[Clinical and psychopathological characteristics of patients with late-onset schizophrenia and schizophrenia-like psychoses in clusters identified by biological parameters]. / Kliniko-psikhopatologicheskie kharakteristiki bol'nykh s pozdno manifestiruyushchimi shizofreniei i shizofrenopodobnymi psikhozami v klasterakh, vydelennykh po biologicheskim parametram.

OBJECTIVE: To assess clinical and psychopathological characteristics of late-aged female patients with late-onset psychoses in clusters formed on the basis of biochemical and immunological blood parameters. MATERIAL AND METHODS: We examined 59 women with schizophrenia and schizophrenia-like psychoses with onset after 40 years (ICD-10 F20, F22.8, F25, F23, F06.2), including 34 women with late-onset (40-60 years) and 25 with very late onset psychoses (after 60 years). At the time of hospitalization, a clinical/ psychopathological study was carried out using CGI-S, PANSS, CDSS, and HAMD-17, as well as the activities of glutathione reductase (GR) and glutathione-S-transferase (GT) have been determined in erythrocyte hemolysates, and the activities of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) have been assessed in blood plasma. Biochemical and immunological parameters have been also determined in 34 age-matched mentally healthy women. RESULTS: Clustering by signs such as GR, GT, LE and α1-PI has yielded two clusters of objects (patients) significantly different in GT (p<0.0001), LE (p<0.0001), and α1-PI (p<0.001) activities. Relatively to the controls, in the cluster 1 patients, the activities of GST and α1-PI are increased, the activity of LE is decreased, whereas, in the cluster 2 patients, the activity of GR is decreased, and the activities of LE and α1-PI are increased. Cluster 1 patients differ from cluster 2 patients in greater severity of the condition (CGI-S, p=0.04) and higher total scores on PANSS subscales' items. Cluster 1 includes 76% of patients with very late onset. Different correlations between clinical and biological signs are found in two clusters. CONCLUSION: The identified clusters have different clinical and psychopathological characteristics. Dividing patients into subgroups according to biochemical and immunological parameters is promising for the search for differentiated therapeutic approaches.

Hemostasis System in Patients with Schizophrenia and Schizophrenia Spectrum Disorders.

Hemostasis system in patients with schizophrenia and schizophrenia spectrum disorders was examined using "Fibrinodynamics" technology that allows evaluating the overal coagulation, fibrinolysis, and hemostasis potentials. All indices, except for the parameter characterizing the hemostasis balance, were statistically higher (p<0.0001) in patients than in healthy volunteers (control). In most patients, the hemostasis system remained balanced despite changes in individual coagulation and fibrinolysis parameters. The obtained results have a fundamental importance, expand the understanding of the pathogenesis of endogenous mental disorders, and are useful for the development of personalized approaches to the treatment of these patients.

[Features of inflammatory reactions in patients with juvenile depression with a clinically high risk of psychosis]. / Osobennosti vospalitel'nykh reaktsii u patsientov s yunosheskimi depressiyami s klinicheski vysokim riskom psikhoza.

OBJECTIVE: To determine the levels of pro-inflammatory and anti-inflammatory cytokines and inflammatory markers such as C-reactive protein, leukocyte elastase, α1-proteinase inhibitor, autoantibodies to neuroantigens in the blood of patients with adolescent depression with clinical high risk for psychosis (CHR-P) and to study the relation of these biological markers to the features of psychopathological symptomatology of the patients. MATERIAL AND METHODS: Eighty young adults, aged 16-24 years, with the first depressive episode (F32.1-2, F32.38, F32.8) were studied. Based on the presence of attenuated positive symptoms in the structure of depression, all patients were divided into two groups: with CHR-P (clinical group, n=58) and without CHR-P (comparative group, n=22). The HDRS-21, SOPS, and SANS were used for psychometric assessment of the patients. Serum levels of cytokines TNF-α, IL-6, IL-8, IL-10, and concentration of C-reactive protein (CRP) were determined. Leukocyte elastase (LE) activity, α1-proteinase inhibitor (α1-PI) activity, and plasma levels of autoantibodies to S100B protein and myelin basic protein (MBP) were assessed. RESULTS: Both groups of patients were characterized by the high levels of inflammation as assessed by LE (250.5 (226.2-280.8) nmol/min·ml vs 248.3 (226.8-284.5) nmol/min·ml) and α1-PI activity (44.4 (37.5-50.1) IE/ml vs 45.2 (36.4-49.9) IE/ml). Higher levels (p<0.05) of IL-6 (1.22 (0.64-2.2) pg/ml), CRP (0.93 (0.18-3.18) mg/l), and TNF-α/IL-10 (0.34 (0.2-0.47)) were detected in the group with CHR-P. This group was also characterized by higher levels of antibodies to the S100B protein 0.78 (0.69-0.84 units of opt.density) compared with the group without CRH-P (p<0.05). In each clinical group, different correlations between clinical, psychometric and biological parameters were revealed. CONCLUSIONS: The results confirm the involvement of inflammation in the development of depression in youth and indicate a different role of the inflammatory markers analyzed in the formation of CHR-P. The differences in the spectrum of inflammatory markers in depressed patients suggest a more pronounced pro-inflammatory potential in the group with CHR-P.

