4. Depressive Disorders
4.1. Disruptive Mood Dysregulation Disorder
4.2. Major Depressive Disorder
4.3. Persistent Depressive Disorder (Dysthymia)
4.4. Premenstrual Dysphoric Disorder
4.5. Substance/Medication-Induced Depressive Disorder
4.6. Depressive Disorder Due to Another Medical Condition
Depressive disorders include disruptive mood deregulation disorder, major
depressive disorder (including major depressive episode), persistent depressive disorder
(dysthymia), premenstrual dysphonic disorder, substance/medication-induced depressive
disorder, depressive disorder due to another medical condition, other specified depressive
disorder, and unspecified depressive disorder. This chapter
"Depressive Disorders" has been separated from the previous chapter "Bipolar and Related
Disorders." The common feature of all of these disorders is the presence of sad,
empty, or irritable mood, accompanied by somatic and cognitive changes that significantly
affect the individual's capacity to function. What differs among them are issues of
duration, timing, or presumed etiology.
In order to address concerns about the potential for the overdiagnosis of and treatment
for bipolar disorder in children, a new diagnosis, disruptive mood dysregulation disorder,
referring to the presentation of children with persistent irritability and frequent episodes
of extreme behavioral dyscontrol, is added to the depressive disorders for children up to
12 years of age. Its placement in this chapter reflects the finding that children with this
symptom pattern typically develop unipolar depressive disorders or anxiety disorders,
rather than bipolar disorders, as they mature into adolescence and adulthood.
Major depressive disorder represents the classic condition in this group of disorders. It
is characterized by discrete episodes of at least 2 weeks' duration (although most episodes
last considerably longer) involving clear-cut changes in affect, cognition, and neurovegetative
functions and inter-episode remissions. A diagnosis based on a single episode is
possible, although the disorder is a recurrent one in the majority of cases. Careful consideration
is given to the delineation of normal sadness and grief from a major depressive episode.
Bereavement may induce great suffering, but it does not typically induce an episode
of major depressive disorder. When they do occur together, the depressive symptoms and
functional impairment tend to be more severe and the prognosis is worse compared with
bereavement that is not accompanied by major depressive disorder. Bereavement-related
depression tends to occur in persons with other vulnerabilities to depressive disorders,
and recovery may be facilitated by antidepressant treatment.
A more chronic form of depression, persistent depressive disorder (dysthymia), can be
diagnosed when the mood disturbance continues for at least 2 years in adults or 1 year in
children.
Almost 20 years of additional of research on this condition
has confirmed a specific and treatment-responsive form of depressive disorder that begins
sometime following ovulation and remits within a few days of menses and has a marked
impact on functioning.
A large number of substances of abuse, some prescribed medications, and several
medical conditions can be associated with depression-like phenomena. This fact is recognized
in the diagnoses of substance/medication-induced depressive disorder and depressive
disorder due to another medical condition.
The core feature of disruptive mood dysregulation disorder is chronic, severe persistent irritabihty.
This severe irritability has two prominent clinical manifestations, the first of
which is frequent temper outbursts. These outbursts typically occur in response to frustration
and can be verbal or behavioral (the latter in the form of aggression against property,
self, or others). They must occur frequently (i.e., on average, three or more times per
week) (Criterion C) over at least 1 year in at least two settings (Criteria E and F), such as in
the home and at school, and they must be developmentally inappropriate (Criterion B).
The second manifestation of severe irritability consists of chronic, persistently irritable or
angry mood that is present between the severe temper outbursts. This irritable or angry
mood must be characteristic of the child, being present most of the day, nearly every day,
and noticeable by others in the child's environment (Criterion D).
The clinical presentation of disruptive mood dysregulation disorder must be carefully
distinguished from presentations of other, related conditions, particularly pediatric bipolar
disorder. In fact, disruptive mood dysregulation disorder was added to DSM-5 to
address the considerable concern about the appropriate classification and treatment of
children who present with chronic, persistent irritability relative to children who present
with classic (i.e., episodic) bipolar disorder.
