Depression: Etiology and Pathophysiology, Integration of Genetic and Environmental Theories

Etiology and Pathophysiology

Depressive disorders are common and recurrent, and associated with substantial psychosocial dysfunction as well as excess mor-bidity and mortality. Greater understanding of the underlying etiology and pathophysiology of MDD is the focus of genetic, neurobiologic and psychosocial investigation.

Integration of Genetic and Environmental Theories

Unipolar or nonbipolar MDD has been demonstrated to cluster in the first-degree relatives of patients with depression. The observation that MDD is familial, however, does not address whether the familial aggregation may be due to genetic or familial environmental factors. All attempts to develop integrated etiologic models of depression have identified multiple psychosocial risk factors. In particular, female gender, limited social support, dependent, self-critical and neurotic personality traits, and stressful life events appear to influence the vulnerability to MDD. Whether specific life events are as important later in the course of MDD as in the precipitation of initial episodes is the subject of ongoing investigation. Post (1992) argued that negative, stressful life events are associated with the initial or second episode of recurrent MDD whereas neurobiological factors are most relevant with subsequent recurrent episodes. Post asserted that sensitization to stressors and episodes may become encoded at the level of gene expression, underscoring the role of neurobiological factors in the progression of the illness.

Since genetic factors are operative in the etiology of MDD and prior depressive episodes place an individual at risk for fu-ture depression, indirect genetic factors operate in the vulner-ability to lifetime risk. In summary, clinical and genetic epide-miologic studies suggest that MDD is a multifactorial disorder influenced by several genetic and environmental risk factors. The effectiveness of the individual’s social support network in asso-ciation with successful treatment may protect the individual from the vulnerability to recurrent MDD.