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, Emily Drabant Conley, Qiang Chen, Daniel Weinberger, Ahmad R. Hariri

Research output: Contribution to journalArticle


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.

Original languageEnglish (US)
Pages (from-to)844-853
Number of pages10
JournalSchizophrenia Bulletin
Issue number4
Publication statusPublished - Jun 6 2018



  • fMRI
  • genetic risk
  • prefrontal cortex
  • working memory

ASJC Scopus subject areas

  • Psychiatry and Mental health

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