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Proc Natl Acad Sci U S A. 2016 Apr 5;113(14):3879-84. doi: 10.1073/pnas.1503252113. Epub 2016 Mar 21.

Neural basis of reward anticipation and its genetic determinants.

Author information

1
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, United Kingdom; Medical Research Council Social, Genetic and Developmental Psychiatry Centre, London SE5 8AF, United Kingdom;
2
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390;
3
Center for Computational Systems Biology, Fudan University, Shanghai 200433, People's Republic of China;
4
Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Heidelberg, Germany; Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Heidelberg, Germany;
5
Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Heidelberg, Germany;
6
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, United Kingdom;
7
Trinity College Institute of Neuroscience and Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin 2, Ireland;
8
Department of System Neuroscience, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;
9
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, United Kingdom; Department of Psychiatry, Université de Montréal, Centre Hospitalier Universitaire Ste Justine Hospital, Montréal, QC, Canada H3T 1C5;
10
Neurospin, Commissariat à l'Energie Atomique et aux Energies Alternatives, 91190 Paris, France;
11
Clinic for Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;
12
Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT 05401; Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland;
13
School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD, United Kingdom;
14
Physikalisch-Technische Bundesanstalt, Braunschweig und Berlin, D-10587 Medizinische Messtechnik, Germany;
15
McGill University and Genome Quebec Innovation Centre, Montréal, QC, Canada H3A 0G1;
16
INSERM Commissariat à l'énergie atomique et aux énergies alternatives Unit 1000 "Imaging & Psychiatry," University Paris Sud, 91401 Orsay, France;
17
Rotman Research Institute, University of Toronto, Toronto, ON, Canada M6A 2E1; School of Psychology, University of Nottingham, Nottingham NG7 2RD, United Kingdom; Montreal Neurological Institute, McGill University, Montréal, QC, Canada H3A 2B4;
18
The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada M5G 1X8;
19
Neurospin, Commissariat à l'Energie Atomique et aux Energies Alternatives, 91190 Paris, France; Henry H. Wheeler, Jr. Brain Imaging Center, University of California, Berkeley, CA 94720;
20
Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Heidelberg, Germany; Department of Genetic Epidemiology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Heidelberg, Germany;
21
Behavioural and Clinical Neurosciences Institute, Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom;
22
Department of Psychiatry and Psychotherapy, and Neuroimaging Center, Technische Universität Dresden, 01187 Dresden, Germany;
23
Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany;
24
Center for Computational Systems Biology, Fudan University, Shanghai 200433, People's Republic of China; Department of Mathematics, Warwick University, Coventry CV4 7AL, United Kingdom.
25
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, United Kingdom; Medical Research Council Social, Genetic and Developmental Psychiatry Centre, London SE5 8AF, United Kingdom; gunter.schumann@kcl.ac.uk.

Abstract

Dysfunctional reward processing is implicated in various mental disorders, including attention deficit hyperactivity disorder (ADHD) and addictions. Such impairments might involve different components of the reward process, including brain activity during reward anticipation. We examined brain nodes engaged by reward anticipation in 1,544 adolescents and identified a network containing a core striatal node and cortical nodes facilitating outcome prediction and response preparation. Distinct nodes and functional connections were preferentially associated with either adolescent hyperactivity or alcohol consumption, thus conveying specificity of reward processing to clinically relevant behavior. We observed associations between the striatal node, hyperactivity, and the vacuolar protein sorting-associated protein 4A (VPS4A) gene in humans, and the causal role of Vps4 for hyperactivity was validated in Drosophila Our data provide a neurobehavioral model explaining the heterogeneity of reward-related behaviors and generate a hypothesis accounting for their enduring nature.

KEYWORDS:

GWAS; VPS4A; dopamine receptor; fMRI; neural network

PMID:
27001827
PMCID:
PMC4833244
DOI:
10.1073/pnas.1503252113
[Indexed for MEDLINE]
Free PMC Article

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