Some researchers view severe, non-episodic irritability as characteristic of bipolar disorder
in children, although both DSM-IV and DSM-5 require that both children and adults
have distinct episodes of mania or hypomania to qualify for the diagnosis of bipolar I disorder.
During the latter decades of the 20th century, this contention by researchers that
severe, nonepisodic irritability is a manifestation of pediatric mania coincided with an upsurge
in the rates at which clinicians assigned the diagnosis of bipolar disorder to their
pediatric patients. This sharp increase in rates appears to be attributable to clinicians combining
at least two clinical presentations into a single category. That is, both classic, episodic
presentations of mania and non-episodic presentations of severe irritability have
been labeled as bipolar disorder in children. In DSM-5, the term bipolar disorder is explicitly
reserved for episodic presentations of bipolar symptoms. DSM-IV did not include a diagnosis
designed to capture youths whose hallmark symptoms consisted of very severe, nonepisodic
irritability, whereas DSM-5, with the inclusion of disruptive mood dysregulation
disorder, provides a distinct category for such presentations.
Disruptive mood dysregulation disorder is common among children presenting to pediatric mental health clinics. Prevalence estimates of the disorder in the community are unclear. Based on rates of chronic and severe persistent irritability, which is the core feature of the disorder, the overall 6-month to 1-year period-prevalence of disruptive mood dysregulation disorder among children and adolescents probably falls in the 2%-5% range. However, rates are expected to be higher in males and school-age children than in females and adolescents.
Children presenting to clinics with features of disruptive mood dysregulation disorder are predominantly male. Among community samples, a male preponderance appears to be supported. This difference in prevalence between males and females differentiates disruptive mood dysregulation disorder from bipolar disorder, in which there is an equal gender prevalence.
In general, evidence documenting suicidal behavior and aggression, as well as other severe functional consequences, in disruptive mood dysregulation disorder should be noted when evaluating children with chronic irritability.
Chronic, severe irritability, such as is seen in disruptive mood dysregulation disorder, is
associated with marked disruption in a child's family and peer relationships, as well as in
school performance. Because of their extremely low frustration tolerance, such children
generally have difficulty succeeding in school; they are often unable to participate in the
activities typically enjoyed by healthy children; their family life is severely disrupted by
their outbursts and irritability; and they have trouble initiating or sustaining friendships.
Levels of dysfunction in children with bipolar disorder and disruptive mood dysregulation
disorder are generally comparable. Both conditions cause severe disruption in the lives of
the affected individual and their families. In both disruptive mood dysregulation disorder
and pediatric bipolar disorder, dangerous behavior, suicidal ideation or suicide attempts,
severe aggression, and psychiatric hospitalization are common.
The criterion symptoms for major depressive disorder must be present nearly every day to
be considered present, with the exception of weight change and suicidal ideation. Depressed
mood must be present for most of the day, in addition to being present nearly every
day. Often insomnia or fatigue is the presenting complaint, and failure to probe for
accompanying depressive symptoms will result in underdiagnosis. Sadness may be denied
at first but may be elicited through interview or inferred from facial expression and
demeanor. With individuals who focus on a somatic complaint, clinicians should determine
whether the distress from that complaint is associated with specific depressive
symptoms. Fatigue and sleep disturbance are present in a high proportion of cases; psychomotor
disturbances are much less common but are indicative of greater overall severity,
as is the presence of delusional or near-delusional guilt.
The essential feature of a major depressive episode is a period of at least 2 weeks during
w^hich there is either depressed mood or the loss of interest or pleasure in nearly all activities
(Criterion A). In children and adolescents, the mood may be irritable rather than sad.
The individual must also experience at least four additional symptoms drawn from a list
that includes changes in appetite or weight, sleep, and psychomotor activity; decreased energy;
feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions;
or recurrent thoughts of death or suicidal ideation or suicide plans or attempts. To
count toward a major depressive episode, a symptom must either be newly present or must
have clearly worsened compared with the person's pre-episode status. The symptoms
must persist for most of the day, nearly every day, for at least 2 consecutive weeks. The episode
must be accompanied by clinically significant distress or impairment in social, occupational,
or other important areas of functioning. For some individuals with milder
episodes, functioning may appear to be normal but requires markedly increased effort.
