title: Neural basis of reward anticipation and its genetic determinants.
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.
authors.affiliation: 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;
authors.forename: Tianye
authors.initials: T
authors.lastname: Jia
authors.affiliation: 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;
authors.forename: Christine
authors.initials: C
authors.lastname: Macare
authors.affiliation: 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;
authors.forename: Sylvane
authors.initials: S
authors.lastname: Desrivières
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Dante A
authors.initials: DA
authors.lastname: Gonzalez
authors.affiliation: Center for Computational Systems Biology, Fudan University, Shanghai 200433, People's Republic of China;
authors.forename: Chenyang
authors.initials: C
authors.lastname: Tao
authors.affiliation: Center for Computational Systems Biology, Fudan University, Shanghai 200433, People's Republic of China;
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Ji
authors.affiliation: 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;
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruggeri
authors.affiliation: 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;
authors.forename: Frauke
authors.initials: F
authors.lastname: Nees
authors.affiliation: Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Heidelberg, Germany;
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, United Kingdom;
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Barker
authors.affiliation: Trinity College Institute of Neuroscience and Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Arun L W
authors.initials: AL
authors.lastname: Bokde
authors.affiliation: Department of System Neuroscience, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;
authors.forename: Uli
authors.initials: U
authors.lastname: Bromberg
authors.affiliation: Department of System Neuroscience, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
authors.affiliation: 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;
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Conrod
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Rachel
authors.initials: R
authors.lastname: Dove
authors.affiliation: Neurospin, Commissariat à l'Energie Atomique et aux Energies Alternatives, 91190 Paris, France;
authors.forename: Vincent
authors.identifier: http://orcid.org/0000-0001-9360-6623
authors.initials: V
authors.lastname: Frouin
authors.affiliation: Clinic for Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
authors.affiliation: Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT 05401; Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Hugh
authors.initials: H
authors.lastname: Garavan
authors.affiliation: School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD, United Kingdom;
authors.forename: Penny A
authors.initials: PA
authors.lastname: Gowland
authors.affiliation: Clinic for Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.affiliation: Physikalisch-Technische Bundesanstalt, Braunschweig und Berlin, D-10587 Medizinische Messtechnik, Germany;
authors.forename: Bernd
authors.initials: B
authors.lastname: Ittermann
authors.affiliation: McGill University and Genome Quebec Innovation Centre, Montréal, QC, Canada H3A 0G1;
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.affiliation: INSERM Commissariat à l'énergie atomique et aux énergies alternatives Unit 1000 "Imaging & Psychiatry," University Paris Sud, 91401 Orsay, France;
authors.forename: Hervé
authors.initials: H
authors.lastname: Lemaitre
authors.affiliation: INSERM Commissariat à l'énergie atomique et aux énergies alternatives Unit 1000 "Imaging & Psychiatry," University Paris Sud, 91401 Orsay, France;
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Martinot
authors.affiliation: 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;
authors.forename: Tomáš
authors.initials: T
authors.lastname: Paus
authors.affiliation: The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada M5G 1X8;
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pausova
authors.affiliation: 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;
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Poline
authors.affiliation: 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;
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Behavioural and Clinical Neurosciences Institute, Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom;
authors.forename: Trevor
authors.initials: T
authors.lastname: Robbins
authors.affiliation: Department of Psychiatry and Psychotherapy, and Neuroimaging Center, Technische Universität Dresden, 01187 Dresden, Germany;
authors.forename: Michael N
authors.identifier: http://orcid.org/0000-0001-5398-5569
authors.initials: MN
authors.lastname: Smolka
authors.affiliation: Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany;
authors.forename: Christian P
authors.initials: CP
authors.lastname: Müller
authors.affiliation: Center for Computational Systems Biology, Fudan University, Shanghai 200433, People's Republic of China; Department of Mathematics, Warwick University, Coventry CV4 7AL, United Kingdom.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Adrian
authors.initials: A
authors.lastname: Rothenfluh
authors.affiliation: 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;
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.affiliation: 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.
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000293:Adolescent; D000428:Alcohol Drinking / Q000523:psychology; D000818:Animals; D059031:Anticipation, Psychological / Q000502:physiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000503:physiopathology*; D001931:Brain Mapping; D002648:Child; D003342:Corpus Striatum / Q000503:physiopathology*; D004330:Drosophila; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics*; D005260:Female; D005544:Forecasting; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D009042:Motivation; D009483:Neuropsychological Tests; D012201:Reward; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D025262:Vacuolar Proton-Translocating ATPases; D000074183:ATPases Associated with Diverse Cellular Activities; C490305:VPS4A protein, human
keywords: GWAS; VPS4A; dopamine receptor; fMRI; neural network