[Prognosis of late-life depression: clinical and immunological features]. / Prognoz pozdnevozrastnykh depressii: kliniko-immunologicheskie osobennosti.

OBJECTIVE: To study the outcomes of depression at a late age during a 3-year prospective follow-up in patients with various immunophenotypes. MATERIAL AND METHODS: A cohort of patients with depressive disorders who were treated in a gerontopsychiatric hospital and re-examined after 1 and 3 years. The group with immunophenotype A (with increased activity of leukocyte elastase (LE) and complex depressions, comorbid with anxiety and senesto-hypochondriac disorders) included 20 people: 6 men (30%) and 14 women (70%), median age was 68 years. A depressive episode (DE) was diagnosed in 13 patients (65%) with recurrent depressive disorder (RDD) and in 7 patients (35%) with bipolar affective disorder (BAD). The group with immunophenotype B (with reduced activity of LE and prolonged apathetic-adynamic depression) included 31 people: 10 men (32.3%) and 21 women (67.7%), the median age was 68 years. DE was diagnosed in 20 patients (64.5%) with RDD, 9 patients (29%) with BAD, and in 2 patients (6.5%) with a single DE. The patients were examined using clinical, psychometric, immunological and clinical- follow-up methods (after 1 and 3 years). RESULTS: More favorable course of the disease with the formation of high-quality remission was observed in patients with immunophenotype A (95% of cases after 1 and 3 years; χ2=10.44; p=0.001 and χ2=11.97; p=0.001, respectively). In patients with immunophenotype B, an unfavorable course of the disease prevailed (83.9 and 87.1% of cases after 1 and 3 years) with the formation of low-quality remissions (with residual depressive disorders, the development of repeated depressive phases and chronification of depression). CONCLUSION: The study revealed the relationship between clinical and biological features and the course of late-life depression.

[Bimodal model of delusional psychoses (on the problem of the correlation of paranoid dimensions in the psychopathological space of schizophrenia)]. / Bimodal'naya model' bredovykh psikhozov (k probleme sootnosheniya paranoidnykh dimensii v psikhopatologicheskom prostranstve shizofrenii).

OBJECTIVE: To establish clinico-pathogenetic ratios of delusional psychoses constituting the psychopathological space of paranoid schizophrenia and to determine clinical and pathogenetic validity of concepts of a single delusional psychosis (a model of chronic delusion with a staged course) and two endogenous delusional psychoses. MATERIAL AND METHODS: A sample consisted of 56 patients (19 women, 37 men; the average age 39.7±9.3 years; average duration of the disease 10.6±9.1 years) with a diagnosis of paranoid schizophrenia, continuous type of course (F20.00), developed at the age above 18 years. At the time of examination, the condition of the patients was determined by persistent delusional or hallucinatory delusional disorders. Clinical, pathopsychological, psychometric (SANS, SAPS, PANSS), immunological and statistical methods were used. RESULTS: The study substantiates a bimodal model of a single delusional psychosis with a polar arrangement of interpretive delusions and delusions of influence based on the phenomena of mental automatism, both in terms of the vector of development (toward the poles of negative/positive disorders) and in terms of the rate of progression. Psychopathological manifestations of interpretive delusions correlate with the slow evolving development of psychosis, the dimensional structure of the paranoid is limited to the limits of the delusional register; functional activity is represented by affiliation to negative changes, integration with personality anomalies ends with the transformation of positive disorders into pathocharacterological ones, corresponding to the post-processual development of the personality. Manifestation of delusional impact (syndrome of mental automatism) is manifested by the complication and maximum expansion of the spectrum of positive disorders; the dimensional structure is represented by a wide range of psychopathological disorders and is formed with the participation of processes of mental dissociation, reaching the level of delusional depersonalization; functional activity is high, which creates conditions for the formation of a «new¼ subpsychotic structure, a «psychotic character¼, which is an attenuated duplicate of delusional psychosis. In both groups of patients, a significant increase in the activity of inflammatory markers of leukocyte elastase (249.2 ((231.1-270.0); 272.2 (236.0-292.6) nmol/min∙ml) and alpha - 1 proteinase inhibitor (48.8 (46.0-55.0); 50.4 (42.1-54.8) IU/ml) was shown compared with controls (205.0 (199.8-217.3) nmol/min∙mL and 33.0 (31.0-36.0) IU/mL, p<0.01, respectively). In the group of patients with delusions of influence, an increased level of antibodies to S-100B was also observed (0.88 (0.67-1.0) opt.density units) compared with the control values (0.7 (0.65-0.77) opt.density units, p<0.05). CONCLUSION: The concept of the model is supported by the results of the immunological study, according to which interpretive delusions and delusion based on the mental automatism, indicates the different level of immunity tension, and a qualitative changes in immune reactivity (also due to different genetic burden).