The mood in a major depressive episode is often described by the person as depressed,
sad, hopeless, discouraged, or "down in the dumps" (Criterion Al). In some cases, sadness
may be denied at first but may subsequently be elicited by interview (e.g., by pointing out
that the individual looks as if he or she is about to cry). In some individuals who complain
of feeling "blah," having no feelings, or feeling anxious, the presence of a depressed mood
can be inferred from the person's facial expression and demeanor. Some individuals emphasize
somatic complaints (e.g., bodily aches and pains) rather than reporting feelings of
sadness. Many individuals report or exhibit increased irritability (e.g., persistent anger, a
tendency to respond to events with angry outbursts or blaming others, an exaggerated
sense of frustration over minor matters). In children and adolescents, an irritable or cranky
mood may develop rather than a sad or dejected mood. This presentation should be differentiated
from a pattern of irritability when frustrated.
Loss of interest or pleasure is nearly always present, at least to some degree. Individuals
may report feeling less interested in hobbies, "not caring anymore," or not feeling any
enjoyment in activities that were previously considered pleasurable (Criterion A2). Family
members often notice social withdrawal or neglect of pleasurable avocations (e.g., a formerly
avid golfer no longer plays, a child who used to enjoy soccer finds excuses not to
practice). In some individuals, there is a significant reduction from previous levels of sexual
interest or desire.
Appetite change may involve either a reduction or increase. Some depressed individuals
report that they have to force themselves to eat. Others may eat more and may crave
specific foods (e.g., sweets or other carbohydrates). When appetite changes are severe (in
either direction), there may be a significant loss or gain in weight, or, in children, a failure
to make expected weight gains may be noted (Criterion A3).
Sleep disturbance may take the form of either difficulty sleeping or sleeping excessively
(Criterion A4). When insomnia is present, it typically takes the form of middle insonrmia
(i.e., waking up during the night and then having difficulty returning to sleep) or
terminal insomnia (i.e., waking too early and being unable to return to sleep). Initial insomnia
(i.e., difficulty falling asleep) may also occur. Individuals who present with oversleeping
(hypersomnia) may experience prolonged sleep episodes at night or increased
daytime sleep. Sometimes the reason that the individual seeks treatment is for the disturbed
sleep.
Psychomotor changes include agitation (e.g., the inability to sit still, pacing, handwringing;
or pulling or rubbing of the skin, clothing, or other objects) or retardation (e.g.,
slowed speech, thinking, and body movements; increased pauses before answering;
speech that is decreased in volume, inflection, amount, or variety of content, or muteness)
(Criterion A5). The psychomotor agitation or retardation must be severe enough to be observable
by others and not represent merely subjective feelings.
Decreased energy, tiredness, and fatigue are common (Criterion A6). A person may report
sustained fatigue without physical exertion. Even the smallest tasks seem to require
substantial effort. The efficiency with which tasks are accomplished may be reduced. For
example, an individual may complain that washing and dressing in the morning are exhausting
and take twice as long as usual.
The sense of worthlessness or guilt associated with a major depressive episode may include
unrealistic negative evaluations of one's worth or guilty preoccupations or ruminations
over minor past failings (Criterion A7). Such individuals often misinterpret neutral
or trivial day-to-day events as evidence of personal defects and have an exaggerated sense
of responsibility for untoward events. The sense of worthlessness or guilt may be of delusional
proportions (e.g., an individual who is convinced that he or she is personally responsible
for world poverty). Blaming oneself for being sick and for failing to meet
occupational or inteφersonal responsibilities as a result of the depression is very common
and, unless delusional, is not considered sufficient to meet this criterion.
Many individuals report impaired ability to think, concentrate, or make even minor
decisions (Criterion A8). They may appear easily distracted or complain of memory difficulties.
