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In the treatment of experimental neurodegeneration with disaccharide trehalose, various regimens are used, predominantly a 2% solution, drunk for several weeks. We studied the effects of different regimens of dietary trehalose treatment in an amyloid-β (Aβ) 25-35-induced murine model of Alzheimer's disease (AD). Aβ-treated mice received 2% trehalose solution daily, 4% trehalose solution daily (continuous mode) or every other day (intermittent mode), to drink for two weeks. We revealed the dose-dependent effects on autophagy activation in the frontal cortex and hippocampus, and the restoration of behavioral disturbances. A continuous intake of 4% trehalose solution caused the greatest activation of autophagy and the complete recovery of step-through latency in the passive avoidance test that corresponds to associative long-term memory and learning. This regimen also produced an anxiolytic effect in the open field. The effects of all the regimens studied were similar in Aβ load, neuroinflammatory response, and neuronal density in the frontal cortex and hippocampus. Trehalose successfully restored these parameters to the levels of the control group. Thus, high doses of trehalose had increased efficacy towards cognitive impairment in a model of early AD-like pathology. These findings could be taken into account for translational studies and the development of clinical approaches for AD therapy using trehalose.

In an experimental model of Alzheimer's disease in mice, oral administration of trehalose disaccharide reduces neuroinflammation assessed by the expression level of microglia activation marker Iba1 and affects the neutrophil degranulation activity. A potential anti-inflammatory effect of 4% trehalose solution associated with a decrease in the activity of leukocyte elastase in plasma was revealed., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

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 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., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

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; χ 2 =10.44; p =0.001 and χ 2 =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.

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 «new» subpsychotic structure, a «psychotic character», 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).

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.

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)·10 9 /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., (© Springer Nature Switzerland AG 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

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 fatigue» (75.8%) and «physical fatigue» (72.6%), more rarely «mental fatigue» was observed (32.2%). Correlations of «general fatigue» 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 fatigue» and reduced ejection fraction (EF) of the left ventricle ( p =0.005), as well as «physical fatigue» 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.

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) disorder» (F06.6) and «Organic Anxiety Disorder» (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.

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.

Induction of autophagy is a prospective approach to the treatment of neurodegeneration. In the recent decade, trehalose attracted special attention. It is an autophagy inducer with negligible adverse effects and is approved for use in humans according to FDA requirements. Trehalose has a therapeutic effect in various experimental models of diseases. This glucose disaccharide with a flexible α-1-1'-glycosidic bond has unique properties: induction of mTOR-independent autophagy (with kinase AMPK as the main target) and a chaperone-like effect on proteins imparting them natural spatial structure. Thus, it can reduce the accumulation of neurotoxic aberrant/misfolded proteins. Trehalose has an anti-inflammatory effect and inhibits detrimental oxidative stress partially owing to the enhancement of endogenous antioxidant defense represented by the Nrf2 protein. The disaccharide activates lysosome and autophagosome biogenesis pathways through the protein factors TFEB and FOXO1. Here we review various mechanisms of the neuroprotective action of trehalose and touch on the possibility of pleiotropic effects. Current knowledge about specific features of trehalose pharmacodynamics is discussed. The neuroprotective effects of trehalose in animal models of major neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases are examined too. Attention is given to translational transition to clinical trials of this drug, especially oral and parenteral routes of administration. Besides, the possibility of enhancing the therapeutic benefit via a combination of mTOR-dependent and mTOR-independent autophagy inducers is analyzed. In general, trehalose appears to be a promising multitarget tool for the inhibition of experimental neurodegeneration and requires thorough investigation of its clinical capabilities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

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 «Neuroimmunotest» 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).

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.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

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.

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-test» 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.

