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Introduction: Alzheimer's disease (AD) is a multifactorial disease that leads to a progressive memory loss, visualspatial impairments, emotional and personality changes. As its earliest pre-dementia clinical stage, amnestic mild cognitive impairment syndrome (aMCI) is currently considered. Neuroinflammation plays a role in the development and progression of aMCI and the initial stage of AD, which can be supported by immunological disorders of a systemic character. Study of factors, including infections, influencing immune disorders and systemic inflammatory response in patients with aMCI, is of great importance.The aim of this study was to obtain new data on the possible role of herpesvirus infections in the development and progression of aMCI., Material and Methods: 100 patients with aMCI diagnosis, 45 patients with AD, 40 people from the control group were enrolled into the study. The frequency of DNA detection of herpesviruses (Epstein-Barr virus (EBV), human herpesviruses (HHV) type 6 and 7, cytomegalovirus (CMV)), the levels of viral load and the serological markers of herpesvirus infections (IgG to HHV-1, IgG to CMV) were determined. Immunological studies included an assessment of the level of the main pro-inflammatory and anti-inflammatory cytokines, and indicators of humoral and cellular immunity., Results: The study found an increased detection rate of EBV in saliva and a higher level of EBV DNA in saliva in aMCI and AD than in the control group. A relationship between the presence of active EBV infection and changes in immunological parameters in patients with aMCI were found. It was also discovered that the level of IgG antibodies to CMV is associated with the stage of AD., Discussion: The results indicate a possible role of EBV- and CMV-induced infections in the development of immunological changes which are typical for mild cognitive impairment and in the progression of AD., Conclusion: The obtained data can be important for prognostic methods addressing AD development, including its pre-dementia stage, and for new approaches to individualized treatment and prevention.

Introduction: Associations of disturbances in innate and adaptive immunity during the clinical course of schizophrenia have been found in a number of studies. Yet, the relationship of immune parameters and systemic inflammation in relation to the clinical course of the disease and its prognosis, remains poorly understood, which highlights an interesting topic for further research. The goal of this study was to research the immuno-inflammatory changes in patients with clinical continuous and episodic paranoid schizophrenia, to assess the pathogenetic significance of these changes., Methods: Thirty-six patients with paranoid schizophrenia, of which 20 had episodic symptoms and 16 had continuous symptoms, consented to participate in the study, together with 30 healthy volunteers. In the study we assessed the parameters of innate immune response (serum levels of key pro-inflammatory and anti-inflammatory cytokines, C-reactive protein) and the adaptive immune response, including humoral-mediated immunity (serum immunoglobulins IgA, IgM, IgG, circulating immune complexes), as well as the cell link of adaptive immunity (key lymphocyte subpopulations). Positive and negative symptoms were assessed with the positive and negative symptoms scale; frontal dysfunction was assessed by Frontal Assessment Battery (FAB)., Results: Both patient groups had higher than normal levels of C-reactive protein and IL-8. There was a significant elevation of circulating immune complexes among patients with continuous symptoms of schizophrenia, compared to patients with episodic symptoms and healthy controls. Levels of CD45+CD3+ lymphocytes (T-cells) differed between clinical groups, with higher values identified among patients with episodic symptoms and lower values among those with continuous symptoms. In addition, patients with episodic symptoms had significantly increased levels of CD45+CD3+CD4+CD25+CD127- regulatory T-cells. Finally, the level of CD45+CD3-CD19+ B-cells was significantly higher among patients with continuous symptoms vs. patients with episodic symptoms and the control groups. Markers of activation of humoral immunity were associated with the severity of frontal disorders in these patients., Discussion: Comprehensive data on the serum level of cytokines and the parameters of adaptive immunity among individuals with continuous schizophrenia, by comparison with patients with episodic schizophrenia, are practically absent in the literature. We have shown that among those with continuous schizophrenia, there are signs of systemic inflammation and chronic activation of the adaptive humoral immune response, while among patients with episodic symptoms of the disease, there are signs of systemic inflammation and certain activation of cell-mediated immunity, without significant changes in the humoral link of adaptive immunity., Conclusion: More studies are needed, but the data obtained in this study are important for subsequent clinical studies of new treatment methods, based on various immunophenotypes of schizophrenia., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021, Malashenkova I.K., Krynskiy S.A., Ogurtsov D.P., Hailov N.A., Zakharova N.V., Bravve L.V., Kaydan M.A., Chekulaeva E.I., Andreyuk D.S., Ushakov V.L., Didkovsky N.A., Kostyuk G.P.)

