Neither our primary nor our secondary analyses found compelling evidence that the 5-HTTLPR S allele increases risk of major depression in individuals exposed to stress. These results are in marked contrast to the robust main effect signals seen for the sex and stress exposure, where p-values less than 10−60 were seen in our most inclusive primary analyses (Supplemental Table S12). In our effort to determine conditions for which the interaction might be reliably detected, we investigated both childhood maltreatment and other life experiences as stressors. Because major depression is a recurring and remitting disease subject to recall bias, both current depression and lifetime depression were examined. Data from subjects of any age and data limited to young adults were both studied. We examined life stress known to precede depression (thereby limiting the sample to studies that documented the relative timing of stress and depression) and we investigated whether the hypothesized interaction could be more effectively detected using all available data with stress and depression assessed. In secondary analyses, we also examined multiple models for the coding of the genotype (additive,
