Effects of Schizophrenia Polygenic Risk Scores on Brain Activity and Performance During Working Memory Subprocesses in Healthy Young Adults.
- Authors
- Miller, Jacob A; Scult, Matthew A; Conley, Emily Drabant; Chen, Qiang; Weinberger, Daniel R; Hariri, Ahmad R
- Year
- 2018
- Journal
- Schizophrenia bulletin
- PMID
- 29040762
- DOI
- 10.1093/schbul/sbx140
- PMCID
- PMC6007653
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.
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