Schizophrenia and neuroinflammation: Pathogenetic and therapeutic aspects

Introduction. Schizophrenia is a complex mental disorder with heterogeneous symptoms, including psychotic, negative, cognitive, affective, and psychomotor symptoms. Although the pathogenesis of schizophrenia is mainly associated with neurotransmitter imbalance, recent studies have suggested the importance of neuroinflammation in the pathogenesis of this disease. Objective. To study the involvement of neuroinflammation in the pathogenesis of schizophrenia and a prognostic assessment of the potential anti-inflammatory effect of antipsychotic medications. Discussion. Current data indicate a significant role of neuroinflammation in the development and course of schizophrenia. At the initial stages of its development, the number of lymphocytes and the level of some proinflammatory cytokines (IL-1, IL-6, TNF-α, IL-1β) increase, which can be decreased by antipsychotic therapy. Studies involving experimental models of maternal immune activation (MIA) and data obtained by immunohistochemical and PET studies confirm an abnormal activation of microglia, indicating the involvement of innate immune cells. Adaptive immune response cells can also play a significant role in the development of neuroinflammation in schizophrenia. Thus, an increased level of Th17 cells and an increase in the production of proinflammatory cytokines, correlating with the disease severity, were revealed. The role of neurotransmitters in modulating the immune-inflammatory response is discussed. Available data suggest that the participation of dopamine in the schizophrenia pathogenesis can be mediated by its immunomodulatory effect. The role of neuroinflammation in schizophrenia is also indicated by the clinical effectiveness of anti-inflammatory treatment in this disease. On the other hand, the immunomodulatory effect of antipsychotics has been established, which, at least in part, may mediate their clinical effectiveness in schizophrenia. Conclusions. Given the importance of neuroinflammation in the schizophrenia pathogenesis, further studies into both the anti-inflammatory properties of antipsychotics and the effects of anti-inflammatory drugs in schizophrenia are promising in order to further optimize the treatment of this disease.