Those engaged in cognitively demanding pursuits are often unable to function. In
children, a precipitous drop in grades may reflect poor concentration. In elderly individuals,
memory difficulties may be the chief complaint and may be mistaken for early signs
of a dementia (''pseudodementia"). When the major depressive episode is successfully
treated, the memory problems often fully abate. However, in some individuals, particularly
elderly persons, a major depressive episode may sometimes be the initial presentation
of an irreversible dementia.
Thoughts of death, suicidal ideation, or suicide attempts (Criterion A9) are common.
They may range from a passive wish not to awaken in the morning or a belief that others
would be better off if the individual were dead, to transient but recurrent thoughts of committing
suicide, to a specific suicide plan. More severely suicidal individuals may have put
their affairs in order (e.g., updated wills, settled debts), acquired needed materials (e.g., a
rope or a gun), and chosen a location and time to accomplish the suicide. Motivations for
suicide may include a desire to give up in the face of perceived insurmountable obstacles,
an intense wish to end what is perceived as an unending and excruciatingly painful emotional
state, an inability to foresee any enjoyment in life, or the wish to not be a burden to
others. The resolution of such thinking may be a more meaningful measure of diminished
suicide risk than denial of further plans for suicide.
The evaluation of the symptoms of a major depressive episode is especially difficult
when they occur in an individual who also has a general medical condition (e.g., cancer,
stroke, myocardial infarction, diabetes, pregnancy). Some of the criterion signs and symptoms
of a major depressive episode are identical to those of general medical conditions
(e.g., weight loss with untreated diabetes; fatigue with cancer; hypersomnia early in pregnancy;
insonmia later in pregnancy or the postpartum). Such symptoms count toward a
major depressive diagnosis except when they are clearly and fully attributable to a general
medical condition. Nonvegetative symptoms of dysphoria, anhedonia, guilt or worthlessness,
impaired concentration or indecision, and suicidal thoughts should be assessed with
particular care in such cases. Definitions of major depressive episodes that have been modified
to include only these nonvegetative symptoms appear to identify nearly the same individuals
as do the full criteria.
Major depressive disorder is associated with high mortality, much of which is accounted
for by suicide; however, it is not the only cause. For example, depressed individuals admitted
to nursing homes have a markedly increased likelihood of death in the first year. Individuals
frequently present with tearfulness, irritability, brooding, obsessive rumination,
anxiety, phobias, excessive worry over physical health, and complaints of pain (e.g., headaches;
joint, abdominal, or other pains). In children, separation anxiety may occur.
Although an extensive literature exists describing neuroanatomical, neuroendocrinological,
and neurophysiological correlates of major depressive disorder, no laboratory test
has yielded results of sufficient sensitivity and specificity to be used as a diagnostic tool for
this disorder. Until recently, hypothalamic-pituitary-adrenal axis hyperactivity had been
the most extensively investigated abnormality associated v^ith major depressive episodes,
and it appears to be associated with melancholia, psychotic features, and risks for eventual
suicide. Molecular studies have also implicated peripheral factors, including genetic variants
in neurotrophic factors and pro-inflammatory cytokines. Additionally, functional
magnetic resonance imaging studies provide evidence for functional abnormalities in specific
neural systems supporting emotion processing, reward seeking, and emotion regulation
in adults with major depression.
Twelve-month prevalence of major depressive disorder in the United States is approximately 7%, with marked differences by age group such that the prevalence in 18- to 29-year-old individuals is threefold higher than the prevalence in individuals age 60 years or older. Females experience 1.5- to 3-fold higher rates than males beginning in early adolescence.
Surveys of major depressive disorder across diverse cultures have shown sevenfold differences in 12-month prevalence rates but much more consistency in female-to-male raho, mean ages at onset, and the degree to which presence of the disorder raises the likelihood of comorbid substance abuse. While these findings suggest substantial cultural differences in the expression of major depressive disorder, they do not permit simple linkages between particular cultures and the likelihood of specific symptoms. Rather, clinicians should be aware that in most countries the majority of cases of depression go unrecognized in primary care settings and that in many cultures, somatic symptoms are very likely to constitute the presenting complaint. Among the Criterion A symptoms, insomnia and loss of energy are the most uniformly reported.
