Interaction of chronic stress with serotonin transporter and catechol-O-methyltransferase polymorphisms in predicting youth depression

• Type of Material: Article
• Authors: Christopher C. Conway, University of California, Los Angeles; Constance Hammen, University of California, Los Angeles; Patricia Brennan, Emory University; Penelope A. Lind, QIMR Berghofer Medical Research Institute; Jake M. Najman, University of Queensland
• Language: English
• Date: 2010-08-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 Wiley-Liss, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/da.20715
• Title of Journal or Parent Work: Depression and Anxiety
• ISSN: 1091-4269
• Volume: 27
• Issue: 8
• Start Page: 737
• End Page: 745
• Grant/Funding Information: This study was supported by NIMH R01 MH52239 to Brennan, Hammen, and Najman.
• Keywords: Male; Statistics as Topic; Gene Frequency; Cohort Studies; Young Adult; Adult; Genetic Predisposition to Disease; Female; Risk Factors; Stress, Psychological; Social Environment; Psychometrics; Serotonin Plasma Membrane Transport Proteins; Depressive Disorder; Alleles; Catechol O-Methyltransferase; Epistasis, Genetic; Genotype; Chromosome Deletion; Mother-Child Relations; Adolescent; Polymorphism, Genetic; Personality Inventory; Family Conflict; Humans
• Research Categories: Health Sciences, Mental Health; Psychology, Clinical; Biology, Genetics

Abstract

Background: Investigations of gene-environment interaction (G×E) in depression have implicated a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) as a moderator of the stress-depression relationship. However, recent evidence for 5-HTTLPR G×E in depression has been inconsistent. This study examined the moderating effect of the val158met polymorphism in the catechol-O-methyltransferase (COMT) gene on the strength of 5-HTTLPR G×E. Methods: A community sample of youth (n5384) was genotyped for 5-HTTLPR and COMT. A multi-method, multiinformant index of chronic family stress was derived from interviews and questionnaires administered at youth age 15. G×G×E was examined inrelation to depression diagnoses between ages 15 and 20 and depressive symptoms at age 20. Results: Significant three-way interactions were observed for both depressive symptoms and diagnoses, such that 5-HTTLPR G×E occurred only in the context of COMT val158 allele homozygosity. For val158 homozygotes, the 5-HTTLPR LL genotype exerted a protective effect in the face of stress. No genetic main effect or two-way G×E was found for 5-HTTLPR. Conclusions: Inconsistent 5-HTTLPR G×E findings to date may be partly attributable to unmeasured epistatic effects between 5-HTTLPR and COMT val158met. Identifying the conditions under which 5-HTTLPR G×E is most likely to operate may allow depression prevention and treatment efforts to target youth at highest risk.