[Immune mechanisms of complicity of somatic pathology in the pathogenesis of mental disorders]. / Immunnye mekhanizmy souchastiya somaticheskoi patologii v patogeneze psikhicheskikh rasstroistv.

Understanding the mechanisms of the relationship between the nervous and immune systems within the framework of the concept of the key role of inflammation, taking into account the involved genetic factors in the development of a wide range of combined forms of somatic and mental diseases, is of interest for research as well as for the development of new approaches to early diagnosis and more effective treatment of these diseases. This review analyzes the immune mechanisms of the development of mental disorders in patients with somatic diseases, in particular, the transmission of an inflammatory signal from the periphery to the CNS and the implementation of the influence of inflammatory factors on neurochemical systems that determine the characteristics of mental functioning. Particular attention is paid to the processes underlying the disruption of the blood-brain barrier caused by peripheral inflammation. Modulation of neurotransmission, changes in neuroplasticity, changes in regional activity of the brain in areas associated with the functions of threat recognition, cognitive processes and memory function, the effect of cytokines on the hypothalamic-pituitary-adrenal system are considered as mechanisms of action of inflammatory factors in the brain. The need to take into account variations in the genes of pro-inflammatory cytokines, which may be the cause of increased genetic vulnerability associated with the risk mental disorders in patients suffering from a certain somatic disease, is emphasized.

[Genome-wide studies of comorbidity of somatic and mental diseases]. / Polnogenomnye issledovaniya komorbidnosti somaticheskikh i psikhicheskikh zabolevanii.

Studies of the genomic architecture of complex phenotypes, which include common somatic and mental diseases, have shown that they are characterized by a high degree of polygenicity, i.e. participation of a large number of genes associated with the risk of developing these diseases. In this regard, it is of interest to establish the genetic overlapping between these two groups of diseases. The aim of the review is to analyze genetic studies of the comorbidity of somatic and mental diseases in terms of the universality and specificity of mental disorders in somatic diseases, the reciprocal relationships of these types of pathologies, and the modulating influence of environmental factors on comorbidity. The results of the analysis indicate the existence of a common genetic predisposition to mental and somatic diseases. At the same time, the presence of common genes does not exclude the specificity of the development of mental disorders depending on a specific somatic pathology. It can be assumed that there are genes that are both unique to a particular somatic and comorbid mental illness, and genes that are common to these diseases. Common genes may have varying degrees of specificity, that is, they may be of a universal nature, which, for example, manifests itself in the development of MDD in various somatic diseases, or be specific only for a couple of individual diseases (schizophrenia - breast cancer). At the same time, common genes can have a multidirectional effect, which also contributes to the specificity of comorbidity. In addition, when searching for common genes for somatic and mental diseases, it is necessary to take into account the modulating influence of such confounders as treatment, unhealthy life style, behavioral characteristics, which can also differ in specificity depending on the diseases under consideration.

Clinical-Immunological Correlates in Post-COVID-19 Endogenous Psychoses.

