray matter between
the twins.
e
Source: Cannon et al. (2001).
ut
t rib
d is
FIGURE 13.8 Gray Matter
Reductions After 5 Years or
t,
Gray matter continue to decrease as schizophrenia
s
develops. This figure shows early and late gray matter
po
deficits in schizophrenia. Note: Color represents the

difference in gray matter between individuals with
schizophrenia and matched controls.
Source: From Paul M. Thompson,
,
et al. “Mapping adolescent brain change reveals

py
dynamic wave of accelerated gray matter loss in very

early-onset schizophrenia.” Proceedings of the National
Academy of Sciences of the United States of America.
2001 September 25; 98(20). © 2001 National Academy
co
of Sciences, U.S.A.
t
FIGURE 13.9 Annual Loss of Gray

no
Matter in Those With Schizophrenia

As shown, gray matter loss is less in typical
adolescents as compared to those with
o
schizophrenia. Typical adolescents show around 1%

or 2%, whereas those with schizophrenia show as
D
much as 4% or 5% in some areas of the brain. The

color represents percentage of gray loss.
Source: From Paul M. Thompson,
et al. “Mapping adolescent brain change reveals
dynamic wave of accelerated gray matter loss in very
early-onset schizophrenia.” Proceedings of the National
Academy of Sciences of the United States of America.
2001 September 25; 98(20). © 2001 National
Academy of Sciences, U.S.A.

(Shenton et al., 2001). Gray matter reductions have also been seen in cases when one identical
twin has schizophrenia and the other does not (see Figure 13.7).
Since brain changes in chronic schizophrenia can be influenced by both the disorder itself
and the medications that the individual has taken over a number of years, researchers have
sought to determine gray matter changes in individuals who display their first episode of schizo-
phrenia. These studies also suggest a reduction in gray matter in schizophrenia (Whitford,
Kubicki, & Shenton, 2011). Further, similar reduction in gray matter was seen in a group of indi-
viduals who had been diagnosed with schizophrenia for an average of 21 years but had never
received medications (Zhang et al., 2015). Overall, these studies rule out the possibility that brain
volume reductions result from medication alone.
e
What might be at the heart of this gray matter reduction? One possibility is that the neurons
ut
actually die. However, a number of studies suggest this is not the case. What has been found is
that the neurons in the brains of individuals with schizophrenia are more densely packed. This
rib
implies that the substance found between neurons—neuropil—was reduced, resulting in
a greater density of neurons. Further, gray matter abnormalities have been shown to be partly
hereditary and also related to trauma during pregnancy (Karlsgodt et al., 2010). Figure 13.8
t
shows the reduction of gray matter in the same set of individuals with schizophrenia over a 5-year
is
period (Thompson et al., 2001). Figure 13.9 shows the differences in gray matter between indi-
viduals with schizophrenia and normal controls.
d
White matter changes have also been observed in individuals with schizophrenia. One
study compared 114 individuals with schizophrenia with 138 matched controls in terms of
or
white matter (White et al., 2011). Using a brain imaging technique—diffusion tensor imag-
ing (DTI)—sensitive to white matter, individuals with chronic schizophrenia, individuals
with first episode schizophrenia, and matched controls were compared. Figure 13.10 shows
t,
an example of tracking white matter through DTI. Measures of white matter were lower for
s
individuals with chronic schizophrenia in the four lobes of the brain but not in the cerebel-
lum or brain stem. Individuals experiencing their first episode of schizophrenia did not show
po
significant differences from controls, which suggests that white matter reduction is part of the
progression of the disorder over time.
In summary, gray matter and white matter changes in schizophrenia have been found in
,
a large number of studies. In addition to white matter and gray matter changes in the brains of
py
co
FIGURE 13.10 White Matter 0.2

Brain Frontal Parietal Temporal Occipital
Reductions Throughout the
t
0.1
no
Whole Brain in Those With

z−Transformed Fractional Anisotropy
0
Schizophrenia
−0.1
Those with long-term schizophrenia show
white matter reductions throughout the −0.2
o
brain, whereas those who just begin to −0.3

experience symptoms appear more like
D
−0.4
their matched controls. This figure
shows differences in z-transformed DTI −0.5
measures of cortical white matter between −0.6
first episode and chronic patients with
−0.7
schizophrenia and matched controls.
−0.8
Note: The z score for the chronic control
group was set to zero; −0.9
FE= first episode.
Chronic Schizophrenia FE Schizophrenia FE Controls
Source: White et al. (2011, p. 228), by
permission of Oxford University Press.

individuals with schizophrenia, researchers have sought to

FIGURE 13.11 Location of Ventricles in the Brain
study cortical networks. I turn to this topic in more detail soon.
Ventricle Changes in Schizophrenia

There are four ventricles in the brain (see Figure 13.11).
These ventricles contain cerebrospinal fluid. From a num-
ber of studies, individuals with schizophrenia show larger
ventricles (see Vita, de Peri, Silenzi, & Dieci, 2006, for a
meta-analysis). Since the walls of the ventricles are not rigid,
e
it is assumed that larger ventricles result from a decrease
in volume in other areas of the brain. Some of the other
ut
areas that have been shown to be smaller in individuals with
schizophrenia are the frontotemporal cortices, the ante-
rib
rior cingulate cortex (ACC), and the right insular cortex.
One question is whether this reduction could be related
to the medications that individuals with schizophrenia
t
take. To answer this question, one study examined indi-
is
viduals with first episode schizophrenia and compared their
brain structure with that of matched healthy controls (Rais
d
et al., 2012). These researchers found brain volume loss in the
individuals with schizophrenia. This suggests that the brain
or
FIGURE 13.12 Magnetic Resonance Imaging
volume loss is present when symptoms begin. They found
Showing Differences in Brain Ventricle Size in
reduced volume in the temporal and insular cortex. Figure
Twins—One With Schizophrenia, One Not
13.12 shows a larger ventricle in an MZ twin who had schizo-
t,
Source: Image courtesy of NIH, Dr. Daniel Weinberger, phrenia and a smaller one in the twin who did not.
Clinical Brain Disorders Branch.
s
po
Schizophrenia and Brain Networks

