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

BJPsych Open. 2025 Sep 8;11(5):e197. doi: 10.1192/bjo.2025.10825.

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.

PMID:40916608 | DOI:10.1192/bjo.2025.10825