Neurobiology of Schizophrenia (to the Construction of Clinical and Biological Model)

Abstract

The objective: of the study was to present the main provisions of a new clinical and biological model of schizophrenia, which establishes links between disorders in the field of biological processes and the formation of positive and negative in the general psychopathological space of schizophrenia on the basis of the analysis of long-term results of clinical and biological research of the Mental Health Research Centre.Material and method: by keywords “schizophrenia”, “biological hypotheses of schizophrenia”, “neuroinflammation”, “neurodegeneration”; “positive disorders”, “negative disorders”, “neuroimmune relationships”, “catabolismof tryptophan”, “activation of microglia”, publications from PubMed/MEDLINE databases, RSCI and other sources were analyzedover the past 10 years in comparison with the results of clinical and biological studies of schizophrenia at the Mental Health Science Center.Results: comparison and analysis of current biological hypotheses of schizophrenia indicates that immunological studies are the most promising for solving the problem of establishing links between disorders of  neurobiological processes and psychopathological specificities of  schizophrenia. Within the framework of the new clinical and biological  model, a key role is assigned to the process of neuroinflammation, which determines the pathogenesis of both negative and positive disorders by various, albeit interrelated, molecular mechanisms. One of these mechanisms,  associated with the development of reversible positive symptom complexes, is based on an imbalance in the neurotransmitter  systems, which is formed as a result of the effect of proinflammatory  cytokines on tryptophan catabolism. Another mechanism that determines the  development of negative symptom complexes is associated with the influence of cytotoxic metabolites on the processes of neurodegeneration. Conclusion:  a new clinical and biological model of schizophrenia establishes a paradigm of the relationship between disorders in the sphere of biological processes determined by neuroinflammation/inflammation and the  formation of the main procedural dimensions — positive and negative disorders in the general psychopathological space of schizophrenia. This model makes it possible to clarify some general provisions related to the pharmacotherapy of schizophrenia and the relief of negative disorders, and also serves as the basis for the development of new approaches to early diagnosis, clinical and social prognosis.