Associations between polygenic risk for schizophrenia and brain function during probabilistic learning in healthy individuals

Lancaster, Thomas ORCID: https://orcid.org/0000-0003-1322-2449, Ihssen, Niklaas, Brindley, Lisa ORCID: https://orcid.org/0000-0002-6673-3800, Tansey, Katherine E., Mantripragada, Kiran Kumar ORCID: https://orcid.org/0000-0003-2070-8105, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 and Linden, David Edmund Johannes ORCID: https://orcid.org/0000-0002-5638-9292 2016. Associations between polygenic risk for schizophrenia and brain function during probabilistic learning in healthy individuals. Human Brain Mapping 37 (2) , pp. 491-500. 10.1002/hbm.23044

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Abstract

A substantial proportion of schizophrenia liability can be explained by additive genetic factors. Risk profile scores (RPS) directly index risk using a summated total of common risk variants weighted by their effect. Previous studies suggest that schizophrenia RPS predict alterations to neural networks that support working memory and verbal fluency. In this study, we apply schizophrenia RPS to fMRI data to elucidate the effects of polygenic risk on functional brain networks during a probabilistic-learning neuroimaging paradigm. The neural networks recruited during this paradigm have previously been shown to be altered to unmedicated schizophrenia patients and relatives of schizophrenia patients, which may reflect genetic susceptibility. We created schizophrenia RPS using summary data from the Psychiatric Genetic Consortium (Schizophrenia Working Group) for 83 healthy individuals and explore associations between schizophrenia RPS and blood oxygen level dependency (BOLD) during periods of choice behavior (switch–stay) and reflection upon choice outcome (reward–punishment). We show that schizophrenia RPS is associated with alterations in the frontal pole (PWHOLE-BRAIN-CORRECTED = 0.048) and the ventral striatum (PROI-CORRECTED = 0.036), during choice behavior, but not choice outcome. We suggest that the common risk variants that increase susceptibility to schizophrenia can be associated with alterations in the neural circuitry that support the processing of changing reward contingencies.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Neuroscience and Mental Health Research Institute (NMHRI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	fMRI; polygenic; schizophrenia; reward; reversal learning
Publisher:	Wiley-Blackwell
ISSN:	1065-9471
Funders:	MRC
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	19 October 2015
Last Modified:	17 Jan 2024 07:22
URI:	https://orca.cardiff.ac.uk/id/eprint/84158

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