Although the most reproducible finding in the epidemiology of major depressive disorder has been a higher prevalence in females, there are no clear differences between genders in symptoms, course, treatment response, or functional consequences. In w^omen, the risk for suicide attempts is higher, and the risk for suicide completion is lower. The disparity in suicide rate by gender is not as great among those with depressive disorders as it is in the population as a whole.
The possibility of suicidal behavior exists at all times during major depressive episodes. The most consistently described risk factor is a past history of suicide attempts or threats, but it should be remembered that most completed suicides are not preceded by unsuccessful attempts. Other features associated with an increased risk for completed suicide include male sex, being single or living alone, and having prominent feelings of hopelessness. The presence of borderline personality disorder markedly increases risk for future suicide attempts.
Many of the functional consequences of major depressive disorder derive from individual
symptoms. Impairment can be very mild, such that many of those who interact with the affected
individual are unaware of depressive symptoms. Impairment may, however, range
to complete incapacity such that the depressed individual is unable to attend to basic selfcare
needs or is mute or catatonic. Among individuals seen in general medical settings,
those with major depressive disorder have more pain and physical illness and greater decreases
in physical, social, and role functioning.
The essential feature of persistent depressive disorder (dysthymia) is a depressed mood
that occurs for most of the day, for more days than not, for at least 2 years, or at least 1 year
for children and adolescents (Criterion A). This disorder represents a consolidation of
DSM-IV-defined chronic major depressive disorder and dysthymic disorder. Major depression
may precede persistent depressive disorder, and major depressive episodes may
occur during persistent depressive disorder. Individuals whose symptoms meet major depressive
disorder criteria for 2 years should be given a diagnosis of persistent depressive
disorder as well as major depressive disorder.
Individuals with persistent depressive disorder describe their mood as sad or "down
in the dumps." During periods of depressed mood, at least two of the six symptoms from
Criterion B are present. Because these symptoms have become a part of the individual's
day-to-day experience, particularly in the case of early onset (e.g., "I've always been this
way"), they may not be reported unless the individual is directly prompted. E>uring the 2-year
period (1 year for children or adolescents), any symptom-free intervals last no longer than
2 months (Criterion C).
Persistent depressive disorder is effectively an amalgam of DSM-IV dysthymic disorder and chronic major depressive episode. The 12-month prevalence in the United States is approximately 0.5% for persistent depressive disorder and 1.5% for chronic major depressive disorder.
The degree to which persistent depressive disorder impacts social and occupational functioning
is likely to vary widely, but effects can be as great as or greater than those of major
depressive disorder.
The essential features of premenstrual dysphoric disorder are the expression of mood lability,
irritability, dysphoria, and anxiety symptoms that occur repeatedly during the premenstrual
phase of the cycle and remit around the onset of menses or shortly thereafter.
These symptoms may be accompanied by behavioral and physical symptoms. Symptoms
must have occurred in most of the menstrual cycles during the past year and must have an
adverse effect on work or social functioning. The intensity and/or expressivity of the accompanying
symptoms may be closely related to social and cultural background characteristics
of the affected female, family perspectives, and more specific factors such as
religious beliefs, social tolerance, and female gender role issues.
Typically, symptoms peak around the time of the onset of menses. Although it is not
uncommon for symptoms to linger into the first few days of menses, the individual must
have a symptom-free period in the follicular phase after the menstrual period begins.
While the core symptoms include mood and anxiety symptoms, behavioral and somatic
symptoms commonly also occur. However, the presence of physical and/or behavioral
symptoms in the absence of mood and/or anxious symptoms is not sufficient for a diagnosis.
Symptoms are of comparable severity (but not duration) to those of another mental
disorder, such a^ a major depressive episode or generalized anxiety disorder. In order to
confirm a provisional diagnosis, daily prospective symptom ratings are required for at
least two symptomatic cycles.
Delusions and hallucinations have been described in the late luteal phase of the menstrual cycle but are rare. The premenstrual phase has been considered by some to be a risk period for suicide.
Delusions and hallucinations have been described in the late luteal phase of the menstrual cycle but are rare. The premenstrual phase has been considered by some to be a risk period for suicide.