Objectives. To carry out a clinical and immunological study of the potential impact of coronavirus infection on the course of endogenous psychoses. Materials and methods. A total of 33 female patients aged 16-48 years with depressive-delusional states (F20.01, F21, F31) developing after coronavirus infections took part; group 1 consisted of 15 people who developed depressive-delusional states 1-2 months after COVID-19; group 2 consisted of 18 people with similar psychoses developing at later time points (2-6 months). The severity of psychopathological symptoms was assessed using the PANSS and HDRS-21 scales. The activity of inflammatory markers leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) was determined in patients' blood. Absolute neutrophil and lymphocyte contents and their ratio (the neutrophil:lymphocyte index) were also evaluated. Standard values for indicators from healthy donors corresponding to patients in terms of age and sex were used as control values. Results. Endogenous psychosis developing at longer intervals after coronavirus infection (group 2) was found to be associated with "typical" inflammatory reactions, with increases in the activity of acute-phase proteins (α1-PI: 43.0 (35.6-49.7) IU/ml, p = 0.001) and neutrophil degranulation activity (LE - 254.8 (238.0-271.0) nmol/min·ml, p < 0.001), which was associated with the development of depressive-delusional states with dominance of manifestations of positive affectivity (anxiety, melancholy) and the extended nature of delusional disorders, which were mostly incongruent to affect. Conversely, development of endogenous psychosis during the first two months after COVID-19 (group 1) was characterized by a spectrum of inflammatory biomarkers with a decrease in neutrophil count ((2.6 ± 0.9)·109/liter, p < 0.05) and low LE activity (196 (172-209.4) nmol/min·ml, p < 0.001). This immunological profile was associated with predominance of manifestations of negative affectivity (apathy, asthenia, adynamia) in the structure of depressive-delusional states and the relatively undeveloped nature of delusional disorders, which were predominantly congruent to affect. Conclusions. The clinical and biological correlates found here presumptively indicate that experience of COVID-19 infection has a modulatory effect on neuroinflammation and the structure of endogenous psychosis.

[Inflammatory markers in organic nonpsychotic disorders]. / Vospalitel'nye markery pri organicheskikh nepsikhoticheskikh rasstroistvakh.

OBJECTIVE: To determine the indicators of systemic inflammation in peripheral blood samples of patients with organic non-psychotic disorders. MATERIAL AND METHODS: The study included 60 patients, aged 56.9±7.7 years, with a disease duration of 7.3±5.55 years, with a verified ICD-10 diagnosis «Organic emotionally labile (asthenic) disorder¼ (F06.6) and «Organic Anxiety Disorder¼ (F06.4). Patients with organic asthenic disorder were divided into two groups according to the prevailing symptoms: 36 patients with asthenic-cephalgic syndrome (AC); 10 patients with astheno-dysthymic syndrome (AD); the third group (n=14) included patients with organic anxiety disorder (AND). The control group consisted of 65 people matched for age and sex with patients. The activity of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) was determined by the spectrophotometric method, the levels of aAB to S100b and MBP were determined by ELISA. The protease-inhibitory index (PII), i.e., the ratio of LE activity to α1-PI, was calculated. RESULTS: A significant increase in LE (235.4 [216.4; 258.1] nmol/min*ml, p<0.001), the functional activity of α1-PI (43.1 [38.7; 47.6] u/ml, p<0.001), the level of aAB to S100b (0.78 [0.70; 0.89] opt.units, p<0.05) and a decrease in PII (6.19 [5.32; 6.9], p<0.05) in the group of patients with organic non-mental disorders compared with controls were shown. Deviations from the normal values of immune markers of inflammation in blood samples were also found in various syndromes. Clustering of the total group of patients by LE activity made it possible to identify 2 immunotypes with a balanced and unbalanced inflammatory process, confirming the clinical diversity of the disease: 60% of patients with AC syndrome belong to the 1st cluster, in which the ratio of immune markers characterizes a balanced inflammatory process aimed at restoration of homeostasis; 80% of patients with organic AND belong to the second cluster, which characterizes low proteolytic activity and imbalance of inflammation, which is an unfavorable prognostic factor in terms of the further course of the disease and therapy. CONCLUSION: The results confirm the importance of the inflammatory link in the neuroprogression of organic non-psychotic disorders. The identified features of the immune response can serve as an additional paraclinical criterion for differential diagnosis and evaluation of the prognosis of the further development of the disease.

[Clinical features of asthenic disorders in chronic heart failure]. / Klinicheskie osobennosti astenicheskikh rasstroistv pri khronicheskoi serdechnoi nedostatochnosti.

