3 years ago

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

Jacob A Miller, Matthew A Scult, Ahmad R Hariri, Daniel R Weinberger, Qiang Chen, Emily Drabant Conley
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 (r2 = .0576, P = .018). Post hoc analyses revealed that PRS-modulated dlPFC hypoactivity correlated with faster reaction times during WM manipulation (r2 = .0967, P = .002), and faster processing speed (r2 = .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.

Publisher URL: http://doi.org/10.1093/schbul/sbx140

DOI: 10.1093/schbul/sbx140

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