The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study

Diego Quattrone, Ulrich Reininghaus, Alex L. Richards, Giada Tripoli, Laura Ferraro, Andrea Quattrone, Paolo Marino, Victoria Rodriguez, Edoardo Spinazzola, Charlotte Gayer-Anderson, Hannah E. Jongsma, Peter B. Jones, Caterina La Cascia, Daniele La Barbera, Ilaria Tarricone, Elena Bonora, Sarah Tosato, Antonio Lasalvia, Andrei Szöke, Celso ArangoMiquel Bernardo, Julio Bobes, Cristina Marta Del Ben, Paulo Rossi Menezes, Pierre Michel Llorca, Jose Luis Santos, Julio Sanjuán, Manuel Arrojo, Andrea Tortelli, Eva Velthorst, Steven Berendsen, Lieuwe de Haan, Bart P.F. Rutten, Michael T. Lynskey, Tom P. Freeman, James B. Kirkbride, Pak C. Sham, Michael C. O’Donovan, Alastair G. Cardno, Evangelos Vassos, Jim van Os, Craig Morgan, Robin M. Murray, Cathryn M. Lewis, Marta Di Forti, Kathryn Hubbard, Stephanie Beards, Simona A. Stilo, Mara Parellada, David Fraguas

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number423
JournalTranslational Psychiatry
Volume11
Issue number1
DOIs
Publication statusPublished - 10 Aug 2021

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

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