OBJECTIVE: The aim of the study is to study the clinical features of asthenic disorders in chronic heart failure (CHF) considering the reaction to the disease. MATERIAL AND METHODS: 62 inpatients with CHF II-IV functional class (FC) according to NYHA were examined. Research methods included somatic, psychopathological and pathopsychological examination using psychometric scales. RESULTS: According to a pathopsychological study using the Multidimensional Fatigue Inventory (MFI-20), asthenic disorders were discovered in all examined patients, realized mainly by «general fatigue¼ (75.8%) and «physical fatigue¼ (72.6%), more rarely «mental fatigue¼ was observed (32.2%). Correlations of «general fatigue¼ with the age of patients were revealed (p=0.018). There was a relationship between the severity of asthenic disorders and the severity of CHF, as evidenced by the correlation between «general fatigue¼ and reduced ejection fraction (EF) of the left ventricle (p=0.005), as well as «physical fatigue¼ and FC according to NYHA (p=0.022). The negative impact of all components of the dimensions of asthenic disorders on the quality of life was determined (p<0.05). According to the concept of the formation of different perceptions of the manifestations of a somatic disease, two types of reactions to asthenic disorders were identified: 1. Dissociative reactions, manifested by a discrepancy between the severity of CHF and a subjective assessment of the condition with an underestimation of the asthenic symptoms denial of its influence on the usual lifestyle and associated with an unfavorable course of CHF and 2. Adaptive reactions, realized by a harmonious perception of asthenia, awareness of the need to change lifestyle considering the presence of CHF symptoms. CONCLUSION: In accordance with the results, the described clinical features of asthenic disorders allow to distinguish asthenia in CHF and other pathology, and the identified types of reactions can contribute to the timely verification of asthenia, prevention of further progression of CHF, and the development of appropriate treatment approaches.

Epidemiological Screening for the Risk of Mental, Behavioral and Developmental Disorders, Including Autism, in Early Childhood: Data for Russia 2017-2019.

We aimed to screen children aged 18-48 months in the general population of nine Russian regions for risk of mental, behavioral and developmental disorders (MBDDs) including autism spectrum disorders (ASD) using an original screening tool. The prevalence of the risk for MBDDs is 1307:10,000 (13.07%), the prevalence of clinically verified cases of MBDDs is 151:10,000 (1.51%), whereas the prevalence of ASD among them is 18:10,000 (0.18%). Basing on our results, the screening procedures are already integrated into the Russian primary care system since the end of 2019. Screening of the risk for MBDDs including ASD in Russia among children in the general pediatric population is a promising area of preventive medicine.

[Clinical-neurobiological correlations in young depressive patients with a history of suicidal attempts]. / Kliniko-neirobiologicheskie korrelyatsii u bol'nykh depressiei molodogo vozrasta s suitsidal'nymi popytkami v anamneze.

The processes of neuroinflammation play an important role in the pathogenesis of endogenous mental disorders, including in patients with autoaggressive behavior. OBJECTIVE: Is to identify the relationships of quantitative clinical, EEG and neuroimmunological parameters in young female patients with depression and a history of suicidal attempts in order to clarify the role of neuroimmune interaction in the pathogenesis of suicidal behavior. MATERIAL AND METHODS: In 35 female patients aged 16-25 years the pre-treatment severity of the depressive state was quantitatively assessed (according to the HDRS-17 scale), and immunological parameters - markers of neuroinflammation (activity of leukocyte elastase and of α1-proteinase inhibitor) in blood plasma using the laboratory technology «Neuro-immuno-test¼ and the EEG absolute spectral power in narrow frequency sub-bands were measured. The relationships between clinical, neuroimmunological and EEG parameters was determined by correlation analysis (according to Spearman). RESULTS: The values of immunological markers of neuroinflammation correlated with EEG signs of increased activation of the cerebral cortex and with the severity of the anxiety component of the depressive state. CONCLUSION: The structure of clinical-neurobiological correlations in the examined patients indicates the involvement of neuroinflammation processes in the pathogenesis of their condition. The results make it possible to clarify the neurobiological factors of the pathogenesis of suicidal behavior in young depressive patients.

[Molecular-genetic and immunological aspects of the formation of psychopathological symptoms in schizophrenia]. / Molekulyarno-geneticheskii i immunologicheskii aspekty formirovaniya psikhopatologicheskikh simptomov pri shizofrenii.

