Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence

Travis E Baker; Natalie Castellanos-Ryan; Gunter Schumann; Anna Cattrell; Herta Flor; Frauke Nees; Tobias Banaschewski; Arun Bokde; Rob Whelan; Christian Buechel; Uli Bromberg; Dimitri Papadopoulos Orfanos; Juergen Gallinat; Hugh Garavan; Andreas Heinz; Henrik Walter; Rüdiger Brühl; Penny Gowland; Tomáš Paus; Luise Poustka; Jean-Luc Martinot; Herve Lemaitre; Eric Artiges; Marie-Laure Paillère Martinot; Michael N Smolka; Patricia Conrod; IMAGEN consortium

doi:10.1017/S0033291718001459

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Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence

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Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence

Travis E Baker, Natalie Castellanos-Ryan, Gunter Schumann, Anna Cattrell, Herta Flor, Frauke Nees, Tobias Banaschewski, Arun Bokde, Rob Whelan, Christian Buechel, …

Psychological medicine, Vol.49(5), pp.801-810

04/2019

DOI: https://doi.org/10.1017/S0033291718001459

PMID: 29909784

Abstract

Adolescent

Alcoholism - etiology

Alcoholism - genetics

Alcoholism - metabolism

Female

Frontal Lobe - diagnostic imaging

Frontal Lobe - metabolism

Genetic Predisposition to Disease

Humans

Magnetic Resonance Imaging

Male

Polymorphism, Genetic

Protein-Serine-Threonine Kinases - genetics

Receptors, Dopamine D1 - genetics

Receptors, Dopamine D1 - metabolism

Receptors, Dopamine D2 - metabolism

Reward

Ventral Striatum - diagnostic imaging

Ventral Striatum - metabolism

Abnormalities in reward circuit function are considered a core feature of addiction. Yet, it is still largely unknown whether these abnormalities stem from chronic drug use, a genetic predisposition, or both. In the present study, we investigated this issue using a large sample of adolescent children by applying structural equation modeling to examine the effects of several dopaminergic polymorphisms of the D1 and D2 receptor type on the reward function of the ventral striatum (VS) and orbital frontal cortex (OFC), and whether this relationship predicted the propensity to engage in early alcohol misuse behaviors at 14 years of age and again at 16 years of age. The results demonstrated a regional specificity with which the functional polymorphism rs686 of the D1 dopamine receptor (DRD1) gene and Taq1A of the ANKK1 gene influenced medial and lateral OFC activation during reward anticipation, respectively. Importantly, our path model revealed a significant indirect relationship between the rs686 of the DRD1 gene and early onset of alcohol misuse through a medial OFC × VS interaction. These findings highlight the role of D1 and D2 in adjusting reward-related activations within the mesocorticolimbic circuitry, as well as in the susceptibility to early onset of alcohol misuse.

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Title: Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence
Creators: Travis E Baker - Department of Psychiatry,Universite de Montreal, CHU Ste Justine Hospital,Montreal,Canada
Natalie Castellanos-Ryan - Department of Psychiatry,Universite de Montreal, CHU Ste Justine Hospital,Montreal,Canada
Gunter Schumann - Institute of Psychiatry, King's College London,London,UK
Anna Cattrell - Institute of Psychiatry, King's College London,London,UK
Herta Flor - Department of Cognitive and Clinical Neuroscience,Central Institute of Mental Health,Medical Faculty Mannheim,Heidelberg University,Square J5, Mannheim,Germany
Frauke Nees - Department of Cognitive and Clinical Neuroscience,Central Institute of Mental Health,Medical Faculty Mannheim,Heidelberg University,Square J5, Mannheim,Germany
Tobias Banaschewski - Department of Child and Adolescent Psychiatry,Central Institute of Mental Health,Faculty of Clinical Medicine Mannheim,Medical Faculty Mannheim,Heidelberg University,Square J5, 68159 Mannheim,Germany
Arun Bokde - Discipline of Psychiatry,School of Medicine and Trinity College Institute of Neurosciences, Trinity College,Dublin,Ireland
Rob Whelan - Discipline of Psychiatry,School of Medicine and Trinity College Institute of Neurosciences, Trinity College,Dublin,Ireland
Christian Buechel - University Medical Centre Hamburg-Eppendorf,Haus S10, Martinistr. 52, Hamburg,Germany
Uli Bromberg - University Medical Centre Hamburg-Eppendorf,Haus S10, Martinistr. 52, Hamburg,Germany
Dimitri Papadopoulos Orfanos - Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center,Paris,France
Juergen Gallinat - Department of Psychiatry and Psychotherapy,Campus Charité Mitte, Charité,Universitätsmedizin Berlin,Charitéplatz 1, Berlin,Germany
Hugh Garavan - Departments of Psychiatry and Psychology,University of Vermont,05405 Burlington, Vermont,USA
Andreas Heinz - Department of Psychiatry and Psychotherapy,Campus Charité Mitte, Charité,Universitätsmedizin Berlin,Charitéplatz 1, Berlin,Germany
Henrik Walter - Department of Psychiatry and Psychotherapy,Campus Charité Mitte, Charité,Universitätsmedizin Berlin,Charitéplatz 1, Berlin,Germany
Rüdiger Brühl - Physikalisch-Technische Bundesanstalt,Abbestr. 2 - 12, Berlin,Germany
Penny Gowland - School of Psychology, University of Nottingham, University Park,Nottingham,UK
Tomáš Paus - Rotman Research Institute, University of Toronto,Toronto,Canada
Luise Poustka - Department of Child and Adolescent Psychiatry,Central Institute of Mental Health,Faculty of Clinical Medicine Mannheim,Medical Faculty Mannheim,Heidelberg University,Square J5, 68159 Mannheim,Germany
Jean-Luc Martinot - Rotman Research Institute, University of Toronto,Toronto,Canada
Herve Lemaitre - Institut National de la Sante et de la Recherche Medicale, INSERM CEAUnit1000, Imaging & Psychiatry, University Paris Sud,91400 Orsay,France
Eric Artiges - Department of Psychiatry,Universite de Montreal, CHU Ste Justine Hospital,Montreal,Canada
Marie-Laure Paillère Martinot - Department of Psychiatry,Universite de Montreal, CHU Ste Justine Hospital,Montreal,Canada
Michael N Smolka - Department of Psychiatry and Neuroimaging Center,Technische Universität Dresden,Dresden,Germany
Patricia Conrod - Department of Psychiatry,Universite de Montreal, CHU Ste Justine Hospital,Montreal,Canada
IMAGEN consortium
Publication Details: Psychological medicine, Vol.49(5), pp.801-810
Date published: 04/2019
Grant note: 93 558 / Medical Research Council CIHR G0901858 / Medical Research Council
Academic Unit: Center for Molecular and Behavioral Neuroscience
Language: English
Resource Type: Journal article
Identifiers: 991031665267804646