Global epidemiologic studies of depression show considerable variations across and within countries, to a large extent due to the cross-cultural unsuitability of assessment instruments. About 18.8 million adults, or about 9.5% of the US population aged 18 years or older, have a depressive disorder in a given year. Nearly twice as many women (6.5%) as men (3.3%) suffer from a major depressive disorder every year, with the average age of onset being the mid-20s. Dysthymic disorder affects about 5.4% of the US population.

Patients at highest risk for recurrent depressive disorders include those whose first depression was before age 25, those who have had more than 16 weeks of depression in their lifetime, and those who have had a recurrence of depression within 2 months of discontinuing an antidepressant.

Mood disorders in children and teenagers are a significant problem in the US. Studies have reported that up to 2.5% of children and up to 8.3% of adolescents in the US suffer from mood disorders. One longitudinal prospective study found that early-onset depression often continues into adulthood, which indicates that mood disorders in youth may also predict more severe illness in adult life.

Mood disorders in older adults also are a significant problem. A conservative estimate is that about 6% of the US population aged 65 years or older have a diagnosable depressive illness (major depressive disorder or dysthymic disorder). Depression in older adults often co-occurs with other illnesses. Suicide is a frequent companion to mood disorders and has been identified recently as an emergent national public health priority (see Chapter 38). Older Americans are disproportionately likely to commit suicide.

Although the anatomical and physiological basis of depression is far from being completely understood, a major depressive disorder most likely involves the limbic structures in circuits involving the cingulate, hippocampus, mamillary bodies, and anterior thalamus, reward circuits (nucleus accumbens, sublenticular extended amygdala, amygdala, ventral tegmentum, cingulate, insula, thalamus, parahippocampal gyrus, and prefrontal cortex), hypothalamus, and anterior temporal cortex. Deficiencies of neurotransmitters involved in these circuitries, as well as damage to neurons and loss of connectivity (e.g., by enduring hypercortisolemia), can underlie what manifests clinically as depression.

Three principal neurotransmitters have been implicated in the pathophysiology and the treatment of depression: norepinephrine (noradrenaline), dopamine, and serotonin. They comprise what is known as the “trimonoaminergic neurotransmitter system.” These three monoamines often work in concert. Many of the symptoms of all mood disorders are hypothesized to involve dysfunction of various combinations of these three, and essentially all known treatments of mood disorders act on one or more of them.

The monoamine hypothesis of depression represents an oversimplified idea about depression that was valuable in focusing attention on the three neurotransmitters. However, the focus of hypotheses for the etiology of depression has shifted from the monoamine neurotransmitters themselves to their receptors and the downstream molecular events that these receptors trigger, including the regulation of gene expression.

Family studies have reported an approximately threefold increased risk for a major depressive disorder (MDD) in the first-degree relatives of individuals with MDD as compared to the general population. Family studies, however, do not allow one to distinguish the effects of genetic factors versus family environment. Extensive research continues in the area of behavioral genetics, or how genes influence human behavior. Depression is a complex disorder and as such is likely to involve a relatively large number of individual genes, none of which may themselves have a major impact on risk, as well as interactions with environmental factors.

The mood disorders can be categorized in various ways, depending on the number of symptoms, their severity, and persistence. Clinically significant depressive disorders can be grouped by their severity and distance from the euthymic state.

14.4.1 Dysthymic Disorder

The word dysthymia comes from the Greek prefix dys, meaning difficult or bad, and thymos, meaning mind. DSM-IV-TR considers dysthymia a mild form of depressive illness in which the symptoms – poor appetite, overeating, difficulty falling asleep, excessive sleep, low energy, fatigue, low self-esteem, poor concentration, or difficulty making decisions – are less severe than in depressive disorder but are chronic. Diagnostic criteria for dysthymic disorder include depressed or irritable mood most of the day, occurring more days than not for at least 2 years (1 year in children and adolescents). During this time, the patient has had no more than 2 months in which symptoms are not present and has not experienced a manic or depressive episode.

The chronic nature of dysthymia is a cause for concern, because it often presents as a lifelong struggle against depression, which can assume various forms and cause significant distress. In an attempt to escape negative self-esteem, feelings of self-depreciation, emptiness, low energy and fatigue, pessimism about the future, and hopelessness with suicidal ideations, the patient may engage in certain activities to generate excitement. He or she may focus heavily on work, spend money, engage in sexual behavior, or become preoccupied with religious and mystic involvement in the struggle against depression. The patient with dysthymia may turn to substance abuse or food to dull or escape psychic pain. Many times, the patient with dysthymia has become accustomed to the chronic, negative, oppressive effect of the disorder and, therefore, does not readily recognize symptoms as being abnormal.

