[Proinflammatory activity of monocytes and activity of glutathione-dependent enzymes in red blood cells in women with depressive conditions]. / Provospalitel'naya aktivnost' monotsitov i aktivnost' glutation-zavisimykh fermentov v eritrotsitakh krovi u zhenshchin s depressivnymi sostoyaniyami.

OBJECTIVE: To search for possible connections between the anti-inflammatory activity of monocytes (PAM) and the activity of glutathione metabolic enzymes: glutathione reductase (GR) and glutathione-S-transferase (GT) in patients with depressive states (DS) within various mental pathologies, as well as between the studied biological parameters and clinical condition of patients. MATERIAL AND METHODS: Sixty-one women, aged 18-56 years, with DC were examined before and after treatment. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depressive Symptom Rating Scale (HDRS-21). The control group included 23 women of the corresponding age without mental pathology. Biological parameters were assessed in the peripheral blood of patients and healthy people. RESULTS: Patients with a high level of PAM compared to the control (p<0.001) (subgroup 1, n=31) and with a low (at the control level) level (subgroup 2, n=30) were identified. In the subgroup 1, the values of GR and GT were significantly lower than in patients of subgroup 2 (p<0.05 and p<0.01, respectively). Negative correlations between the level of PAM before treatment and GR before and after treatment were revealed in patients who responded to treatment (r=-0.67; p=0.0041; r=-0.76; p=0.0001). CONCLUSION: The results may indicate the inverse relationship between the level of PAM and the activity of GR and GT, which are involved in the pathogenesis of DC, and can also serve as criteria for assessing the response of patients to treatment.

[The regulatory role of gut microbiota in inflammation in depression and anxiety]. / Regulyatornaya rol' kishechnoi mikrobioty v vospalenii pri depressii i trevoge.

Numerous studies have identified the important role of the gut microbiota in maintaining of the CNS normal functioning and in the pathogenesis of mental disorders as one of the systems regulating the bidirectional communication between the gut and the brain. The microbiota has been found to be involved in the modulation of inflammation as well as in the development and function of the immune and nervous systems. It is assumed that in multicellular organisms, the nervous and immune systems have evolved together with the microbiota, being in interaction with it, in order to optimize the body's ability to adapt to a wide range of environmental stresses in order to maintain the constancy of its homeostasis. Normally, microbes live in stable communities, while under conditions of even mild or chronic social stress, significant shifts in the composition of the microbiota occur, which lead to the development of dysbiosis associated with changes in microbiota metabolites, which can lead to the formation of physiology and behavior characteristic of stress and depression. Microbes influence the activation of peripheral immune cells that regulate the response to neuroinflammation, brain damage, autoimmune responses, and neurogenesis. The review provides a brief overview of the normal gut microbiota, describes the factors influencing the state of the microbiota, and also discusses recent discoveries concerning the regulatory effect of the gut microbiota on CNS functions, the immune system, and inflammation in the pathogenesis of depression and anxiety.

[Evaluation of the levels of proinflammatory activity of monocytes in depressed patients with schizophrenia]. / Provospalitel'naya aktivnost' monotsitov u bol'nykh s depressivnymi sostoyaniyami v ramkakh shizofrenii.

OBJECTIVE: To evaluate the proinflammatory activity of monocytes (PAM) in depressed patients with schizophrenia by counting the proinflammatory monocyte number and to identify possible correlations between PAM and clinical indicators. MATERIAL AND METHODS: Sixty-eight women with depressive states in schizophrenia and 23 mentally and somatically healthy age- and sex-matched people were examined. The clinical condition of the patients was assessed by the total PANSS (PANSS_tot) and HDRS (HDRS_tot) scores. PAM was determined in the peripheral blood of patients and healthy controls by counting the number of large monocytes with a diameter of 12.5 to 15 microns on a cell counter and analyzer using the positive magnetic separation method to isolate a pure population of CD14 monocytes. RESULTS: Before treatment, the level of PAM significantly exceeded the corresponding value in controls (p<0.001) in half of the patients; after treatment, the level of PAM decreased to control values (p<0.001). Linear regression revealed in a subgroup of patients with an initially low PAM level a positive correlation between its value and HDRS tot (r=0.5, p<0.05) before treatment, that is, a low PAM level before treatment was accompanied by low-severity depressive disorders. The analysis of PAM level in the subgroups of patients responding and not responding to treatment revealed a decrease in the PAM value after treatment in the responding patients assessed by PANSS_tot (p<0.05) and in the responding patients assessed by HDRS_tot (p=0.06). Similar patterns were not detected in the subgroups of nonresponders. CONCLUSION: The correlations between the PAM level and the severity of depressive and other psychopathological disorders in patients with depressive states in schizophrenia may indicate the involvement of immune inflammation in the pathogenesis of this disease. The positive relationship between the initially low PAM level and the mild severity of depressive disorders can be used as a prognostic sign of patients' response to treatment.

