Neuroimmunological Mechanisms Linking Childhood Malaria Exposure and Adult Psychosis Risk in Nigeria: A Multi-Site Case-Control Study

Childhood malaria, highly endemic in sub-Saharan Africa, has been proposed as a neuroinflammatory risk factor for psychotic disorders in adulthood, yet empirical evidence linking neuroimmunological mechanisms to psychosis risk remains limited in West Africa. This multi-site case-control study investigates neuroimmunological pathways through which childhood malaria exposure increases psychosis risk in adult Nigerians. Cases with first-episode schizophrenia spectrum psychosis (N=120) and matched healthy controls (N=120) will be recruited from psychiatric hospitals in Ibadan, Kano, and Enugu, representing three geopolitical zones. Retrospective childhood malaria exposure will be documented through structured interviews and maternal recall. Fasting serum samples will be analyzed for inflammatory biomarkers including IL-6, TNF-alpha, CRP, and kynurenic acid. Cerebrospinal fluid (CSF) cytokine profiles will be analyzed in a sub-sample of 40 willing participants. Logistic regression and mediation analyses will examine whether neuroimmunological markers mediate the malaria-psychosis association. This study represents an original contribution to global psychiatric epidemiology by proposing a biologically plausible Africa-specific pathway to psychosis. Findings will have implications for malaria prevention as a mental health intervention and for inflammatory biomarker research in low-income settings. Keywords: malaria, psychosis, neuroimmunology, Nigeria, inflammatory biomarkers