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General Considerations

A. Epidemiology

The separation into bipolar and non-bipolar disorder has proved clinically and diagnostically useful. It is supported by family studies, twin studies, and biological studies. It is supported further by differential clinical responses to treatment and differential disease onsets and outcomes. To these factors, we can add the epidemiologic risk factors detailed in Table 17–1.

Table 17–1Risk Factors for Major Depressive Disorder

Symptoms and disorders of the depression spectrum are rather common. Lifetime prevalence rates for significant depressive symptoms are 13–20% and for major depressive disorder 3.7–6.7%. Major depressive disorder is about two to three times as common in adolescent and adult females as in adolescent and adult males. In prepubertal children, boys and girls are affected equally. Rates in women and men are highest in the 25–44-year-old age group.

Boyd  JH, Weissman  MM: Epidemiology. In: Paykel  ES, ed. Handbook of Affective Disorders. New York: Guilford Press; 1982:109–125.
Weissman  MN, Livingston Bruce  M, Leaf  PJ,  et al. Affective disorders. In: Robins  LN, Regier  DA, eds. Psychiatric Disorders in America. New York: Free Press; 1991:53–80.

B. Etiology

Despite intensive attempts to establish its etiologic or pathophysiologic basis, the precise cause of major depressive disorder is not known. There is consensus that multiple etiologic factors—genetic, biochemical, psychodynamic, and socioenvironmental—may interact in complex ways and that the modern-day understanding of depressive disorder requires an understanding of the interrelationships among these factors.

1. Life events

Recent evidence confirms that crucial life events, particularly the death or loss of a loved one, can precede the onset of depression. However, such losses precede only a small (though substantial) number of cases of depression. Fewer than 20% of individuals experiencing losses become clinically depressed. Although other major life events may occur prior to the onset of depression, many patients become depressed with little or no apparent provocation. These observations argue strongly for a predisposing factor, probably genetic, developmental, or temperamental in nature.

2. Biological theories
i. Neurotransmitters

Associations between mood and monoamines (i.e., norepinephrine, serotonin, and dopamine) were first indicated serendipitously by the mood-altering effects of isoniazid (used initially for the treatment of ...

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