Interaction of chronic stress with serotonin transporter and catechol-O-methyltransferase polymorphisms in predicting youth depression.
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.
Conway
Christopher C
CC
Department of Psychology, University of California, Los Angeles, 90095-1563, USA. conwayc@ucla.edu
Hammen
Constance
C
Brennan
Patricia A
PA
Lind
Penelope A
PA
Najman
Jake M
JM
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002872:Chromosome Deletion; D015331:Cohort Studies; D003866:Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D004843:Epistasis, Genetic / Q000235:genetics; D054541:Family Conflict / Q000523:psychology*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics / Q000523:psychology; D005838:Genotype; D006801:Humans; D008297:Male; D009034:Mother-Child Relations; D010555:Personality Inventory / Q000706:statistics & numerical data; D011110:Polymorphism, Genetic / Q000235:genetics*; D011594:Psychometrics; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012931:Social Environment; D013223:Statistics as Topic; D013315:Stress, Psychological / Q000150:complications*; D055815:Young Adult
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D002394:Catechol O-Methyltransferase