Abstract:
BACKGROUND:Investigations of gene-environment interaction (GxE) 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 GxE 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 GxE. METHODS:A community sample of youth (n=384) was genotyped for 5-HTTLPR and COMT. A multi-method, multi-informant index of chronic family stress was derived from interviews and questionnaires administered at youth age 15. GxGxE was examined in relation 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 GxE 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 GxE was found for 5-HTTLPR. CONCLUSIONS:Inconsistent 5-HTTLPR GxE findings to date may be partly attributable to unmeasured epistatic effects between 5-HTTLPR and COMT val158met. Identifying the conditions under which 5-HTTLPR GxE is most likely to operate may allow depression prevention and treatment efforts to target youth at highest risk.
journal_name
Depress Anxietyjournal_title
Depression and anxietyauthors
Conway CC,Hammen C,Brennan PA,Lind PA,Najman JMdoi
10.1002/da.20715subject
Has Abstractpub_date
2010-08-01 00:00:00pages
737-45issue
8eissn
1091-4269issn
1520-6394journal_volume
27pub_type
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