Twelve-month prevalence of premenstrual dysphoric disorder is between 1.8% and 5.8% of menstruating women. Estimates are substantially inflated if they are based on retrospective reports rather than prospective daily ratings. However, estimated prevalence based on a daily record of symptoms for 1-2 months may be less representative, as individuals with the most severe symptoms may be unable to sustain the rating process. The most rigorous estimate of premenstrual dysphoric disorder is 1.8% for women whose symptoms meet the full criteria without functional impairment and 1.3% for women whose symptoms meet the current criteria with functional impairment and without co-occurring symptoms from another mental disorder.
Premenstrual dysphoric disorder is not a culture-bound syndrome and has been observed in individuals in the United States, Europe, India, and Asia. It is unclear as to whether rates differ by race. Nevertheless, frequency, intensity, and expressivity of symptoms and helpseeking patterns may be significantly influenced by cultural factors.
Symptoms must be associated with clinically meaningful distress and/or an obvious and marked impairment in the ability to function socially or occupationally in the week prior to menses. Impairment in social functioning may be manifested by marital discord and problems with children, other family members, or friends. Chronic marital or job problems should not be confused with dysfunction that occurs only in association with premenstrual dysphoric disorder.
The diagnostic features of substance/medication-induced depressive disorder include the
symptoms of a depressive disorder, such as major depressive disorder; however, the depressive
symptoms are associated with the ingestion, injection, or inhalation of a substance
(e.g., drug of abuse, toxin, psychotropic medication, other medication), and the
depressive symptoms persist beyond the expected length of physiological effects, intoxication,
or withdrawal period. As evidenced by clinical history, physical examination, or
laboratory findings, the relevant depressive disorder should have developed during or
within 1 month after use of a substance that is capable of producing the depressive disorder
(Criterion Bl). In addition, the diagnosis is not better explained by an independent
depressive disorder. Evidence of an independent depressive disorder includes the depressive
disorder preceded the onset of ingestion or withdrawal from the substance; the
depressive disorder persists beyond a substantial period of time after the cessation of substance
use; or other evidence suggests the existence of an independent non-substance/
medication-induced depressive disorder (Criterion C). This diagnosis should not be made
when symptoms occur exclusively during the course of a delirium (Criterion D). The depressive
disorder associated with the substance use, intoxication, or withdrawal must
cause clinically significant distress or impairment in social, occupational, or other important
areas of functioning to qualify for this diagnosis (Criterion E).
Some medications (e.g., stimulants, steroids, L-dopa, antibiotics, central nervous
system drugs, dermatological agents, chemotherapeutic drugs, immunological agents)
can induce depressive mood disturbances. Clinical judgment is essential to determine
whether the medication is truly associated with inducing the depressive disorder or
whether a primary depressive disorder happened to have its onset while the person was
receiving the treatment. For example, a depressive episode that developed within the first
several weeks of beginning alpha-methyldopa (an antihypertensive agent) in an individual
with no history of major depressive disorder would qualify for the diagnosis of medication-
induced depressive disorder. In some cases, a previously established condition
(e.g., major depressive disorder, recurrent) can recur while the individual is coincidentally
taking a medication that has the capacity to cause depressive symptoms (e.g., L-dopa, oral
contraceptives). In such cases, the clinician must make a judgment as to whether the medication
is causative in this particular situation.
A substance/medication-induced depressive disorder is distinguished from a primary
depressive disorder by considering the onset, course, and other factors associated with the
substance use. There must be evidence from the history, physical examination, or laboratory
findings of substance use, abuse, intoxication, or withdrawal prior to the onset of the
depressive disorder. The withdrawal state for some substances can be relatively protracted,
and thus intense depressive symptoms can last for a long period after the cessation
of substance use.
In a nationally representative U.S. adult population, the lifetime prevalence of substance/ medication-induced depressive disorder is 0.26%.
In a nationally representative U.S. adult population, the lifetime prevalence of substance/ medication-induced depressive disorder is 0.26%.
