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J Child Psychol Psychiatry. 2018 Jun;59(6):650-658. doi: 10.1111/jcpp.12843. Epub 2017 Dec 2.

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

Author information

1
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
2
MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, UK.
3
School of Pharmacy, University of Camerino, Camerino, Italy.
4
Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
5
Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
6
Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany.
7
Department of Psychiatry, Université de Montreal, Montreal, QC, Canada.
8
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany.
9
Neurospin, Commissariat à l'Energie Atomique et aux Energies Alternatives, Paris, France.
10
Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.
11
Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
12
School of Psychology, University of Nottingham, Nottingham, UK.
13
Physikalisch-Technische Bundesanstalt (PTB), Braunschweig und Berlin, Germany.
14
Institut National de la Santé et de la Recherche Médicale, INSERM CEA Unit 1000 "Imaging & Psychiatry", University Paris Sud, Orsay, France.
15
Rotman Research Institute, University of Toronto, Toronto, ON, Canada.
16
Child Mind Institute, New York, NY, USA.
17
Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
18
Department of Psychology, University College Dublin, Dublin, Ireland.
19
Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.

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.

KEYWORDS:

OPRL1 methylation; adolescence; binge drinking; nucleus accumbens; stressful life events

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