Gene-Environment Interaction in Youth Depression: Replication of the 5-HTTLPR Moderation in a Diverse Setting

Replication of scientific findings is a major challenge in biomedical research. In psychiatry, the identification of measured gene-environment interactions (G×E) has promoted a heated debate over the past decade, with controversial results about its influence on disorders such as major depression. The authors sought to replicate a 2003 study on G×E in youth depression in a large birth cohort from a diverse setting.

Using data from the 1993 Pelotas Birth Cohort Study, and adopting a design as similar as possible to that of the original study, the authors tested whether the relationship between childhood maltreatment and a subsequent depressive episode diagnosis was moderated by 5-HTTLPR genotype. Of 5,249 individuals assessed at birth and followed up to age 18, data on the evaluation for depressive episodes in early adulthood, on childhood maltreatment, and on genotype were available for 3,558 participants, of whom 2,392 remained after conservative screening for previous depressive symptoms. Associations were investigated with logistic regression analyses and controlling for potential confounders.

The results replicated important findings of the original study, this time in a sample of young adults from a middle-income country: there was a differential dose-response relationship between childhood maltreatment and major depression according to 5-HTTLPR genotype.

After following a research strategy as comparable as possible to that of the original study, the results corroborated the existence of a measured G×E, now in a large sample from a different sociocultural context. These findings provide further evidence that a genetic variant in the 5-HTTLPR moderates the link between childhood maltreatment and youth depression.