The influence of GABRA2, childhood trauma, and their interaction on alcohol, heroin, and cocaine dependence

Enoch, Mary-Anne; Hodgkinson, Colin A.; Yuan, Qiaoping; Shen, Pei-Hong; Goldman, David; Roy, Alec

doi:10.1016/j.biopsych.2009.08.019

Cited by 130Neurotransmitter Receptor Influence on BehaviorGenetic Associations and EpidemiologyChild Abuse and Trauma

The influence of GABRA2, childhood trauma, and their interaction on alcohol, heroin, and cocaine dependence

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Enoch, Mary-Anne, Hodgkinson, Colin A., Yuan, Qiaoping, Shen, Pei-Hong, Goldman, David, Roy, Alec·2010·Biological Psychiatry

DOI 10.1016/j.biopsych.2009.08.019PMC PMC2964936

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Abstract

Background The GABRA2 gene has been implicated in addiction. Early life stress has been shown to alter GABRA2 expression in adult rodents. We hypothesized that childhood trauma, GABRA2 variation, and their interaction would influence addiction vulnerability.Methods African-American men were recruited for this study: 577 patients with lifetime DSM-IV single and comorbid diagnoses of alcohol, cocaine, and heroin dependence, and 255 control subjects. The Childhood Trauma Questionnaire (CTQ) was administered. Ten GABRA2 haplotype-tagging single-nucleotide polymorphisms (SNPs) were genotyped.Results We found that exposure to childhood trauma predicted substance dependence (p < .0001). Polysubstance dependence was associated with the highest CTQ scores (p < .0001). The African Americans had four common haplotypes (frequency: .11-.30) within the distal haplotype block: two that correspond to the Caucasian and Asian yin-yang haplotypes, and two not found in other ethnic groups. One of the unique haplotypes predicted heroin addiction, whereas the other haplotype was more common in control subjects and seemed to confer resilience to addiction after exposure to severe childhood trauma. The yin-yang haplotypes had no effects. Moreover, the intron 2 SNP rs11503014, not located in any haplotype block and potentially implicated in exon splicing, was independently associated with addiction, specifically heroin addiction (p < .005). Childhood trauma interacted with rs11503014 variation to influence addiction vulnerability, particularly to cocaine (p < .005).Conclusions Our results suggest that at least in African-American men, childhood trauma, GABRA2 variation, and their interaction play a role in risk-resilience for substance dependence.

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GABAARs in brain reward circuits may be involved in the development of brain changes that mediate the addictive properties of drugs in general.
“The involvement of GABAAR genes in the abuse of and dependence on drugs that do not directly affect the GABAARs suggest that the GABAARs in brain reward circuits may be involved in the development of brain changes that mediate the addictive properties of drugs in general.”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [100]

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Authors: Enoch, M.-A., Hodgkinson, C. A., Yuan, Q., Shen, P.-H., Goldman, D., & Roy, A.
Affiliations: National Institutes of Health (US)
VA New Jersey Health Care System (US)
Corresponding author: Enoch, Mary-Anne
ORCID: Hodgkinson, Colin A.
Yuan, Qiaoping
Shen, Pei-Hong
Goldman, David
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2010-01
Volume: 67
Issue: 1
Pages: 20-27
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2009.08.019
PMC: PMC2964936
OpenAlex: W1965623485
Cited by: 130
References: 62
Citations by year: 2026: 5 · 2025: 2 · 2024: 6 · 2023: 6 · 2022: 3 · 2021: 12 · 2020: 3 · 2019: 9 · 2018: 5 · 2017: 7 · 2016: 12 · 2015: 7 · 2014: 7 · 2013: 13 · 2012: 17
FWCI: 4.56
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Alcohol Abuse and Alcoholism (ZIAAA000305, ZIAAA000306)
National Institute on Drug Abuse (R01DA010336, R01DA10336-02)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
Keywords: GABRA2, childhood trauma, early life stress, substance dependence, heroin addiction, cocaine dependence, alcoholism, polysubstance dependence, gene-environment interaction, haplotype variation, exon splicing, addiction vulnerability, African American men
MeSH terms: Adult, Alcoholism, Black or African American, Environment, Exons, Gene Frequency, Genotype, Heroin Dependence, Humans, Male, Middle Aged, Surveys and Questionnaires, Receptors, GABA-A, Statistics as Topic, Incidence, Chi-Square Distribution, Databases, Factual, Substance-Related Disorders, Cocaine-Related Disorders, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Adult Survivors of Child Abuse

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The influence of GABRA2, childhood trauma, and their interaction on alcohol, heroin, and cocaine dependence

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