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Background: Studies assessing sex differences in the associations of psychosocial strain with depression have shown mixed and inconsistent results. Our objective was to examine prospective associations of job strain and family strain with risk of major depressive episode (MDE) among United States workers, as well as assess potential effect modification by sex.Methods: Using data from the nationally representative and population-based Mid-life in the United States (MIDUS) study with a prospective cohort design and a 9-year follow-up period, the effects of job strain and family strain at baseline on risk of MDE within the 12 months prior to the follow-up assessment were examined in 1581 workers (805 men, 776 women) who were free from MDE within the 12 months prior to the baseline survey, by multivariate Poisson regression analysis.Results: After adjustment for relevant covariates, there was evidence for effect modification by sex for the association between job strain and MDE but not for the association between family strain and MDE. Indeed, high job strain was prospectively associated with the risk of MDE (RR and 95% CI = 2.14 [1.14, 4.03]) in men but not in women. Moreover, high family strain was prospectively associated with a higher risk of MDE (RR and 95% CI = 1.57 [1.05, 2.37]) in the whole sample.Conclusion: Family strain was associated with risk of MDE regardless of the sex of a person. In contrast, high job strain may involve an increased risk of developing MDE only in men but not in women. [ABSTRACT FROM AUTHOR]