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Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking in adolescents.

ABSTRACT: BACKGROUND:Nociceptin is a key regulator linking environmental stress and alcohol drinking. In a genome-wide methylation analysis, we recently identified an association of a methylated region in the OPRL1 gene with alcohol-use disorders. METHODS:Here, we investigate the biological basis of this observation by analysing psychosocial stressors, methylation of the OPRL1 gene, brain response during reward anticipation and alcohol drinking in 660 fourteen-year-old adolescents of the IMAGEN study. We validate our findings in marchigian sardinian (msP) alcohol-preferring rats that are genetically selected for increased alcohol drinking and stress sensitivity. RESULTS:We found that low methylation levels in intron 1 of OPRL1 are associated with higher psychosocial stress and higher frequency of binge drinking, an effect mediated by OPRL1 methylation. In individuals with low methylation of OPRL1, frequency of binge drinking is associated with stronger BOLD response in the ventral striatum during reward anticipation. In msP rats, we found that stress results in increased alcohol intake and decreased methylation of OPRL1 in the nucleus accumbens. CONCLUSIONS:Our findings describe an epigenetic mechanism that helps to explain how psychosocial stress influences risky alcohol consumption and reward processing, thus contributing to the elucidation of biological mechanisms underlying risk for substance abuse.

SUBMITTER: Ruggeri B

PROVIDER: S-EPMC5975104 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking in adolescents.

Ruggeri Barbara B Macare Christine C Stopponi Serena S Jia Tianye T Carvalho Fabiana M FM Robert Gabriel G Banaschewski Tobias T Bokde Arun L W ALW Bromberg Uli U Büchel Christian C Cattrell Anna A Conrod Patricia J PJ Desrivières Sylvane S Flor Herta H Frouin Vincent V Gallinat Jürgen J Garavan Hugh H Gowland Penny P Heinz Andreas A Ittermann Bernd B Martinot Jean Luc JL Martinot Marie-Laure Paillère MP Nees Frauke F Papadopoulos-Orfanos Dimitri D Paus Tomáš T Poustka Luise L Smolka Michael N MN Vetter Nora C NC Walter Henrik H Whelan Robert R Sommer Wolfgang H WH Bakalkin Georgy G Ciccocioppo Roberto R Schumann Gunter G

Journal of child psychology and psychiatry, and allied disciplines 20171202 6

<h4>Background</h4>Nociceptin is a key regulator linking environmental stress and alcohol drinking. In a genome-wide methylation analysis, we recently identified an association of a methylated region in the OPRL1 gene with alcohol-use disorders.<h4>Methods</h4>Here, we investigate the biological basis of this observation by analysing psychosocial stressors, methylation of the OPRL1 gene, brain response during reward anticipation and alcohol drinking in 660 fourteen-year-old adolescents of the IM ...[more]

PMID: 29197086

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Project description:Background and aimsNearly all the research conducted on high-intensity drinking has focused on college and school-based samples, with recent calls for research to understand this risky drinking pattern in non-school-based samples and across time. This study aimed to characterize predictors and consequences of non-binge drinking, age- and gender-adjusted binge drinking (level I) and drinking at levels representing two or more times (level II) and three or more times the level I binge threshold (level III) in a clinical sample of adolescents followed into young adulthood.DesignCross-sectional associations between non-binge drinking, binge levels, and negative alcohol-related consequences were examined during adolescence; prospective analyses tested whether adolescent non-binge drinking and binge levels predicted alcohol use disorder (AUD) symptoms in young adulthood and whether changes in drinking motives over time were associated with binge levels in young adulthood.SettingUS clinical settings.ParticipantsA total of 432 adolescents (aged 12-18 years) with alcohol-related problems followed into young adulthood (aged 19-25 years).MeasurementsLife-time drinking history, Structured Clinical Interview for DSM AUDs, and Inventory of Drinking Situations.FindingsResults were generally consistent with a distinction between binge level I versus levels II-III on various negative alcohol-related consequences in adolescence (Ps < 0.05) that were maintained in young adulthood (Ps < 0.01). The maintenance of relatively high endorsement of enhancement and social motives over time was associated with binge levels II-III in young adulthood (Ps < 0.001); decreases in coping motives were associated with less risky drinking in adulthood (P = 0.003).ConclusionsAmong US adolescents with alcohol-related problems who were followed-up in young adulthood (aged 19-25 years), standard threshold binge drinking (five or more drinks per occasion; level I) was generally associated with fewer alcohol-related consequences and problem behaviors than binge drinking at two or more times (level II) or three or more times (level III) the standard binge threshold.

Project description:BackgroundAs epidemiological surveys have shown, binge drinking is a constant and wide-spread problem behavior in adolescents. It is not rare to find that more than half of all adolescents engage in this behavior when assessing only the last 4 weeks of time independent of the urbanity of the region they live in. There have been several reviews on predictors of substance consumption in adolescents in general, but there has been less high quality research on predictors of binge drinking, and most studies have not been theoretically based. The current study aimed to analyze the ultimate and distal factors predicting substance consumption according to Petraitis' theory of triadic influence. We assessed the predictive value of these factors with respect to binge drinking in German adolescents, including the identification of influence direction.MethodsIn the years 2007/2008, a representative written survey of N = 44,610 students in the 9th grade of different school types in Germany was carried out (net sample). The return rate of questionnaires was 88% regarding all students whose teachers or school directors had agreed to participate in the study. In this survey, prevalence of binge drinking was investigated as well as potential predictors from the social/interpersonal, the attitudinal/environmental, and the intrapersonal fields (3 factors of Petraitis). In a multivariate logistic regression analysis, these variables were included after testing for multicollinearity in order to assess their ability to predict binge drinking.ResultsPrevalence of binge drinking in the last 30 days was 52.3% for the surveyed adolescents with a higher prevalence for boys (56.9%) than for girls (47.5%). The two most influential factors found to protect against binge drinking with p < .001 were low economic status and importance of religion. The four most relevant risk factors for binge drinking (p < .001) were life-time prevalence of school absenteeism/truancy, academic failure, suicidal thoughts, and violence at school in the form of aggressive behavior of teachers. The model of Petraitis was partly confirmed for Binge Drinking in German adolescents and the direction of influence factors was clarified.ConclusionsWhereas some of the risk and protective factors for binge drinking are not surprising since they are known for substance abuse in general, there are two points that could be targeted in interventions that do not focus on adolescents alone: (a) training teachers in positive, reassuring behavior and constructive criticism and (b) a focus on high risk adolescents either because they have a lack of coping strategies when in a negative mood or because of their low academic achievement in combination with absenteeism from school.

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Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking in adolescents.

Publications

Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking in adolescents.

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