Polygenic risk of psychosis and ventral striatal activation during reward processing in healthy adolescents
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 as...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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American Medical Association
2016
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| Online Access: | https://eprints.nottingham.ac.uk/39607/ |
| _version_ | 1848795875249225728 |
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| author | Lancaster, Thomas M. Linden, David E. Tansey, Katherine E. Banaschewski, Tobias Bokde, Arun L.W. Bromberg, Uli Büchel, Christian Cattrell, Anna Conrod, Patricia J. Flor, Herta Frouin, Vincent Gallinat, Jürgen Garavan, Hugh Gowland, Penny A. Heinz, Andreas Ittermann, Bernd Martinot, Jean-Luc Paillère Martinot, Marie-Laure Artiges, Eric Lemaitre, Herve Nees, Frauke Orfanos, Dimitri Papadopoulos Paus, Tomáš Poustka, Luise Smolka, Michael N. Vetter, Nora C. Jurk, Sarah Mennigen, Eva Walter, Henrik Whelan, Robert Schumann, Gunter |
| author_facet | Lancaster, Thomas M. Linden, David E. Tansey, Katherine E. Banaschewski, Tobias Bokde, Arun L.W. Bromberg, Uli Büchel, Christian Cattrell, Anna Conrod, Patricia J. Flor, Herta Frouin, Vincent Gallinat, Jürgen Garavan, Hugh Gowland, Penny A. Heinz, Andreas Ittermann, Bernd Martinot, Jean-Luc Paillère Martinot, Marie-Laure Artiges, Eric Lemaitre, Herve Nees, Frauke Orfanos, Dimitri Papadopoulos Paus, Tomáš Poustka, Luise Smolka, Michael N. Vetter, Nora C. Jurk, Sarah Mennigen, Eva Walter, Henrik Whelan, Robert Schumann, Gunter |
| author_sort | Lancaster, Thomas M. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:39:02Z |
| format | Article |
| id | nottingham-39607 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:39:02Z |
| publishDate | 2016 |
| publisher | American Medical Association |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-396072020-05-04T18:03:16Z https://eprints.nottingham.ac.uk/39607/ Polygenic risk of psychosis and ventral striatal activation during reward processing in healthy adolescents Lancaster, Thomas M. Linden, David E. Tansey, Katherine E. Banaschewski, Tobias Bokde, Arun L.W. Bromberg, Uli Büchel, Christian Cattrell, Anna Conrod, Patricia J. Flor, Herta Frouin, Vincent Gallinat, Jürgen Garavan, Hugh Gowland, Penny A. Heinz, Andreas Ittermann, Bernd Martinot, Jean-Luc Paillère Martinot, Marie-Laure Artiges, Eric Lemaitre, Herve Nees, Frauke Orfanos, Dimitri Papadopoulos Paus, Tomáš Poustka, Luise Smolka, Michael N. Vetter, Nora C. Jurk, Sarah Mennigen, Eva Walter, Henrik Whelan, Robert Schumann, Gunter 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. American Medical Association 2016-07-06 Article PeerReviewed Lancaster, Thomas M., Linden, David E., Tansey, Katherine E., Banaschewski, Tobias, Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Cattrell, Anna, Conrod, Patricia J., Flor, Herta, Frouin, Vincent, Gallinat, Jürgen, Garavan, Hugh, Gowland, Penny A., Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Paillère Martinot, Marie-Laure, Artiges, Eric, Lemaitre, Herve, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomáš, Poustka, Luise, Smolka, Michael N., Vetter, Nora C., Jurk, Sarah, Mennigen, Eva, Walter, Henrik, 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 http://jamanetwork.com/journals/jamapsychiatry/fullarticle/2532233 doi:10.1001/jamapsychiatry.2016.1135 doi:10.1001/jamapsychiatry.2016.1135 |
| spellingShingle | Lancaster, Thomas M. Linden, David E. Tansey, Katherine E. Banaschewski, Tobias Bokde, Arun L.W. Bromberg, Uli Büchel, Christian Cattrell, Anna Conrod, Patricia J. Flor, Herta Frouin, Vincent Gallinat, Jürgen Garavan, Hugh Gowland, Penny A. Heinz, Andreas Ittermann, Bernd Martinot, Jean-Luc Paillère Martinot, Marie-Laure Artiges, Eric Lemaitre, Herve Nees, Frauke Orfanos, Dimitri Papadopoulos Paus, Tomáš Poustka, Luise Smolka, Michael N. Vetter, Nora C. Jurk, Sarah Mennigen, Eva Walter, Henrik Whelan, Robert Schumann, Gunter Polygenic risk of psychosis and ventral striatal activation during reward processing in healthy adolescents |
| title | Polygenic risk of psychosis and ventral striatal activation during reward processing in healthy adolescents |
| title_full | Polygenic risk of psychosis and ventral striatal activation during reward processing in healthy adolescents |
| title_fullStr | Polygenic risk of psychosis and ventral striatal activation during reward processing in healthy adolescents |
| title_full_unstemmed | Polygenic risk of psychosis and ventral striatal activation during reward processing in healthy adolescents |
| title_short | Polygenic risk of psychosis and ventral striatal activation during reward processing in healthy adolescents |
| title_sort | polygenic risk of psychosis and ventral striatal activation during reward processing in healthy adolescents |
| url | https://eprints.nottingham.ac.uk/39607/ https://eprints.nottingham.ac.uk/39607/ https://eprints.nottingham.ac.uk/39607/ |