One common network studied in functional magnetic reso-
nance imaging (fMRI) research is the default mode network
,
(Raichle et al., 2001). This network is activated when individu-

py
als are not performing a task and letting their mind wander. The
network involves both the frontal part of the brain (i.e., ventro-
medial prefrontal cortex [vmPFC]) and the posterior part of the
co
brain (e.g., posterior cingulate, and the angular gyrus/inferior

parietal lobe). Once an individual engages in a task, this network
is suppressed and specific task-related networks become active.
t
In healthy individuals, greater suppression of the default

no
network during a task is associated with better perfor-

mance on that task (A. Kelly, Uddin, Biswal, Castellanos, &
Milham, 2008). Individuals with schizophrenia and their first-degree relatives do not show
the normal suppression of the default network when performing cognitive tasks (Whitfield-
o
Gabrieli et al., 2009). Further, individuals who experience auditory hallucinations also show
D
non-typical brain connections in the default network (Alderson-Day, McCarthy-Jones &

Fernyhough, 2015). Individuals with schizophrenia also show weaker connections between
brain areas than healthy controls, and the strength of connections is correlated with mea-
sures of memory, attention, and negative symptoms (Bassett, Nelson, Mueller, Camchong, &
Lim, 2012).
Current brain imaging has allowed researchers to better identify cortical areas involved
in hallucinations (P. Allen, Larøi, McGuire, & Aleman, 2008; Ford & Hoffman, 2013; Jardri &
Sommer, 2013). It is suggested that in addition to sensory cortices, dysfunctions in prefrontal

premotor, cingulate, subcortical, and cerebellar regions also seem to contribute to hallucinatory
experiences. One model suggests that a disruption in the information transfer from the left infe-
rior frontal gyrus to Wernicke’s area contributes to the failure to perceive that inner experiences
are actually coming from one’s self (Ford & Hoffman, 2013). That is, the person has the experi-
ence without knowing that it comes from his or her own brain.
Brain imaging research has suggested that individuals with schizophrenia show fewer
connections between frontal and temporal areas of the brain while performing tasks.
EEG measures offer one way of determining degree of connectivity. In a number of
studies, Ford and her colleagues (e.g., Ford, Roach, Faustman, & Mathalon, 2007) have shown
that individuals without schizophrenia show a cortical reduction of responsiveness to hear-
e
ing their own voice talking, whereas those with schizophrenia do not. These researchers
ut
also reported that less connectivity between the frontal and temporal regions of the brain was
seen when people with schizophrenia were talking versus individuals without schizophre-
rib
nia (see Figure 13.13; Ford, Mathalon, Whitfield, Faustman, & Roth, 2002). Since there was
even less connectivity in those individuals prone to hallucinate, this may be one mechanism
involved in the mistaken experience that internal voices are produced externally (see also
t
Fletcher & Frith, 2009).
d is
Neurotransmitters Involved in Schizophrenia
There are certain neurotransmitters that are especially important in relation to schizophre-
or
nia (see Figure 13.14). The first is dopamine. It has been suggested that dopamine neurons are
overactive in schizophrenia in midbrain areas and underactive in higher cortical areas (Abi-
Dargham & Grace, 2011). These activations can in turn influence other brain areas with dopa-
t,
mine projections. This is referred to as the dopamine imbalance hypothesis. Supporting this
hypothesis is the finding that there is a direct relationship between drugs that treat schizophrenia
s
and their ability to bind to dopamine receptors in the brain. Further, stress not only increases
po
symptoms in schizophrenia but also causes an activation of the hippocampus and an increase in
dopamine activity.
,
py
FIGURE 13.13 Left Hemisphere Right Hemisphere

Brain Connections
co
and Schizophrenia
Normal Controls
Individuals with schizophrenia

F3 P4 F4
show fewer and weaker C3P P3 C4P
t
connections between frontal and

no
F7 T6 P8
temporal areas of the brain when T5
T3L T4L
performing tasks. This figure T3 T4
shows differences in connectivity N.S.
between the frontal and temporal P<.05
Schizophrenic Patients
o
regions of the brain for normal P<.01

P<.005
controls and patients with P<.001
D
schizophrenia.
F3 C3P P3 F4
Note: Thickness of the lines P4 C4P
reflects the difference in strength
of the connections between brain F7 T5 T6 F8
T3L T4L
areas in those with schizophrenia T3 T4
and matched controls.
Source: Ford et al. (2002, p. 489),
with permission from Elsevier.

FIGURE 13.14 Two Neurotransmitters, Dopamine and Glutamate, Operate Differently in Schizophrenia

Source: From Daniel C. Javitt and Joseph T. Coyle, Decoding Schizophrenia. Scientific American, January 2004, Volume 290, Number 1.
DIFFERENT NEUROTRANSMITTERS, SAME RESULTS
SOME SCIENTISTS have proposed that too

much dopamine leads to symptoms
emanating from the basal ganglia and that
too little dopamine leads to symptoms
IN THE REST
associated with the frontal cortex. OF THE CORTEX,
e
Insufficient glutamate signaling could glutamate is
produce those same symptoms, however. prevalent, but
ut
dopamine is
largely absent.
rib
IN THE FRONTAL CORTEX, where dopamine IN THE BASAL GANGLIA, where dopamine normally inhibits
promotes cell firing (by acting on 01 receptors), cell firing (by acting on D2 receptors on nerve cells),
t
glutamate’s stimulatory signals amplify those of glutamate’s stimulatory signals oppose those of dopamine;
is
dopamine; hence, a shortage of glutamate would hence, a shortage of glutamate would increase inhibition,
decrease neural activity, just as if too little dopamine just as if too much dopamine were present.
d
were present. ALFRED T. KAMAJIAN
or
On a broader level, creative ability in humans has been associated with dopamine func-
t,
tioning, especially in the thalamus. Specifically, decreased dopamine D2 receptor densities in
the thalamus resulted in a lower gating threshold and thus increased information flow. This,
s
in turn, could result in more creative thinking (Manzano, Cervenka, Karabanov, Farde, &
po
Ullén, 2010).
Other researchers have suggested it is not the dopamine system per se that is involved in
schizophrenia but that it is the result of other transmitters that regulate the dopamine system
(Grace, 2010). This is supported by the fact that dopamine levels are not strongly elevated in
,
py
schizophrenia. What is greater in individuals with schizophrenia is the induced release of dopa-
mine by amphetamines. Further, the increased release is proportional to the ability of amphet-
amines to exacerbate psychosis.
co
The second neurotransmitter involved in schizophrenia is glutamate (Krystal &

Moghaddam, 2011). Glutamate is an excitatory neurotransmitter in the brain. Further,
another neurotransmitter, GABA (γ-aminobutyric acid), is involved in nearly all neuronal
processes that engage the glutamate system. If the glutamate receptors in the brain are blocked
t
no
in normal individuals, those individuals display psychotic-like symptoms.

