Stressful life events, genetic liability, and onset of an episode of major depression in women

Am J Psychiatry. 1995 Jun;152(6):833-42. doi: 10.1176/ajp.152.6.833.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Depressive Disorder / etiology*
  • Depressive Disorder / genetics
  • Diseases in Twins / epidemiology
  • Diseases in Twins / genetics*
  • Female
  • Genotype
  • Humans
  • Life Change Events*
  • Odds Ratio
  • Probability
  • Regression Analysis
  • Risk Factors
  • Social Support
  • Twins, Dizygotic
  • Twins, Monozygotic