Associations between polygenic risk for schizophrenia and brain function during probabilistic learning in healthy individuals.
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. Hum Brain Mapp 37:491-500, 2016. © 2015 Wiley Periodicals, Inc.
Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom.|School of Psychology, Cardiff University, Cardiff University Brain Research Imaging Centre (CUBRIC), 70 Park Place, Cardiff, CF10 3AT, Wales, United Kingdom.|Cardiff School of Medicine, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff, United Kingdom.
Thomas M
TM
Lancaster
School of Psychology, Cardiff University, Cardiff University Brain Research Imaging Centre (CUBRIC), 70 Park Place, Cardiff, CF10 3AT, Wales, United Kingdom.|Cardiff School of Medicine, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff, United Kingdom.
Niklas
N
Ihssen
School of Psychology, Cardiff University, Cardiff University Brain Research Imaging Centre (CUBRIC), 70 Park Place, Cardiff, CF10 3AT, Wales, United Kingdom.|Cardiff School of Medicine, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff, United Kingdom.
Lisa M
LM
Brindley
Cardiff School of Medicine, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff, United Kingdom.
Katherine E
KE
Tansey
Cardiff School of Medicine, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff, United Kingdom.
Kiran
K
Mantripragada
Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom.|Cardiff School of Medicine, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff, United Kingdom.
Michael C
MC
O'Donovan
Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom.|Cardiff School of Medicine, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff, United Kingdom.
Michael J
MJ
Owen
Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom.|School of Psychology, Cardiff University, Cardiff University Brain Research Imaging Centre (CUBRIC), 70 Park Place, Cardiff, CF10 3AT, Wales, United Kingdom.|Cardiff School of Medicine, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff, United Kingdom.
David E J
DE
Linden
D000328:Adult; D001921:Brain / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D003657:Decision Making / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011337:Probability Learning; D012201:Reward; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D014796:Visual Perception / Q000502:physiology; D055815:Young Adult
D010100:Oxygen
fMRI; polygenic; reversal learning; reward; schizophrenia