Synaptic and Neuronal Autoantibodies in Psychosis (SNAP): clinical significance, neuroimaging correlates, infective/immune risk factors. (360G-Wellcome-105758_Z_14_Z)

Anti-neuronal surface autoantibodies (ANSAs) such as antibodies to the NMDA receptor can cause encephalopathies that feature psychosis alongside neurological symptoms. ANSAs may also cause a purely psychiatric phenotype that is a phenocopy of first episode psychosis (FEP). Moreover, ANSA prevalence in FEP cohorts is between 5-10%, suggesting they might underlie a significant proportion of FEP. These findings have however often been derived from relatively small or heterogenous samples, and the c linical significance of ANSA-positivity in psychosis remains uncertain. I will address this by assessing the prevalence of multiple ANSAs in large samples of FEP patients and individuals at ultra-high risk (UHR) for psychosis. I will examine how ANSA status relates to i) presenting symptomatology; ii) the main clinical outcomes in these groups: onset of psychosis in UHR subjects and response to treatment in FEP; iii) neuroimaging measures of brain structure and chemistry. In order to investiga te a neurodevelopmental model of autoimmunity in psychosis, markers of previous infection with neurotropic viral/other organisms will be measured, along with measures of blood-brain barrier dysfunction. Finally, I will assess the utility of using these autoimmune markers as a means of stratifying patients in the early phase of psychosis according to future clinical outcomes.