Polygenic risk of psychosis and ventral striatal activation during reward processing in healthy adolescents

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Cardiff University
  • University of Bristol
  • Heidelberg University 
  • Trinity College Dublin
  • University of Hamburg
  • Medical Research Council (MRC)
  • University of Montreal
  • King's College London (KCL)
  • French Alternative Energies and Atomic Energy Commission (CEA)
  • University of Vermont
  • University of Nottingham
  • Physikalisch-Technische Bundesanstalt
  • INSERM - Institut national de la santé et de la recherche médicale
  • Université Paris Cité
  • Hospital Group Nord-Essonne
  • University of Toronto
  • Medical University of Vienna
  • University College Dublin

Abstract

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.

Details

Original languageEnglish
Pages (from-to)852-861
Number of pages10
JournalJAMA psychiatry
Volume73
Issue number8
Publication statusE-pub ahead of print - 6 Jul 2016
Peer-reviewedYes

External IDs

PubMed 27384424
ORCID /0000-0001-5099-0274/work/161409337
ORCID /0000-0003-1477-5395/work/161409607
ORCID /0000-0001-5398-5569/work/161409037

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