Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
20577990
TITLE
Interaction of chronic stress with serotonin transporter and catechol-O-methyltransferase polymorphisms in predicting youth depression.
ABSTRACT
BACKGROUND NlmCategory: 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 NlmCategory: 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 NlmCategory: 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 NlmCategory: 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.
2010 Wiley-Liss, Inc.
DATE PUBLISHED
2010 Aug
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2010/06/26 06:00
pubmed 2010/06/26 06:00
medline 2010/12/29 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Conway CC Conway Christopher C CC Department of Psychology, University of California, Los Angeles, 90095-1563, USA. conwayc@ucla.edu
Hammen C Hammen Constance C
Brennan PA Brennan Patricia A PA
Lind PA Lind Penelope A PA
Najman JM Najman Jake M JM
INVESTIGATORS
JOURNAL
VOLUME: 27
ISSUE: 8
TITLE: Depression and anxiety
ISOABBREVIATION: Depress Anxiety
YEAR: 2010
MONTH: Aug
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1520-6394
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Depress Anxiety
COUNTRY: United States
ISSNLINKING: 1091-4269
NLMUNIQUEID: 9708816
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
R01 MH052239 NIMH NIH HHS United States
R01 MH052239-10 NIMH NIH HHS United States
R01 MH52239 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Alleles
Catechol O-Methyltransferase genetics
Chromosome Deletion genetics
Cohort Studies genetics
Depressive Disorder psychology
Epistasis, Genetic genetics
Family Conflict psychology
Female psychology
Gene Frequency genetics
Genetic Predisposition to Disease psychology
Genotype psychology
Humans psychology
Male psychology
Mother-Child Relations psychology
Personality Inventory statistics & numerical data
Polymorphism, Genetic genetics
Psychometrics genetics
Risk Factors genetics
Serotonin Plasma Membrane Transport Proteins genetics
Social Environment genetics
Statistics as Topic genetics
Stress, Psychological complications
Young Adult complications
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 SLC6A4 protein, human
0 Serotonin Plasma Membrane Transport Proteins
EC 2.1.1.6 Catechol O-Methyltransferase
OTHER ID's
OTHERID SOURCE
NIHMS213940 NLM
PMC2918677 NLM