At one time, the dopamine hypothesis and the glutamate hypothesis were seen as compet-
ing explanations involving the mechanisms of schizophrenia. Research has shown that giv-
ing substances that modify the activity of dopamine or glutamate could produce psychotic-like
o
symptoms in healthy humans (Krystal et al., 2005). However, the type of psychotic presentation
D
differed in terms of whether dopamine or glutamate receptors were affected.
How Are Cognitive Processes Changed in Schizophrenia?

Since cognitive tasks utilize specific cognitive networks, one approach to understanding
the brains of individuals with schizophrenia is to note deficits in solving cognitive problems
(Barch & Ceaser, 2012; Pearlson, 2011). Individuals with schizophrenia show cognitive def-
icits in a variety of cognitive domains, including executive function, working memory, and
episodic memory. Overall, these cognitive processes all involve the DLPFC and its connec-
tions to other brain areas.

One suggestion is to develop a cognitive stress test similar to physical stress tests that
determine the integrity of the heart. Two types of cognitive tasks that distinguish individuals with
schizophrenia from healthy controls are those using working memory and those using attention.
Working memory is the ability to keep information available for a short period of time, including
its manipulation in planning and goal-directed behaviors. Disturbances in working memory are
found in individuals with both acute and chronic schizophrenia as well as in their first-degree
relatives without the disorder.
Imaging studies suggest the involvement of the DLPFC as well as the ACC, inferior pari-
etal lobule, and hippocampus. The inferior parietal lobule is located just behind Wernicke’s area
and is connected with large fiber tracts to both Broca’s and Wernicke’s areas. Overall, this area is
e
associated with processing and integrating auditory, visual, and sensorimotor information. As
ut
suggested by DTI brain imaging measures, the problems seen with schizophrenia are probably
better thought of as network problems rather than a deficit in a particular brain area.
rib
One classic example of differential brain processing in individuals with schizophrenia
is the Charlie Chaplin illusion. If healthy individuals look at a mask of Charlie Chaplin as it
rotates, they will see the reverse side of the mask not as hollow but as convex. A video of the
t
mask rotating can be seen at www.richardgregory.org/experiments. As you can see in the
is
video, as the mask turns, an individual initially sees the hollow mask, but this changes into a
normal face. Individuals with schizophrenia do not see the illusion and view the reverse side of
d
the mask as hollow.
The Charlie Chaplin illusion has been studied with fMRI (Dima et al., 2009). What these
or
researchers found was that individuals with schizophrenia and those without showed different
types of connectivity in the brain. Specifically, individuals without schizophrenia showed more
top-down processing when perceiving the illusion. This suggests that part of the illusion is the
t,
sensory expectation of how a face should appear. Thus, in healthy individuals, the brain creates
s
the face as it should appear and not hollow as it actually is. Individuals with schizophrenia, on
the other hand, show weakened top-down processes and stronger bottom-up ones. As a result,
po
they see the sensory stimuli as they are without expectation. Overall, this is consistent with other
research that suggests that individuals with schizophrenia lack the top-down expectations neces-
sary to predict future events (e.g., P. Allen et al., 2008).
,
Individuals with schizophrenia may describe complex emotional processes when writing in
py
a journal while at the same time showing limited emotional expression when interacting with
others (Kring & Elis, 2013). Further, people with schizophrenia report similar emotional expe-
riences as those without schizophrenia. However, individuals with schizophrenia do appear to
co
have problems connecting emotions of others in a social situation with the context in which they
occur. For example, in one study, those with schizophrenia as compared to control individuals
showed less brain activity in the amygdala and visual cortex when shown faces of fear or happi-
t
ness (Maher, Ekstrom, & Chen, 2015). Moreover, they tend to experience positive and neutral
no
situations as more negative than those who do not have schizophrenia. Philosophical Transactions of the Royal Society of London B
l997; 352:1 121–8, by permission of the Royal Society.
© Gregory RL. “Knowledge in perception and illusion.”
o
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Charlie Chaplin Illusion

•• What structural brain changes in white matter and gray matter are characteristic of those with
schizophrenia?
•• Individuals with schizophrenia show larger ventricles in the brain. What do larger ventricles
represent? When do they appear?
•• What are the impacts of deficits in the brain’s default network and connectivity within and across
networks in individuals with schizophrenia?
•• “At one time, the dopamine hypothesis and the glutamate hypothesis were seen as competing
explanations involving the mechanisms of schizophrenia.” What is the support for each
e
hypothesis? What evidence suggests a more complex relationship?
•• What is a cognitive stress test? What are three cognitive domains that show deficits in
ut
individuals with schizophrenia that would be the focus of the stress test?
•• What are some of the problems in emotional processing experienced by individuals with
rib
schizophrenia?
Treating Individuals With Schizophrenia
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Until about the 1960s, individuals with schizophrenia were placed in mental hospitals, often
with little real treatment other than controlling them. With the advent of medications in the
d
middle of the past century, it became possible for individuals with schizophrenia to live within
community or home settings. In fact, individuals with schizophrenia tend to show more posi-
or
tive mental health behaviors when living within a community. In some cultures, small towns
saw it as their duty to take care of these individuals. Today, after initial hospitalizations to gain
control over symptoms, many individuals with schizophrenia return to their family. Other
t,
individuals continue their education or work. Some individuals, such as the ones noted at the
s
beginning of this chapter, are able to be productive and succeed in high-level jobs with appro-
priate support. However, some individuals with schizophrenia become homeless and are at
po
the mercy of their community. LENS: Mercy Bookings of Mental Patients describes how police
around the United States try to protect these individuals.
,
FIGURE 13.15 Interventions Used at Each Stage of the Development of Schizophrenia

