Background and Aims

The autoimmune hypothesis of schizophrenia has become the most relevant in the last decade. There is a theory that schizophrenia is an autoimmune disease caused by the autoantibodies that affect neural receptors of the limbic system (anti-neuronal antibodies, autoantibodies against the brain vascular endothelium, abzymes with RNase and protease activities).

Methods

We analyzed a possible role of autoimmune processes in the pathogenesis of schizophrenia and the dynamics of views on this issue.

Results

An increase in the levels of proinflammatory cytokines and chemokines, as well as a decrease in the levels of anti-inflammatory ones, contribute to schizophrenia risks. Schizophrenia often occurs in patients and their first-degree relatives with various autoimmune diseases.

Risks of an autoimmune process and development of schizophrenia are associated with: an impaired functioning of dopaminergic and glutamatergic systems in the brain, kynurenine pathway (overproduction of quinolinic, anthranilic and kynurenic acids), stress, and increased intestinal permeability, microflora alterations as well as food antigens’ effects. Various infections at different stages of ontogenesis (Coxsackie, Hepatitis C viruses, Herpesviridae, influenza, SARS, Toxoplasma, Borrelia, etc.) also can play the triggering role in pathologic autoimmunity and schizophrenia.

Cases of schizophrenia associated with autoimmune mechanisms (including autoimmune encephalitis with its autoantibodies against various neuronal antigens) are characterized by severe cognitive and psychotic symptoms and less favorable prognosis.

Conclusions

Thus, autoimmune alterations in combination with other mechanisms may be important factors in the etiology and links in the pathogenesis of schizophrenia.

Acknowledgments: This work was supported by the grant of the Russian Federation Government, contract 14.W03.31.0009