TY - JOUR
T1 - Psychotic-like Experiences and Polygenic Liability in the Adolescent Brain Cognitive Development Study
AU - Karcher, Nicole R.
AU - Paul, Sarah E.
AU - Johnson, Emma C.
AU - Hatoum, Alexander S.
AU - Baranger, David A.A.
AU - Agrawal, Arpana
AU - Thompson, Wesley K.
AU - Barch, Deanna M.
AU - Bogdan, Ryan
N1 - Publisher Copyright:
© 2021 Society of Biological Psychiatry
PY - 2022/1
Y1 - 2022/1
N2 - Background: Childhood psychotic-like experiences (PLEs) often precede the development of later severe psychopathology. This study examined whether childhood PLEs are associated with several psychopathology-related polygenic scores (PGSs) and additionally examined possible neural and behavioral mechanisms. Methods: Adolescent Brain Cognitive Development Study baseline data from children with European ancestry (n = 4650, ages 9–10 years, 46.8% female) were used to estimate associations between PLEs (i.e., both total and presence of significantly distressing) and PGSs for psychopathology (i.e., schizophrenia, psychiatric cross-disorder risk, PLEs) and related phenotypes (i.e., educational attainment [EDU], birth weight, inflammation). We also assessed whether variability in brain structure indices (i.e., volume, cortical thickness, surface area) and behaviors proximal to PGSs (e.g., cognition for EDU) indirectly linked PGSs to PLEs using mediational models. Results: Total and significantly distressing PLEs were associated with EDU and cross-disorder PGSs (all %ΔR2s = 0.202%–0.660%; false discovery rate–corrected ps <.006). Significantly distressing PLEs were also associated with higher schizophrenia and PLE PGSs (both %ΔR2 = 0.120%–0.216%; false discovery rate–corrected ps <.03). There was evidence that global brain volume metrics and cognitive performance indirectly linked EDU PGS to PLEs (estimated proportion mediated = 3.33%–32.22%). Conclusions: Total and significantly distressing PLEs were associated with genomic risk indices of broad-spectrum psychopathology risk (i.e., EDU and cross-disorder PGSs). Significantly distressing PLEs were also associated with genomic risk for psychosis (i.e., schizophrenia, PLEs). Global brain volume metrics and PGS-proximal behaviors represent promising putative intermediary phenotypes that may indirectly link genomic risk to psychopathology. Broadly, polygenic scores derived from genome-wide association studies of adult samples generalize to indices of psychopathology risk among children.
AB - Background: Childhood psychotic-like experiences (PLEs) often precede the development of later severe psychopathology. This study examined whether childhood PLEs are associated with several psychopathology-related polygenic scores (PGSs) and additionally examined possible neural and behavioral mechanisms. Methods: Adolescent Brain Cognitive Development Study baseline data from children with European ancestry (n = 4650, ages 9–10 years, 46.8% female) were used to estimate associations between PLEs (i.e., both total and presence of significantly distressing) and PGSs for psychopathology (i.e., schizophrenia, psychiatric cross-disorder risk, PLEs) and related phenotypes (i.e., educational attainment [EDU], birth weight, inflammation). We also assessed whether variability in brain structure indices (i.e., volume, cortical thickness, surface area) and behaviors proximal to PGSs (e.g., cognition for EDU) indirectly linked PGSs to PLEs using mediational models. Results: Total and significantly distressing PLEs were associated with EDU and cross-disorder PGSs (all %ΔR2s = 0.202%–0.660%; false discovery rate–corrected ps <.006). Significantly distressing PLEs were also associated with higher schizophrenia and PLE PGSs (both %ΔR2 = 0.120%–0.216%; false discovery rate–corrected ps <.03). There was evidence that global brain volume metrics and cognitive performance indirectly linked EDU PGS to PLEs (estimated proportion mediated = 3.33%–32.22%). Conclusions: Total and significantly distressing PLEs were associated with genomic risk indices of broad-spectrum psychopathology risk (i.e., EDU and cross-disorder PGSs). Significantly distressing PLEs were also associated with genomic risk for psychosis (i.e., schizophrenia, PLEs). Global brain volume metrics and PGS-proximal behaviors represent promising putative intermediary phenotypes that may indirectly link genomic risk to psychopathology. Broadly, polygenic scores derived from genome-wide association studies of adult samples generalize to indices of psychopathology risk among children.
KW - Educational attainment
KW - MRI
KW - Polygenic
KW - Psychopathology
KW - Psychotic-like experiences
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=85122175297&partnerID=8YFLogxK
U2 - 10.1016/j.bpsc.2021.06.012
DO - 10.1016/j.bpsc.2021.06.012
M3 - Article
C2 - 34271214
AN - SCOPUS:85122175297
SN - 2451-9022
VL - 7
SP - 45
EP - 55
JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
IS - 1
ER -