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This figure show the stages of schizophrenia and opportunities for intervention at each stage.
Source: From Tandon, 2012.
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Prodromal Relapses
Premorbid With Incomplete
t
Recognition of Risk and Prevention Remissions Recovery

no
(Identify individual risk factors and

provide specific targeted interventions First
to reduce risk) Psychotic
Future possibility
Recognition and Early
o
Intervention
(Reducing risk of conversion in
D
those at high risk. Reduce Remediation (reduce symptoms)

treatment delay) Antipsychotics and other medications
Can do now Cognitive behavioral therapy Relapse Prevention and Rehabilitation
Can do now (Maintenance of remission [medications,
family psychoeducation]
Enhance adaptive function
[e.g., social skills training]
Environmental supports [e.g., supported
housing/employment])
Can do now
Primary, Secondary, and Tertiary Prevention

LENS
Mercy Bookings of Mental Patients

family, or the streets. This leaves some of these
individuals, especially women, open to becoming
victims of robbery or even rape. Mercy booking is the
situation in which police fabricate a charge to enable
jailing the person in order to protect him or her.
e
© iStockphoto.com/piskunov
Police from around the United States have
ut
described their involvement in mercy booking
(see Reisig & Kane, 2014; Torrey, 1997). One police
rib
officer in Los Angeles, California, described
mercy booking as crisis intervention in that
the individuals arrested were malnourished, in
need of medical care, and often hallucinating. By
t
is
During the 1800s, individuals with mental disorders arresting the individuals, they were able to obtain
would be placed in jails and prisons in the United shelter and food and the necessary medications.
d
States. Dorothea Dix and others pushed for more
Sometimes, it is the person with a mental disorder
humane treatment, and state mental hospitals began
himself that creates the arrest situation. In this
to be built. During the 1950s, another movement
situation, he commits a minor crime near a police
or
began to overcome the lack of adequate treatment
station so that he can be arrested and live in the
found in many state hospitals. This community
protected context of a jail. There are also cases of
mental health movement sought to give individuals
families who are unable to care for an individual
with mental disorders more freedom and dignity by
t,
who refuses her medications and shows disruptive
moving their care and treatment out of institutions
behaviors. The family will often use the police to
s
and into the community. However, the lack of
protect the individual through having her arrested.
funding for community facilities has left many of
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these individuals without treatment and literally It is a critical question for society to determine
on the streets of many cities. This has involved the who should be responsible for treating individuals
police in dealing with those with mental illness. with mental disorders and how that should be
done. In the 1800s, jails were shown not to be
,
Traditionally, law enforcement is there to protect the best solution. In the 1900s, mental hospitals
py
the public, while the mental health system is offered an alternative that came to have a number
there to treat the individual. However, these roles of problems in terms of humane treatment. In the
become more ambiguous in what is referred to as 2000s, those with mental disorders experience a
co
mercy booking. As mental hospitals were closed patchwork of agencies including the police that
in the last half of the twentieth century, many of determine their treatment. A consistent approach
the individuals who would previously have been is sorely lacking and seems long overdue.
hospitalized found themselves in the community
Thought Question: What do you think are the
t
or literally on the streets. Mental hospitals or wards

no
currently give priority to those who are a danger to pros and cons of mercy booking? What would you
themselves or others. Others with mental disorders recommend as a consistent approach to community
find themselves released to the community, their mental health treatment?
o
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Over the past 100 years, there has been a shift in viewing schizophrenia as a disorder with
inevitable deterioration to one in which recovery is possible (Frese, Knight, & Saks, 2009).
Recovery includes having a career. Living with schizophrenia depends on the resources of the
individual in terms of intellectual abilities, coping techniques, and willingness to accept the
advice of professionals.
Treatment for schizophrenia involves addressing the specific stage of the illness. Figure 13.15
shows the major stages of the development of schizophrenia and some suggested treatment
approaches at each stage. One major focus of treatment and research is the manner in which
early intervention at each stage can reduce the severity of that stage. There are studies currently

underway that are seeking to identify reliable indicators as to who will develop schizophrenia
later in life (e.g., Cornblatt & Carrión, 2016). However, at this point the research is not definitive.
Thus, knowing who should intervene and how remains a future possibility, although a number
of programs are testing it out. Once signs of schizophrenia develop, early intervention becomes
important. With signs of a psychotic episode, antipsychotic medication and psychological treat-
ments are essential. Following this, supportive mechanisms such as family therapy and the cre-
ation of living and work conditions that help to reduce relapse are critical. I will discuss these
approaches in more detail in this section of the chapter.
The Internet provides access to local and national groups that offer support for those with
schizophrenia as well as their caregivers. In order to help individuals with schizophrenia cope
e
in the community, a number of support procedures have been developed. These include anti-
ut
psychotic medications as well as educational procedures to help the individual with schizo-
phrenia and his or her family understand the course of the illness and the types of support
rib
available. As with other mental health disorders, specific psychotherapies for the person him-
self have been developed. Research suggests that the most effective treatment of schizophre-
nia should involve both medication and psychosocial approaches (A. T. Beck & Rector, 2005;
t
Kane et al., 2016).
is
Antipsychotic Medications
d
A variety of medications have been used in the treatment of schizophrenia (Gopalakrishna,
or
Ithman, & Lauriello, 2016; Hyman & Cohen, 2013; Kutscher, 2008; Minzenberg, Yoon, & Carter,
2010). The treatment of schizophrenia changed drastically in 1954 with the discovery of chlor-
promazine (brand name Thorazine). When effective, this drug reduced agitation, hostility, and
t,
aggression. It also reduced the positive symptoms such as hallucinations and delusions and
increased the time between hospitalizations associated with schizophrenia. However, negative
s
symptoms and cognitive deficits were not changed by the drug.
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One problem of this and other initial drugs were side effects such as tardive dyskinesia, which
is a movement disorder that results in involuntary movement of the lower face and at times the
limbs. These purposeless movements include sucking, smacking the lips, and making tongue
movements. These and other movement side effects are difficult to reverse if the medication was
,
given over a period of time. Weight gain is also seen with antipsychotic medications. In subse-
py
quent years, new and different classes of neuroleptic medications have been developed with dif-
ferent or fewer side effects (Gopalakrishna et al., 2016). These newer drugs tend to reduce the
co
positive symptoms of schizophrenia such as hallucinations and delusions. They also help the
individual think more clearly and remain calmer. Not all medications work for all individuals.
There is also some suggestion that different ethnic groups respond differently to neuroleptics,
although it is less clear whether it is genetic factors or diet that influences these differences.
t
Overall, medications for schizophrenia have been referred to as first-generation or sec-

