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Association of opioid receptor gene polymorphisms with drinking severity and impulsivity related to alcohol use disorder in a Korean population.

ABSTRACT: AIMS:Recent evidence suggests that the opioid system is implicated in the pathophysiology of alcohol use disorder (AUD). We aimed to examine the genetic influence of opioid receptors on susceptibility to AUD and its clinical and psychological characteristics including harmful drinking behavior and various aspects of impulsivity in AUD patients. METHODS:Three ?-opioid receptor gene (OPRM1) variants and two ?-opioid receptor gene (OPRK1) variants were examined in 314 male patients with AUD and 324 male controls. We applied the Alcohol Use Disorders Identification Test (AUDIT), Obsessive Compulsive Drinking Scale (OCDS), and Alcohol Dependence Scale. AUD patients also completed the stop-signal task, delay discounting task, balloon analogue risk task, and the Barratt Impulsiveness Scale version 11 (BIS-11). RESULTS:No significant differences in genotype distributions or haplotype frequencies were found between AUD patients and controls. However, OPRK1 SNP rs6473797 was significantly related to the severity of alcohol-related symptoms as measured by AUDIT and OCDS and a haplotype containing rs6473797 was also related to OCDS scores in AUD patients. For other psychological traits, OPRM1 SNP rs495491 was significantly associated with scores on the motor subfactor of the BIS-11. CONCLUSION:Genetic variations in opioid receptors may contribute to symptom severity and impulsivity in AUD patients.

SUBMITTER: Park CI

PROVIDER: S-EPMC6930822 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Association of opioid receptor gene polymorphisms with drinking severity and impulsivity related to alcohol use disorder in a Korean population.

Park Chun Il CI Hwang Syung Shick SS Kim Hae Won HW Kang Jee In JI Lee Sang Hak SH Kim Se Joo SJ

CNS neuroscience & therapeutics 20190419 1

<h4>Aims</h4>Recent evidence suggests that the opioid system is implicated in the pathophysiology of alcohol use disorder (AUD). We aimed to examine the genetic influence of opioid receptors on susceptibility to AUD and its clinical and psychological characteristics including harmful drinking behavior and various aspects of impulsivity in AUD patients.<h4>Methods</h4>Three μ-opioid receptor gene (OPRM1) variants and two κ-opioid receptor gene (OPRK1) variants were examined in 314 male patients w ...[more]

PMID: 31004399

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Project description:BackgroundExtensive research indicates that having a positive family history of alcohol use disorder (FHP) and impulsivity are 2 risk factors for problem drinking. To our knowledge, no study has investigated which facets of impulsivity interact with family history to increase risk for problem drinking. The goal of this study was to: (i) examine whether FHP individuals with higher levels of impulsivity are more likely to engage in problematic drinking, and (ii) identify which facets of impulsivity interact with FHP to increase risk for problems.MethodsThe data consisted of a combined sample of 757 participants (50% female, 73% White, mean age = 32.85, SD = 11.31) drawn from the Transdisciplinary Tobacco Use Research Center and the Center for the Translational Neuroscience of Alcohol. Analyses of covariance and cumulative logistic regression models investigated the association of family history and impulsivity-related traits with drinking quantity, frequency, and alcohol-related problems. Models were adjusted for age, sex, race, ethnic group, education level, and data source.ResultsSignificant interactions between impulsivity and family history were found for measures of alcohol-related problems. Specifically, there was a stronger positive association of Barratt Impulsiveness Scale (BIS) poor self-regulation with interpersonal, F(1, 504) = 6.27, p = 0.01, and impulse control alcohol-related problems, F(1, 504) = 6.00, p = 0.01, among FHP compared to FHN individuals. Main effects of family history and impulsivity on alcohol quantity and frequency of use and problems were also found.ConclusionsThese findings suggest that having both a family history of AUD and high BIS poor self-regulation is more strongly associated with alcohol-related consequences in the interpersonal and impulse control domains. Given the heterogeneity of impulsivity, these findings highlight the need for additional research to examine which facets of impulsivity are associated with which alcohol outcomes to narrow phenotypic risk for alcohol misuse.

Project description:BackgroundImpulsivity is genetically correlated with, and precedes, addictive behaviors and alcoholism. If impulsivity or attention is causally related to addiction, certain pharmacological manipulations of impulsivity and/or attention may affect alcohol drinking, and vice versa. The current studies were designed to explore the relationship among impulsivity, drinking, and vigilance in selectively bred High Alcohol Preferring (HAP) mice, a line that has previously demonstrated both high impulsivity and high alcohol consumption. Amphetamine, naltrexone, and memantine were tested in a delay discounting (DD) task for their effects on impulsivity and vigilance. The same drugs and doses were also assessed for effects on alcohol drinking in a 2-bottle choice test.MethodsHAP mice were subjected to a modified version of adjusting amount DD using 0.5-second and 10-second delays to detect decreases and increases, respectively, in impulsive responding. In 2 experiments, mice were given amphetamine (0.4, 0.8, or 1.2 mg/kg), naltrexone (3 and 10 mg/kg), and memantine (1 and 5 mg/kg) before DD testing. Another pair of studies used scheduled access, 2-bottle choice drinking to assess effects of amphetamine (0.4, 1.2, or 3.0 mg/kg), naltrexone (3 and 10 mg/kg), and memantine (1 and 5 mg/kg) on alcohol consumption.ResultsAmphetamine dose-dependently reduced impulsivity and vigilance decrement in DD, but similar doses left alcohol drinking unaffected. Naltrexone and memantine decreased alcohol intake at doses that did not affect water drinking but had no effects on impulsivity or vigilance decrement in the DD task.ConclusionsContrary to our hypothesis, none of the drugs tested here, while effective on either alcohol drinking or impulsivity, decreased both behaviors. These findings suggest that the genetic association between drinking and impulsivity observed in this population is mediated by mechanisms other than those targeted by the drugs tested in these studies.

Dataset Information

Association of opioid receptor gene polymorphisms with drinking severity and impulsivity related to alcohol use disorder in a Korean population.

Publications

Association of opioid receptor gene polymorphisms with drinking severity and impulsivity related to alcohol use disorder in a Korean population.

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