Major Depressive Disorder disability) may include the feelings of intense

sadness, rumination about the loss, insomnia,

Diagnostic Criteria
poor appetite, and weight loss noted in Criterion
A. Five (or more) of the following symptoms
A, which may resemble a depressive episode.
have been present during the same 2-week
Although such symptoms may be
period and represent a change from previous
understandable or considered appropriate to
functioning; at least one of the symptoms is
the loss, the presence of a major depressive
either (1) depressed mood or (2) loss of interest
episode in addition to the normal response to a
or pleasure.
significant loss should also be carefully
Note: Do not include symptoms that are clearly
considered. This decision inevitably requires
attributable to another medical condition.
the exercise of clinical judgment based on the
1. Depressed mood most of the day, nearly
individual’s history and the cultural norms for
every day, as indicated by either subjective
the expression of distress in the context of loss.
report (e.g., feels sad, empty, hopeless) or
D. At least one major depressive episode is not
observation made by others (e.g., appears
better explained by schizoaffective disorder and
tearful). (Note: In children and adolescents,
is not superimposed onschizophrenia,
can be irritable mood.)
schizophreniform disorder, delusional
2. Markedly diminished interest or pleasure in
disorder, or other specified and unspecified
all, or almost all, activities most of the day,
schizophrenia spectrum and other psychotic
nearly every day (as indicated by either
disorders.
subjective account or observation).
E. There has never been a manic episode or a
3. Significant weight loss when not dieting or
hypomanic episode.
weight gain (e.g., a change of more than 5% of
Note: This exclusion does not apply if all of the
body weight in a month), or decrease or
manic-like or hypomanic-like episodes are
increase in appetite nearly every day. (Note: In
substance-induced or are
children, consider failure to make expected
attributable to the physiological effects of
weight gain.)
another medical condition.
4. Insomnia or hypersomnia nearly every day.
Coding and Recording Procedures
5. Psychomotor agitation or retardation nearly
The diagnostic code for major depressive
every day (observable by others, not merely
disorder is based on
subjective feelings of restlessness or being
whether this is a single or recurrent episode,
slowed down).
current severity, presence of psychotic
6. Fatigue or loss of energy nearly every day.
features, and remission status. Current severity
7. Feelings of worthlessness or excessive or
and psychotic features are only indicated if full
inappropriate guilt (which may be delusional)
criteria are currently met for a major depressive
nearly every day (not merely self-reproach or
episode. Remission specifiers are only
guilt about being sick).
indicated if the full criteria are not currently met
8. Diminished ability to think or concentrate, or
for a major depressive episode. Codes are as
indecisiveness, nearly every day (either by
follows:
subjective account or as observed by others).
9. Recurrent thoughts of death (not just fear of
dying), recurrent suicidal ideation without a
specific plan, or a suicide attempt or a specific
plan for committing suicide.
B. The symptoms cause clinically significant
distress or impairment in social, occupational,
or other important areas of functioning.
C. The episode is not attributable to the
physiological effects of a substance or another
medical condition.
Note: Criteria A–C represent a major *For an episode to be considered recurrent, there must be
depressive episode. an interval of at least 2 consecutive months between
Note: Responses to a significant loss (e.g., separate episodes in which criteria are not met for a major
bereavement, financial ruin, losses from a depressive episode. The definitions of specifiers are found
on the indicated pages.
natural disaster, a serious medical illness or
**If psychotic features are present, code the “with and attempting suicide or making a specific
psychotic features” specifier irrespective of episode plan, which only needs to occur once. The
severity.
episode must be accompanied by clinically
In recording the name of a diagnosis, terms
significant distress or impairment in social,
should be listed in the following order: major
occupational, or other important areas of
depressive disorder, single or recurrent
functioning. For some individuals with milder
episode, severity/psychotic/remission
episodes, functioning may appear to be normal
specifiers, followed by as many of the following
but requires markedly increased effort. The
specifiers without codes that apply to the
presenting complaint is often insomnia or
current episode (or the most recent episode if
fatigue rather than depressed mood or loss of
the major depressive disorder is in partial or full
interest; thus, the failure to probe for
remission). Note: The specifier “with seasonal
accompanying depressive symptoms can result
pattern” describes the pattern of recurrent
in underdiagnosis. Fatigue and sleep
major depressive episodes.
disturbance are present in a high proportion of
Specify if:
cases; psychomotor disturbances are much
With anxious distress (pp. 210–211)
less common but are indicative of greater
With mixed features (p. 211)
overall severity, as is the presence of
With melancholic features (pp. 211–212)
delusional or near-delusional guilt.