no
ond-generation antipsychotics. Second-generation antipsychotics are also known as atypical

antipsychotics. First-generation antipsychotics influence dopamine receptors (D2), although
the exact mechanism by which they work is still being studied. One example of a first-gen-
o
eration antipsychotic medication is haloperidol, which has a number of trade names world-
wide, one being Haldol. Second-generation or atypical antipsychotic medications influence
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the dopamine receptors differently. Both first- and second-generation antipsychotics are suc-
cessful in treating the positive symptoms seen in schizophrenia. One advantage of the second-
generation antipsychotics is that they are also able to treat the negative symptoms. Initially, it
was thought that the second-generation antipsychotics had fewer motor side effects, but this
has not always been shown to be the case (Peluso, Lewis, Barnes, & Jones, 2012). In fact, large-
scale studies suggest that second-generation drugs are no more effective than the older ones
(Hyman & Cohen, 2013).
One large-scale study of effectiveness of antipsychotic medication was conducted at 57
clinical sites in the United States in the early 2000s and involved almost 1,500 individuals with

schizophrenia (see Lieberman & Stroup, 2011, for

an overview and update). This is referred to as the
CATIE (Clinical Antipsychotic Trials of Intervention
Effectiveness) study. Individuals with schizophre-
nia were randomly assigned to one of five anti-
psychotic medications (olanzapine [Zyprexa],
quetiapine [Seroquel], risperidone [Risperdal], ziprasi-
© iStockphoto.com/Imagesbybarbara
done [Geodon], and perphenazine [Trilafon]) and fol-
lowed for 18 months. An important aspect of the study
was to compare first- and second-generation antipsy-
e
chotic medications. One surprising result was that the
ut
second-generation medications did not show greater
effectiveness than the first-generation medication, per-
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phenazine. This included no greater effectiveness in
terms of negative symptoms and cognitive impairment. Families play an important role
These results had implications not only for treatment effectiveness, but also for economic con- in supporting individuals with
t
schizophrenia.
siderations, since first-generation medications are less expensive. The CATIE study brought forth
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much controversy in the years following its publication (Lieberman & Stroup, 2011).
d
Psychosocial Interventions for Schizophrenia
or
Psychosocial factors play an important role in the overall treatment of individuals with schizo-
phrenia. It has been estimated that over 60% of people with a first episode of a major mental
illness return to live with relatives. Thus, families play an important role in supporting these
t,
individuals. In fact, family interventions for schizophrenia reduce relapse and hospitaliza-
tions. A number of meta-analyses looked at evidence supporting family interventions (see
s
Barrowclough & Lobban, 2008, for an overview). In general, family interventions involve the
po
following key components:
1. Provide practical emotional support to family members.

,
2. Provide information about schizophrenia, what mental health services are available
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in the community, and nationwide support services (such as those found on the
Internet).
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3. Help the family develop a model of schizophrenia (including not blaming themselves).
4. Modify beliefs about schizophrenia that are unhelpful or inaccurate.
5. Increase coping for all family members.
t
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6. Enhance problem-solving skills.

7. Enhance positive communications.
8. Involve everyone in a relapse prevention plan.
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A number of manuals involving cognitive behavioral therapy (CBT) approaches to

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schizophrenia are available (e.g., Kingdon & Turkington, 1994; L. Smith, Nathan, Juniper,
Kingsep, & Lim, 2003). The basic model suggests that what is important is the manner
in which individuals interpret psychotic phenomena (Beck & Rector, 2005; A. Morrison,
2008). The overall model suggests that neurocognitive impairment in the premorbid state
makes the individual vulnerable to difficulties in school or work, which leads to non-
functional beliefs such as “I am inferior,” maladaptive cognitive appraisals, and in turn
nonfunctional behavior such as social withdrawal (Beck & Rector, 2005). The cognitive
approach is aimed at helping the client understand the psychotic experience as well as cope
with the experience and reduce distress. One key feature of schizophrenia is the disruption

