Adolescent depression: The role of serotonergic genes, temperament, and gender

Adolescence represents a key time in which to study the development of depression given that depression surges in adolescence, particularly among girls. Numerous biological, cognitive, and affective theories have been proposed to explain the development of adolescent depression. The current study examined how two genetic variants, the serotonin transporter-linked polymorphic region (5-HTTLPR) and the monoamine oxidase A-upstream variable number tandem repeat (MAOA-uVNTR), interacted with stressful experiences to predict adolescent depression. The study also examined whether one form of temperament, negative affectivity, mediated the association of genes with depression. Finally, the study considered whether these pathways to depression were moderated by gender. Participants were 309 adolescents from a community-based longitudinal study who reported depressive symptoms and stressful experiences at ages 11, 13, and 15. Adolescents also completed a diagnostic interview and provided DNA samples at age 15. Temperament was assessed via mother-report during infancy. Four-way interactions of 5-HTTLPR, MAOA-uVNTR, stressful experiences, and gender predicted depressive symptoms at age 15. Girls were most likely to exhibit elevated depressive symptoms when experiencing stress if they possessed low-expression MAOA-uVNTR alleles and short 5-HTTLPR alleles, whereas low-expression MAOA-uVNTR alleles but long 5-HTTLPR alleles were implicated in boys. Genetic variants predicted a small and generally not significant proportion of variance in negative affectivity. Negative affectivity interacted with stressful experiences to predict depressive symptoms in both girls and boys. Evidence that negative affectivity mediated the link between genes and depression was inconclusive. The findings indicate that there may be important developmental and gender effects that influence how genes and temperament affect the onset of adolescent depression.