With atypical features (p. 212)
The mood in a major depressive
With mood-congruent psychotic features (p.
episode is often described by the individual as
213)
depressed, sad, hopeless, discouraged, or
With mood-incongruent psychotic features
“down in the dumps” (Criterion A1). In some
(p. 213)
cases, sadness may be denied at first but may
With catatonia (p. 213). Coding note: Use
subsequently be elicited by interview (e.g., by
additional code F06.1.
pointing out that the individual looks as if he or
With peripartum onset (p. 213)
she is about to cry). In some individuals who
With seasonal pattern (applies to pattern of
complain of feeling “blah,” having no feelings,
recurrent major depressive episodes) (p. 214)
or feeling anxious, the presence of a depressed
Diagnostic Features mood can be inferred from the individual’s facial
Major depressive disorder is defined by the expression and demeanor. Some individuals
presence of at least one major depressive emphasize somatic complaints (e.g., bodily
episode occurring in the absence of a history of aches and pains) rather than reporting feelings
manic or hypomanic episodes. The essential of sadness. Many individuals report or exhibit
feature of a major depressive episode is a increased irritability (e.g., persistent anger, a
period lasting at least 2 weeks during which tendency to respond to events with angry
there is either depressed mood or the loss of outbursts or blaming others, an exaggerated
interest or pleasure in all or nearly all activities sense of frustration over minor matters). In
for most of the day nearly every day (Criterion children and adolescents, an irritable or cranky
A). The individual must alsoexperience at least mood may develop rather than a sad or
four additional symptoms during the same 2- dejected mood. This presentation should be
week period, drawn from a list that includes differentiated from a pattern of irritability when
changes in appetite or weight, sleep, and frustrated.
psychomotor activity; decreased energy; Diminished interest or pleasure in usual
feelings of worthlessness or guilt; difficulty activities is nearly always present, at least to
thinking, concentrating, or making decisions; or some degree. Individuals may report feeling
thoughts of death, suicidal ideation, a suicide less interested in hobbies, “not caring
attempt, or a specific plan for suicidal behavior. anymore,” or not feeling any enjoyment in
To count toward a diagnosis of a major activities that were previously considered
depressive episode, a symptom must either be pleasurable (Criterion A2).
newly present or have clearly worsened Family members often notice social withdrawal
compared with the individual’s pre-episode or neglect of pleasurable avocations (e.g., a
status. Moreover, the symptoms must occur formerly avid golfer no longer plays, a child who
nearly every day, for at least 2 consecutive used to enjoy soccer finds excuses not to
weeks, with the exception of thoughts of death practice). In some individuals, there is a
and suicidal ideation, which must be recurrent,
significant reduction from previous levels of The sense of worthlessness or guilt
sexual interest or desire. associated with a major depressive episode
Appetite change may involve either a may include unrealistic negative evaluations of
reduction or an increase. Some depressed one’s worth or guilty preoccupations or
individuals report that they have to force ruminations over minor past failings (Criterion
themselves to eat. Others may eat more and A7). Such individuals often misinterpret neutral
may crave specific foods (e.g., sweets or other or trivial day-to-day events as evidence of
carbohydrates). When appetite changes are personal defects and have an exaggerated
severe (in either direction), there may be a sense of responsibility for untoward events. The
significant loss or gain in weight, or, in children, sense of worthlessness or guilt may be of
a failure to make expected weight gains may be delusional proportions (e.g., an individual who
noted (Criterion A3). is convinced that he or she is personally
Sleep disturbance may take the form of responsible for world poverty). Blaming oneself
either difficulty sleeping or sleeping excessively for being sick and for failing to meet
(Criterion A4). When insomnia is present, it occupational or interpersonal responsibilities as
typically takes the form of middle insomnia (i.e., a result of the depression is very common and,
waking up during the night and then having unless delusional, is not considered sufficient to
difficulty returning to sleep) or terminal meet this criterion.
