Stressful Life Events, Genetic Liability, and Onset of an Episode of Major Depression in Women

Objective This study was undertaken to clarify how genetic liability and stressful life events interact in the etiology of major depression. Method Information about stressful life events and onset of major depressive episodes in the past year was collected in a population-based sample of female-female twin pairs including 2,164 individuals, 53,215 person-months of observation, and 492 onsets of depression. Results Nine "personal" and three aggregate "network" stressful events significantly predicted onset of major depression in the month of occurrence, four of which predicted onset with an odds ratio of > 10 and were termed "severe": death of a close relative, assault, serious marital problems, and divorce/breakup. Genetic liability also had a significant impact on risk of onset of depression. For severe stressful events, as well as for 10 of the 12 individual stressful events, the best-fitting model for the joint effect of stressful events and genetic liability on onset of major depression suggested genetic control of sensitivity to the depression-inducing effects of stressful life events. In individuals at lowest genetic risk (monozygotic twin, co-twin unaffected), the probability of onset of major depression per month was predicted to be 0.5% and 6.2%, respectively, for those unexposed and exposed to a severe event. In those at highest genetic risk (monozygotic twin, co-twin affected), these probabilities were 1.1% and 14.6%, respectively. Linear regression analysis indicated significant Genotype by Environment interaction in the prediction of onset of major depression. Conclusions Genetic factors influence the risk of onset of major depression in part by altering the sensitivity of individuals to the depression-inducing effect of stressful life events.