Merck Manual of Diagnosis and Therapy
Section 15. Psychiatric Disorders
Chapter 189. Mood Disorders
Topics
[General]
Depression
Dysthymic Disorder
Bipolar Disorders
Cyclothymic Disorder

[General]

Mood disorders (affective disorders): A group of heterogeneous, typically recurrent illnesses including unipolar (depressive) and bipolar (manic-depressive) disorders that are characterized by pervasive mood disturbances, psychomotor dysfunction, and vegetative symptoms.

(For mood disorders in children, see Ch. 274.)

Current diagnostic practice emphasizes depression and elation as the core affective components of mood disorders. However, anxiety and irritability are equally common, explaining the continued popularity of the broader rubric "affective disorder," the previous official designation.

Sadness and joy are part of everyday life and should be differentiated from clinical depression and morbid elation. Sadness, or normal depression, is a universal human response to defeat, disappointment, and other adverse situations; the response may be adaptive by permitting withdrawal to conserve inner resources. Transient depression ("blues") may occur as a reaction to certain holidays or significant anniversaries, during the premenstrual phase, and during the first 2 wk postpartum. Such reactions are not abnormal, but persons predisposed to depression may break down during such times.

Grief (normal bereavement), the prototype of reactive depression, occurs in response to significant separations and losses (eg, death, marital separation, romantic disappointment, leaving a familiar environment, forced emigration, or civilian catastrophes). Grief may be manifested by anxiety symptoms, such as insomnia, restlessness, and autonomic nervous system hyperactivity. Like other adversities, separations and losses generally do not cause clinical depression, except in persons predisposed to a mood disorder.

Elation, usually linked to success and achievement, is sometimes considered a defense against depression or a denial of the pain of loss (eg, a rare form of bereavement reaction in which elated hyperactivity may completely replace the expected grief). In predisposed persons, such reactions may lead to mania. Paradoxical depression may follow positive events, possibly because the associated increased responsibilities often have to be faced alone.

Depression or mania is diagnosed when sadness or elation is overly intense and continues beyond the expected impact of a life stressor or arises in the absence of a stressor. Symptoms and signs often cluster into discrete syndromes that typically recur or, less commonly, persist without remission. Clinical depression and mania, unlike normal emotional reactions, cause marked impairment in physical function, social function, and work capacity.

Epidemiology

Some type of mood disturbance, which may require clinical attention, affects 20% of women and 12% of men during their lifetime. These figures largely represent unipolar major depressive disorder and its variants. Although the incidence of bipolar disorder in the general population was estimated at < 2%, new estimates are closer to 4 to 5%. Depression affects twice as many women as men; bipolar disorder affects the sexes equally, but depressive forms predominate in women and manic forms in men. Bipolar disorder usually begins in the teens, 20s, or 30s; unipolar disorders begin, on average, in the 20s, 30s, or 40s. Persons born in the 2 decades after World War II have higher rates of depression and suicide, often associated with higher rates of substance abuse, than those born earlier. Female sex is the major demographic risk factor for depression; social class, culture, and race have not been consistently associated with depression. However, bipolar disorder is somewhat more common in upper socioeconomic classes. Cultural factors seem to modify the clinical manifestations of mood disorders. For example, physical complaints, worry, tension, and irritability are more common manifestations in lower socioeconomic classes; guilty ruminations and self-reproach are more characteristic of depression in Anglo-Saxon cultures; and mania tends to manifest itself more floridly in some Mediterranean and African countries and among black Americans. Economic factors, such as unemployment and sudden financial reversals, have been linked to increased suicide rates in men.

Mood disorders are the most prevalent psychiatric disorders, accounting for 25% of patients in public mental institutions, 65% of psychiatric outpatients, and as many as 10% of all patients seen in nonpsychiatric medical settings.

Etiology

Primary mood disorders: The interaction of several factors contributes to these disorders. Heredity is the most important predisposing factor. The precise mode of inheritance is uncertain, but dominant genes (X-linked or autosomal) may be involved in some forms of bipolar disorder. Polygenic inheritance as a common genetic substrate for bipolar and recurrent unipolar disorders is a more popular hypothesis. What is inherited is unknown. But the final common pathway of mood disorders is believed to be impaired limbic-diencephalic function; recent brain imaging studies further implicate subcortical extrapyramidal structures and their prefrontal connections. Cholinergic, catecholaminergic (noradrenergic or dopaminergic), and serotonergic (5-HT) neurotransmission appears to be dysregulated. Heredity may also increase the likelihood of depression by exposing children to the negative effects of their parent's mood disorders (eg, disruption of affective bonds).

Childhood loss of a parent does not increase a person's risk of developing a mood disorder. However, if such a person develops a mood disorder, depression tends to develop at a younger age and follow a chronically intermittent course, leading to marked personality disturbance and suicide attempts.

