Schizophrenia as autoimmune disease: Involvement of Anti-NCAM antibodies

Understanding the etiopathogenesis of schizophrenia has always been an unsolved puzzle for modern medicine. This seems to be due to both disease complexity and lack of sufficient knowledge regarding the biological and non-biological anomalies that exhibit schizophrenia subjects. However, dysregulated immunity is a commonly identified feature in affected individuals. Thus, recently, a hallmark study showed causality relationship between anti-NCAM antibodies and schizophrenia-related behaviors in mice. NCAM plays crucial role in neurodevelopment during early life and neuroplasticity against different stressors during adulthood, and its dysfunction in schizophrenia is increasingly proven. The present review provides the main evidence that support the contribution of autoimmunity and NCAM abnormalities in the development of schizophrenia. Furthermore, it introduces five hypotheses that may explain the mechanism by which anti-NCAM antibodies are produced in the context of schizophrenia: (i) molecular mimicry, (ii) gut dysbiosis, (iii) viral infection, (iv) exposure to environmental pollutants, (v) and NCAM production anomalies.