Associations between psychotic experience dimensions and polygenic liability to schizophrenia in a longitudinal birth cohort

Cardno, Alastair G., Heuvelman, Hein, Legge, Sophie E., Walters, James T. R. ORCID: https://orcid.org/0000-0002-6980-4053, Zammit, Stanley ORCID: https://orcid.org/0000-0002-2647-9211 and Jones, Hannah J. 2025. Associations between psychotic experience dimensions and polygenic liability to schizophrenia in a longitudinal birth cohort. BJPsych Open 11 (5) , e197. 10.1192/bjo.2025.10825

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Abstract

Background: Some psychotic experiences in the general population show associations with higher schizophrenia and other mental health-related polygenic risk scores (PRSs), but studies have not usually included interviewer-rated positive, negative and disorganised dimensions, which show distinct associations in clinical samples. Aims: To investigate associations of these psychotic experience dimensions primarily with schizophrenia PRS and, secondarily, with other relevant PRSs. Method: Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort participants were assessed for positive, negative and disorganised psychotic experience dimensions from interviews, and for self-rated negative symptoms, at 24 years of age. Regression models were used to investigate associations between psychotic experience dimensions and schizophrenia and other PRSs (2500+ participants for each analysis). Results: Against expectation, none of the positive, negative or disorganised dimensions was associated with schizophrenia PRS. In secondary analysis, self-rated negative symptoms were associated with higher depression (β = 0.10 [95% CI 0.06–0.15]), anxiety (β = 0.09 [95% CI 0.04–0.13]), neuroticism (β = 0.11 [95% CI 0.06–0.15]) and autism (β = 0.09 [95% CI 0.05–0.13]) PRSs (all P < 0.001); and first-rank delusions were nominally associated with higher schizophrenia PRS (odds ratio 7.35 [95% CI 2.10–25.77], P = 0.002), although these experiences/symptoms were rare. Conclusions: Positive, negative and disorganised psychotic experiences are probably not strongly associated with polygenic liability to schizophrenia in this general population cohort of young adults. Self-rated negative symptoms may indicate social withdrawal/low motivation due to higher polygenic liability to affective disorders or autism, and first-rank delusions may indicate higher polygenic liability to schizophrenia, but these findings require independent confirmation.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Schools > Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Cambridge University Press
ISSN:	2056-4724
Date of First Compliant Deposit:	17 September 2025
Date of Acceptance:	21 July 2025
Last Modified:	17 Sep 2025 07:45
URI:	https://orca.cardiff.ac.uk/id/eprint/181136

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