Polygenic Risk of Psychosis and Ventral Striatal Activation During Reward Processing in Healthy Adolescents.
JAMA Psychiatry. 2016-08-01; 73(8): 852
DOI: 10.1001/jamapsychiatry.2016.1135
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Lancaster TM(1), Linden DE(2), Tansey KE(3), Banaschewski T(4), Bokde AL(5),
Bromberg U(6), Büchel C(6), Cattrell A(7), Conrod PJ(8), Flor H(9), Frouin V(10),
Gallinat J(11), Garavan H(12), Gowland P(13), Heinz A(14), Ittermann B(15),
Martinot JL(16), Paillère Martinot ML(17), Artiges E(18), Lemaitre H(16), Nees
F(19), Orfanos DP(10), Paus T(19), Poustka L(20), Smolka MN(21), Vetter NC(21),
Jurk S(21), Mennigen E(21), Walter H(14), Whelan R(22), Schumann G(7); IMAGEN
Consortium.
Author information:
(1)Neuroscience and Mental Health Research Institute, Cardiff University,
Cardiff, United Kingdom2Cardiff University Brain Imaging Research Centre, Cardiff
University, Cardiff, United Kingdom.
(2)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.
(3)MRC Integrative Epidemiology Unit, School of Social and Community Medicine,
Faculty of Medicine and Dentistry, University of Bristol, Bristol, United
Kingdom.
(4)Department of Child and Adolescent Psychiatry and Psychotherapy, Central
Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University,
Mannheim, Germany.
(5)Discipline of Psychiatry, School of Medicine and Trinity College Institute of
Neuroscience, Trinity College Dublin, Dublin, Ireland.
(6)University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
(7)MRC Social, Genetic and Developmental Psychiatry Centre, Institute of
Psychiatry, Psychology, and Neuroscience, King’s College, London, United Kingdom.
(8)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.
(9)Department of Cognitive and Clinical Neuroscience, Central Institute of Mental
Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
(10)Neurospin, Commissariat à l’Energie Atomique, Paris, France.
(11)Department of Psychiatry and Psychotherapy, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany.
(12)Departments of Psychiatry and Psychology, University of Vermont, Burlington.
(13)Sir Peter Mansfield Imaging Centre School of Physics and Astronomy,
University of Nottingham, Nottingham, United Kingdom.
(14)Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin,
Berlin, Germany.
(15)Physikalisch-Technische Bundesanstalt, Berlin, Germany.
(16)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.
(17)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.
(18)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.
(19)Rotman Research Institute, Baycrest Health Sciences, and Departments of
Psychology and Psychiatry, University of Toronto, Toronto, Ontario, Canada.
(20)Department of Child and Adolescent Psychiatry and Psychotherapy, Medical
University of Vienna, Vienna, Austria.
(21)Department of Psychiatry and Neuroimaging Center, Technische Universität
Dresden, Dresden, Germany.
(22)Department of Psychology, University College Dublin, Dublin, Ireland.
Erratum in
JAMA Psychiatry. 2016 Oct 1;73(10):1099.
Comment in
JAMA Psychiatry. 2016 Aug 1;73(8):777-8.
IMPORTANCE: 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.
DESIGN, SETTING, AND PARTICIPANTS: 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).
MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.