ABSTRACT Early treatment of schizophrenia (SZ) is linked to better outcomes, and accurately identifying individuals before illness onset holds promise for prevention. This is especially relevant in sub-Saharan Africa, where financial and health care resources for managing psychotic disorders are extremely limited. Our current proposal aims to introduce cutting-edge psychiatric neuroimaging research to Kenya, and involves multi-modal imaging in adolescents and young adults at clinical high risk (CHR) of developing SZ and other psychotic disorders. Assessing clinical risk symptoms in youth has significantly advanced the possibility of indicated prevention of a full-blown psychotic disorder. Through our previous work, we pioneered prodromal behavioral assessments in Africa, and remain the only group in the continent actively investigating this risk population. Our existing studies in Kenya have suggested some behavioral phenotypes may help better identify those individuals who would transition to SZ. Studies in developing countries have also identified potential neuroimaging predictors of psychosis progression, but such studies have not been previously conducted in African populations. In the United States, our group has had longstanding experience with image analyses involving brain structure and connectivity in SZ and other groups. In the current study, we will use our Washington University Human Connectome Project processing pipeline on imaging data to provide a unique opportunity to characterize the pathological substrates of early psychosis in a racially homogenous African cohort. Building on our existing collaborations, our proposal pioneers a new psychiatric research modality in Kenya and builds capacity for future neuroimaging studies in the country (Aim 1). We will study brain morphometry, as well as structural and functional connectivity in CHR and healthy control groups (Aim 2). Additionally, we will investigate the longitudinal stability of brain findings and potential predictors of clinical change (Aim 3). This would expand our understanding of brain neurobiology in psychotic disorders, paving the path for translation of this knowledge to indicated prevention. Our proposal pioneers a new psychiatric research modality in Kenya, and builds capacity for future neuroimaging studies in the country.

PROJECT NARRATIVE Our study builds on our previous behavioral research in Kenya studying risk factors for psychosis progression in high-risk youth. The current study investigates brain structure and connectivity in psychosis-risk adolescents and young adults, and their role in predicting illness progression. Results from our proposal would also build the neuroimaging research infrastructure and expertise in Kenya, which will enable the identification of brain abnormalities in Kenyan schizophrenia and related populations.