Gender differences in the genetic and environmental determinants of adolescent depression

Background: The well-documented gender differences in the risk for depression may be explained by genetic factors, by different responses to social context, or by a combination of both.We sought to assess whether there were gender differences in the longitudinal associations between serotonin transporter promoter (5-HTTLPR) genotype and depressive symptoms in adolescents, and whether macrosocial context plays a role in explaining any observed differences. Methods: Using data from a nationally representative survey of adolescents, we applied multilevel mixed models to assess, separately for adolescent males and females (a) the relation between 5-HTTLPR genotype and depressive symptoms and (b) the interaction of county-level deprivation and 5-HTTLPR genotype in models predicting depressive symptoms. All models adjusted for age and other covariates. Results: Among females (n5560), main effects models showed an association between the sl genotype and lowered risk of depressive symptoms (b5=.18, P5.03). Among males (n5524), interaction models showed anassociation between sl genotype and lowered risk of depressive symptoms in deprived counties only (b5=.32, P5.04). Conclusions: In adolescent females, the 5-HTTLPR sl genotype confers protection against depressive symptoms independent of county-level social context, whereas in adolescent males, protection by the same genotype is conferred only within the context of countylevel deprivation. Future work should aim to understand how genetic and macrosocial factors jointly shape risk for mental illness, and how these factors shape gender differences in mental illness. Depression and Anxiety 27:658-666, 2010.