BACKGROUND: Cardiometabolic dysfunction is common in young people with psychosis. Recently, the Psychosis Metabolic Risk Calculator (PsyMetRiC) was developed and externally validated in the UK, predicting up-to six-year risk of metabolic syndrome (MetS) from routinely collected data. The full-model includes age, sex, ethnicity, body-mass index, smoking status, prescription of metabolically-active antipsychotic medication, high-density lipoprotein, and triglyceride concentrations; the partial-model excludes biochemical predictors. METHODS: To move toward a future internationally-useful tool, we externally validated PsyMetRiC in two independent European samples. We used data from the PsyMetab (Lausanne, Switzerland) and PAFIP (Cantabria, Spain) cohorts, including participants aged 16-35y without MetS at baseline who had 1-6y follow-up. Predictive performance was assessed primarily via discrimination (C-statistic), calibration (calibration plots), and decision curve analysis. Site-specific recalibration was considered. FINDINGS: We included 1024 participants (PsyMetab n=558, male=62%, outcome prevalence=19%, mean follow-up=2.48y; PAFIP n=466, male=65%, outcome prevalence=14%, mean follow-up=2.59y). Discrimination was better in the full- compared with partial-model (PsyMetab=full-model C=0.73, 95% C.I., 0.68-0.79, partial-model C=0.68, 95% C.I., 0.62-0.74; PAFIP=full-model C=0.72, 95% C.I., 0.66-0.78; partial-model C=0.66, 95% C.I., 0.60-0.71). As expected, calibration plots revealed varying degrees of miscalibration, which recovered following site-specific recalibration. PsyMetRiC showed net benefit in both new cohorts, more so after recalibration. INTERPRETATION: The study provides evidence of PsyMetRiC's generalizability in Western Europe, although further local and international validation studies are required. In future, PsyMetRiC could help clinicians internationally to identify young people with psychosis who are at higher cardiometabolic risk, so interventions can be directed effectively to reduce long-term morbidity and mortality. FUNDING: NIHR Cambridge Biomedical Research Centre (BRC-1215-20014); The Wellcome Trust (201486/Z/16/Z); Swiss National Research Foundation (320030-120686, 324730- 144064, and 320030-173211); The Carlos III Health Institute (CM20/00015, FIS00/3095, PI020499, PI050427, and PI060507); IDIVAL (INT/A21/10 and INT/A20/04); The Andalusian Regional Government (A1-0055-2020 and A1-0005-2021); SENY Fundacion Research (2005-0308007); Fundacion Marques de Valdecilla (A/02/07, API07/011); Ministry of Economy and Competitiveness and the European Fund for Regional Development (SAF2016-76046-R and SAF2013-46292-R).For the Spanish and French translation of the abstract see Supplementary Materials section.

Cambridgeshire and Peterborough NHS Foundation Trust Cambridge England United Kingdom

Center for Research and Innovation in Clinical Pharmaceutical Sciences Lausanne University Hospital and University of Lausanne Switzerland

Centre for Academic Mental Health Population Health Sciences Bristol Medical School University of Bristol Bristol England United Kingdom

Department of Kinanthropology Charles University Prague Czech Republic

Department of Psychiatry Marques de Valdecilla University Hospital Institute of Biomedicine Marqués de Valdecilla Universidad de Cantabria Santander Spain

Department of Psychiatry University of Cambridge Cambridge England United Kingdom

Early Intervention Service Birmingham Womens and Childrens NHS Foundation Trust

Institute for Mental Health and Centre for Human Brain Health University of Birmingham Birmingham England United Kingdom

Institute of Pharmaceutical Sciences of Western Switzerland University of Geneva University of Lausanne Geneva Switzerland

Les Toises Psychiatry and Psychotherapy Centre Lausanne Switzerland

MRC Integrative Epidemiology Unit Population Health Sciences Bristol Medical School University of Bristol Bristol England United Kingdom

MRC London Institute of Medical Sciences Institute of Clinical Sciences Imperial College Hammersmith Campus London England United Kingdom

School of Pharmaceutical Sciences University of Geneva Geneva Switzerland

Service of Child and Adolescent Psychiatry Department of Psychiatry Lausanne University Hospital University of Lausanne Prilly Switzerland

Service of General Psychiatry Department of Psychiatry Lausanne University Hospital University of Lausanne Prilly Switzerland

Unit of Pharmacogenetics and Clinical Psychopharmacology Centre for Psychiatric Neuroscience Department of Psychiatry Lausanne University Hospital and University of Lausanne Prilly Switzerland

Virgen del Rocío University Hospital Network Centre for Biomedical Research in Mental Health Spain

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