insomnia (i.e., waking too early and being Many individuals report impaired ability
unable to return to sleep). Initial insomnia (i.e., to think, concentrate, or make even minor
difficulty falling asleep) may also occur. decisions (Criterion A8). They may appear
Individuals who present with oversleeping easily distracted or complain of memory
(hypersomnia) may experience prolonged sleep difficulties. Those engaged in cognitively
episodes at night or increased daytime sleep. demanding pursuits are often unable to
Sometimes the reason that the individual seeks function. In children, a precipitous drop in
treatment is for the disturbed sleep. grades may reflect poor concentration. In
Psychomotor changes include agitation elderly individuals, memory difficulties may be
(e.g., the inability to sit still, pacing, hand- the chief complaint and may be mistaken for
wringing; or pulling or rubbing of the skin, early signs of a dementia (“pseudodementia”).
clothing, or other objects) or retardation (e.g., When the major depressive episode is
slowed speech, thinking, and body movements; successfully treated, the memory problems
increased pauses before answering; speech often fully abate. However, in
that is decreased in volume, inflection, amount, some individuals, particularly elderly persons, a
or variety of content, or muteness) (Criterion major depressive episode may sometimes be
A5). The psychomotor agitation or retardation the initial presentation of an irreversible
must be severe enough to be observable by dementia.
others and not represent merely subjective Thoughts of death, suicidal ideation, or
feelings. Individuals who display either suicide attempts (Criterion A9) are common.
psychomotor disturbance (i.e., psychomotor They may range from a passive wish not to
agitation or retardation) are likely to have awaken in the morning or a belief that others
histories of the other. would be better off if the individual were dead,
Decreased energy, tiredness, and to transient but recurrent thoughts of dying by
fatigue are common (Criterion A6). An suicide, to a specific suicide plan. More
individual may report sustained fatigue without severely suicidal individuals may have put their
physical exertion. Even the smallest tasks affairs in order (e.g., updated wills, settled
seem to require substantial effort. The debts), acquired needed materials (e.g., a rope
efficiency with which tasks are accomplished or a gun), and chosen a location and time to
may be reduced. For example, an individual accomplish the suicide.Motivations for suicide
may complain that washing and dressing in the may include a desire to give up in the face of
morning are exhausting and take twice as long perceived insurmountable obstacles, an intense
as usual. This symptom accounts for much of wish to end what is perceived as an unending
the impairment resulting from major depressive and excruciatingly painful emotional state, an
disorder, both during acute episodes and when inability to foresee any enjoyment in life, or the
remission is incomplete. wish to not be a burden to others. The
resolution of such thinking may be a more
meaningful measure of diminished suicide risk Associated Features
than denial of further plans for suicide. Major depressive disorder is associated with
The degree of impairment associated high mortality, much of which is accounted for
with a major depressive episode varies, but by suicide; however, it is not the only cause.
even in milder cases, there must be either For example, depressed individuals admitted to
clinically significant distress or some nursing homes have a markedly increased
interference in social, occupational, or other likelihood of death in the first year. Individuals
important areas of functioning (Criterion B). If frequently present with tearfulness, irritability,
impairment is severe, the individual may lose brooding, obsessive rumination, anxiety,
the ability to function socially or occupationally. phobias, excessive worry over physical health,
In extreme cases, the individual may be unable and complaints of pain (e.g., headaches; joint,
to perform minimal self-care (e.g., feeding and abdominal, or other pains). In children,
clothing self) or to maintain minimal personal separation anxiety may occur.
hygiene. Although an extensive literature exists
The individual’s report of symptoms may describing neuroanatomical,
be compromised by difficulties in concentrating, neuroendocrinological, and neurophysiological
impaired memory, or a tendency to deny, correlates of major depressive disorder, no
discount, or explain away symptoms. laboratory test has yielded results of sufficient
Information from additional informants can be sensitivity and specificity to be used as a
especially helpful in clarifying the course of diagnostic tool for this disorder. Until recently,
current or prior major depressive episodes and hypothalamic-pituitary-adrenal axis
in assessing whether there have been any hyperactivity had been the most extensively
manic or hypomanic episodes. Because major investigated abnormality associated with major
depressive episodes can begin gradually, a depressive episodes, and it appears to be
review of clinical information that focuses on associated with melancholia (a particularly
the worst part of the current episode may be severe type of depression), psychotic features,
most likely to detect the presence of symptoms. and risks for eventual suicide. Molecular
The evaluation of the symptoms of a studies have also implicated peripheral factors,
major depressive episode is especially difficult including genetic variants in neurotrophic
when they occur in an individual who also has factors and pro-inflammatory cytokines.