Drug-induced or treatment-emergent suicidality represents a marked change in thoughts and behavior from the person's baseline, is usually temporally associated with initiation of a substance, and must be distinguished from the underlying primary mental disorders. In regard to the treatment-emergent suicidality associated with antidepressants, a U.S. Food and Drug Administration (FDA) advisory committee considered meta-analyses of 99,839 participants enrolled in 372 randomized clinical trials of antidepressants in trials for mental disorders. The analyses showed that when the data were pooled across all adult age groups, there was no perceptible increased risk of suicidal behavior or ideation. However, in age-stratified analyses, the risk for patients ages 18-24 years was elevated, albeit not significantly (odds ratio [OR] = 1.55; 95% confidence interval [Cl] = 0.91-2.70). The FDA meta-analyses reveal an absolute risk of suicide in patients taking investigational antidepressants of 0.01%. In conclusion, suicide is clearly an extremely rare treatment-emergent phenomenon, but the outcome of suicide was serious enough to prompt the FDA to issue an expanded black-box warning in 2007 regarding the importance of careful monitoring of treatment-emergent suicidal ideation in patients receiving antidepressants.
The essential feature of depressive disorder due to another medical condition is a prominent and persistent period of depressed mood or markedly diminished interest or pleasure in all, or almost all, activities that predominates in the clinical picture (Criterion A) and that is thought to be related to the direct physiological effects of another medical condition (Criterion B). In determining whether the mood disturbance is due to a general medical condition, the clinician must first establish the presence of a general medical condition. Further, the clinician must establish that the mood disturbance is etiologically related to the general medical condition through a physiological mechanism. A careful and comprehensive assessment of multiple factors is necessary to make this judgment. Although there are no infallible guidelines for determining whether the relationship between the mood disturbance and the general medical condition is etiological, several considerations provide some guidance in this area. One consideration is the presence of a temporal association between the onset, exacerbation, or remission of the general medical condition and that of the mood disturbance. A second consideration is the presence of features that are atypical of primary Mood Disorders (e.g., atypical age at onset or course or absence of family history). Evidence from the literature that suggests that there can be a direct association between the general medical condition in question and the development of mood symptoms can provide a useful context in the assessment of a particular situation.
Etiology (i.e., a causal relationship to another medical condition based on best clinical evidence) is the key variable in depressive disorder due to another medical condition. The listing of the medical conditions that are said to be able to induce major depression is never complete, and the clinician's best judgment is the essence of this diagnosis. There are clear associations, as well as some neuroanatomical correlates, of depression with stroke, Huntington's disease, Parkinson's disease, and traumatic brain injury. Among the neuroendocrine conditions most closely associated with depression are Cushing's disease and hypothyroidism. There are numerous other conditions thought to be associated with depression, such as multiple sclerosis. However, the literature's support for a causal association is greater with some conditions, such as Parkinson's disease and Huntington's disease, than with others, for which the differential diagnosis may be adjustment disorder, with depressed mood.
Gender differences pertain to those associated with the medical condition (e.g., systemic lupus erythematosus is more common in females; stroke is somewhat more common in middle-age males compared with females).
Diagnostic markers pertain to those associated with the medical condition (e.g., steroid levels in blood or urine to help corroborate the diagnosis of Cushing's disease, which can be associated with manic or depressive syndromes).
There are no epidemiological studies that provide evidence to differentiate the risk of suicide from a major depressive episode due to another medical condition compared with the risk from a major depressive episode in general. There are case reports of suicides in association with major depressive episodes associated with another medical condition. There is a clear association between serious medical illnesses and suicide, particularly shortly after onset or diagnosis of the illness. Thus, it would be prudent to assume that the risk of suicide for major depressive episodes associated with medical conditions is not less than that for other forms of major depressive episode, and might even be greater.
Functional consequences pertain to those associated with the medical condition. In general, it is believed, but not established, that a major depressive episode induced by Cushing's disease will not recur if the Cushing's disease is cured or arrested. However, it is also suggested, but not established, that mood syndromes, including depressive and manic/ hypomanie ones, may be episodic (i.e., recurring) in some individuals with static brain injuries and other central nervous system diseases.