Сellular and Molecular Mechanisms of Proinflammatory Monocytes Participation in the Pathogenesis of Mental Disorders. Part 2

Abstract

Introduction: at the end of the last century, the macrophage-T-lymphocyte theory of the development of mental disorders was formulated. It underlines the important role of monocytes/macrophages and cytokines produced by them in the pathogenesis of schizophrenia, bipolar affective disorder (BAD) and depression. The first part of our review is dedicated to the analysis of the mechanisms of cellular and molecular interactions of activated monocytes/macrophages synthesizing proinflammatory CD16 receptors with endothelial cells, platelets, and microglia cells in the pathogenesis of systemic immune inflammation, including CNS as a result of violation of the integrity of the blood-brain barrier (BBB), activate microglia and cause the development of neuroinflammation in patients.The aim of work: to analyze and summarize the results of the main scientific publications for the role of cell-molecular mechanisms of the monocyte-macrophage immunity link activation in the pathogenesis of schizophrenia, BAD and depression. Material and methods: keywords “proinflammatory monocytes, cytokines, chemokines, molecules of cell adhesion, microglia, neuroinflammation, mental disorders” were used to search for data published over the past 20 years in domestic and foreign studies in PubMed, eLIBRARY, Science direct and EMBASE.Conclusion: the present review is dedicated to the analysis of the latest research data concerning an increase in the number of active circulating monocytes/macrophages and an increased level of proinflammatory cytokines, chemokines and receptors for them produced by monocytes in patients with schizophrenia, BAD and depression, what allows to associate these disorders with systemic immune inflammation. The data reasearches on cellular and molecular mechanisms of proinflammatory monocytes/macrophages interaction with microglia cells that initiate neuroinflammation in the CNS and lead to destabilization of brain function and the development of psychotic disorders are presented. The association of high levels of proinflammatory cytokines with somatic comorbidity, including metabolic syndrome, diabetes, atherosclerosis and other systemic diseases is shown in patients with mental disorders.Findings: the presented review of the research data allows us to better understand the cellular and molecular aspects of activation of the monocyte-macrophage immunity link in the development of neuroinflammation and cognitive decline in the pathogenesis of mental disorders, as well as helps in the search for informative biomarkers of the positive treatment of these disorders and the new approaches in the treatment of patients, based on the complex use of psychotropic and anti-inflammatory drugs.