Genetic risk, number of previous depressive episodes, and stressful life events in predicting onset of major depression

Objective: The association between stressful life events and the onset of m ajor depression decreases as the number of previous depressive episodes inc reases. How do genetic risk factors for major depression impact on this "ki ndling" phenomenon? In particular, do those at high genetic risk exhibit an increase in the speed of kindling, or are they "prekindled"? Method: Using discrete-time survival analysis, the authors examined the int eraction between genetic risk, number of previous depressive episodes, and life event exposure in the prediction of episodes of major depression in fe male-female twin pairs from a population-based registry. The twins were int erviewed four times over a 9-year period, producing 92,521 person-months of exposure. Results: The decline in the association between stressful life events and r isk for major depression as the number of previous depressive episodes incr eased was strongest in those at low genetic risk and was weak to absent in those at high genetic risk. in the absence of previous depressive episodes, those at high genetic risk frequently experienced depressive episodes with out major environmental stressors. Conclusions: Genetic risk factors for depression produce a "prekindling" ef fect rather than increase the speed of kindling. The "kindled" state, where in depressive episodes occur with little provocation, may be reached by two pathways: many previous depressive episodes, perhaps driven by multiple ad versities, and high genetic risk.