Causes

The biopsychosocial model proposes that biological, psychological, and social factors all play a role to varying degrees in causing depression. The diathesis–stress model posits that depression results when a preexisting vulnerability, or diathesis, is activated by stressful life events. The preexisting vulnerability can be either genetic, implying an interaction between nature and nurture, or schematic, resulting from views of the world learned in childhood. These interactive models have gained empirical support. For example, a prospective, longitudinal study uncovered a moderating effect of the serotonin transporter (5-HTT) gene on stressful life events in predicting depression. Specifically, depression may follow such events, but is more likely to appear in people with one or two short alleles of the 5-HTT gene.

A Swedish study estimated the heritability of depression—the degree to which individual differences in occurrence are associated with genetic differences—to be approximately 40 percent for women and 30 percent for men, and evolutionary psychologists have proposed that the genetic basis for depression lies deep in the history of naturally-selected adaptations. A substance-induced mood disorder resembling major depression has been causally linked to long-term drug use or abuse or withdrawal from certain sedative and hypnotic drugs.