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Methylation of OPRL 1 mediates the effect of psychosocial stress on binge drinking in adolescents
Author(s) -
Ruggeri Barbara,
Macare Christine,
Stopponi Serena,
Jia Tianye,
Carvalho Fabiana M.,
Robert Gabriel,
Banaschewski Tobias,
Bokde Arun L.W.,
Bromberg Uli,
Büchel Christian,
Cattrell Anna,
Conrod Patricia J.,
Desrivières Sylvane,
Flor Herta,
Frouin Vincent,
Gallinat Jürgen,
Garavan Hugh,
Gowland Penny,
Heinz Andreas,
Ittermann Bernd,
Martinot Jean Luc,
Martinot MarieLaure Paillère,
Nees Frauke,
PapadopoulosOrfanos Dimitri,
Paus Tomáš,
Poustka Luise,
Smolka Michael N.,
Vetter Nora C.,
Walter Henrik,
Whelan Robert,
Sommer Wolfgang H.,
Bakalkin Georgy,
Ciccocioppo Roberto,
Schumann Gunter
Publication year - 2018
Publication title -
journal of child psychology and psychiatry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.652
H-Index - 211
eISSN - 1469-7610
pISSN - 0021-9630
DOI - 10.1111/jcpp.12843
Subject(s) - psychology , binge drinking , anticipation (artificial intelligence) , nucleus accumbens , methylation , psychosocial , epigenetics , dna methylation , clinical psychology , poison control , psychiatry , genetics , injury prevention , medicine , gene , neuroscience , biology , gene expression , dopamine , environmental health , artificial intelligence , computer science
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 OPRL 1 gene with alcohol‐use disorders. Methods Here, we investigate the biological basis of this observation by analysing psychosocial stressors, methylation of the OPRL 1 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 OPRL 1 are associated with higher psychosocial stress and higher frequency of binge drinking, an effect mediated by OPRL 1 methylation. In individuals with low methylation of OPRL 1 , 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 OPRL 1 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.