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Background. Both generalized anxiety disorder (GAD) and stressful life events (SLEs) are established risk factors for major depressive disorder, but no studies exist that examine the interrelationship of their impact on depressive onsets. In this study, we sought to analyze the joint effects of prior history of GAD and recent SLEs on risk for major depressive episodes, comparing these in men and women.Method. In a population-based sample of 8068 adult twins, Cox proportional hazard models were used to predict onsets of major depression from reported prior GAD and last-year SLEs rated on long-term contextual threat.Results. For all levels of threat, prior GAD increases risk for depression, with a monotonic relationship between threat level and risk. While females without prior GAD consistently show higher depressive risk than males, this is no longer the case in subjects with prior GAD who have experienced SLEs. Rather, males appear to be more vulnerable to the depressogenic effects of both prior GAD and SLEs.Conclusion. The effects of prior GAD and SLEs jointly increase the risk of depression in both sexes, but disproportionately so in males. [ABSTRACT FROM AUTHOR]