[A comparative analysis of two methods for assessing the proinflammatory activity of monocytes in patients with juvenile depression]. / Sravnitel'nyi analiz dvukh sposobov otsenki provospalitel'noi aktivnosti monotsitov pri depressii u bol'nykh yunosheskogo vozrasta.

OBJECTIVE: To show that the results of evaluation of monocyte pro-inflammatory activity (PA) in patients with juvenile depression and healthy donors, obtained using a new method developed by us for counting the relative number of large monocytes on a multifunctional counter and cell analyzer, are similar to the results obtained using a standard assessment of the level of proinflammatory CD14+/CD16+ - monocytes on a flow cytofluorimeter. MATERIAL AND METHODS: The PA of monocytes, isolated from the peripheral venous blood of 18 patients with juvenile depression and 12 mentally and somatically healthy age and gender-matched persons was evaluated in two ways: using the generally accepted method of determining the relative number of monocytes with the proinflammatory phenotype CD14+/CD16+ on a flow cytofluorometer FC-500 and by counting the relative number of large monocytes on a multifunctional counter and cell analyzer Multisizer MS-4. PA of monocytes in patients was studied by using both methods in different variants: in the general group and in the subgroups of patients with low and high levels of active monocytes. RESULTS: The levels of monocyte PA determined in patients using the two methods did not statistically differ from each other in all variants of the analysis (p=0.6). The equivalence of the obtained results was confirmed by the Chi-square test (r=0.77, p=0.05), as well as by the detection of a statistically significant positive correlation between the number of monocytes with the pro-inflammatory CD14+/CD16+ phenotype, on the one hand, and the relative number of large monocytes, on the other hand (Spearman r=0.75; p<0.05). At the same time, a comparative analysis of the level of monocyte PA in the general groups of patients and healthy controls revealed significantly higher values of this indicator in patients compared with healthy persons when evaluated by both methods (p<0.05). Definition of monocytes PA using the new method developed by us for counting the relative number of large monocytes on the analyzer and cell counter is more economical and easier to perform, since it does not require the use of expensive devices and reagents, as well as complex device settings and a high level of operator qualification, as in the common method, and is carried out only by two parameters: by counting the number of large monocytes with a diameter of 12.5 to 15 microns and the total number of monocytes with a diameter of 9 to 15 microns. CONCLUSION: The proposed method for assessing monocyte PA by counting the relative number of large monocytes on the cell counter and analyzer can be used to analyze the activity of monocytes for research purposes.

[Platelets, hemostasis and mental disorders]. / Trombotsity, gemostaz i psikhicheckie rasstroistva.

Platelets are an easily accessible model for the study of biochemical mechanisms of mental diseases, including schizophrenia and depression. This literature review addresses a role of platelet activation in the pathogenesis of mental diseases. Platelet activation observed in patients with schizophrenia, depression and other mental illnesses is associated with the development of cardiovascular disease and an increased risk of thrombotic complications, which can be the main cause of morbidity and mortality in patients with mental disorders. A deeper understanding of the biochemical mechanisms of mental disorders will help in the study of clinical consequences of these disorders and in choosing the right therapeutic strategy for patients.