Introduction: Schizophrenia, although a debilitating mental illness, greatly affects individuals' physical health as well. One of the leading somatic comorbidities associated with schizophrenia is cardiovascular disease, which has been estimated to be one of the leading causes of excess mortality in patients diagnosed with schizophrenia. Although the shared susceptibility to schizophrenia and cardiovascular disease is well established, the mechanisms linking these two disorders are not well understood. Genetic studies have hinted toward shared lipid metabolism abnormalities co-occurring in the two disorders, while lipid compounds have emerged as prognostic markers for cardiovascular disease. In particular, three ceramide species in the blood plasma, Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1), have been robustly linked to the latter disorder., Aim: We aimed to assess the differences in abundances of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) in the blood plasma of schizophrenia patients compared to healthy controls., Methods: We measured the abundances of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) in a cohort of 82 patients with schizophrenia and 138 controls without a psychiatric diagnosis and validated the results using an independent cohort of 26 patients with schizophrenia, 55 control individuals, and 19 patients experiencing a first psychotic episode., Results: We found significant alterations for all three ceramide species Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) and a particularly strong difference in concentrations between psychiatric patients and controls for the ceramide species Cer(d18:1/18:0)., Conclusions: The alteration of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) levels in the blood plasma might be a manifestation of metabolic abnormalities common to both schizophrenia and cardiovascular disease., Competing Interests: Conflict of interests: The authors declare no conflict of interest., (© Authors, 2021.)

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-test» 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.

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 1 st 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 2 nd 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 technology»., Results: In the 1 st 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 2 nd 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.

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 «classic» 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.

Objective: An analysis of inflammatory and autoimmune markers in schizophrenic patients with- and without catatonic symptoms in comparison to healthy controls., Material and Methods: A sample of 170 patients with paranoid schizophrenia was stratified by the presence of catatonic symptoms in the structure of psychosis (66 patients with catatonia and 104 patients without catatonia), inclusion threshold was >10 points on the Bush-Francis catatonia scale. The examination was carried out in the early days of inpatient treatment using psychopathological, psychometric and immunological methods., Results: Quantitative and qualitative differences in the spectrum of immune indicators in both groups of patients are revealed. A higher level of the immune system activation is found in the group with catatonic symptoms that indicates a worsening of the pathological process. A specific feature of the immunological profile of catatonic syndrome in schizophrenia is a decrease in ratio between leukocyte elastase and a1-proteinase inhibitor (leukocyte-inhibitory index) accompanied by the increase of other inflammatory markers that, presumably, indicates the deterioration of the phagocyte component of the inflammatory response., Conclusion: The results suggest that the decrease in leukocyte-inhibitory index is a potential biomarker of catatonic syndrome in schizophrenia.

Objective: To study the efficacy of the immunomodulatory drug γ-D-glutamyl-L-tryptophan in complex therapy of asthenic disorders in remissions in patients with schizophrenia and to analyze clinical and immunological indicators., Materials and Methods: Sixty-three male patients (aged 41.9±9.46 years) with paroxysmal-progressive schizophrenia in remission (ICD-10 F20.x1; F20.x2), including 24 patients with affective-asthenic and 39 with negative-asthenic types, were studied. The assessment of the patients' condition was carried out using PANSS, SANS, CDSS, MFI-20. The activity of inflammatory markers: leukocyte elastase (LE) and α1-proteinase inhibitor (a1-PI) was determined in blood serum. The clinical and immunological assessment was performed before, after therapy (in 5 days) and at the remote stage (in a month)., Results: Augmentation of standard therapy with γ-D-glutamyl-L-tryptophan facilitated positive reduction in the main clinical manifestations of endogenous asthenia of both types in comparison with placebo ( p <0.02). The features of the protease inhibitor system revealed in the patients confirm their clinical heterogeneity and also determine varying efficacy of augmentation by the immunotropic medicine. For patients with the low level of protease activity, which is characteristic of endogenous asthenia with prevalence of negative disorders in clinical picture, the augmentation by γ-D-glutamyl-L-tryptophan was more effective: the decrease in severity of asthenic symptoms was followed by the significant increase in the relatively reduced LE activity ( p <0.01), which presumably, relates to the insufficiency of functional activity of neutrophils., Conclusion: Augmentation of complex therapy of asthenic disorders in schizophrenia by γ-D-glutamyl-L-tryptophan can be recommended.