of thought processes, and one part of the treatment is directed at these illogical associa-
tions. Another focus of the treatment is directed at interpersonal relationships and success
at work. This approach may also involve skills training such as self-monitoring and activ-
ity scheduling. Since individuals with schizophrenia may also show mood and anxiety
problems, CBT aimed at these processes can also be utilized. The key features of CBT for
schizophrenia can be summarized as follows (Beck & Rector, 2005; Turkington, Kingdon,
& Weiden, 2006):
1. Develop a therapeutic alliance based on the client’s perspective.
e
2. Understand the client’s interpretation of past and present events.
ut
3. Develop alternative explanations of schizophrenia symptoms.
4. Normalize and reduce the impact of positive and negative symptoms.
rib
5. Educate the client in terms of the role of stress.
6. Teach the client about the cognitive model including the relationships between
t
thoughts, feelings, and behaviors.
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7. Offer alternatives to the medical model to address medication adherence.
d
Developing a therapeutic alliance, that is, a relationship between the therapist and client
or
that helps the work of therapy, is an initial task of therapy. Part of this may include talking
with the client about his delusional beliefs. For example, if a client says that he invented a
machine to solve the world’s problems, then the therapist might ask when the person had
t,
this idea and what he has done to create the machine. The therapist might also ask him about
others who had helped him with his ideas. As with CBT for other disorders, the basic idea is
s
to look for inconsistent thoughts and conclusions that do not follow logically. For example,
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if no one would help the person with his machine, it does not follow logically that everyone
is out to get him.
Another major task of therapy is helping the individual develop an alternative understanding
of his or her symptoms. For example, some individuals with schizophrenia experience the voices
,
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that they hear as coming from outside of them. One goal of therapy would be to help the client
reinterpret the source of the voices. Part of this may also include a cognitive assessment of alter-
natives to obeying the voices.
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The role of stress in increasing symptoms of schizophrenia is an important concept for cli-
ents to understand. It is also important for them to understand the problems associated with
not taking medication to control the symptoms of schizophrenia. Keeping individuals with
schizophrenia on their medications is a difficult problem. In studies involving active medica-
t
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tion alone versus a placebo alone, the relapse rates are about one half with medication com-
pared with a placebo (32% vs. 72%) (Hogarty & Goldberg, 1973). Based on current studies,
treating individuals with schizophrenia with both CBT and psychotropic medication appears
to be the most effective approach (see Beck & Rector, 2005, for outcome studies).
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In the 1950s, George Brown in London, England, sought to understand why some individu-
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als with schizophrenia were readmitted soon after their hospital discharge with their symptoms
reoccurring (Brown, 1985). He discovered that one important factor was the emotional envi-
ronment in the home. This came to be referred to as expressed emotion, which refers to the emo-
tions that the person with schizophrenia would experience from others. That is, homes in which
the person experienced critical comments, hostility, and angry arguments were associated with
relapse, whereas homes with warmth and positive remarks were not. Since that time, a number of
intervention programs have been developed involving caregivers and others who live with those
with schizophrenia (Amaresha & Venkatasubramanian, 2012).
A new approach is being tried in the treatment of schizophrenia—early intervention
(M. Fisher, Loewy, Hardy, Schlosser, & Vinogradov, 2013). This approach seeks out those who

LENS
Mental Health Networks of Those

With Serious Mental Health Disorders
•• Successfully living with a mental
health condition(s), such as
depression, anxiety, schizophrenia,
e
and bipolar disorder (per the National
© iStockphoto.com/Steve Debenport
ut
Alliance on Mental Illness definition).
•• Willing to openly speak out about
your mental health condition(s), using
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both your first and last name.
•• Committed to taking individual and
collective action to improve the lives
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of those living with mental health
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conditions.
•• Committed to staying healthy.
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Something new is happening in major corporations
and institutions in this country. Successful We ask our leaders to make specific commitments to
individuals who have experienced such disorders as
or
schizophrenia, depression, and bipolar disorder are •• SHARE their stories.
forming networks to support and educate others. •• IMPROVE mental health in the
One of these is The Stability Network (http://www. workplace.
thestabilitynetwork.org/). This particular network •• RAISE funding for mental health.
t,
consists of over 30 individuals who will speak publicly
We provide leaders with
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about their mental health experiences. They are also
successfully employed in all forms of employment.
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One of these people is Robert Boorstin who was a •• A NETWORK of peers to collaborate
former director of public policy at Google. Another with on improving the lives of others
is Elyn Saks, whose experiences with schizophrenia with mental health conditions.
are offered in the LENS: Elyn Saks Describes Her •• SUPPORT to increase their impact.
,
Day-to-Day Experiences With Schizophrenia. All of •• MECHANISMS for collective impact.

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the people involved can describe their experiences

and beliefs. One person thought she could walk on Mental health disorders often carry with them a
the Charles River in Boston when she was at the stigma. However, psychological research tells us that
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Harvard Business School. Another believed his hotel actually meeting and talking with someone about his
room was the Starship Enterprise. However, each has or her condition can change that stigma.
worked with professionals and developed routines for
stabilizing his or her condition. Thought Question: You’ve now read a lot of
psychological research concerning mental health
t
disorders: What specific actions would you

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The Stability Network set as its goal the following:

recommend that your university or community take
We seek people who are to reduce the stigma of psychological disorders?
•• Successfully employed in business,

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government, the nonprofit sector,

academia, or the arts.
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are at high risk for developing schizophrenia. The basic approach is to help these individuals
develop cognitive skills as a way to increase attention, memory, executive control, and other cog-
nitive processes. In addition, cognitive therapy is being used to reduce the reactivity to stress seen
in the period prior to the development of psychosis and to better understand these individuals’
thoughts and feelings. Although some success has been reported, this approach for the preven-
tion of schizophrenia is still early in its development.

Another new approach, referred to as NAVIGATE, has been designed for the treatment
of first episode psychosis (Kane et al., 2016). NAVIGATE is a multidisciplinary, team-based
approach that emphasizes low-dose antipsychotic medications, cognitive behavioral psycho-
therapy, family education and support, and vocational and educational support. The program
also helps the person to engage in his or her community. One advantage of this approach is that
the individual with first episode psychosis receives all of these different treatment approaches.
In a randomized control study involving 34 community mental health centers in 21 U.S. states,
the NAVIGATE program was shown to be more effective than the standard care found in the
community health center. Further, the earlier the person entered treatment after the first psy-
e
chotic episode, the better his or her outcome measures were. Based on these types of results, the
National Institute of Mental Health has announced the Early Psychosis Intervention Network
ut
(EPINET) (http://www.nimh.nih.gov/concept-clearance/EPINET).
Many professionals involved in the treatment of schizophrenia have come to realize that
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people are more likely to accept treatment and follow directions if they are involved in their own
treatment. A number of states have coordinated treatment approaches such as NAVIGATE that
use a multidisciplinary team as well as input from the person with schizophrenia. This is critical,
t
since many youth in the early stages of schizophrenia drop out of conventional medication-alone
is
treatment.
d
or
•• What are three critical shifts in the past 60 years that have transformed the treatment of
schizophrenia from institution-based to community-based?
•• “Treatment for schizophrenia involves addressing the specific stage of the illness.” What specific
t,
treatments are suggested for different stages of the illness, and why?
•• A variety of classes of medications have been used in the treatment of schizophrenia. What are
s
they, and what are the advantages and disadvantages of each?
po
•• What four psychosocial approaches are currently used in the treatment of individuals with
schizophrenia, and what is the primary focus of each approach?
,
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SUMMARY
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Schizophrenia is one of the most debilitating of the men- symptoms. This has led some researchers to suggest that
tal disorders. It is part of a broad category of mental illness there exist a variety of similar disorders that are currently
t
referred to as psychotic disorders, all of which involve a loss described by the term schizophrenia.
no
of being in touch with reality and problems with cognitive,

