Schizophrenia polygenic risk score and cannabis use modify psychosis expression in first episode psychosis patients and population controls

Year: 2019

Type: preprint

Abstract: Background Diagnostic 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. Methods As 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. Results SZ-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. Conclusions We 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.

Source: medRxiv

DOI: 10.1101/19013284

Institutions: King's College London, South London and Maudsley NHS Foundation Trust, Heidelberg University, National Institute for Health and Care Research, Central Institute of Mental Health, Medizinische Fakultät Mannheim, NIHR Maudsley Biomedical Research Centre, Maastricht University Medical Centre, Maastricht University, Cardiff University, University of Palermo, University College London, University of Cambridge, Cambridgeshire and Peterborough NHS Foundation Trust, University of Bologna, University of Verona, Inserm, Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Salud Mental, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Universidad de Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias, Universidade de São Paulo, Université Clermont Auvergne, Hospital Virgen de la Luz, Universitat de València, Amsterdam UMC Location University of Amsterdam, University of Amsterdam, Icahn School of Medicine at Mount Sinai, University of Bath, University of Hong Kong, University of Leeds, Utrecht University, University Medical Center Utrecht

Language: English

Topic: Schizophrenia research and treatment

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: South London and Maudsley NHS Foundation Trust, King's College Hospital NHS Foundation Trust, National Institute for Health and Care Research, Department of Health and Social Care, King's College London, Fundação de Amparo à Pesquisa do Estado de São Paulo, Medical Research Council

Awards: G1332902014, G2322212988, Biological mechanisms underlying the onset and outcome of cannabis-associated psychosis.

OpenAlex ID: W2990061840