Many bipolar illnesses begin with one or more depressive episodes, and a substantial proportion of individuals who initially appear to have major depressive disorder will prove, in time, to instead have a bipolar disorder. This is more likely in individuals with onset of the illness in adolescence, those with psychotic features, and those with a family history of bipolar illness. The presence of a "with mixed features” specifier also increases the risk for future manic or hypomanic diagnosis. Major depressive disorder, particularly with psychotic features, may also transition into schizophrenia, a change that is much more frequent than the reverse.
ders, there appear to be no clear differences by gender in phenomenology, course, or treat- ment response. Similarly, there are no clear effects of current age on the course or treatment response of major depressive disorder. Some symptom differences exist, though, such that hypersomnia and hyperphagia are more likely in younger individuals, and melancholic symptoms, particularly psychomotor disturbances, are more common in older individuals.
The likelihood of suicide attempts lessens in middle and late life, although the risk of com- pleted suicide does not. Depressions with earlier ages at onset are more familial and more likely to involve personality disturbances. The course of major depressive disorder within individuals does not generally change with aging. Mean times to recovery appear to be sta— ble over long periods, and the likelihood of being in an episode does not generally increase or decrease with time.
Temperamental. Neuroticism (negative affectivity) is a well-established risk factor for the onset of major depressive disorder, and high levels appear to render individuals more likely to develop depressive episodes in response to stressful life events.
Environmental. Adverse childhood experiences, particularly when there are multiple experiences of diverse types, constitute a set of potent risk factors for major depressive dis- order. Stressful life events are well recognized as precipitants of major depressive epi— sodes, but the presence or absence of adverse life events near the onset of episodes does not appear to provide a useful guide to prognosis or treatment selection.
Genetic and physiological. First—degree family members of individuals with major de~ pressive disorder have a risk for major depressive disorder two- to fourfold higher than that of the general population. Relative risks appear to be higher for early-onset and re- current forms. Heritability is approximately 40%, and the personality trait neuroticism ac- counts for a substantial portion of this genetic liability.
Course modifiers. Essentially all major nonmood disorders increase the risk of an indi- vidual developing depression. Major depressive episodes that develop against the back- ground of another disorder often follow a more refractory course. Substance use, anxiety, and borderline personality disorders are among the most common of these, and the pre- senting depressive symptoms may obscure and delay their recognition. However, sus- tained clinical improvement in depressive symptoms may depend on the appropriate treatment of underlying illnesses. Chronic or disabling medical conditions also increase risks for major depressive episodes. Such prevalent illnesses as diabetes, morbid obesity, and cardiovascular disease are often complicated by depressive episodes, and these epi- sodes are more likely to become chronic than are depressive episodes in medically healthy individuals.
Surveys of major depressive disorder across diverse cultures have shown sevenfold dif- ferences in 12-month prevalence rates but much more consistency in female-to-male ratio, 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 be- tween particular cultures and the likelihood of specific symptoms. Rather, clinicians should be aware that in most countries the majority of cases of depression go unrecog- nized 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.