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, A. Richards, Giada Tripoli, L. Ferraro, A. Quattrone, Paolo Marino, Victoria Rodriguez, Edoardo Spinazzola, Charlotte Gayer‐Anderson, Hannah E. Jongsma, Peter B. Jones, Caterina la Cascia, Daniele la Barbera, Ilaria Tarricone, E. Bonora, Sarah Tosato, Antonio Lasalvia, Andreı̈ Szöke, Celso Arango, Miquel Bernardo, Julio Bobes, C. M. del Ben, P. Menezes, P. Llorca, J. Santos, Julio Sanjuán, M. Arrojo, Andrea Tortelli, Eva Velthorst, S. Berendsen, Lieuwe de Haan, Bart P. F. Rutten, Michael T. Lynskey, Tom P. Freeman, James B. Kirkbride, Pak C. Sham, M. O’Donovan, Alastair G. Cardno, Evangelos Vassos, Jim van Os, C. Morgan, Robin Murray, C. Lewis, Marta Di Forti, Kathryn Stephanie Simona A. Mara David Marta Rapado Álvaro Hubbard Beards Stilo Parellada Fraguas Castro Andr, Kathryn Hubbard, S. Beards, Simona A. Stilo, M. Parellada, D. Fraguas, M. Castro, Á. Andreu-Bernabeu, G. López, M. Matteis, Emiliano González, Manuel Durán-Cutilla, C. Díaz-Caneja, P. Cuadrado, José Juan Rodríguez Solano, Á. Carracedo, J. Costas, E. Sánchez, S. Amoretti, E. Lorente‐Rovira, P. García-Portilla, E. Jiménez-López, Nathalie Franke, Daniëlla S. van Dam, F. Termorshuizen, Els van der Ven, Elles Messchaart, M. Leboyer, F. Schürhoff, S. Jamain, G. Baudin, A. Ferchiou, B. Pignon, J. Richard, T. Charpeaud, A. Tronche, Flora Frijda, G. Marrazzo, Lucia Sideli, C. Sartorio, F. Seminerio, C. Loureiro, Rosana Shuhama, Mirella Ruggeri, C. Bonetto, D. Cristofalo, Domenico Berardi, M. Seri, Giacomo D’andrea
Translational Psychiatry August 10, 2021 DOI: 10.1038/s41398-021-01526-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 1,596 |
| Population | First-episode psychosis patients and controls from the EU-GEI study |
| Topics | Cannabis |
| Key findings | Schizophrenia polygenic risk score was associated with negative and positive symptom dimensions in first-episode psychosis patients and with all psychotic experience dimensions in controls; daily and current cannabis use were associated with positive dimensions beyond genetic risk. |
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.