Abstract
Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03–0.33) and positive (B = 0.19; 95%CI 0.03–0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11–0.52) and in controls (B = 0.26; 95%CI 0.06–0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.
Highlights
The nosology of psychotic disorders relies on operationalised criteria
We identified, in the EU-GEI sample, finest ancestry clusters of individuals through iterative pruning of principal component analysis of single nucleotide polymorphisms (SNPs), and we tested for each cluster whether schizophrenia polygenic risk score (SZ-polygenic risk score (PRS)) discriminated cases from controls
SZ-PRS was associated with a higher score for both the positive (B = 0.19, 95% CI 0.03–0.35; p = 0.019) and negative (B = 0.18, 95% CI 0.03–0.33; p = 0.021) symptom dimensions
Summary
The nosology of psychotic disorders relies on operationalised criteria These criteria are based on the type and course of symptomatology and neglect the currently known risk factors for psychosis [1]. The clear-cut division of non-affective and affective psychosis has been unsatisfactory both in clinical practice [3] and genetic epidemiology; the latter has consistently shown that the diagnostic categories of schizophrenia and bipolar disorder share much of their biological roots [4]. Due to the traditional focus on diagnostic categories, questions as to whether there is a continuity of risk factors across the transdiagnostic continuum of psychosis have been marginally investigated. An approach based on continuous, transdiagnostic symptom dimensions across the psychosis spectrum might be more appropriate to address this question [5]
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