Stressors that provoke affective episodes can be psychologic or biologic. Traumatic life events, especially separations, commonly precede depressive and manic episodes; however, such events may represent the prodromal manifestations of a mood disorder rather than its cause (eg, affectively ill persons often alienate their loved ones). The switch from depression to mania is often heralded by reduced sleep for 1 to 3 days and can be experimentally induced by sleep deprivation, particularly of rapid eye movement (REM) sleep. Such a switch commonly follows therapy with antidepressants. Stimulant use, sedative-hypnotic withdrawal, transmeridian travel, and seasonal changes in light may also induce mania.

Although persons with any personality type can develop clinical depression, it is more common in persons with temperaments inclined to dysthymia and cyclothymia. Unipolar depression is more likely to develop in persons who are introverted and have anxious tendencies. Such persons often lack the requisite social skills to adjust to significant life pressures and have difficulty recovering from a depressive episode. Persons with bipolar disorders tend to be extroverted and achievement-oriented; they often use activity to combat depression.

Female sex as a risk factor for depression is customarily explained by women's presumed more affiliative nature, dependency traits, and helplessness in controlling their destiny in male-oriented societies. However, biologic vulnerabilities are also relevant. Having two X chromosomes is important in bipolar disorders if dominant X-linkage is involved. Compared with men, women have higher levels of monoamine oxidase (the enzyme that degrades neurotransmitters considered important for mood). Thyroid function is more commonly dysregulated in women. Women may use oral contraceptives containing progesterone, believed to be a depressant, and undergo premenstrual and postpartum endocrine changes. Depressed women are more likely to exhibit the introverted, brooding/inhibited personality style typical of unipolar disorders, whereas depressed men are significantly more likely to exhibit the extroverted, action-oriented personality style typical of bipolar disorders.

Secondary mood disorders: Often, a mood disorder develops in association with a nonaffective disorder via a physiologic or psychologic mechanism or both (see Table 189-1). Some disorders, such as myxedema depression, result from physiochemical factors and are considered symptomatic depressions. Others, such as the depression that accompanies debilitating cardiopulmonary disorders, are usually explained as depressive reactions to the underlying disorder. Often, both mechanisms are operative (eg, in patients with AIDS who have cerebral dysfunction and profound sadness). Bipolar disorder rarely complicates another psychiatric disorder; if alcohol or substance use precedes a bipolar disorder, it is most likely an attempt to self-treat the prodromal manifestations of the disorder.

The foregoing findings concerning nonaffective disorders and drugs that produce depression suggest that the pathogenesis for all mood disorders forms a continuum and that the distinction between primary and secondary mood disorders is arbitrary. All patients who meet the criteria for a mood disorder must be treated regardless of whether other disorders are present and no matter how understandable the depression seems in light of the underlying disorder.

Risk of Suicide

Suicide, the most serious complication in patients with mood disorders, is the cause of death in 15 to 25% of untreated patients with mood disorders; unrecognized or inadequately treated depression contributes to 50 to 70% of all completed suicides. Suicide, which is most common in young and elderly men who do not have good social support, tends to occur within 4 to 5 yr of the first clinical episode. The immediate recovery phase from depression (when psychomotor activity is returning to normal, but the mood is still dark), mixed bipolar states, the premenstrual state, and personally significant anniversaries are major risk periods (see also Ch. 190). Concurrent alcohol and substance abuse also increases the risk of suicide. Serotonin dysfunction appears to be one of the biochemical factors in suicide, and prophylaxis with lithium (which stabilizes the serotonin system) is effective in suicide prevention.

Of drugs prescribed for mood disorders, an overdose with a heterocyclic antidepressant or lithium (see also Table 307-3) is most likely to be life threatening; alcohol is often a complicating factor. Heterocyclic antidepressant overdose causes a hyperactive coma with atropinism; cause of death is usually cardiac arrhythmia or status epilepticus. Because of protein-binding, forced diuresis and hemodialysis are useless, and treatment focuses on stabilizing cardiac and cerebral function. For lithium overdose, forced diuresis with sodium chloride or mannitol, alkalinization of urine, and hemodialysis may be lifesaving. Monoamine oxidase inhibitors, less commonly prescribed now, rarely result in overdose. Newer antidepressants (eg, selective serotonin reuptake inhibitors, venlafaxine, nefazodone, mirtazapine, bupropion) appear to be usually nonfatal in suicidal overdose--one of their major advantages.

Diagnosis

Diagnosis is based on the symptomatic picture (see Table 189-2), course, family history, and, sometimes, the unequivocal response to somatic interventions. Secondary medical or neurologic causes should be excluded, especially after age 40.

