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Association of the PDYN gene with alcohol dependence and the propensity to drink in negative emotional states.

ABSTRACT: Synthetic ?-opioid receptor (KOR) agonists induce dysphoric and pro-depressive effects and variations in the KOR (OPRK1) and prodynorphin (PDYN) genes have been shown to be associated with alcohol dependence. We genotyped 23 single nucleotide polymorphisms (SNPs) in the PDYN and OPRK1 genes in 816 alcohol-dependent subjects and investigated their association with: (1) negative craving measured by a subscale of the Inventory of Drug Taking Situations; (2) a self-reported history of depression; (3) the intensity of depressive symptoms measured by the Beck Depression Inventory-II. In addition, 13 of the 23 PDYN and OPRK1 SNPs, which were previously genotyped in a set of 1248 controls, were used to evaluate association with alcohol dependence. SNP and haplotype tests of association were performed. Analysis of a haplotype spanning the PDYN gene (rs6045784, rs910080, rs2235751, rs2281285) revealed significant association with alcohol dependence (p = 0.00079) and with negative craving (p = 0.0499). A candidate haplotype containing the PDYN rs2281285-rs1997794 SNPs that was previously associated with alcohol dependence was also associated with negative craving (p = 0.024) and alcohol dependence (p = 0.0008) in this study. A trend for association between depression severity and PDYN variation was detected. No associations of OPRK1 gene variation with alcohol dependence or other studied phenotypes were found. These findings support the hypothesis that sequence variation in the PDYN gene contributes to both alcohol dependence and the induction of negative craving in alcohol-dependent subjects.

SUBMITTER: Karpyak VM

PROVIDER: S-EPMC3901318 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Association of the PDYN gene with alcohol dependence and the propensity to drink in negative emotional states.

Karpyak Victor M VM Winham Stacey J SJ Preuss Ulrich W UW Zill Peter P Cunningham Julie M JM Walker Denise L DL Lewis Kriste A KA Geske Jennifer R JR Colby Colin L CL Abulseoud Osama A OA Hall-Flavin Daniel K DK Loukianova Larissa L LL Schneekloth Terry D TD Frye Mark A MA Bazov Igor I Heit John A JA Bakalkin Georgy G Mrazek David A DA Biernacka Joanna M JM

The international journal of neuropsychopharmacology 20121029 5

Synthetic κ-opioid receptor (KOR) agonists induce dysphoric and pro-depressive effects and variations in the KOR (OPRK1) and prodynorphin (PDYN) genes have been shown to be associated with alcohol dependence. We genotyped 23 single nucleotide polymorphisms (SNPs) in the PDYN and OPRK1 genes in 816 alcohol-dependent subjects and investigated their association with: (1) negative craving measured by a subscale of the Inventory of Drug Taking Situations; (2) a self-reported history of depression; (3 ...[more]

PMID: 23101464

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Project description:Background and aimsDepression and anxiety are often comorbid with alcoholism and contribute to craving and relapse. We aimed to estimate the prevalence of life-time diagnoses of major depressive disorder (MDD), substance-induced depression (SID), anxiety disorder (AnxD) and substance-induced anxiety (SIA), the effects of these comorbidities on the propensity to drink in negative emotional states (negative craving), and test whether these effects differ by sex.DesignSecondary analyses of baseline data collected in a single-arm study of pharmacogenetic predictors of acamprosate response.SettingAcademic medical center and affiliated community-based treatment programs in the American upper mid-west.ParticipantsA total of 287 males and 156 females aged 18-80 years, meeting DSM-IV criteria for alcohol dependence.MeasurementsThe primary outcome measure was 'propensity to drink in negative emotional situations' (determined by the Inventory of Drug Taking Situations) and the key predictors/covariates were sex and psychiatric comorbidities, including MDD, SID, AnxD and SIA (determined by Psychiatric Research Interview of Substance and Mood Disorders).FindingsThe prevalence of the MDD, SID and AnxD was higher in females compared with males (33.1 versus 18.4%, 44.8 versus 26.4% and 42.2 versus 27.4%, respectively; P < 0.01, each), while SIA was rare (3.3%) and did not differ by sex. Increased propensity to drink in negative emotional situations was associated with comorbid MDD (β = 6.6, P = 0.013) and AnxD (β = 4.8, P = 0.042) as well as a SID × sex interaction effect (P = 0.003), indicating that the association of SID with propensity to drink in negative emotional situations differs by sex and is stronger in males (β = 7.9, P = 0.009) compared with females (β = -6.6, P = 0.091).ConclusionsThere appears to be a higher prevalence of comorbid depression and anxiety disorders as well as propensity to drink in negative emotional situations in female compared with male alcoholics. Substance-induced depression appears to have a sex-specific effect on the increased risk for drinking in negative emotional situations in males.

Dataset Information

Association of the PDYN gene with alcohol dependence and the propensity to drink in negative emotional states.

Publications

Association of the PDYN gene with alcohol dependence and the propensity to drink in negative emotional states.

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