The authors present the data indicating that the formation of psychopathological symptoms of schizophrenia is due to complex and diverse genetic factors associated with various functional and metabolic pathways at different stages of ontogenesis. Despite the fact that at present the genetic basis of positive and negative symptoms as the main pathophysiological manifestations of schizophrenia remains largely unknown, the current level of research allows the identification of some common and unique associations for positive and negative disorders. Based on the analysis of the literature, the specificity of the association of genetic variants with negative symptoms of schizophrenia is shown. It has been also suggested that genes of the immune system may be specifically associated with negative symptoms of schizophrenia. The relevance of studying the relationship of immune system genes, in particular, pro- and anti-inflammatory cytokines, with dimensional characteristics of negative symptoms (abulia-apathy and expressive deficit) is substantiated. Studies of this type have not yet been conducted, despite accumulating data indicating that the heterogeneity of negative symptoms is based on different neurobiological mechanisms. It is concluded that the immunological and molecular genetic study of the subdomains of psychopathological symptoms can be promising as part of the transition to deep phenotyping, which seems to be especially relevant for the study of such an extremely heterogeneous disease from a clinical point of view as schizophrenia. The development of this area is important for solving the problems of precision medicine, which aims to provide the most effective therapy for a particular patient by stratifying the disease into subclasses, taking into account their biological basis.

Thermal Balance of the Brain and Markers of Inflammatory Response in Patients with Schizophrenia.

In patients with schizophrenia, the thermal balance of the cerebral cortex was studied by means of microwave radiothermometry method and compared with the markers of systemic inflammation and clinical features of the disease course during therapy. Low temperature heterogeneity of the cerebral cortex was associated with an increase in the activity of inflammatory markers in the blood and, in most cases, with a positive response to therapy. High temperature heterogeneity of the cerebral cortex was typical of patients with insufficient activity of the inflammatory proteolytic system, high levels of antibodies to brain antigens, a more severe course of the disease and, in most cases, with resistance to therapy. A conclusion was made about the diagnostic value of the study of the thermal balance of the brain in patients with schizophrenia.

[Paired and partial correlations of immune parameters of neuro-immuno-test and coagulation parameters of thrombodynamics test in children with children's autism]. / Parnye i chastnye korrelyatsionnye svyazi immunnykh pokazatelei neiroimmunotesta i koagulyatsionnykh parametrov trombodinamiki u bol'nykh detskim autizmom.

OBJECTIVE: To reveal paired and partial correlations of values of neuro-immuno-test and thrombodynamics test in children with childhood autism and schizophrenia in childhood in a state of exacerbation. MATERIAL AND METHODS: The study used a database of children with childhood autism, obtained by us in 2028-2019. The study included 46 patients with childhood autism (CA) aged 2 to 13 years: median age [Q1; Q3] - 5 years [4; 7], 10 girls (22%) and 36 boys (78%)). The thrombodynamics test (TD) was performed on a T-2 thrombodynamics analyzer according to the manufacturer's instructions. RESULTS: It was shown that there is a statistically significant positive correlation (R=0.369, p=0.018) between the acquired immunity parameter: the level of serum antibodies to myelin basic protein (BMP): abBMP parameter, and the main parameter of platelet hemostasis - the time of appearance of spontaneous clots (Tsp). It can be assumed that autoantibodies to BMP block the procoagulant effect of myelin basic protein and thus have an anticoagulant effect. However, this analysis did not take into account the possible effects of other parameter of the neuro-immuno-test and thrombodynamics test. Therefore, when studying the correlation of specific parameters of the neuro-immuno-test and thrombodynamics, it is necessary to take into account the possible modifying effect of other parameters of these tests. It was shown that after subtracting the influence on the main correlation (abBMP & Tsp) of individual thrombodynamic parameters (Vi, V and D), as well as their total influence, the partial correlations become statistically insignificant. This indicates that these TD parameters can, individually or in total, determine the revealed correlation between the levels of antibodies to the basic myelin protein (Basic Myelin Protein) and the time of the appearance of spontaneous clots. CONCLUSION: Thus, it was shown that the correlations between the studied parameters of the neuro-immuno-test and the indicators of the thrombodynamics test mutually depend on the other indicators of these tests. This confirms the hypothesis that the immune system and the hemostatic system are two different sides of a single supersystem.

[Clinical and immunological correlates in endogenous psychoses developed after COVID-19]. / Kliniko-immunologicheskie korrelyaty pri endogennykh psikhozakh, razvivshikhsya posle perenesennogo COVID-19.

