Psychotic disorders such as schizophrenia, bipolar disorder, or schizoaffective disorder affect approximately 3% of the population. The pathophysiology of these highly debilitating illnesses is still poorly understood and current treatments fail to adequately alleviate symptoms in at least 30% of patients. There is growing evidence for a role of autoimmunity in psychiatric disorders. In the present study, we aimed to explore the IgG repertoire in a cohort of 473 Australian patients diagnosed with psychotic disorders to reveal potential autoantibody repertoires and their relationship to disease phenotypes and functional outcomes.
In an initial screening experiment, we used an in-house planar protein array containing 42000 protein fragments representing approximately 18000 human proteins on eight patient pools representative of diagnostic and phenotypic groups within SHIP. Based on the results from these arrays, previous findings, and literature mining, we then designed a 384-plex suspension bead array (SBA) for analysis of all individuals in the cohort.
Using the planar protein arrays, we found 181 protein fragments that were defined as reactive in one or several of the sample pools. Out of the 181, 20 fragments were found reactive in at least two of the sample pools. Follow-up of these findings in the entire SHIP cohort showed that reactivity profiles are highly individual, but also revealed novel autoantibody targets in psychotic disorders that are associated with specific phenotypic characteristics. The current study represents that largest investigation of autoimmunity profiles in psychosis undertaken to date. Findings may be of relevance for stratification of diagnosis and treatment in psychiatry.