emotional, and motor processes. Schizophrenia affects about Disorders with psychotic-like symptoms have been
1% of the population. It is seen throughout the world with described for at least 4,000 years, and ancient medical
similar symptoms regardless of culture or geographical loca- texts suggest that psychosis was present in all cultures. The
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tion. Onset of schizophrenia occurs in the late teens or early present-day concept of schizophrenia began to evolve in
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twenties. Males show an earlier onset than females by about the middle of the 1800s. Beginning in the 1950s, the DSM
5 years. Symptoms are referred to as positive or negative. The was introduced and described psychosis in broad terms.
more familiar positive symptoms are hallucinations, delu- By DSM–III, schizophrenia was defined by more explicit
sions, disorganized thinking, and disorganized behavior. The criteria, and in DSM–IV and DSM–IV–TR, the criteria for
more familiar negative symptoms include lack of affect in schizophrenia were broadened to become similar to the
situations that call for it, poor motivation, and social with- diagnostic criteria used by ICD. Most recently, the text revi-
drawal. Not everyone with schizophrenia displays the same sion of the fourth edition of DSM (DSM–IV–TR) and DSM–5

set forth a multilevel process for diagnosing schizophrenia: Presently, there is no one biomarker that can identify a
(1) symptoms, (2) functioning, and (3) duration; the final person with schizophrenia. However, in comparing indi-
levels are designed to rule out psychotic-like symptoms viduals with schizophrenia, their relatives, and healthy
found in other disorders. Since individuals with schizophre- control individuals, endophenotypes have been found in
nia have a variety of different symptoms and show an incon- six major areas: (1) minor physical anomalies, (2) physi-
sistent presentation of the disorder, some have suggested ologic abnormalities due to normal metabolism in the
that there is not a single schizophrenia disorder but rather a brain being disturbed, (3) neuropsychological measures,
variety of syndromes. DSM–IV divided schizophrenia into (4) neuromotor abnormalities, and (5) sensory process-
five subtypes: paranoid, disorganized, catatonic, undiffer- ing and event-related potentials. Another physiological
e
entiated, and residual. There has been considerable debate marker that distinguishes individuals with schizophrenia
as to the value of using the five subtypes due to the larger is larger ventricles in the brain resulting from a decrease in
ut
question of whether schizophrenia should be considered in volume in other areas of the brain.
terms of discrete categories or existing along a dimension.
rib
Although ICD-10 uses subtypes, DSM–5 removed the clas- Schizophrenia manifests on a variety of levels includ-
sification of subtypes but left the diagnostic criteria. ing abnormal sensory experiences such as hallucinations,
problems in cognitive processes such as delusions and dis-
t
There is an evolutionary paradox with schizophrenia: How ordered thought, changes in affect such as lack of expres-
is
can the disorder exist without a reproductive advantage? sion, and in some cases problems with language and future
One possible answer is that the genes associated with directed planning. This presents a challenge to describe
d
schizophrenia are also associated with positive traits such the manner in which brain processes relate to the disorder.
as creativity, since it has been noted that highly gifted and Current research examining individuals with schizophre-
or
creative individuals manifest schizophrenic-like character- nia has emphasized five different levels of analysis from a
istics, referred to as schizotypal traits, without having the neuroscience perspective. The first is anatomical changes
disorder. Other scientists propose different evolutionary such as the loss of brain volume in particular areas. The
t,
paths: Crow theorizes that the development of language second is functional processes such as the manner in which
s
and the genetic changes required for producing and under- cortical areas and networks process information as seen in
standing speech were associated with the development of brain imaging. The third is neural oscillations that underlie
po
schizophrenia, while Burns suggests that schizophrenia is the cortical networks. The fourth is changes in neurotrans-
better understood as a disorder of the social brain rather mitters such as dopamine and glutamate. And the fifth is
than language. the development of cortical processes beginning in utero.
,
py
Schizophrenia typically is first manifested during the Until about the 1960s, individuals with schizophrenia were
transition from late adolescence to adulthood at a time of placed in mental hospitals, often with little real treatment
great reorganization of cortical networks. However, cur- other than controlling them. With the advent of medica-
co
rent research literature suggests that we consider schizo- tions in the middle of the last century, it became possible for
phrenia as a neurodevelopmental disorder that begins individuals with schizophrenia to live within community
early in life. The basic idea is that during the time the fetus or home settings. In fact, they tend to show more positive
mental health behaviors when living within a community.
t
is in utero, an insult happens that influences the changes

no
to the brain that take place during adolescence. Schizo- In addition, over the past 100 years, there has been a shift
phrenia has a strong genetic component; however, the in viewing schizophrenia as a disorder with inevitable dete-
genetic underpinnings of schizophrenia are not simple. rioration to one in which recovery is possible. In order to
The number of genetic variants seen in individuals with help individuals with schizophrenia cope in the commu-
o
schizophrenia is very large, and these genes may act in nity, a number of support procedures have been developed.
D
an additive or interactive manner, leading to a variety These include antipsychotic medications; educational
of genetic combinations associated with schizophrenia. procedures to help the individual with schizophrenia and
Genetic differences may result not from differences in the his or her family to understand the course of the illness and
DNA itself but from epigenetic factors, suggesting inter- the types of support available; and specific psychotherapies,
nal and external environmental factors play a role. Finally, particularly CBT approaches. Research suggests that the
environmental factors that do not involve genetic changes most effective treatment of schizophrenia should involve
may also play a role. both medication and psychosocial approaches.