another medical condition (e.g., cancer, stroke, Additionally, volumetric and functional magnetic
myocardial infarction, diabetes, pregnancy). resonance imaging studies provide evidence for
Some of the criterion signs and symptoms of a abnormalities in specific neural systems
major depressive episode are identical to those supporting emotion processing, reward
of another medical condition (e.g., weight loss seeking, and emotion regulation in adults with
with untreated diabetes; fatigue with cancer; major depression.
hypersomnia early in pregnancy; insomnia later
in pregnancy or the postpartum). Such Prevalence
symptoms count toward a major depressive Twelve-month prevalence of major depressive
diagnosis except when they are clearly and disorder in the United States is approximately
fully attributable to another medical condition. 7%, with marked differences by age group such
Non-vegetative symptoms of dysphoria, that the prevalence in 18- to 29-year-old
anhedonia, guilt or worthlessness, individuals is threefold higher than the
impairedconcentration or indecision, and prevalence in individuals age 60 years or older.
suicidal thoughts should be assessed with The most reproducible finding in the
particular care in such cases. Definitions of epidemiology of major depressive disorder has
major depressive episodes that have been been a higher prevalence in females, an effect
modified to include only these nonvegetative that peaks in adolescence and then stabilizes.
symptoms appear to identify nearly the same Women experience approximately twofold
individuals as do the full criteria. higher rates than men, especially between
menarche and menopause. Women report
more atypical symptoms of depression
characterized by hypersomnia, increased
appetite, and leaden paralysis compared with who have been depressed for only several
men. months can be expected to recover
Systematic reviews show that the 12- spontaneously. Features associated with lower
month and point prevalence of major recovery rates, other than current episode
depressive disorder vary eight- to ninefold duration, include psychotic features, prominent
across global geographic regions. In the United anxiety, personality disorders, and symptom
States, prevalence increased from 2005 to severity.
2015, with steeper rates of increase for youth The risk of recurrence becomes
compared with older groups. After stratification progressively lower over time as the duration of
by ethnoracial groups, non-Hispanic Whites remission increases. The risk is higher in
showed a significant increase in prevalence individuals whose preceding episode was
after adjustment for demographic severe, in younger individuals, and in
characteristics, whereas no significant change individuals who have already experienced
in rate of depression was observed among non- multiple episodes. The persistence of even mild
Hispanic Blacks or Hispanics. depressive symptoms during remission is a
Development and Course powerful predictor of recurrence.
Major depressive disorder may first appear at Many bipolar illnesses begin with one or
any age, but the likelihood of onset increases more depressive episodes, and a substantial
markedly with puberty. In the United States, proportion of individuals who initially appear to
incidence appears to peak in the 20s; however, have major depressive disorder will prove, in
first onset in late life is not uncommon. time, to instead have a bipolar disorder. This is
The course of major depressive disorder more likely in individuals with onset of the
is quite variable, such that some individuals illness in adolescence, those with psychotic
rarely, if ever, experience remission (a period of features, and those with a family history of
2 or more months with no symptoms, or only bipolar illness. The presence of a “with mixed
one or two symptoms to no more than a mild features” specifier also increases the risk for
degree), while others experience many years future manic or hypomanic diagnosis. Major
with few or no symptoms between discrete depressive disorder, particularly with psychotic
episodes. The course of depression may reflect features, may also transition into schizophrenia,
socialstructural adversity associated with a change that is much more frequent than the
poverty, racism, and marginalization. reverse.
