Schizophrenia polygenic risk score and cannabis use modify psychosis expression in first episode psychosis patients and population controls
| Autor: | Peter B. Jones, Robin M. Murray, Jose Luis Santos, Di Forti M, Ilaria Tarricone, Tom P. Freeman, Bart P. F. Rutten, Sarah Tosato, Giada Tripoli, Craig Morgan, Elena Bonora, James B. Kirkbride, Cathryn M. Lewis, Celso Arango, Pak C. Sham, Charlotte Gayer-Anderson, Julio Bobes, Hannah E. Jongsma, Paolo Marino, Ulrich Reininghaus, Rodriguez, Alastair G. Cardno, van os J, Eva Velthorst, Evangelos Vassos, Michael T. Lynskey, La Barbera D, Miguel Bernardo, Paulo Rossi Menezes, Andrea Tortelli, Laura Ferraro, de Haan L, Pierre-Michel Llorca, Alexander Richards, Del Ben Cm, Andrei Szöke, Antonio Lasalvia, Diego Quattrone, La Cascia C, Julio Sanjuán, M O'Donovan |
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| Rok vydání: | 2019 |
| Předmět: |
education.field_of_study
Psychosis business.industry Population Cannabis use medicine.disease 030227 psychiatry 03 medical and health sciences 0302 clinical medicine Environmental risk Schizophrenia First episode psychosis Medicine Polygenic risk score In patient business education 030217 neurology & neurosurgery Clinical psychology |
| Popis: | BackgroundDiagnostic categories within the psychosis spectrum are widely used in clinical practice, however psychosis may occur on a continuum. Therefore, we explored whether the continuous distribution of psychotic symptoms across categories is a function of genetic as well as environmental risk factors, such as polygenic risk scores (PRSs) and cannabis use.MethodsAs part of the EU-GEI study, we genotyped first episode psychosis patients (FEP) and population controls, for whom transdiagnostic dimensions of psychotic symptoms or experiences were generated using item response bi-factor modelling. Linear regression was used, separately in patients and controls, to test the associations between these dimensions and schizophrenia (SZ) PRSs, as well as the combined effect of SZ-PRS and cannabis use on the positive symptom/experience dimensions.ResultsSZ-PRS was associated with negative (B=0.18; 95%CI 0.03 to 0.34) and positive (B=0.19; 95%CI 0.03 to 0.36) symptom dimensions in 617 FEP, and with all the psychotic experience dimensions in 979 controls. The putative effect of SZ-PRS on either symptom or experience dimensions was of a small magnitude. Cannabis use was additionally associated with the positive dimensions both in FEP (B=0.31; 95%CI 0.11 to 0.52) and in controls (B=0.26; 95%CI 0.06 to 0.46), independently from SZ-PRS.ConclusionsWe report two validators to the latent dimensional structure of psychosis. SZ risk variants and cannabis use independently map onto specific dimensions, contributing to variation across the psychosis continuum. Findings support the hypothesis that psychotic experiences have similar biological substrates as clinical disorders. |
| Databáze: | OpenAIRE |
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