STUDY RESOURCES
RE VIE W QU E S TION S
1. This chapter states that “individuals with schizophrenia 4. “Psychosocial factors play an important role in the over-
have a variety of different symptoms and show an incon- all treatment of individuals with schizophrenia.” What
sistent picture of the disorder. This has led some to sug- are the characteristics of each factor, and what role does
gest that there is not a single schizophrenia disorder but each play in treatment?
e
rather a variety of syndromes.” What do you think: Is a. Family interventions
schizophrenia one disorder? What evidence would you b. CBT approach
ut
cite to support your position? c. Early intervention
2. What are the environmental and genetic factors that play 5. “Over the past 100 years, there has been a shift in viewing
rib
a role in the development of schizophrenia? schizophrenia as a disorder with inevitable deterioration
to one in which recovery is possible.” What impact does
3. “Current research examining individuals with schizo-
this shift suggest for changes in research, education, and
t
phrenia has emphasized five different levels of research
is
public policy?
from a neuroscience perspective.” For each type, what
has been the focus of the research, and what brain
d
changes have been found in schizophrenia?
a. Anatomical changes
or
b. Functional processes
c. Neural oscillations
d. Neurotransmitters
t,
e. Development of cortical processes
s
po
F OR F U R TH E R RE ADIN G
McLean, R. (2003). Recovered, not cured: A journey through Schiller, L., & Bennett, A. (1994). The quiet room. New
schizophrenia. Australia: Allen Unwin. York: Warner Books.
,
py
Mukherjee, S. (2016, March 28). Runs in the family: New Steele, K., & Berman, C. (2001). The day the voices stopped.
findings about schizophrenia rekindle old questions New York: Basic Books.
about genes and identity. The New Yorker.
Torrey, E. (1997). Out of the shadows: Confronting
co
Nasar, S. (1998). A beautiful mind. New York: Simon & America’s mental illness crisis. New York: Wiley.
Schuster.
t
Saks, E. (2007). The center cannot hold: My journey

no
through madness. New York: Hyperion.
KE Y TE RM S AN D CONCE P T S
o
alogia 461 disorganized subtype 463 psychotic disorders 455

D
anhedonia 461 hallucinations 457 schizophrenia 455

avolition 461 negative symptoms 457 schizotypal traits 467
catatonic subtype 463 paranoid subtype 462
delusions 455 positive symptoms 457

edge.sagepub.com/rayabnormal2e
Master these Learning Objectives with SAGE edge!
SAGE edge offers a robust online environment featuring an impressive array of free tools and resources for review, study,
and further exploration, keeping both instructors and students on the cutting edge of teaching and learning.
e
Describe the prevalence of schizophrenia and the
13.1 Schizophrenia
ut
time course of its development.
rib
Identify the positive and negative symptoms of
13.2 Distressing Voices and Hallucinations
schizophrenia.
Discuss the historical and evolutionary contexts
13.3 Going to Extremes
t
of schizophrenia.
is
Identify genetic and environmental factors in the
13.4 Schizophrenia Research
d
development of schizophrenia.
Describe the brain changes seen in individuals
13.5 Hating Schizophrenia Before It Starts
or
with schizophrenia. Biology of Schizophrenia
Identify the treatments available to individuals
13.6 Educating Patients With Schizophrenia
t,
with schizophrenia. Treating Schizophrenia
s
, po
py
t co
no
o
D


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Schizophrenia 13

CHAPTER OUTLINE LEARNING OBJECTIVES

Schizophrenia and Brain Networks

LENS: Mercy Bookings of Mental Patients

For Further Reading

Key Terms and Concepts

Copyright ©2017 by SAGE Publications, Inc.

—From Richard McLean. (2003). Recovered, Not Cured:

ready to give up, believing they had won.

—From The Quiet Room, by Lori Schiller and Amanda Bennett.

Copyright ©2017 by SAGE Publications, Inc.

Schizophrenia Basics: Prevalence, Course, and Symptoms

Substance/Medication-Induced Delusions or hallucinations related to drugs or medications

Psychotic Disorder Due to Another Delusions or hallucinations related to a medical condition

Medical Condition mutism, mannerisms, or grimacing

Copyright ©2017 by SAGE Publications, Inc.

Schizophrenia affects one’s ability to express one-

schizophrenia over the past 100 years is a belief that oth-

Prevalence and Course of Schizophrenia

lar symptoms regardless of culture or geographical location. Onset of schizophrenia occurs

with schizophrenia are able to be part of the social and

economic world experienced by healthy individuals.

The symptoms of schizophrenia are not constantly

present. There are examples of individuals with schizo-

tain jobs, even high-level jobs. Thus, individuals with

Copyright ©2017 by SAGE Publications, Inc.

individuals may hear voices but never see

varies greatly across individuals.

population. The life span of individuals with schizophrenia is abbreviated by 15 to 20 years. Of

Positive and Negative Symptoms

Copyright ©2017 by SAGE Publications, Inc.

Elyn Saks Describes Her Day-to-Day

What you don’t hear

ravings seemed crazy to most of the students, and healthy self.”

me as I walked back to my office. He said I looked as if

then?” Up shot the hands.

That was in September of 1991, and it was one of my

to be unable to live independently, let alone work.

Copyright ©2017 by SAGE Publications, Inc.

and the behavioral sciences at the University of Southern

Copyright ©2017 by SAGE Publications, Inc.

over that time, another 26% displayed delusions at each

of the six assessments, and the remaining individuals

Negative symptoms seen in schizophrenia tend to be

more constant and stable than positive symptoms.

poorer prognosis (see Foussias & Remington, 2010, for

Copyright ©2017 by SAGE Publications, Inc.

Not all individuals with schizophrenia show

% Pts. With Delusional

The first level is symptoms, which includes delusions, hallucinations, or disorganized

Are There Subtypes of Schizophrenia?

Copyright ©2017 by SAGE Publications, Inc.

TABLE 13.2 DSM–5 Diagnostic Criteria for Schizophrenia

E. Substance/general medical condition exclusion: The disturbance is not due to the

F. Relationship to a Pervasive Developmental Disorder: If there is a history of Autistic

Disorder or another Pervasive Developmental Disorder or other communication

delusions whose themes generally

Copyright ©2017 by SAGE Publications, Inc.

schizophrenia. such as auditory or visual hallucinations.