Evaluating the Exposome Score for Schizophrenia in a Transdiagnostic Psychosis Cohort: Associations With Psychosis Risk, Symptom Severity, and Personality Traits

Abstract Background Investigations of causal pathways for psychosis can be guided by the identification of environmental risk factors. A recently developed composite risk tool, the exposome score for schizophrenia (ES-SCZ), which controls for intercorrelations between risk factors, has shown fair to good performance. We tested the transdiagnostic psychosis classifier performance of the ES-SCZ with the Bipolar-Schizophrenia Network for Intermedial Phenotypes data and examined its relationship with clinical-level outcomes. Study Design We computed the case-control classifier performance for the ES-SCZ from cross-sectional data on 1055 volunteers with psychotic diagnoses (schizophrenia, schizoaffective, bipolar psychosis) and 510 controls. Multivariate regression models were used to control for the correlations between outcomes and to correct for the effects of age, sex, and family socioeconomic status across outcomes. We estimated association for the ES-SCZ with psychosis and mood symptom severity, the 5-factor model of personality, and function across biologically defined biotypes, traditional diagnostic categories, and controls. Study Results ES-SCZ classifier performance for psychosis was fair to good. ES-SCZ associations with personality factor scores were qualitatively similar between psychosis groups and controls with decreased conscientiousness and agreeableness and increased neuroticism. The patterns of associations between ES-SCZ and symptoms differed across biotypes and diagnoses. Biotype 3 and bipolar disorder had consistent within-group associations where greater exposome score predicted more severe symptoms and worse function. Conclusions ES-SCZ performance was consistent with previous reports in this transdiagnostic psychosis sample (adjusted odds ratio: 3.331 [2.834, 3.915], P < .001; area under the curve: 0.762 [0.735, 0.789]). Individual differences in ES-SCZ magnitude may be useful for investigating causal pathways between developmentally relevant exposures and symptomatic expression of psychosis.