OBJECTIVE: The clinical and immunological study of the potential impact of coronavirus infection on the course of endogenous psychosis. MATERIAL AND METHODS: Thirty-three female patients, aged 16 to 48 years, with depressive-delusional conditions (ICD-10 F20.01, F21, F31) developed after coronavirus infection, of whom 15 people (group 1) had depressive-delusional states 1-2 months after COVID-19 and 18 people (group 2), who developed similar psychoses in later periods (2-6 months). The severity of the psychopathologic symptoms was evaluated with PANSS and HDRS-21 scales. The activity of inflammatory markers - leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) in the blood was determined. The absolute neutrophil count, the absolute lymphocyte count and the neutrophil/lymphocyte ratio were calculated. As a control, we used standard values of indicators of age - and sex-matched healthy donors. RESULTS: The endogenous psychosis that developed later after a coronavirus infection (group 2) is associated with a "typical" inflammatory reaction with an increase in the activity of acute phase proteins (according to α1-PI) and degranulation activity of neutrophils (according to LE), which is associated with the development of depressive-delusional states in patients with the dominance of manifestations of positive affectivity (anxiety, melancholy) and the extended nature of delusional disorders, which were predominantly incongruent to affect. On the contrary, the development of endogenous psychosis during the first two months after COVID-19 (group 1) is characterized by a spectrum of inflammatory biomarkers with a decrease in the number of neutrophils and low activity of LE. This immunological profile is associated with the predominance of manifestations of negative affectivity (apathy, asthenia, adynamia) in the structure of depressive-delusional states and the relatively undeveloped nature of delusional disorders, which were predominantly congruent to affect. CONCLUSION: The clinical and biological correlates presumably indicate the modulating effect of the coronavirus infection (COVID-19) on neuroinflammation and the structure of endogenous psychosis.

[Immunological and clinical aspects of the long-term stages of youth schizophrenia]. / Immunologicheskie i klinicheskie aspekty otdalennykh etapov yunosheskoi shizofrenii.

OBJECTIVE: To study the spectrum of inflammatory markers and their association with the psychopathological symptoms in patients with youth schizophrenia in the long-term follow-up study. MATERIAL AND METHODS: Thirty-four male patients with schizophrenia (ICD-10 F20) first manifested at the age of 16-25 years were followed-up for 20-25 years (mean duration 22±2.9 years). The mean age of patients at the time of follow-up examination was 46.7±3.2 years. PANSS and PSP scales were used to quantify the severity of psychopathological symptoms. The control group consisted of 20 mentally and somatically healthy people matched for age with the patient group. The immunological parameters (the activity of the neutrophil protease of leukocyte elastase (LE) and its endogenous inhibitor α1-PI, as well as the level of antibodies to S100B and basic myelin protein) included in the medical technology «Neuroimmunotest¼ were determined in blood plasma. RESULTS: Three types of follow-up outcomes of youth schizophrenia were found: the first type - with a predominance of personality dynamics (n=10); the second type - with actual negative disorders (n=9), the third type - with relevant positive and negative disorders (n=15). All patients showed a significant increase in the activity of LE (227.9 nmol/min ml) and α1-PI (45.8 IU/ml) compared with the controls. There were a significant increase in LE and α1-PI in patients of the first type (245 nmol/min ml and 46.4 IU/ml), a significant increase in α1-PI in patients of the second type (42.0 IE/ml) compared with the controls and the absence of significant differences with the controls in LE and α1-PI in patients of the third type (226.8 nmol/min ml and 49.6 IE/ml). These differences reveal the immunological heterogeneity of the types that makes it possible to identify immunological groups of patients, differing in the level of activation of inflammation. CONCLUSION: Residual psychopathological symptoms observed in the late stages of schizophrenia can be determined by both low/moderate inflammation and genetic mechanisms (in patients with damped inflammation or depletion of the inflammatory potential).

[The status of leukocyte-inhibitory system of inflammation in different age groups of patients with endogenous depression]. / Status leikotsitarno-ingibitornoi sistemy vospaleniya pri endogennykh depressiyakh u patsientov raznykh vozrastnykh grupp.

