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

Quattrone, Diego, Reininghaus, Ulrich, Richards, Alex L., Tripoli, Giada, Ferraro, Laura, Quattrone, Andrea, Marino, Paolo, Rodriguez, Victoria, Spinazzola, Edoardo, Gayer-Anderson, Charlotte, Jongsma, Hannah E., Jones, Peter B., La Cascia, Caterina, La Barbera, Daniele, Tarricone, Ilaria, Bonora, Elena, Tosato, Sarah, Lasalvia, Antonio, Szöke, Andrei, Arango, Celso, Bernardo, Miquel, Bobes, Julio, Del Ben, Cristina Marta, Menezes, Paulo Rossi, Llorca, Pierre-Michel, Santos, Jose Luis, Sanjuán, Julio, Arrojo, Manuel, Tortelli, Andrea, Velthorst, Eva, Berendsen, Steven, de Haan, Lieuwe, Rutten, Bart P. F., Lynskey, Michael T., Freeman, Tom P., Kirkbride, James B., Sham, Pak C., O'Donovan, Michael C. ORCID: https://orcid.org/0000-0001-7073-2379, Cardno, Alastair G., Vassos, Evangelos, van Os, Jim, Morgan, Craig, Murray, Robin M., Lewis, Cathryn M., Di Forti, Marta, Hubbard, Kathryn, Beards, Stephanie, Stilo, Simona A., Parellada, Mara, Fraguas, David, Castro, Marta Rapado, Andreu-Bernabeu, Álvaro, López, Gonzalo, Matteis, Mario, González, Emiliano, Durán-Cutilla, Manuel, Díaz-Caneja, Covadonga M., Cuadrado, Pedro, Rodríguez Solano, José Juan, Carracedo, Angel, Costas, Javier, Sánchez, Emilio, Amoretti, Silvia, Lorente-Rovira, Esther, Garcia-Portilla, Paz, Jiménez-López, Estela, Franke, Nathalie, van Dam, Daniella, Termorshuizen, Fabian, Franke, Nathalie, van der Ven, Elsje, Messchaart, Elles, Leboyer, Marion, Schu?rhoff, Franck, Jamain, Stéphane, Baudin, Grégoire, Ferchiou, Aziz, Pignon, Baptiste, Richard, Jean-Romain, Charpeaud, Thomas, Tronche, Anne-Marie, Frijda, Flora, Marrazzo, Giovanna, Sideli, Lucia, Sartorio, Crocettarachele, Seminerio, Fabio, Loureiro, Camila Marcelino, Shuhama, Rosana, Ruggeri, Mirella, Bonetto, Chiara, Cristofalo, Doriana, Berardi, Domenico, Seri, Marco and D?Andrea, Giuseppe 2021. 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. Translational Psychiatry 11 (1) , 423. 10.1038/s41398-021-01526-0

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	2158-3188
Date of First Compliant Deposit:	25 August 2021
Date of Acceptance:	30 June 2021
Last Modified:	11 May 2023 05:53
URI:	https://orca.cardiff.ac.uk/id/eprint/143652

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