There are no pathognomonic laboratory findings in mood disorders. Tests for limbic-diencephalic dysfunction, such as the thyrotropin-releasing hormone (TRH) stimulation test, the dexamethasone suppression test (DST), and sleep EEG for rapid eye movement (REM) latency, are sometimes used in academic settings. There is no consensus on the diagnostic sensitivities and specificities of these tests, and the tests are not useful for screening. A negative test result does not exclude a depressive disorder; a positive result is more significant clinically.

Diagnosis of depression may be difficult when anxiety symptoms are the prominent presentation (see Table 189-3). Excessive worrying, panic attacks, and obsessions are common in primary depressive disorders and disappear when the depressive episode remits. Conversely, in primary anxiety disorders, these symptoms usually fluctuate irregularly and remission of depressive symptoms typically does not eliminate them. Prominent anxiety symptoms first appearing after age 40 most likely represent a primary mood disorder.

Mixed anxiety-depression (anxious depression) refers to conditions in which mild symptoms common to anxiety and mood disorders are present. They usually pursue a chronically intermittent course. Because of the greater gravity of depressive disorders and the risk of suicide, patients with mixed anxiety-depression should be treated for depression. Obsessions, panic, and social phobias with hypersomnic depression suggest bipolar II disorder.

In the elderly, depressive pseudodementia is associated with psychomotor retardation, decreased concentration, and memory impairment and therefore may be confused with early dementia, which often begins with affective changes (see Dementia in Ch. 171). In general, when the diagnosis is uncertain, treatment of depressive disorder should be tried, because of its better prognosis. Several features (see Table 189-4) can help in differential diagnosis.

The terms masked depression and affective equivalents are often used to explain prominent physical symptoms (eg, headache, fatigue, insomnia) or behavioral disturbance when mood change is minimal or absent. Affective equivalents include antisocial acting out (especially in children and adolescents), impulsive risk taking, gambling, chronic pain, hypochondriasis, anxiety states, and so-called psychosomatic disorders. Without core affective symptoms, the diagnosis of a mood disorder is not appropriate unless affective episodes have occurred in the past, the condition recurs periodically, and the family history includes mood disorders. Because diagnosis may be difficult, therapeutic trials with antidepressants and/or mood stabilizers are often conducted.

Differentiating chronically intermittent mood disorders, such as cyclothymia and dysthymia, from substance use disorders is difficult. Unipolar depression is a less common cause of alcoholism and drug abuse than was once thought (see Ch. 195). Depressed and manic patients may use alcohol or drugs in an attempt to treat sleep disturbances, and manic patients may seek drugs (eg, cocaine) to enhance excitement, usually with catastrophic effects on their illness. Toxic effects of drugs, drug withdrawal, or social complications may accompany substance use disorders, causing transient or intermittent depression. Episodic substance abuse, especially of alcohol (dipsomania), or onset after age 30 suggests diagnosis of a primary mood disorder with secondary substance abuse. When the diagnosis is in doubt, a therapeutic trial with antidepressant or mood-stabilizing drugs can often be defended clinically.

Differentiating between affective psychosis and schizophrenia or schizoaffective disorder (see Ch. 193) may be difficult because many schizophrenic features (eg, mood-incongruent delusions or hallucinations) occur in mood disorders. The correct diagnosis is important because lithium may cause neurotoxicity in schizophrenia, and neuroleptics may cause tardive dyskinesia in mood disorders. Diagnosis must be based on the overall clinical picture, family history, course, and associated features (see Table 189-5). Alcoholic hallucinosis, sedative-hypnotic withdrawal, psychedelic-induced psychosis, and other systemic or brain disorders may also produce psychotic symptoms. Diagnosis of a schizoaffective disorder should not be made until such complicating factors are excluded. When the diagnosis is in doubt, a therapeutic trial with an antidepressant, a mood stabilizer, or electroconvulsive therapy is indicated, because of the better prognosis of mood disorders.

Differentiating mood disorders from severe personality disorders (eg, borderline personality) is also difficult, especially when the mood disorder has a chronic or intermittent course--eg, dysthymia, cyclothymia, or bipolar II disorder. Past course with affective manifestations, especially when biphasic, and a family history of mood disorders support a diagnosis of mood disorder. Some laboratory findings (especially REM latency and TRH stimulation) in patients with borderline personality disorder and in those with mood disorder are similar; this similarity can be interpreted to mean that the two disorders are related or that these tests are not helpful in differential diagnosis. Some experts believe that at least some forms of borderline personality disorder represent a mood disorder variant, but this theory is controversial. For young patients pursuing a tempestuous, impulsive course that could culminate in serious suicide attempts, a trial with thymoleptic and mood-stabilizing drugs conducted by experts in a controlled setting--a hospital or mood clinic--is recommended.