Background. In animals, early trauma can produce long-lasting changes in sensitivity to the pathogenic effects of stress. To explore whether similar processes occur in humans, we examine whether childhood sexual abuse (CSA) in women alters sensitivity in adulthood to the depressogenic effects of stressful life events (SLEs).

Method. A history of CSA was obtained from a population-based sample of 1404 female adult twins. Cox Proportional hazard models were used to predict onsets of episodes of DSM-III-R major depression (MD) in the past year from previously assessed levels of neuroticism (N), CSA and past-year SLEs scored on long-term contextual threat.

Results. In the best-fit model, onset of MD was predicted by CSA, SLEs and N. Individuals with CSA (and especially with severe CSA) had both an overall increased risk for MD and a substantially increased sensitivity to the depressogenic effects of SLEs. A ‘dose–response’ relationship between severity of CSA and sensitivity to SLEs was clearer in those with low to average levels of N than in those with high levels of N.

Conclusion. As documented with physiological responses to a standardized laboratory stressor, CSA increases stress sensitivity in women in a more naturalistic setting. Both genetic and early environmental risk factors can produce long-term increase in the sensitivity of individuals to depressogenic life experiences.