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PTSD risk associated with a functional DRD2 polymorphism in heroin‐dependent cases and controls is limited to amphetamine‐dependent individuals
Author(s) -
Nelson Elliot C.,
Heath Andrew C.,
Lynskey Michael T.,
Agrawal Arpana,
Henders Anjali K.,
Bowdler Lisa M.,
Todorov Alexandre A.,
Madden Pamela A. F.,
Moore Elizabeth,
Degenhardt Louisa,
Martin Nicholas G.,
Montgomery Grant W.
Publication year - 2014
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12062
Subject(s) - impulsivity , single nucleotide polymorphism , methamphetamine , snp , amphetamine , psychology , addiction , odds ratio , candidate gene , dopaminergic , psychiatry , medicine , genetics , clinical psychology , genotype , biology , gene , dopamine
Posttraumatic stress disorder ( PTSD ), a pathologic response to severe stress, is a common co‐morbid disorder in substance‐dependent individuals. Evidence from twin studies suggests that PTSD is moderately heritable. Genetic association studies to date have reported a limited number of replicated findings. We conducted a candidate gene association study in trauma‐exposed individuals within the C omorbidity and T rauma Study's sample (1343 heroin‐dependent cases and 406 controls from economically disadvantaged neighborhoods). After data cleaning, the 1430 single nucleotide polymorphisms ( SNP s) retained for analyses provided coverage of 72 candidate genes and included additional SNP s for which association was previously reported as well as 30 ancestry‐informative markers. We found a functional DRD2 promoter polymorphism (rs12364283) to be most highly associated with PTSD liability [odds ratio ( OR ) 1.65 (1.27–2.15); P = 1.58 × 10 −4 ]; however, this association was not significant, with a stringent B onferroni correction for multiple comparisons. The top hits include SNP s from other dopaminergic system genes: DRD2 DRD3 , TH and DBH . Additional analyses revealed that the association involving rs12364283 is largely limited to amphetamine‐dependent individuals. Substantial risk is observed in amphetamine‐dependent individuals, with at least one copy of this SNP [ OR 2.86 (1.92–4.27); P = 2.6 × 10 −7 ]. Further analyses do not support extensive mediation of PTSD risk via self‐reported impulsivity ( BIS total score). These findings suggest roles for impairment in inhibitory control in the pathophysiology of PTSD and raise questions about stimulant use in certain populations (e.g. those in combat).