title: Polygenic Risk of Psychosis and Ventral Striatal Activation During Reward Processing in Healthy Adolescents.
abstract: OBJECTIVE
  Psychotic disorders are characterized by attenuated activity in the brain's valuation system in key reward processing areas, such as the ventral striatum (VS), as measured with functional magnetic resonance imaging.
  
  
  OBJECTIVE
  To examine whether common risk variants for psychosis are associated with individual variation in the VS.
  
  
  METHODS
  A cross-sectional study of a large cohort of adolescents from the IMAGEN study (a European multicenter study of reinforcement sensitivity in adolescents) was performed from March 1, 2008, through December 31, 2011. Data analysis was conducted from October 1, 2015, to January 9, 2016. Polygenic risk profile scores (RPSs) for psychosis were generated for 1841 healthy adolescents. Sample size and characteristics varied across regression analyses, depending on mutual information available (N = 1524-1836).
  
  
  METHODS
  Reward-related brain function was assessed with blood oxygen level dependency (BOLD) in the VS using the monetary incentive delay (MID) task, distinguishing reward anticipation and receipt. Behavioral impulsivity, IQ, MID task performance, and VS BOLD were regressed against psychosis RPS at 4 progressive P thresholds (P < .01, P < .05, P < .10, and P < .50 for RPS models 1-4, respectively).
  
  
  RESULTS
  In a sample of 1841 healthy adolescents (mean age, 14.5 years; 906 boys and 935 girls), we replicated an association between increasing psychosis RPS and reduced IQ (matrix reasoning: corrected P = .003 for RPS model 2, 0.4% variance explained), supporting the validity of the psychosis RPS models. We also found a nominally significant association between increased psychosis RPS and reduced MID task performance (uncorrected P = .03 for RPS model 4, 0.2% variance explained). Our main finding was a positive association between psychosis RPS and VS BOLD during reward anticipation at all 4 psychosis RPS models and for 2 P thresholds for reward receipt (RPS models 1 and 3), correcting for the familywise error rate (0.8%-1.9% variance explained).
  
  
  CONCLUSIONS
  These findings support an association between psychosis RPS and VS BOLD in adolescents. Genetic risk for psychosis may shape an individual's response to rewarding stimuli.
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom2Cardiff University Brain Imaging Research Centre, Cardiff University, Cardiff, United Kingdom.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Lancaster
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom2Cardiff University Brain Imaging Research Centre, Cardiff University, Cardiff, United Kingdom3MRC Centre for Neuropsychiatric Genetics and Genomics, Institute o.
authors.forename: David E
authors.initials: DE
authors.lastname: Linden
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, Faculty of Medicine and Dentistry, University of Bristol, Bristol, United Kingdom.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Tansey
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.affiliation: Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Arun L W
authors.initials: AL
authors.lastname: Bokde
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Uli
authors.initials: U
authors.lastname: Bromberg
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Cattrell
authors.affiliation: Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal, Quebec, Canada10Department of Psychological Medicine and Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, United Kingdom.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Conrod
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.affiliation: Neurospin, Commissariat à l'Energie Atomique, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Frouin
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
authors.affiliation: Departments of Psychiatry and Psychology, University of Vermont, Burlington.
authors.forename: Hugh
authors.initials: H
authors.lastname: Garavan
authors.affiliation: Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Penny
authors.initials: P
authors.lastname: Gowland
authors.affiliation: Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.affiliation: Physikalisch-Technische Bundesanstalt, Berlin, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Ittermann
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1000, Neuroimaging and Psychiatry Research Unit, University Paris-Sud, Orsay, France19University Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Martinot
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1000, Neuroimaging and Psychiatry Research Unit, University Paris-Sud, Orsay, France19University Paris Descartes, Sorbonne Paris Cité, Paris, France20Assistance Publique-Hôpitaux de P.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Paillère Martinot
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1000, Neuroimaging and Psychiatry Research Unit, University Paris-Sud, Orsay, France21Orsay Hospital, Orsay, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Artiges
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1000, Neuroimaging and Psychiatry Research Unit, University Paris-Sud, Orsay, France19University Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Herve
authors.initials: H
authors.lastname: Lemaitre
authors.affiliation: Rotman Research Institute, Baycrest Health Sciences, and Departments of Psychology and Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Frauke
authors.initials: F
authors.lastname: Nees
authors.affiliation: Neurospin, Commissariat à l'Energie Atomique, Paris, France.
authors.forename: Dimitri Papadopoulos
authors.initials: DP
authors.lastname: Orfanos
authors.affiliation: Rotman Research Institute, Baycrest Health Sciences, and Departments of Psychology and Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Paus
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Luise
authors.initials: L
authors.lastname: Poustka
authors.affiliation: Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Smolka
authors.affiliation: Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Nora C
authors.initials: NC
authors.lastname: Vetter
authors.affiliation: Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jurk
authors.affiliation: Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Mennigen
authors.affiliation: Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Walter
authors.affiliation: Department of Psychology, University College Dublin, Dublin, Ireland.
authors.forename: Robert
authors.initials: R
authors.lastname: Whelan
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, United Kingdom.
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
mesh_terms: D000293:Adolescent; D000483:Alleles; D059031:Anticipation, Psychological / Q000502:physiology*; D001143:Arousal / Q000235:genetics* / Q000502:physiology*; D001714:Bipolar Disorder / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004292:Dominance, Cerebral / Q000235:genetics / Q000502:physiology; D005060:Europe; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020412:Multifactorial Inheritance / Q000187:drug effects*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011618:Psychotic Disorders / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D012201:Reward; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology; D012565:Schizophrenic Psychology; D013223:Statistics as Topic; D066328:Ventral Striatum / Q000503:physiopathology*
chemical_list: D010100:Oxygen