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

Published online by Cambridge University Press:  18 June 2018

Travis E. Baker*
Affiliation:
Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal, Canada
Natalie Castellanos-Ryan
Affiliation:
Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal, Canada
Gunter Schumann
Affiliation:
Institute of Psychiatry, King's College London, London, UK Medical Research Council – Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Kings College London, De Crespigny Park, London, UK
Anna Cattrell
Affiliation:
Institute of Psychiatry, King's College London, London, UK Medical Research Council – Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Kings College London, De Crespigny Park, London, UK
Herta Flor
Affiliation:
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany
Frauke Nees
Affiliation:
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany
Tobias Banaschewski
Affiliation:
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
Affiliation:
Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neurosciences, Trinity College, Dublin, Ireland
Rob Whelan
Affiliation:
Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neurosciences, Trinity College, Dublin, Ireland
Christian Buechel
Affiliation:
University Medical Centre Hamburg-Eppendorf, Haus S10, Martinistr. 52, Hamburg, Germany
Uli Bromberg
Affiliation:
University Medical Centre Hamburg-Eppendorf, Haus S10, Martinistr. 52, Hamburg, Germany
Dimitri Papadopoulos Orfanos
Affiliation:
Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center, Paris, France
Juergen Gallinat
Affiliation:
Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany
Hugh Garavan
Affiliation:
Departments of Psychiatry and Psychology, University of Vermont, 05405 Burlington, Vermont, USA
Andreas Heinz
Affiliation:
Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany
Henrik Walter
Affiliation:
Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany
Rüdiger Brühl
Affiliation:
Physikalisch-Technische Bundesanstalt, Abbestr. 2 – 12, Berlin, Germany
Penny Gowland
Affiliation:
School of Psychology, University of Nottingham, University Park, Nottingham, UK
Tomáš Paus
Affiliation:
Rotman Research Institute, University of Toronto, Toronto, Canada
Luise Poustka
Affiliation:
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
Affiliation:
Rotman Research Institute, University of Toronto, Toronto, Canada
Herve Lemaitre
Affiliation:
Institut National de la Sante et de la Recherche Medicale, INSERM CEAUnit1000, Imaging & Psychiatry, University Paris Sud, 91400 Orsay, France
Eric Artiges
Affiliation:
Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal, Canada Medical Research Council – Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Kings College London, De Crespigny Park, London, UK
Marie-Laure Paillère Martinot
Affiliation:
Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal, Canada Medical Research Council – Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Kings College London, De Crespigny Park, London, UK
Michael N. Smolka
Affiliation:
Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany
Patricia Conrod
Affiliation:
Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal, Canada Institute of Psychiatry, King's College London, London, UK
the IMAGEN consortium
Affiliation:
Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal, Canada Institute of Psychiatry, King's College London, London, UK Medical Research Council – Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Kings College London, De Crespigny Park, London, UK Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany 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 Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neurosciences, Trinity College, Dublin, Ireland University Medical Centre Hamburg-Eppendorf, Haus S10, Martinistr. 52, Hamburg, Germany Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center, Paris, France Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany Departments of Psychiatry and Psychology, University of Vermont, 05405 Burlington, Vermont, USA Physikalisch-Technische Bundesanstalt, Abbestr. 2 – 12, Berlin, Germany School of Psychology, University of Nottingham, University Park, Nottingham, UK Rotman Research Institute, University of Toronto, Toronto, Canada Institut National de la Sante et de la Recherche Medicale, INSERM CEAUnit1000, Imaging & Psychiatry, University Paris Sud, 91400 Orsay, France Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany
*Corresponding
Author for correspondence: Travis E. Baker, PhD, Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, USA. E-mail: travis.e.baker@rutgers.edu

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2018 

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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
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