Psychotic-like experiences and polygenic liability in the ABCD Study®
Abstract 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 %ΔR2s=0.202-0.660%; ps<0.002). Significantly distressing PLEs were also associated with higher SCZ and PLEs PGS (both %ΔR2=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.Funding National Institute of Health.
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Preprint| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
bioRxiv.org - (2021) vom: 15. Dez. Zur Gesamtaufnahme - year:2021 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Karcher, Nicole R. [VerfasserIn] |
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| doi: |
10.1101/2020.07.14.20153551 |
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| PPN (Katalog-ID): |
XBI018361307 |
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| 520 | |a Abstract 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 %ΔR2s=0.202-0.660%; ps<0.002). Significantly distressing PLEs were also associated with higher SCZ and PLEs PGS (both %ΔR2=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.Funding National Institute of Health | ||
| 700 | 1 | |a Paul, Sarah E. |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Emma C. |e verfasserin |4 aut | |
| 700 | 1 | |a Hatoum, Alexander S. |e verfasserin |4 aut | |
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| 700 | 1 | |a Thompson, Wesley K. |e verfasserin |4 aut | |
| 700 | 1 | |a Barch, Deanna M. |e verfasserin |4 aut | |
| 700 | 1 | |a Bogdan, Ryan |e verfasserin |4 aut | |
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