PROJECT SUMMARY/ABSTRACT This project is a collaboration between SUNY Downstate Health Sciences University (Brooklyn, NY), the University of Ibadan (Ibadan, Nigeria) and the University of the West Indies (St. Augustine, Trinidad and Tobago), which aims to examine differences in clinical presentation, health outcome, and treatment response among patients with psychotic disorders around the world, with a novel emphasis on the Global South. Building on extensive pilot work in the INTREPID I and INTREPID II studies, which laid the groundwork for the identification of untreated psychosis in these locales, we newly incorporate a matched cohort of patients receiving inpatient psychiatric care in these settings, and via collaboration with Stanley Center for Psychiatric Research, all participants will undergo state-of-the-art whole genome sequencing (WGS). We will benchmark the current generalizability of current polygenic scores to these populations, and estimate the prevalence of rare, deleterious genomic variations (e.g. copy number variants) of known neurodevelopmental relevance. The resultant clinical and genomic data will serve as the basis for comparative analyses of these populations with US-based and international studies of psychosis in diverse populations, namely VA Cooperative Studies Program #572 and the Million Veteran Program, and the NIMH-supported Populations Underrepresented in Mental illness Association Studies (PUMAS) and All of Us (AoU) studies, particularly with respect to illness presentation, treatment response, and comorbid physical health problems. Collaboration with and equitable participation in large-scale, international research consortia is a major focus of this project, which will also support two trainees at the University of Ibadan, and the establishment of expanded, diverse-ancestry study cohort, with detailed data on untreated psychosis prior and subsequent to the initiation of pharmacological treatment. These activities will also support expanded research infrastructure at University of Ibadan and University of the West Indies, establishing a solid basis for future collaborative research in these areas of utmost