Journal Article

Depression, Stressful Life Events, and the Impact of Variation in the Serotonin Transporter: Findings from the National Longitudinal Study of Adolescent to Adult Health (Add Health)

Siegler, Ilene C., Williams, Redford B., Haberstick, Brett C., Hopfer, Christian J., Brummett, Beverly H., Killeya-Jones, Ley A., Wagner, Brandon, Halpern, Carolyn T., Smolen, Andrew, Hewitt, John K., Boardman, Jason D., Tabor, Joyce, Mullan Harris, Kathleen

2016

Overview

The low transcriptionally efficient short-allele of the 5HTTLPR serotonin transporter polymorphism has been implicated to moderate the relationship between the experience of stressful life events (SLEs) and depression. Despite numerous attempts at replicating this observation, results remain inconclusive. We examined this relationship in young-adult Non-Hispanic white males and females between the ages of 22 and 26 (n = 4724) participating in the National Longitudinal Study of Adolescent to Adult Health (Add Health) with follow-up information every six years since 1995. Linear and logistic regression models, corrected for multiple testing, indicated that carriers of one or more of the S-alleles were more sensitive to stress than those with two L-alleles and at a higher risk for depression. This relationship behaved in a dose-response manner such that the risk for depression was greatest among those who reported experiencing higher numbers of SLEs. In post-hoc analyses we were not able to replicate an interaction effect for suicide ideation but did find suggestive evidence that the effects of SLEs and 5HTTLPR on suicide ideation differed for males and females. There were no effects of childhood maltreatment. Our results provide partial support for the original hypothesis that 5-HTTLPR genotype interacts with the experience of stressful life events in the etiology of depression during young adulthood. However, even with this large sample, and a carefully constructed a priori analysis plan, the results were still not definitive. For the purposes of replication, characterizing the 5HTTLPR in other large data sets with extensive environmental and depression measures is needed.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adolescent / Adolescents / Adult / Alleles / Behavior / Behavioral sciences / Biology and Life Sciences / Child abuse & neglect / Child Abuse - rehabilitation / Childhood / Children / Correlation analysis / Depression - etiology / Depression - genetics / Depression - physiopathology / Etiology / Female / Females / Gene Expression / Genetic Predisposition to Disease / Genetics / Genotype / Genotypes / Health / Heterozygote / Humans / Hypotheses / Life Change Events / Life events / Logistic Models / Longitudinal Studies / Male / Males / Maternal & child health / Medicine and Health Sciences / Mental depression / Mental health / Meta-analysis / People and Places / Polymorphism / Polymorphism, Genetic / Population / Psychiatry / Psychopathology / Regression analysis / Regression models / Replication / Risk Factors / Serotonin / Serotonin Plasma Membrane Transport Proteins - genetics / Serotonin transporter / Sex Factors / Social Sciences / Sociology / Stress, Psychological - complications / Stress, Psychological - genetics / Stress, Psychological - physiopathology / Studies / Suicidal Ideation / Suicide / Suicides & suicide attempts / Systematic review / Teenagers / Transcription / United States / Young adults