Objective: To verify a working hypothesis that thrombodynamic parameters of hypercoagulation and neuro-immune test correlate with the severity of catatonia in patients with autism spectrum disorder (ASD), and the combination of these indicators can predict the severity of catatonia with high accuracy and precision., Material and Methods: Twenty-four patients with ASD (22 boys and 2 girls) with infantile psychosis in childhood autism (ICD-10 F84.02) were studied. The median age of the patients was 5,5 years. Neuro-immune and thrombodynamics tests were performed., Results and Conclusion: Thrombodynamic parameters of clot growth rates from the activator (V, Vi and Vst) are significantly higher than their normal values. The values of the time of spontaneous clots occurrence (Tsp) are significantly less than the lower limit values for the norm (30 min). It was also shown that the activity of leukocyte elastase (LE) and the functional activity of the α1 protein inhibitor (α1-PI) are significantly higher than their normal values. The values of the levels of autoantibodies to S100 protein (aabS100B) and the basic myelin protein (aabOBM) are within the normal range. The initial clot growth rate (Vi) and the time of spontaneous clots occurrence (Tsp) significantly correlate with the severity of catatonia: Spearman's R is 0,55 for Vi ( p =0,009) and -0,61for Tsp ( p =0,002). Among the parameters of the neuro-immuno-test, only aabS100B indicator significantly correlates with the severity of catatonia. To increase the informative significance and accuracy of the contribution of the studied correlates of thrombodynamics and the neuro-immuno-test to the assessment of the severity of catatonia in children with ASD, a multivariate linear regression analysis was performed to construct a linear equation for the relationship between the severity of catatonia and correlates of thrombodynamics and a neuro-immuno-test. The determination coefficient R2, which determines the informational significance of the regression model, is 0,63. The remaining 37% is explained by unaccounted and not yet known factors.

Objective: To determine factors of innate and acquired immunity in adaptation disorders with a predominance of asthenic or anxiety-depressive syndrome., Material and Methods: Twenty-five patients with ICD-10 diagnosis of «Adaptation Disorders» (F43.2), including 9 with asthenic syndrome and 16 with anxiety-depressive syndrome, were examined. The control group consisted of 23 healthy individuals. The relative number of lymphocyte phenotypes was determined by flow cytometry; the concentration of IgM, IgG, IgA, aAB to S100b and MBP - by ELISA; CIC level - by the method of selective precipitation with PEG-6000; phagocytic activity of neutrophils by a test system with melamine-formaldehyde latex; activities of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) by a spectrophotometric method., Results: There were significant changes in the parameters of acquired immunity in the group with asthenic syndrome and those of innate immunity in the group with anxiety-depressive syndrome. An increase in α1-PI activity, in the total number of significant correlations between different immunological parameters, in the involvement of α1-PI in integration of acquired and innate immunity were observed in the anxiety-depressive group compared with the asthenic group., Conclusions: The peculiarities of stress response in patients with leading anxiety-depressive syndrome are the high activity of α1-PI, which, along with the strengthening of correlation intersystem associations and the involvement of this protein in the integration of acquired and innate immunity, allows us to consider α1-PI as a criterion that improves the accuracy of diagnosis of the nature of the course of adaptation disorders.

Objective: Screening of children 18-48 months of age at risk of mental and developmental disorders in the general population., Material and Methods: The survey was conducted by a continuous epidemiological method in primary health care institutions in the nine largest regions of Russia. For the period 2017-2019, 595 691 parents of children, aged 18-48 months, were surveyed., Results and Conclusion: The prevalence risk rate for mental and developmental disorders was determined as 1.307:10 000. The prevalence rate for mental and behavioural disorders (ICD-10) was 151:10 000. The analysis of the structure of mental and behavioural disorders was carried out. An increase in cases of pervasive developmental disorders (item F84) was detected - autism spectrum disorders (ASD) with an increase in the age of children. The prevalence of ASD under the age of 48 months was found to be 18:10 000, compared with 2015-2016 - 5:10 000 under the age of 24 months.

