Major Depression (DSM-IV-R)

The Brain and Mood


  1. Five (or more) of the following symptoms have been present during the same 2- week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.
Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations.
  1. depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (eg., appears tearful).  Note: In children and adolescents, can be irritable mood.
  2. markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others)
  3. significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gaines.
  4. insomnia or hypersomnia nearly every day
  5. psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)
  6. fatigue or loss of energy nearly every day
  7. feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick)
  8. diminished ability to think or concentrate, or indecisiveness, nearly every day (either by 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
  1. The symptoms do not meet criteria for a Mixed Episode.
  2. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
  3. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism).
  4. The symptoms are not better account for by Bereavement, i.e., after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.


The mood in a Major Depressive Episode is often described by the person as depressed, sad, hopeless, discouraged, or "down in the dumps."  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, or 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.

A careful review is essential to elicit symptoms of a Major Depressive Episode.  Reporting may be compromised by difficulties in concentrating, impaired memory, or a tendency to deny, discount, or explain away symptoms.  Information from additional informants can be especially helpful in clarifying the course of current or prior Major Depressive Episodes and in assessing whether that have been any Manic or Hypomanic Episodes.  Because Major Depressive Episodes can begin gradually, a review of clinical information that focuses on the worst part of the current episode may be most likely to detect the presence of symptoms.  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). 

By definition, a Major Depressive Episode is not due to the direct physiological effects of a drug of abuse (e.g., in the context of Alcohol Intoxication or Cocaine Withdrawal), to the side effects of medications or treatments (e.g., steroids), or to toxin exposure.  Similarly, the episode is not due to the direct physiological effects of a general medical condition (e.g., hypothyroidism).  Moreover, if the symptoms begin within 2 months of the loss of a loved one and do not persist beyond these 2 months, they are generally considered to result from Bereavement unless they are associated with marked functional impairment or include morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.



Individuals with a Major Depressive Episode frequently present with tearfulness, irritability, brooding, obsessive remination, anxiety, phobias, excessive worry over physical health, and complaints of pain (e.g., headaches or joint pain, abdominal or other pains).  During a Major Depressive Episode, some individuals have Panic Attacks that occur in a pattern that meets criteria for Panic Disorder.  In children, separation anxiety may occur.  Some individuals note difficulty in intimate relationships, less satisfying social interactions, or difficulties in sexual functioning (e.g., anorgasmia in women or erectile dysfunction in men).  There may be marital problems (e.g., divorce), occupational problems (e.g., loss of job), academic problems (e.g., truancy, school failure), Alcohol or other Substance Abuse, or increased utilization of medical services.  The most serious consequence of a Major Depressive Episode is attempted or completed suicide.  Suicide risk is especially high for individuals with psychotic features, a history of previous suicide attempts, a family history of completed suicides, or concurrent substance use.  There may also be an increased rate of premature death from general medical conditions.  Major Depressive Episodes often follow psychological stressors (e.g., the death of a loved one, marital separation, divorce).  Childbirth may precipitate a Major Depressive Episode, in which case the specifier With Postpartum Onset is noted.



No laboratory findings that are diagnostic of a Major Depressive Episode have been identified.  However, a variety of laboratory findings have been noted to be abnormal more often in groups of individuals with Major Depressive Episodes compared with control subjects.  It appears that the same laboratory abnormalities are associated with a Major Depressive Episode regardless of whether the episode is part of the Major Depressive, Bipolar I, or Bipolar II Disorder.  Most laboratory abnormalities are state dependent (i.e., affected by the presence or absence of depressive symptoms).  Laboratory tests are most likely to be abnormal in episodes with melancholic or psychotic features and in more severely depressed individuals.

Sleep EEG abnormalities may be evident in 40%-60% of outpatients and in up to 90% of inpatients with a Major Depressive Episode.  The most frequently associated polysomnographic findings include 1) sleep continuity disturbances, such as prolonged sleep latency, increased intermittent wakefulness, and early morning awakening; 2) reduced non-rapid eye movement (NREM) stages 3 and 4 sleep (slow-wave sleep) , with a shift in slow-wave activity away from the first NREM period; 3) decreased rapid eye movement (REM) latency (i.e., shortened duration of the first NREM period); 4) increased phasic REM activity (i.e., the number of actual eye movements during REM); 5) increased duration of REM sleep early in the night.  There is evidence that these sleep abnormalities may persist after clinical remission or precede the onset of the initial Major Depressive Episode among those at high risk for a Mood Disorder (e.g, first-degree family members of individuals with Major Depressive Disorder).

The pathophysiology of a Major Depressive Episode may involve a dysregulation of a number of neurotransmitter systems, including the serotonin, norephinephrine, dopamine, acetycholine, and gamma-ambiobutyric acid systems.  There is also evidence of alterations of several neuropeptides, including corticotropin-releasing hormone.  In some depressed individuals, hormonal disturbances have been observed, including elevated glucocorticoid secretion (e.g., elevated urinary free cortisol levels or dexamethasone nonsuppression of plasma cortisol) and blunted growth hormone, thyroid-stimulating hormone, and prolactin responses to various challenge tests.  Functional brain imaging studies document alteration sin cerebral blood flow and limbic regions and decreased blood flow in the lateral prefrontal cortex.  Depression beginning in late life is associated with alterations in brain structure, including periventricular vascular changes.  None of these changes are present in all individuals with a Major Depressive Episode, however, nor is any particular disturbance specific to depression.



