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

• DOI: 10.1038/s41398-021-01526-0
• Publication Date: 2021-08-10T15:37:12Z
• Authors: Diego Quattrone; Ulrich Reininghaus; Alex L. Richards; Giada Tripoli; Laura Ferraro; Andrea Quattrone; Paolo Marino; Victoria Rodriguez; Edoardo Spinazzola; Charlotte Gayer-A...; Hannah E. Jongsma; Peter B. Jones; Caterina La Cascia; Daniele La Barbera; Ilaria Tarricone; Elena Bonora; Sarah Tosato; Antonio Lasalvia; Andrei Szöke; Celso Arango; Miquel Bernardo; Julio Bobes; Cristina Marta De...; 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; Marta Rapado Castro; Álvaro Andreu-Ber...; Gonzalo López; Mario Matteis; Emiliano González; Manuel Durán-Cutilla; Covadonga M. Díaz...; Pedro Cuadrado; José Juan Rodrígu...; Angel Carracedo; Javier Costas; Emilio Sánchez; Silvia Amoretti; Esther Lorente-Ro...; Paz Garcia-Portilla; Estela Jiménez-López; Nathalie Franke; Daniella van Dam; Fabian Termorshuizen; Nathalie Franke; Elsje van der Ven; Elles Messchaart; Marion Leboyer; Franck Schürhoff; Stéphane Jamain; Grégoire Baudin; Aziz Ferchiou; Baptiste Pignon; Jean-Romain Richard; Thomas Charpeaud; Anne-Marie Tronche; Flora Frijda; Giovanna Marrazzo; Lucia Sideli; Crocettarachele S...; Fabio Seminerio; Camila Marcelino ...; Rosana Shuhama; Mirella Ruggeri; Chiara Bonetto; Doriana Cristofalo; Domenico Berardi; Marco Seri; Giuseppe D’Andrea
• Keywords: [SDV]Life Sciences [q-bio]; 150; /45/43; PHENOTYPES; Neurosciences. Biological psychiatry. Neuropsychiatry; ILLNESS; Predictive markers; Article; /631/208/2489; DEFICIT SYNDROME; 03 medical and health sciences; 0302 clinical medicine; Risk Factors; /692/699/476/1799; /692/53/2423; Humans; Clinical genetics; VALIDITY; SCHEDULE; METAANALYSIS; Cannabis; UTILITY; Humans; Linear Models; Risk Factors; Cannabis; Psychotic Disorders; Schizophrenia; /45; Linear Models [MeSH] ; Schizophrenia/genetics [MeSH] ; Article ; Psychotic Disorders/diagnosis [MeSH] ; Cannabis [MeSH] ; Humans [MeSH] ; Psychotic Disorders/genetics [MeSH] ; Predictive markers ; Risk Factors [MeSH] ; Schizophrenia ; Clinical genetics; article; ASSOCIATION; BIFACTOR MODEL; 3. Good health; [SDV] Life Sciences [q-bio]; INTERRATER RELIABILITY; Psychotic Disorders; Linear Models; Schizophrenia; RC321-571

AbstractDiagnostic 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.