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Psychotic-like experiences and polygenic liability in the ABCD Study

By Nicole R. Karcher, Sarah E. Paul, Emma C. Johnson, Alexander S. Hatoum, David AA Baranger, Arpana Agrawal, Wesley K Thompson, Deanna M. Barch, Ryan Bogdan

Posted 17 Jul 2020
medRxiv DOI: 10.1101/2020.07.14.20153551

Background: Psychotic-like experiences (PLEs) during childhood are harbingers for severe psychopathology, including psychotic disorders, and neurodevelopmental impairments in adolescence and adulthood. Methods: Data from children of genomically-confirmed European ancestries (n=4,650; ages 9-10; 46.8% female) who completed the baseline Adolescent Brain Cognitive Development Study session were used to assess whether PLEs (i.e., both total and the presence of significantly distressing) are associated with polygenic scores (PGS) related to psychopathology (i.e., schizophrenia [SCZ], educational attainment [EDU], psychiatric cross-disorder risk [CROSS], PLEs). We also assessed whether variability in global and region indices of brain structure (i.e., volume, cortical thickness, surface area) as well as behaviors proximal to PGS (e.g., cognition for EDU) indirectly linked PGS to PLEs using mediational models. Findings: EDU and CROSS PGS were associated with total and significantly distressing PLEs (all delta R2s=0.202-0.660%; ps<0.002). Significantly distressing PLEs were also associated with higher SCZ and PLEs PGS (both delta R2=0.120-0.171%; ps<0.02). Global brain volume metrics and cognition indirectly linked EDU PGS to PLEs (proportion mediated: 3.33-32.22%). Interpretation: Total and distressing PLEs were associated with genomic risk indices associated with broad spectrum psychopathology risk (i.e., EDU and CROSS PGS). Significantly distressing PLEs were associated with genomic risk for psychosis (i.e., SCZ, PLEs). Global brain volume metrics and PGS-proximal behaviors represent promising putative intermediary phenotypes that may contribute to genomic risk for psychopathology. Broadly, polygenic scores derived from genome-wide association studies of adult samples can generalize to indices of psychopathology risk among children and aid the identification of putative neural and behavioral intermediaries of risk.

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