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

Barbara Ruggeri; Christine Macare; Serena Stopponi; Tianye Jia; Fabiana M. Carvalho; Gabriel Robert; Tobias Banaschewski; Arun L.W. Bokde; Uli Bromberg; Christian Büchel; Anna Cattrell; Patricia J. Conrod; Sylvane Desrivières; Herta Flor; Vincent Frouin; Jürgen Gallinat; Hugh Garavan; Penny Gowland; Andreas Heinz; Bernd Ittermann; Jean Luc Martinot; Marie Laure Paillère Martinot; Frauke Nees; Dimitri Papadopoulos-Orfanos; Tomáš Paus; Luise Poustka; Michael N. Smolka; Nora C. Vetter; Henrik Walter; Robert Whelan; Wolfgang H. Sommer; Georgy Bakalkin; Roberto Ciccocioppo; Gunter Schumann

doi:10.1111/jcpp.12843

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

Barbara Ruggeri, Christine Macare, Serena Stopponi, Tianye Jia, Fabiana M. Carvalho, Gabriel Robert, Tobias Banaschewski, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Anna Cattrell, Patricia J. Conrod, Sylvane Desrivières, Herta Flor, Vincent Frouin, Jürgen Gallinat, Hugh Garavan, Penny Gowland, Andreas Heinz, Bernd IttermannJean Luc Martinot, Marie Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos-Orfanos, Tomáš Paus, Luise Poustka, Michael N. Smolka, Nora C. Vetter, Henrik Walter, Robert Whelan, Wolfgang H. Sommer, Georgy Bakalkin, Roberto Ciccocioppo, Gunter Schumann^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

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.

Original language	English
Journal	Journal of Child Psychology and Psychiatry
Early online date	2 Dec 2017
DOIs	https://doi.org/10.1111/jcpp.12843
Publication status	E-pub ahead of print - 2 Dec 2017

Keywords

Adolescence
Binge drinking
Nucleus accumbens
OPRL1 methylation
Stressful life events

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/jcpp.12843

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Ruggeri, B., Macare, C., Stopponi, S., Jia, T., Carvalho, F. M., Robert, G., Banaschewski, T., Bokde, A. L. W., Bromberg, U., Büchel, C., Cattrell, A., Conrod, P. J., Desrivières, S., Flor, H., Frouin, V., Gallinat, J., Garavan, H., Gowland, P., Heinz, A., ... Schumann, G. (2017). Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking in adolescents. Journal of Child Psychology and Psychiatry. Advance online publication. https://doi.org/10.1111/jcpp.12843

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title = "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.",

keywords = "Adolescence, Binge drinking, Nucleus accumbens, OPRL1 methylation, Stressful life events",

author = "Barbara Ruggeri and Christine Macare and Serena Stopponi and Tianye Jia and Carvalho, {Fabiana M.} and Gabriel Robert and Tobias Banaschewski and Bokde, {Arun L.W.} and Uli Bromberg and Christian B{\"u}chel and Anna Cattrell and Conrod, {Patricia J.} and Sylvane Desrivi{\`e}res and Herta Flor and Vincent Frouin and J{\"u}rgen Gallinat and Hugh Garavan and Penny Gowland and Andreas Heinz and Bernd Ittermann and Martinot, {Jean Luc} and Martinot, {Marie Laure Paill{\`e}re} and Frauke Nees and Dimitri Papadopoulos-Orfanos and Tom{\'a}{\v s} Paus and Luise Poustka and Smolka, {Michael N.} and Vetter, {Nora C.} and Henrik Walter and Robert Whelan and Sommer, {Wolfgang H.} and Georgy Bakalkin and Roberto Ciccocioppo and Gunter Schumann",

year = "2017",

month = dec,

day = "2",

doi = "10.1111/jcpp.12843",

language = "English",

journal = "Journal of Child Psychology and Psychiatry",

issn = "0021-9630",

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Ruggeri, B , Macare, C, Stopponi, S, Jia, T, Carvalho, FM, Robert, G, Banaschewski, T, Bokde, ALW, Bromberg, U, Büchel, C, Cattrell, A , Conrod, PJ , Desrivières, S, Flor, H, Frouin, V, Gallinat, J, Garavan, H, Gowland, P, Heinz, A, Ittermann, B, Martinot, JL, Martinot, MLP, Nees, F, Papadopoulos-Orfanos, D, Paus, T, Poustka, L, Smolka, MN, Vetter, NC, Walter, H, Whelan, R, Sommer, WH, Bakalkin, G, Ciccocioppo, R & Schumann, G 2017, 'Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking in adolescents', Journal of Child Psychology and Psychiatry. https://doi.org/10.1111/jcpp.12843

TY - JOUR

T1 - Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking in adolescents

AU - Ruggeri, Barbara

AU - Macare, Christine

AU - Stopponi, Serena

AU - Jia, Tianye

AU - Carvalho, Fabiana M.

AU - Robert, Gabriel

AU - Banaschewski, Tobias

AU - Bokde, Arun L.W.

AU - Bromberg, Uli

AU - Büchel, Christian

AU - Cattrell, Anna

AU - Conrod, Patricia J.

AU - Desrivières, Sylvane

AU - Flor, Herta

AU - Frouin, Vincent

AU - Gallinat, Jürgen

AU - Garavan, Hugh

AU - Gowland, Penny

AU - Heinz, Andreas

AU - Ittermann, Bernd

AU - Martinot, Jean Luc

AU - Martinot, Marie Laure Paillère

AU - Nees, Frauke

AU - Papadopoulos-Orfanos, Dimitri

AU - Paus, Tomáš

AU - Poustka, Luise

AU - Smolka, Michael N.

AU - Vetter, Nora C.

AU - Walter, Henrik

AU - Whelan, Robert

AU - Sommer, Wolfgang H.

AU - Bakalkin, Georgy

AU - Ciccocioppo, Roberto

AU - Schumann, Gunter

PY - 2017/12/2

Y1 - 2017/12/2

N2 - 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.

AB - 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.

KW - Adolescence

KW - Binge drinking

KW - Nucleus accumbens

KW - OPRL1 methylation

KW - Stressful life events

UR - http://www.scopus.com/inward/record.url?scp=85036522171&partnerID=8YFLogxK

U2 - 10.1111/jcpp.12843

DO - 10.1111/jcpp.12843

M3 - Article

AN - SCOPUS:85036522171

SN - 0021-9630

JO - Journal of Child Psychology and Psychiatry

JF - Journal of Child Psychology and Psychiatry

ER -

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

Abstract

Keywords

UN SDGs

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