Sex differences in the independent and combined effects of genomic and exposomic risks for schizophrenia on distressing psychotic experiences: insights from the ABCD study
Issued Date
2026-02-01
Resource Type
ISSN
14341816
eISSN
14351102
Scopus ID
2-s2.0-105026822109
Pubmed ID
41493491
Journal Title
Archives of Women S Mental Health
Volume
29
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Archives of Women S Mental Health Vol.29 No.1 (2026)
Suggested Citation
Prachason T., Arias-Magnasco A., Lin B.D., van Os J., Rutten B.P.F., Pries L.K., Guloksuz S. Sex differences in the independent and combined effects of genomic and exposomic risks for schizophrenia on distressing psychotic experiences: insights from the ABCD study. Archives of Women S Mental Health Vol.29 No.1 (2026). doi:10.1007/s00737-025-01644-4 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/114353
Title
Sex differences in the independent and combined effects of genomic and exposomic risks for schizophrenia on distressing psychotic experiences: insights from the ABCD study
Author's Affiliation
The University of British Columbia
King's College London
Yale School of Medicine
University Medical Center Utrecht
Maastricht Universitair Medisch Centrum+
University of British Columbia, Faculty of Medicine
Medizinische Fakultät
University of Northern British Columbia
Faculty of Medicine Ramathibodi Hospital, Mahidol University
King's College London
Yale School of Medicine
University Medical Center Utrecht
Maastricht Universitair Medisch Centrum+
University of British Columbia, Faculty of Medicine
Medizinische Fakultät
University of Northern British Columbia
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Corresponding Author(s)
Other Contributor(s)
Abstract
Purpose: To investigate sex-dependent effects of polygenic risk (PRS-SCZ) and exposome score (ES-SCZ) for schizophrenia, both independently and jointly, on distressing psychotic experiences (PEs) in early adolescents. Method: Baseline to 3-year follow-up data of the Adolescent Brain and Cognitive Development Study (ABCD) were used. PRS-SCZ and ES-SCZ were calculated to assess cumulative genetic and environmental (childhood adversity, cannabis use, hearing impairment, and winter births) risk for schizophrenia, respectively. The primary outcome was past-month distressing PEs at the 3-year follow-up. Secondary outcomes included distressing PEs across four yearly assessments: lifetime (≥ 1 wave), repeated (≥ 2 or ≥ 3 waves), and persisting (≥ 4 waves). Sex-stratified multilevel logistic regression models were used to test the independent and joint associations of binary modes (> 75th percentile) of PRS-SCZ (PRS-SCZ<inf>75</inf>) and ES-SCZ (ES-SCZ<inf>75</inf>) on the outcomes. As sensitivity analysis, the sex-stratified analyses were repeated on a randomly selected unrelated sample, and the coefficients of males and females were compared. Results: PRS-SCZ<inf>75</inf> was not associated with past-month distressing PEs in either sex but significantly associated with lifetime and repeated (≥ 2 waves) distressing PEs only in females. In both sexes, ES-SCZ<inf>75</inf> was significantly associated with all PE outcomes but did not additively interact with PRS-SCZ<inf>75</inf> in predicting them. Sensitivity analysis confirmed the findings and revealed a significant sex difference in the association between PRS-SCZ<inf>75</inf> and lifetime distressing PEs. Conclusion: The influence of genomic risk for schizophrenia on distressing PEs might be sex-dependent, whereas that of the exposomic risk was universal in early adolescence. Further studies in larger samples are needed.