Journal
JAMA PSYCHIATRY
Volume 73, Issue 8, Pages 852-861Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/jamapsychiatry.2016.1135
Keywords
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Categories
Funding
- Neuroscience and Mental Health Research Institute
- European Union [LSHM-CT-2007-037286]
- FP7 project IMAGEMEND (Imaging Genetics for Mental Disorders) [602450]
- FP7 project AGGRESSOTYPE [602805]
- FP7 project MATRICS [603016]
- Innovative Medicine Initiative Project EU-AIMS [115300-2]
- Medical Research Council (Developmental Pathways Into Adolescent Substance Abuse) [93558]
- Medical Research Council (Behavioural and Neurophysiological Effects of Schizophrenia Risk Genes: A Multi-locus, Pathway Based Approach) [MR/K004360/1]
- Medical Research Council (Consortium on Vulnerability to Externalizing Disorders and Addictions) [MR/N000390/1]
- MRC Centre for Neuropsychiatric Genetics and Genomics [G0800509]
- Swedish funding agency VR
- Swedish funding agency FORTE
- Swedish funding agency FORMAS
- Medical Research Council
- Wellcome Trust (Behavioural and Clinical Neuroscience Institute, University of Cambridge)
- National Institute for Health Research Biomedical Research Centre at South London and Maudsley National Health Services Foundation Trust and King's College London
- Bundesministeriumfur Bildung und Forschung [01GS08152, 01EV0711]
- Forschungsnetz AERIAL [eMED SysAlc01ZX1311A]
- Deutsche Forschungsgemeinschaft [SM80/7-1, SM 80/7-2, SFB 940/1]
- ANR
- Fondation de France
- Fondation pour la Recherche Medicale
- Mission Interministerielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives
- Assistance Publique-Hopitaux de Paris
- INSERM, Paris Sud University
- Axon, Testosterone, and Mental Health During Adolescence [RO1 MH085772-01A1]
- National Institutes of Health [U54 EB020403]
- cross-National Institutes of Health
- Medical Research Council [G0800509, MR/L010305/1, MR/N000390/1, G0901858, MR/K004360/1] Funding Source: researchfish
- MRC [MR/N000390/1, G0901858, G0800509, MR/K004360/1] Funding Source: UKRI
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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 = 15241836). 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.
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