The treatment for dysthymic disorder includes the same psychotherapies and medications that are discussed below for MDD. Treatment plans should be guided by the severity of the patient’s symptoms.

14.4.2 Major Depressive Disorder

According to DSM-IV-TR, a patient diagnosed with major depressive disorder must have either a depressed mood or a loss of interest or inability to derive pleasure from previously enjoyable activities. Other symptoms include recurrent thoughts of suicide, decreased or increased appetite, inability to concentrate, difficulty making decisions, feelings of worthlessness and self-blame, decreased energy, motor disturbances (agitation or severe slowness), disturbed sleep (insomnia or excessive sleeping), substance abuse, and social withdrawal. Also, the patient with depression often disregards grooming, cleanliness, and personal appearance. These patients may present disheveled, downcast, without eye contact, and tearful. Conversely, they may be agitated but usually do not exhibit bizarre or unusual behaviors. Many patients with depression tend to exhibit withdrawn behavior and they resist attempts by others to engage them in the environment.

Diagnosis of depression in older adults can be difficult because many of them suffer from comorbid physical conditions, such as heart disease, diabetes, cancer, and Parkinson’s disease. Because depression often accompanies these, and older adults often face losses and may experience physical, psychological, and social difficulties, healthcare professionals may mistakenly conclude that depression is a normal consequence of these problems – an attitude often shared by the patients themselves.

For diagnostic purposes, symptoms must be present most of the day nearly every day for at least 2 weeks, and they must cause significant distress or impair functioning. Major depressive disorder is further classified according to severity, longitudinal course of recurrent episodes, and descriptions of the most recent episode. Typically, major depressive episodes last several weeks to several months and are followed by periods of relatively normal mood and behavior. The average major depressive episode lasts about 4 months; however, it can last for 12 months or more without remitting.

14.5.1 Depression with Psychotic Features

Psychotic features of depression such as hallucinations or delusions (e.g., delusional hypochondria, feelings of guilt, nihilistic thoughts) are predominantly mood congruent, but may rarely be incongruent. Psychotic symptoms are in most cases an indicator of the particular severity of depression, including suicide risk.

14.5.2 Catatonic Features

Severe psychomotor retardation, stupor, immobility, or (in contrast) severe agitation can be observed in depressed patients. These are sometimes labeled as catatonic features.

14.5.3 Melancholic Features

According to DSM-IV-TR, melancholia is characterized by a loss of the ability to feel pleasure and a variety of somatic symptoms and psychomotor alterations. Therapeutic consequences of melancholic features are similar to those for severe depression.

14.5.4 Atypical Features

According to DSM-IV-TR, atypical depression is characterized by the presence of at least two of the following criteria: increase in appetite and weight gain, hypersomnia, leaden paralysis, and a longstanding pattern of interpersonal rejection sensitivity. Patients with atypical depression are more likely to have an earlier age at onset, a greater comorbidity with anxiety symptoms, and greater symptom severity compared with typical depression.

14.5.5 Seasonal Pattern

Seasonal affective disorder (SAD) or seasonal depression is a condition that appears during the colder months when there are also fewer hours of sunlight. Depression symptoms can be moderate or severe. They may be accompanied by fatigue, lack of interest in normal activities, weight gain, hypersomnia, craving for foods high in carbohydrates, and social withdrawal. Symptoms typically begin to dissipate when spring begins and the daylight hours are longer.

14.5.6 Depression in the Postpartum Period

During the postpartum period, up to 85% of women experience some type of mood disturbance. For most women, symptoms are transient and relatively mild (i.e., postpartum blues); however, 10–15% of women experience a more disabling and persistent form of mood disturbance (e.g., postpartum depression, postpartum psychosis).

Postpartum blues is typically mild and remits spontaneously, requiring nothing other than support and reassurance. On the other hand, puerperal psychosis is a psychiatric emergency that typically requires inpatient treatment. The severity of the condition should guide treatment. Early intervention is associated with better prognosis. Treatment for severe postpartum depression should continue for 6–12 months or longer if necessary. Clinicians should note that risk factors for postpartum depression include prior episodes of depression after childbirth.

14.5.7 Depressive Syndromes in Pain Conditions

Depressive syndromes and chronic pain are frequent comorbid conditions. Approximately 70% of patients with major depression present with physical complaints. Somatization disorders, fibromyalgia, and similar conditions with predominant pain are often accompanied by depressed mood.

14.5.8 Adjustment Disorders

Adjustment disorder with depressed mood, and mixed anxiety and depressed mood, are covered in Chapter 21.

14.5.9 Dysthymic Disorder and MDD in Combination with Dysthymic Disorder