It is important to distinguish individuals There are no clear effects of current age
who present for treatment during an on the course or treatment response of major
exacerbation of a chronic depressive illness depressive disorder. Some symptom
from those whose symptoms developed differences exist, though, such that
recently. Chronicity of depressive symptoms hypersomnia and hyperphagia are more likely
substantially increases the likelihood of in younger individuals, and melancholic
underlying personality, anxiety, and substance symptoms, particularly psychomotor
use disorders and decreases the likelihood that disturbances, are more common in older
treatment will be followed by full symptom individuals. Depressions with earlier ages at
resolution. It is therefore useful to ask onset are more familial and more likely to
individuals presenting with depressive involve personality disturbances. The course of
symptoms to identify the last period of at least 2 major depressive disorder withinindividuals
months during which they were entirely free of does not generally change with aging. Mean
depressive symptoms. Cases in which times to recovery do not change over multiple
depressive symptoms are present for more episodes, and the likelihood of being in an
days than not might warrant an additional episode does not generally increase or
diagnosis of persistent depressive disorder. decrease with time.
Recovery from a major depressive
episode begins within 3 months of onset for
40% of individuals with major depression and
within 1 year for 80% of individuals. Recency of
onset is a strong determinant of the likelihood
of near-term recovery, and many individuals
Risk and Prognostic Factors depressive symptoms may obscure and delay
Temperamental. Negative affectivity their recognition. However, sustained clinical
(neuroticism) is a well-established risk factor for improvement in depressive symptoms may
the onset of major depressive disorder, and depend on the appropriate treatment of
high levels appear to render individuals more underlying illnesses. Chronic or disabling
likely to develop depressive episodes in medical conditions also increase risks for major
response to stressful life events. depressive episodes. Prevalent illnesses such
Environmental. Adverse childhood as diabetes, morbid obesity, and cardiovascular
experiences, particularly when they are multiple disease are often complicated by depressive
and of diverse types, constitute a set of potent episodes, and these episodes are more likely to
risk factors for major depressive disorder. become chronic than are depressive episodes
Women may be disproportionately at risk for in medically healthy individuals.
adverse childhood experiences, including
sexual abuse, that may contribute to the Culture-Related Diagnostic Issues
increased prevalence of depression in this Although there is substantial cross-cultural
group. Other social determinants of mental variation in the prevalence, course, and
health, such as low income, limited formal symptomatology of depression, a syndrome
education, racism, and other forms of similar to major depressive disorder can be
discrimination, are associated with higher risk identified across diverse cultural contexts.
of major depressive disorder. Stressful life Symptoms commonly associated with
events are well recognized as precipitants of depression across cultural contexts, not listed
major depressive episodes, but the presence or in the DSM criteria, include social isolation or
absence of adverse life events near the onset loneliness, anger, crying, and diffuse pain. A
of episodes does not appear to provide a useful wide range of other somatic complaints are
guide to prognosis or treatment selection. common and vary by cultural context.
Etiologically, women are disproportionately Understanding the significance of these
affected by major risk factors for depression symptoms requires exploring their meaning in
across the life span, including interpersonal local social contexts.
trauma. Symptoms of major depressive disorder
Genetic and physiological. First-degree may be underdetected or underreported,
family members of individuals with potentially leading to misdiagnosis, including
major depressive disorder have a risk for major overdiagnosis of schizophrenia spectrum
depressive disorder two- to fourfold higher than disorders in some ethnic and racialized groups
that of the general population. Relative risks facing discrimination. Cross-nationally, higher
appear to be higher for early-onset and levels of income inequality in a society are
recurrent forms. Heritability is approximately associated with higher prevalence of major
40%, and the personality trait neuroticism depressive disorder. In the United States, the
accounts for a substantial portion of this genetic chronicity of major depressive disorder appears
liability. Women may also be at risk for to be higher among African Americans and
depressive disorders in relation to specific Caribbean Blacks compared with non-Latinx
reproductive life stages, including in the Whites, possibly because of the impact of
premenstrual period, postpartum, and in racism, discrimination, greater sociostructural
perimenopause. adversity, and lack of access to quality mental
Course modifiers. Essentially all major health care.
nonmood disorders (i.e., anxiety, substance
use, trauma- and stressor-related, feeding and
eating, and obsessive-compulsive and related
disorders) increase the risk of anindividual
developing depression. Major depressive
episodes that develop against the background
of another disorder often follow a more
refractory course. Substance use, anxiety, and
borderline personality disorders are among the
most common of these, and the presenting
Sex- and Gender-Related Diagnostic functional impairment, increase risk for future
Issues suicidal behavior.
