Serotonin Transporter Gene as a Predictor of Stress Generation in Depression

Lisa R. Starr, Constance Hammen, Patricia A. Brennan, Jake M. Najman

Research suggests that a polymorphism in the promoter region of the serotonin transporter promoter (5-HTTLPR) interacts with stressful life events to predict depressive onset, with short (s) allele presence associated with greater susceptibility to stressors. However, this research has not considered that depressed individuals often actively generate stressful contexts. Furthermore, little is known about the genetic basis of stress generation. The current study explored the role of 5-HTTLPR genotype in stress generation in a longitudinal sample of 381 adolescents, oversampled for maternal depression, assessed at ages 15 and 20. Genotype did not correlate directly with number or ratings of stressful life events. However, 5-HTTLPR genotype interacted with depression at age 15 to predict dependent stressful events at age 20. Specifically, participants with one or more s alleles showed a stronger association between age 15 depression and age 20 dependent and interpersonal events than long allele homozygotes. Results imply that the 5-HTTLPR genotype predicts reciprocal associations between stress and depression, indicating a more complex relationship between stress, depression, and their genetic underpinnings than previously suggested.