OBJECTIVE: The comparison of inflammatory markers in different age groups of patients with endogenous depression and correlation of immunological parameters with the clinical features of depression. MATERIAL AND METHODS: The study included 140 patients with endogenous depression (ED) (F21, F31-F34, ICD-10) aged 15 to 82 years (39.8±23 years), including 55 patients of adolescent age (18.9±2.8 years), 30 middle-aged patients (38.7±10.3 years) and 55 elderly patients (69.1±7.1 years). The total duration of the disease differed from 5 months to 45 years. Psychometric assessment of patients was carried out using HDRS. The control groups consisted of 143 healthy people aged 16 to 75 years. The activity of inflammatory markers leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI), their ratio (leukocyte-inhibitory index, LII), the levels of antibodies to S100B and myelin basic protein (MBP) were determined in blood. RESULTS: Three immunological clusters were identified that correspond to different clinical variants of ED. A pro-inflammatory status with an activation of the leukocyte-inhibitory system is characteristic of 52.9% of patients (cluster 1). The clinical feature of this status is predominantly «classic¼ ED in the form of anxious, anxious-melancholic or anxious-apathetic depression without pronounced negative symptoms. Two other clusters are characterized by the imbalance of leukocyte-inhibitory system associated with insufficient a1-PI activity (cluster 2) and with insufficient LE activity (cluster 3). A common clinical feature of such ED is an atypical course with the predominance of apathetic-adynamic and dysphoric depression, the presence of negative disorders and a poor prognosis. The imbalance of leukocyte-inhibitory system associated with insufficient LE activity is typical mainly for elderly patients and is characterized by a longer duration of disease. CONCLUSIONS: The status of leukocyte-inhibitory system of inflammation is correlated with the clinical features of ED in different age groups of patients. LII can be considered as an additional paraclinical criterion for differential diagnosis and prognosis of ED.

[Immune-inflammatory markers in remission after a first-episode psychosis in young patients]. / Immunovospalitel'nye markery stanovleniya remissii posle pervogo psikhoticheskogo pristupa v yunosheskom vozraste.

OBJECTIVE: To study clinical, psychopathological and immunological features of remission after first-episode psychosis in young patients to determine the patterns of this stage and the possibility of using the results for monitoring, prognosis and optimization of therapy. MATERIAL AND METHODS: Fifty patients, aged 15-25 years, mean age 20.8±2.2 years, experiencing first-episode psychosis (F20, F25) and 45 healthy age-matched young men (mean age 19.2±3.2 years) were examined. The average age of psychosis manifestation was 19.8±2.5 months. Clinical, psychopathological, psychometric (PANSS and HDRS) and immunological («Neuro-immuno-test¼ technology) examinations were carried out at the psychotic state, during period of psychopathological symptoms reduction and further for 1-2 years until complete/significant reduction of psychotic symptoms. RESULTS: Three stages of remission are revealed: I - the stage of reduction and modification of leading psychotic symptoms, II - the stage of stabilization of mental functions, III - the stage of reintegration of mental functions. It has been shown that each stage corresponds to different features of clinical symptoms and also certain spectra of immune markers (activity of leukocyte elastase, α1-proteinase inhibitor and level of autoantibodies to S100-B and OBM proteins) in blood serum of patients. The differences in the spectra of immune parameters at the second stage of remission in patients with affective (depressive) disorders define various patterns of post-psychotic development of disease. The most representative are immunological features of the third stage of remission. CONCLUSION: The dynamics of immune markers in the course of remission can be considered as a biological criterion for assessment of the outcome of the first first-episode psychosis and the completeness of remission.

[Specific features of immunological reactions in elderly and young patients with exacerbation of schizophrenia]. / Osobennosti immunologicheskikh reaktsii u patsientov pozhilogo i molodogo vozrasta s obostreniem shizofrenii.

OBJECTIVE: To identify levels of inflammation markers (the enzymatic activity of leukocyte elastase (LE), the functional activity of the α1-proteinase inhibitor (α1-PI), autoantibodies to neurotrophin S100b and myelin basic protein (MBP)) in blood plasma of old- and young-aged patients with schizophrenia in comparison with features of the clinical course of schizophrenia. MATERIAL AND METHODS: Two age groups of patients with schizophrenia were examined. The 1st group consisted of 19 female patients, aged 60 to 78 years (mean age 67.3±5.4 years), with disease duration from 0.5 months to 29 years (9.7±7.6). The 2nd group comprised 24 female patients, aged 19 to 42 years (mean age 26.8±6.3 years), with disease duration from 0.15 to 6.6 years (3.3±2.4). Nineteen age-matched healthy women were included in two control groups. Inflammatory and autoimmune markers were measured in blood plasma using «Neuro-immuno-test technology¼. RESULTS: In the 1st group, a relative smoothness and rigidity of the productive symptoms profile, a reduction of disease progression and a tendency to the development of negative symptoms were established. The 2nd group was characterized by polymorphism, severity and dynamism of productive disorders, as well as the progression and lability of the schizophrenic process. The most significant differences in the spectrum of the analysed immune markers relate to the ratio of the activity of LE and its inhibitor α1-PI, i.e. proteinase-inhibitory index (PII). CONCLUSIONS: The identified multidirectional changes of PII in elderly patients compared to the controls may reflect the imbalance of the inflammatory response and the role of this imbalance in shaping the characteristics of psychopathological symptoms in these patients.