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Depression and Genetic variation in serotonin and monoamine transmission have both been associated with body mass index (BMI), but their interaction effects are not well understood. We examined the interaction between depressive symptoms and functional polymorphisms of serotonin transporter (SLC6A4) and monoamine oxidase A (MAOA) on categories of BMI. Participants were from the National Longitudinal Study of Adolescent Health. Multiple logistic regression was used to investigate interactions between candidate genes and depression on risk of obesity (BMIor = 30) or overweight + obese combined (BMIor = 25). Males with an MAOA active allele with high depressive symptoms were at decreased risk of obesity (OR 0.22; 95% CI 0.06-0.78) and overweight + obesity (OR 0.48; 95% CI 0.26-0.89). No similar effect was observed among females. These findings highlight that the obesity-depression relationship may vary as a function of gender and genetic polymorphism, and suggest the need for further study.

The short (s) variant of the serotonin transporter (5-HTT) gene linked functional polymorphic region (5-HTTLPR) is associated with depression. Stressful life events, gender, and race have been shown to moderate this association. We examined the relationship between 5-HTTLPR genotype and symptoms of depression in two samples. Study 1 = 288 participants from a study of caregiver stress; and Study 2 = 142 participants from a study examining psychosocial stressors, genetics, and health. Main effects of 5-HTTLPR on symptoms of depression were examined, along with moderation by stress (care-giving status or low childhood socioeconomic status (SES), gender, and race. The 5-HTTLPR × stress group × gender interaction was significant in both samples (P < 0.003, and P < 0.008, respectively). For females, the s allele, combined with caregiving stress (Study 1) or low childhood SES (Study 2), was associated with higher depression scores as compared to participants in the non-stressor group and those with the long (l) allele; whereas, in males, the l allele, combined with a stressor, was associated with higher depression scores as compared to those in the non-stressor group and those with the s allele. Findings from two independent samples suggest that the association of 5-HTTLPR with depression varies according to gender and stressful life events.