There are no clear differences between
genders in treatment response or functional Functional Consequences of Major
consequences. There is some evidence for sex Depressive Disorder
and gender differences in phenomenology and Many of the functional consequences of major
course of illness. Women tend to experience depressive disorder derive from individual
more disturbances in appetite and sleep, symptoms. Impairment can be very mild, such
including atypical features such as hyperphagia that many of those who interact with the
and hypersomnia, and are more likely to affected individual are unaware of depressive
experience interpersonal sensitivity and symptoms. Impairment may, however, range to
gastrointestinal symptoms. Men with complete incapacity such that the depressed
depression, however, may be more likely than individual is unable to attend to basic self-care
depressed women to report greater frequencies needs or is mute or catatonic. For individuals
and intensities of maladaptive self-coping and seen in general medical settings, those with
problem-solving strategies, including alcohol or major depressive disorder have more pain and
other drug misuse, risk taking, and poor physical illness and greater decreases in
impulse control. physical, social, and role functioning.
Depressed women report greater functional
Association With Suicidal Thoughts impairment in their relationships than men.
or Behavior
Age-adjusted rates of suicide in the United Differential Diagnosis
States have increased from 10.5 to 14.0 per Manic episodes with irritable mood or with
100,000 over the past two decades. An earlier mixed features. Major depressive episodes
review of the literature indicated that individuals with prominent irritable mood may be difficult to
with depressive illness have a 17-fold increased distinguish from manic episodes with irritable
risk for suicide over the age- and sex-adjusted mood or with mixed features. This distinction
general population rate. The likelihood of requires a careful clinical evaluation of the
suicide attempts lessens in middle and late life, presence of sufficient manic symptoms to meet
although the risk of death by suicide does not. threshold criteria (i.e., three if mood is manic,
The possibility of suicidal behavior exists at all four if mood is irritable but not manic).
times during major depressive episodes. The Bipolar I disorder, bipolar II disorder, or
most consistently described risk factor is a past other specified bipolar and related
history of suicide attempts or threats, but it disorder. Major depressive episodes along
should be remembered that most deaths by with a history of a manic or hypomanic episode
suicide are not preceded by nonfatal attempts. preclude the diagnosis of major depressive
Anhedonia has a particularly strong association disorder. Major depressive episodes with a
with suicidal ideation. Other features history of hypomanic episodes and without a
associated with an increased risk for death by history of manic episodes indicate a diagnosis
suicide include being single, living alone, social of bipolar II disorder, whereas major depressive
disconnectedness, early life adversity, episodes with a history of manic episodes (with
availability of lethal methods such as a firearm, or without hypomanic episodes) indicate a
sleep disturbance, cognitive and decision- diagnosis of bipolar I disorder. On the other
making deficits, and having prominent feelings hand, presentations of major depressive
of hopelessness. Women attempt suicide at a episodes with a history of periods of hypomania
higher rate than men, while men are more likely that do not meet criteria for a hypomanic
to complete suicide. The difference in suicide episode may be diagnosed as either other
rate between men and women with depressive specified bipolar and related disorder or major
disorders is smaller than in the population as a depressive disorder depending on where the
whole, however. Comorbidities, including clinician judges the presentation to best fall. For
aggressive-impulsive traits, borderline example, the presentation may be best
personality disorder, substance use disorder, considered other specified bipolar and related
anxiety, other medical conditions, and disorder because of the clinical significance of
the sub-threshold hypomanic symptoms, or the
presentation may be best considered a case of schizophreniform disorder, or other specified or
major depressive disorder with some unspecifiedschizophrenia spectrum and other
subthreshold hypomanic symptoms in between psychotic disorder. Most commonly, such
episodes. depressive symptoms can be considered
Depressive disorder due to another medical associated features of these disorders and do
condition. A diagnosis of depressive disorder not merit a separate diagnosis. However, when
due to another medical condition requires the the depressive symptoms meet full criteria for a
presence of an etiological medical condition. major depressive episode, a diagnosis of other
Major depressive disorder is not diagnosed if specified depressive disorder may be made in
the major depressive–like episodes are all addition to the diagnosis of the psychotic
attributable to the direct pathophysiological disorder.