The aim of the study was to analyze the immune-inflammatory profile of patients with paranoid schizophrenia and relate it to the severity of negative symptoms and the MRI data in order to identify biomarkers of schizophrenia severity, search for new approaches to therapy, and control its effectiveness., Materials and Methods: The main group included 51 patients with paranoid schizophrenia, the control group - 30 healthy subjects. Patients underwent MRI scans and immunological studies, which included an assessment of natural and adaptive immunity, the systemic level of key pro-inflammatory and anti-inflammatory cytokines, and other markers of inflammation., Results: Disorders of immunity and immunoinflammatory profile in patients with paranoid schizophrenia with severe negative symptoms were revealed for the first time: in the presence of severe negative symptoms (>15 points according to the NSA-4 scale), the levels of humoral immunity factors, cytokines IL-10 and IL-12p40 and neurotrophin NGF were increased as well as the markers of systemic inflammation. Morphometric changes in the brain, typical for patients with schizophrenia, and also specific for patients with severe negative symptoms, were determined. The data analysis revealed correlations between the immune changes with structural changes in some of the brain areas, including the frontal cortex and hippocampus. Associations were found between the levels of anti-inflammatory IL-10, IL-12p40 cytokines and morphometric parameters of the brain, specific only for schizophrenic patients with severe negative symptoms., Conclusion: The interdisciplinary approach, combining brain morphometry with in-depth immunological and clinical studies, made it possible to determine neurobiological, immune, and neurocognitive markers of paranoid schizophrenia with severe negative symptoms. The results are important for further deciphering the pathogenesis of schizophrenia and its subtypes, as well as for the search for new approaches to the treatment of severe forms of the disease., Competing Interests: Conflicts of interest. There are no conflicts of interest associated with this study.

Objective: To search for the relationship between the results of functional imaging, immunological parameters and laboratory markers of inflammation in schizophrenia, taking into account cognitive impairment in patients, and to consider the possibility of using a multidisciplinary approach to diagnosis, treatment and prognosis of schizophrenia., Material and Methods: The study included 25 patients with schizophrenia and 13 healthy volunteers. Psychiatric scales were administered to evaluate the patient's condition. The main indicators of humoral immunity, the level of markers of inflammation, key pro-inflammatory and anti-inflammatory cytokines, and growth factor VEGF were determined by ELISA. Brain MRI was performed. All calculated tractographic data are included in the connection database to study the effect of immunological markers and the degree of severity of cognitive impairment., Results and Conclusion: Levels of markers of systemic inflammation and growth factor VEGF-A as well as the activation of humoral immunity are increased in patients with schizophrenia compared with controls. For the first time, the relationship of immunological parameters with the coefficient of quantitative anisotropy in the area of the corpus callosum in schizophrenia was revealed. The results indicate the possible value of indicators of the activation of the humoral immune response and systemic inflammation as markers of neurophysiological changes and cognitive dysfunction in schizophrenia.

Background: Amnestic mild cognitive impairment (aMCI) is considered as a possible earliest pre-dementia clinical stage of Alzheimer's disease (AD). Taking into account the prominent role of neuroinflammation in the pathogenesis of AD, it is quite important to study possible immunological markers of the risk of aMCI progression and the changes in immune parameters in patients., Objective: To study the immunological variants of aMCI and AD based on the parameters of humoral and cell immunity, levels of key cytokines and presence of systemic inflammation, and to explore the link between changes in the immune parameters and clinical prognosis., Material and Methods: One hundred patients with a diagnosis of aMCI, 45 patients with AD at the stage of mild to moderate dementia and 40 people without cognitive impairment (the control group) were enrolled into the study. Immunological assessment included determination of the concentration of key cytokines, C-reactive protein, circulating immune complexes and immunoglobulins (Ig A, M, G) in blood serum by ELISA, determination of the main subpopulations of lymphocytes by flow cytometry., Results and Conclusion: Four main immunological variants of aMCI syndrome associated with clinical prognosis were identified. The detected changes in immune parameters are important for further studies to assess an effect of viral and bacterial infections, intestinal microflora disorders on a clinical prognosis in patients with different immunological variants of aMCI syndrome.