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
22393204
TITLE
Cannabinoid receptor genotype moderation of the effects of childhood physical abuse on anhedonia and depression.
ABSTRACT
CONTEXT NlmCategory: BACKGROUND
The endocannabinoid system has been implicated in stress adaptation and the regulation of mood in rodent studies, but few human association studies have examined these links and replications are limited.
OBJECTIVES NlmCategory: OBJECTIVE
To examine whether a synonymous polymorphism, rs1049353, in exon 4 of the gene encoding the human endocannabinoid receptor (CNR1) moderates the effect of self-reported childhood physical abuse on lifetime anhedonia and depression and to replicate this interaction in an independent sample.
DESIGN, SETTING, AND PARTICIPANTS NlmCategory: METHODS
Genetic association study in 1041 young US women with replication in an independent Australian sample of 1428 heroin-dependent individuals as cases and 506 participants as neighborhood controls.
MAIN OUTCOME MEASURES NlmCategory: METHODS
Self-reported anhedonia and depression (with anhedonia).
RESULTS NlmCategory: RESULTS
In both samples, individuals who experienced childhood physical abuse were considerably more likely to report lifetime anhedonia. However, in those with 1 or more copies of the minor allele of rs1049353, this pathogenic effect of childhood physical abuse was attenuated. Thus, in participants reporting childhood physical abuse, although 57.1% of those homozygous for the major allele reported anhedonia, only 28.6% of those who were carriers of the minor allele reported it (P=.01). The rs1049353 polymorphism also buffered the effects of childhood physical abuse on major depressive disorder; however, this influence was largely attributable to anhedonic depression. These effects were also noted in an independent sample, in which minor allele carriers were at decreased risk for anhedonia even when exposed to physical abuse.
CONCLUSIONS NlmCategory: CONCLUSIONS
Consistent with preclinical findings, a synonymous CNR1 polymorphism, rs1049353, is linked to the effects of stress attributable to childhood physical abuse on anhedonia and anhedonic depression. This polymorphism reportedly resides in the neighborhood of an exon splice enhancer; hence, future studies should carefully examine its effect on expression and conformational variation in CNR1, particularly in relation to stress adaptation.
DATE PUBLISHED
2012 Jul
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2012/03/07 06:00
pubmed 2012/03/07 06:00
medline 2012/09/15 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Agrawal A Agrawal Arpana A Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA. arpana@wustl.edu
Nelson EC Nelson Elliot C EC
Littlefield AK Littlefield Andrew K AK
Bucholz KK Bucholz Kathleen K KK
Degenhardt L Degenhardt Louisa L
Henders AK Henders Anjali K AK
Madden PA Madden Pamela A F PA
Martin NG Martin Nicholas G NG
Montgomery GW Montgomery Grant W GW
Pergadia ML Pergadia Michele L ML
Sher KJ Sher Kenneth J KJ
Heath AC Heath Andrew C AC
Lynskey MT Lynskey Michael T MT
INVESTIGATORS
JOURNAL
VOLUME: 69
ISSUE: 7
TITLE: Archives of general psychiatry
ISOABBREVIATION: Arch. Gen. Psychiatry
YEAR: 2012
MONTH: Jul
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN:
ISSNTYPE:
MEDLINE JOURNAL
MEDLINETA: Arch Gen Psychiatry
COUNTRY: United States
ISSNLINKING: 0003-990X
NLMUNIQUEID: 0372435
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AA007231 NIAAA NIH HHS United States
AA013526 NIAAA NIH HHS United States
AA013987 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA09022 NIAAA NIH HHS United States
AA11998 NIAAA NIH HHS United States
AA19596 NIAAA NIH HHS United States
DA017305 NIDA NIH HHS United States
DA12854 NIDA NIH HHS United States
DA18267 NIDA NIH HHS United States
DA23668 NIDA NIH HHS United States
F31 AA019596 NIAAA NIH HHS United States
K05 AA017242 NIAAA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
P50 AA011998 NIAAA NIH HHS United States
R01 AA007231 NIAAA NIH HHS United States
R01 AA007728 NIAAA NIH HHS United States
R01 AA009022 NIAAA NIH HHS United States
R01 AA013987 NIAAA NIH HHS United States
R01 AA017915 NIAAA NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
R01 DA017305 NIDA NIH HHS United States
R01 DA018267 NIDA NIH HHS United States
R01 DA023668 NIDA NIH HHS United States
R03 DA025886 NIDA NIH HHS United States
T32 AA013526 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Alleles
Anhedonia physiology
Australia physiology
Child physiology
Child Abuse physiology
Depression psychology
Female psychology
Gene-Environment Interaction psychology
Genetic Association Studies psychology
Genotype psychology
Heroin Dependence psychology
Humans psychology
Polymorphism, Single Nucleotide psychology
Receptor, Cannabinoid, CB1 genetics
United States genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 CNR1 protein, human
0 Receptor, Cannabinoid, CB1
OTHER ID's
OTHERID SOURCE
NIHMS463229 NLM
PMC3706194 NLM