consequence of a specific medical condition Schizoaffective disorder. Schizoaffective
(e.g., multiple sclerosis, stroke, disorder differs from major depressive disorder,
hypothyroidism). with psychotic features, by the requirement that
Substance/medication-induced depressive in schizoaffective disorder, delusions or
disorder. This disorder is distinguished from hallucinations are present for at least 2 weeks
major depressive disorder by the fact that a in the absence of a major depressive episode.
substance (e.g., a drug of abuse, a medication, Attention-deficit/hyperactivity disorder.
a toxin) appears to be etiologically related to Distractibility and low frustration tolerance can
the mood disturbance. For example, depressed occur in both attention-deficit/hyperactivity
mood that occurs only in the context of disorder (ADHD) and a major depressive
withdrawal from cocaine would be diagnosed episode; if the criteria are met for both, ADHD
as cocaine-induced depressive disorder. may be diagnosed in addition to the mood
Persistent depressive disorder. Persistent disorder. However, the clinician must be
depressive disorder is characterized by cautious not to overdiagnose a major
depressed mood, more days than not, for at depressive episode in children with ADHD
least 2 years. If criteria are met for both major whose disturbance in mood is characterized by
depressive disorder and persistent depressive irritability rather than by sadness or loss of
disorder, both can be diagnosed. interest.
Premenstrual dysphoric disorder. Adjustment disorder with depressed mood.
Premenstrual dysphoric disorder is A major depressive episode that occurs in
characterized by dysphoric mood that is response to a psychosocial stressor is
present in the final week before the onset of distinguished from adjustment disorder, with
menses, that starts to improve within a few depressed mood, by the fact that the full criteria
days after the onset of menses, and that for a major depressive episode are not met in
becomes minimal or absent in the week adjustment disorder.
postmenses. By contrast, the episodes of major Bereavement. Bereavement is the experience
depressive disorder are not temporally of losing a loved one to death. It generally
connected to the menstrual cycle. triggers a grief response that may be intense
Disruptive mood dysregulation disorder. and may involve many features that overlap
Disruptive mood dysregulation disorder is with symptoms characteristic of a major
characterized by severe, recurrent temper depressive episode, such as sadness, difficulty
outbursts manifested verbally and/or sleeping, and poor concentration. Features that
behaviorally, accompanied by persistent or help differentiate a bereavement-related grief
labile mood, most of the day, nearly every day, response from a major depressive episode
in between the outbursts. In contrast, in major include the following: the predominant affects in
depressive disorder, irritability is confined to the grief are feelings of emptiness and loss,
major depressive episodes. whereas in a major depressive episode they
Major depressive episodes superimposed are persistent depressed mood and a
on schizophrenia, delusional disorder, diminished ability to experience pleasure.
schizophreniform disorder, or other Moreover, the dysphoric mood of grief is likely
specified or unspecified schizophrenia to decrease in intensity over days to weeks and
spectrum and other psychotic disorder. occurs in waves that tend to be associated with
Depressive symptoms may be present during thoughts or reminders of the deceased,
schizophrenia, delusional disorder, whereas the depressed mood in a major
depressive episode is more persistent and not
tied to specific thoughts or preoccupations. It is
important to note that in a vulnerable individual
(e.g., someone with a past history of major
depressive disorder), bereavement may trigger
not only a grief response but also the
development of an episode of depression or the
worsening of an existing episode.
Sadness.Finally, periods of sadness are
inherent aspects of the human experience.
These periods should not be diagnosed as a
major depressive episode unless criteria are
met for severity (i.e., five out of nine
symptoms), duration (i.e., most of the day,
nearly every day for at least 2 weeks), and
clinically significant distress or impairment. The
diagnosis other specified depressive disorder
may be appropriate for presentations of
depressed mood with clinically significant
impairment that do not meet criteria for duration
or severity.

Comorbidity
Other disorders with which major depressive
disorder frequently co-occurs are substance-
related disorders, panic disorder, generalized
anxiety disorder, post-traumatic stress disorder,
obsessive-compulsive disorder, anorexia
nervosa, bulimia nervosa, and borderline
personality disorder.
While women are more likely than men
to report comorbid anxiety disorders, bulimia
nervosa, and somatoform disorder (somatic
symptom and related disorders), men are more
likely to report comorbid alcohol and substance
abuse.