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

Lancaster, Thomas M. and Linden, David E. and Tansey, Katherine E. and Banaschewski, Tobias and Bokde, Arun L.W. and Bromberg, Uli and Büchel, Christian and Cattrell, Anna and Conrod, Patricia J. and Flor, Herta and Frouin, Vincent and Gallinat, Jürgen and Garavan, Hugh and Gowland, Penny A. and Heinz, Andreas and Ittermann, Bernd and Martinot, Jean-Luc and Paillère Martinot, Marie-Laure and Artiges, Eric and Lemaitre, Herve and Nees, Frauke and Orfanos, Dimitri Papadopoulos and Paus, Tomáš and Poustka, Luise and Smolka, Michael N. and Vetter, Nora C. and Jurk, Sarah and Mennigen, Eva and Walter, Henrik and Whelan, Robert and Schumann, Gunter (2016) Polygenic risk of psychosis and ventral striatal activation during reward processing in healthy adolescents. JAMA Psychiatry, 73 (8). pp. 852-861. ISSN 2168-6238

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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.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Physics and Astronomy
Identification Number: https://doi.org/10.1001/jamapsychiatry.2016.1135
Depositing User: Eprints, Support
Date Deposited: 05 Jan 2017 12:18
Last Modified: 05 Jan 2017 12:23
URI: http://eprints.nottingham.ac.uk/id/eprint/39607

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