Culture can influence the experience and communication of symptoms of depression.  Under-diagnosis or misdiagnosis can be reduced by being alert to ethnic and cultural specificity in the presenting complaints of a Major Depressive Episode,  For example, in some cultures, depression may be experience largely in somatic terms, rather than with sadness or guilt.  Complaints of "nerves" and headaches (in Latino and Mediterranean cultures), of weakness, tiredness, or "imbalance" (in Chinese and Asian cultures), of problems of the "heart" (in Middle Eastern cultures), or of being "heart-broken" (among Hopi) may express the depressive experience.  Such presentations combine features of teh Depressive, Anxiety, and Somatoform Disorders.  Cultures also may differ in judgements about the seriousness of experiencing or expressing dysphoria (e.g., irritability may provoke greater concern than sadness or withdrawal).  Culturally distinctive experiences (e.g., fear of being hexed or bewitched, feelings of "heat in the head" or crawling sensations of worms or ants, or vivid feelings of being visited by those who have died) must be distinguished from actual hallucinations or delusions that may be part of a Major Depressive Episode, With Psychotic Features.  It is also imperative that the clinician not routinely dismiss a symptom merely because it is viewed as the "norm" for a culture.

The core symptoms of a Major Depressive Episode are the same for children and adolescents, although there is data that suggest that the prominence of characteristic symptoms may change with age.  Certain symptoms such as somatic complaints, irritability, and social withdrawal are particularly common in children, whereas psychomotor retardation, hypersomnia, and delusions are less common in prepuberty than in adolescence and adulthood.  In prepubertal children, Major Depressive Episodes occur more frequently in conjunction with other mental disorders (especially Disruptive Behavior Disorders, Attention-Deficit Disorders, and Anxiety Disorders) than in isolation.  In adolescents, Major Depressive Episodes are frequently associated with Disruptive Behavior Disorders, Attention-Deficit Disorders, Anxiety Disorders, Substance-Related Disorders, and Eating Disorder.  In elderly adults, cognitive symptoms (e.g., disorientation, memory loss, and distractibility) may be particularly prominent.

Women are at significantly greater risk than men to develop Major Depressive Episodes at some point during their lives, with the greatest differences found in studies conducted in the United States and Europe.  This increased differential risk emerges during adolescence and may coincide with the onset of puberty.  Thereafter, a significant proportion of women report a worsening of the symptoms of a Major Depressive Episode several days before the onset of menses.  Studies indicate that depressive episodes occur twice as frequently in women as in men.



Symptoms of a Major Depressive Episode usually develop over days to weeks.  A prodromal period that may include anxiety symptoms and mild depressive symptoms may last for weeks to months before the onset of a full Major Depressive Episode.  The duration of a Major Depressive Episode is also variable.  An untreated episode typically lasts 4 months or longer, regardless of age at onset.  In a majority of cases, there is complete remission of symptoms, and functioning returns to the premorbid level.  In a significant proportion of cases (perhaps 20%-30%), some depressive symptoms insufficient to meet full criteria for a Major Depressive Episode may persist for months to years and may be associated with some disability or distress.  Partial remission following a Major Depressive Episode appears to be predictive of a similar pattern after subsequent episodes.  In some individuals (5%-10%), the full criteria for a Major Depressive Episode continue to be met for 2 or more years.



A Major Depressive Episode must be distinguished from a Mood Disorder Due to a General Medical Condition.  The appropriate diagnosis would be Mood Disorder Due to a General Medical Condition if the mood disturbance is judged to be the direct physiological consequence of a specific general medical condition (e.g., multiple sclerosis, stroke, hypothyroidism).  This determination is based on history, laboratory findings, or physical examination.  If both a Major Depressive Episode and a general medical condition are present but it is judged that the depressive symptoms are not the direct physiological consequence of the general medical condition, then the primary Mood Disorder is recorded. 

In elderly persons, it is often difficult to determine whether cognitive symptoms (e.g., disorientation, apathy, difficulty concentrating, memory loss) are better accounted for by a dementia or by a Major Depressive Episode.  A thorough medical evaluation and an evaluation of the onset of the disturbance, temporal sequencing of depressive and cognitive symptoms, course of illness, and treatment response are helpful in making this determination.  The premorbid state of the individual may help to differentiate a Major Depressive Episode from a dementia.  In a dementia, there is usually a premorbid history of declining cognitive function, whereas the individual with a Major Depressive Episode is much more likely to have a relatively normal premorbid state and abrupt cognitive decline associated with the depression.

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 Depressive Disorder Not Otherwise Specified may be appropriate for presentations of depressed mood with clinically significant impairment that do not meet the criteria for duration or severity.



When the Limbic system fails for what ever cause, it creates a behavior cluster called Major Depressive Disorder.  For instance, Bipolar Depressive cluster appears to be the same as Unipolar Depression.  Many Bipolar depressed patients never experience hypomania or mania.  Diagnosis into artificially pigeon holes is not necessarily important.

The important point is the mechanism that creates the Depressive Syndrome.  The earlier the onset of depression and the more cycled the depression, the more likely that ion flux in the Limbic System is the cause.  In this case, an ionic flux modulator is medicated such as Lithium or Anticonvulsants (i.e. Lamotrigine/Valproic Acid/Carbamazepine/etc.)  Family history is usually positive.

Major Depressive clusters that are not cyclical are those with an onset later in life (age of onset > 40), and usually related to a medical disorder such as Diabetes Mellitus Type II.  They are often caused by a deficiency of a neurotransmitter modulator, such as serotonin.  In this case, a Serotonin Re-uptake Inhibitor is medicated, such as Lexapro/Celexa/Prozac/etc.