Explanatory and modifying factors of the association between sex and depression onset during adolescence: an exploratory study

Background:The prevalence of Major Depressive Disorder (MDD) is twice as high in women as in men. Because the mechanisms underlying this sex-difference remain poorly understood, we took a bottom-up approach to identify factors explaining the sex-MDD relationship. Methods: Data came from the TRacking Adolescents' Individual Lives Survey (TRAILS), a population study investigating youths’ development from age 11 into adulthood. We assessed multiple baseline covariates at ages 11-13 years and MDD onset at ages 19 and 25 years. In regression analyses, each covariate’s role in the sex-MDD association as an effect modifier or confounder/explanatory variable was investigated. Replicability was evaluated in an independent sample. Results: The analyses identified no effect-modifiers. Baseline internalizing problems, behavioral inhibition, dizziness, comfort in classroom, somatic complaints, attention problems, cooperation and computer use all partially explained the association between sex and MDD at age 19. Largely the same variables explained the association between sex and MDD at age 25. Here, additionally identified explanatory variables were shyness, fear, acne, antisocial behavior, aggression, affection from classmates and time spent shopping. The explanatory roles of internalizing problems, behavioral inhibition and leisure-time spending (computer-use/shopping) were replicated. Limitations:Some potentially important baseline variables were not included (e.g., environmental factors) or had very low endorsement rates. The study focused only on dichotomous biological sex and did not consider gender roles or identification. The presence of MDD at baseline was not adjusted for. Conclusion: The sex-MDD association is partially explained by sex differences in symptoms and vulnerability factors already present in early adolescence.