Epidemiological studies have borne out the association between psychotic disorders and autoimmune disease, while the immunogenetic contribution in psychosis is largely dominated by the major histocompatibility complex genetic diversity. On the other hand, demyelinating diseases, like multiple sclerosis, are characterized by a large array of invading immune cells that degrade the myelin sheath, the myelin producing oligodendrocytes and the nerve itself. Schizophrenia has been proposed to be a dysconnectivity syndrome, and numerous lines of evidence implicate myelin and oligodendrocyte func- tion as critical processes that could affect neuronal connectivity. Disruption in myelination and dysmyelination-induced de- lays in information processing can produce phenocopies of psychosis similar to schizophrenia. Rethinking the clinical and pathophysiological similarities between de- or dysmyelination diseases and psychosis, we may consider that the dyscon- nectivity syndrome of psychosis represents the phenomenological and behavioral result of a multiple-faces dysmyelination disorder, which is based on a lifelong immunogenetic dysregulation process.


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Orestis Giotakos