[Risk assessment of thrombotic events in patients with schizophrenia and schizoaffective disorder in the acute state: the 'fibrinodynamics' technology]. / Otsenka riska tromboticheskikh narushenii u bol'nykh shizofreniei i shizoaffektivnymi rasstroistvami v ostrom periode bolezni s ispol'zovaniem tekhnologii 'fibrinodinamika'.

AIM: To assess the risk of thrombotic events in patients with schizophrenia and schizoaffective disorder based on 'fibrinodynamics' technology. MATERIAL AND METHODS: A group of 76 women, including 38 with paranoid schizophrenia (F20.0), 18 with schizoaffective disorder (F25.1) in the acute stage, and 20 healthy controls, participated in the study. The technology includes the study of coagulation and fibrinolysis, Karmin author software, and calculation of peak time and hemostasis potential of spontaneous clots. Growth and lysis of fibrin clots were studied in plasma purified from platelets. All preanalytic procedures were conducted within 30 minutes after blood sampling. Blood serum was studied separately using the neuroimmunological test. Dynamic of brightness profiles of the clots was determined and a number of parameters (peak time and hemostasis potential of spontaneous clots) were calculated using the Karmin software. RESULTS: In patients with schizophrenia, the dynamic brightness profile of the clots has two peaks: the first peak is formed as a result of the growth and lysis of the clot initiated by the activator, the second peak is due to the growth and lysis of spontaneous clots in the volume of the measuring cuvette far from the activator. In healthy donors, the second peak under experimental conditions is absent. In the group of schizophrenic patients, a strong negative correlation is observed between the peak time of the second peak and the activity of leukocyte elastase (Spearman R = -0.75, p<0.0001), i.e. the greater the activity of elastase, the earlier the maximum of the second peak is formed and vice versa. In the control group, there is no such correlation. Evaluation of the potential of hemostasis of spontaneous clots showed that in 42% of schizophrenic patients this parameter is shifted above the norm, which indicates an increased risk of thrombosis of small brain arteries in these patients. CONCLUSION: The developed technology of 'fibrinodynamics' has a good potential for introduction into personalized medicine to identify increased risks of thrombosis of small cerebral vessels in patients with acute schizophrenia leading to the development of cognitive disorders and to control the normalization of hemostasis with antiplatelet or anticoagulant drugs.

[The cellular factors of innate immunity in nonpsychotic patients at high risk for schizophrenia]. / Kletochnye faktory estestvennogo immuniteta u bol'nykh s nepsikhoticheskimi psikhicheskimi rasstroistvami, otrazhayushchimi vysokii risk razvitiya shizofrenii.

AIM: Changes in the parameters of innate immunity in patients with schizophrenia are observed already in the first episode. The study was performed to find out whether these changes take place prior to disease manifestation, and what role do they play in the pathogenesis of schizophrenia. MATERIAL AND METHODS: Thirty-five male nonpsychotic patients at high risk of psychosis, aged between 17 to 23 years, were examined. Phagocyte activity (PA) of neutrophils in the blood serum was evaluated by the number of active neutrophils, i.e. phagocytic index (PhI), and phagocytic number (PhN), which was determined by counting latex particles absorbed with a single phagocytic cell. Cytotoxic activity of natural killer lymphocytes (NK CA) was evaluated by the number of cell targets K-562, which remained non-degraded after the contact with natural killer cells. The influence of monocytes on NKCA was determined as well. RESULTS AND CONCLUSION: Compared to controls, patients had the lower PhI level (p<0.001) which was compensated by the increase in PhN levels, and the lower NK CA level which was increased due to the influence of monocytes. Negative correlations between PhI and PhN (r= -0.83, p<0.01) and between the level of NKCA and PhI (r= -0.83, p<0.05) as well as the positive correlation between PhN and SOPS scores (r=0.69, p<0.01) were found. After treatment, there was the decreasein the severity of mental disorders (p<0.001). The level of PhAN was normalized in 61.9% of patients compared to 36.7% before treatment. After treatment, the proportion of patients with normal levels of NK CA was the same as before treatment (40 and 35%, respectively). The immune disturbances revealed in the study may play a role in the pathogenesis of the disease and have predictive value for schizophrenia.