Effects of Schizophrenia Polygenic Risk Scores on Brain Activity and Performance during Working Memory Subprocesses in Healthy Young Adults

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Abstract

Recent work has begun to shed light on the neural correlates and possible mechanisms of polygenic risk for schizophrenia. Here, we map a schizophrenia polygenic risk profile score (PRS) based on genome-wide association study significant loci onto variability in the activity and functional connectivity of a frontoparietal network supporting the manipulation versus maintenance of information during a numerical working memory (WM) task in healthy young adults (n = 99, mean age = 19.8). Our analyses revealed that higher PRS was associated with hypoactivity of the dorsolateral prefrontal cortex (dlPFC) during the manipulation but not maintenance of information in WM (r 2 =.0576, P =.018). Post hoc analyses revealed that PRS-modulated dlPFC hypoactivity correlated with faster reaction times during WM manipulation (r 2 =.0967, P =.002), and faster processing speed (r 2 =.0967, P =.003) on a separate behavioral task. These PRS-associated patterns recapitulate dlPFC hypoactivity observed in patients with schizophrenia during central executive manipulation of information in WM on this task.

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Miller, J. A., Scult, M. A., Conley, E. D., Chen, Q., Weinberger, D. R., & Hariri, A. R. (2018). Effects of Schizophrenia Polygenic Risk Scores on Brain Activity and Performance during Working Memory Subprocesses in Healthy Young Adults. Schizophrenia Bulletin, 44(4), 844–853. https://doi.org/10.1093/schbul/sbx140

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