Objective: To identify the association between the changes in the profile of microbial metabolites, inflammatory and autoimmune markers and the dynamics of neurological status in chronic critically ill patients with diseases of the central nervous system (CNS)., Material and Methods: Sixty serum samples from 37 patients, aged 19-77 years, with severe CNS diseases were studied. The changes in clinical condition were assessed with NIHSS, the Rankin scale, the Glasgow Coma Scale, the FOUR Coma Scale and the Rivermead Mobility Index. The levels of aromatic microbial metabolites (AMM) and several inflammatory and autoimmune biomarkers, including the contents of procalcitonin (PCT) and S100, the activity of leukocyte elastase (LE) and a1-proteinase inhibitor a1-PI, the levels of autoantibodies to S100b and MBP were measured. Serum from 60 age- and sex-matched healthy people with no signs of neurological and somatic pathology was used as a control., Results: All patients were divided into groups depending on the neurological dynamics: A - positive ( n =16), B - without dynamics ( n =15), C - negative ( n =6). The study revealed a profile of AMM, as well as inflammatory and autoimmune biomarkers associated with the severity of neurological disorders. A significant increase in acute phase proteins, S-100 level and a decrease in the functional activity of neutrophils (via LE activity) were observed in the serum of patients. The different dynamics of neurological status was associated with the multidirectional changes in the microbial metabolites profile and biomarkers. The correlations between the clinical and biological parameters indicate that AMM might modulate immune reactions in patients with different dynamics of neurological status., Conclusion: The results suggest the involvement of AMM and the level of immune activation via biomarkers in the pathogenesis of neurological dysfunction. Dynamic changes in the profile of microbial metabolites and the level of activation of the immune system may be a promising tool for prediction of neurological recovery.

Aim: To search for the immunological features of depressions in elderly patients, select certain immunophenotypes and analyze their possible connection with clinical and psychopathological features of depression of old age., Material and Methods: The study included 55 inpatients of old age (median 68 years) with a depressive episode of mild or moderate severity. The control group consisted of 41 elderly people (median 67 years) without depressive disorders. Clinical, psychometric, immunological and statistical methods were used. The rating scales were HAMD-17 and MMSE. The activity of inflammatory and autoimmune markers, including enzymatic activity of leukocyte elastase (LE), α1-proteinase inhibitor (α1-PI), level of autoantibodies to neurospecific antigens S-100B and myelin basic protein, in the serum of patients and control subjects was determined., Results and Conclusion: The scatter in the immunological parameters both in the direction of exceeding the average values and their decrease was shown in the group of depressed elderly patients compared to the controls. Cluster analysis revealed two immunophenotypes of elderly patients with depression. Immunophenotype A is a group of patients with increased PE activity and immunophenotype B is a group of patients with decreased LE activity (p<0.0000). Immunophenotype A includes patients with complex depressions, comorbid with anxiety and senesto-hypochondriac disorders. In immunophenotype B, patients with prolonged apatic/adynamic depressions (p<0.05), with an earlier onset and longer duration of the disease, with incomplete remissions and more burdened with cardiovascular diseases were more common (p<0.05).

The study describes the latest recommended and adopted clinical and management practice for children and adults with autistic spectrum disorder (ASD) in Russia and discusses the most recent research work by Russian clinicians and neuroscientists in the field. The study also presents data from the first epidemiological studies on ASD prevalence and explores the latest recommendations for clinical-biological assessments for ASD diagnosis and management in Russia. The authors call for collaboration of experts in ASD field to exchange clinical and research ideas between professionals from Russia and Western European countries and expand our mutual knowledge about ASD. This should include clinical and neurobiological studies aiming to develop differential rational approaches for ASD individual management throughout lifespan of these affected individuals.

We provide an overview of the recent achievements in psychiatric genetics research in the Russian Federation and present genotype-phenotype, population, epigenetic, cytogenetic, functional, ENIGMA, and pharmacogenetic studies, with an emphasis on genome-wide association studies. The genetic backgrounds of mental illnesses in the polyethnic and multicultural population of the Russian Federation are still understudied. Furthermore, genetic, genomic, and pharmacogenetic data from the Russian Federation are not adequately represented in the international scientific literature, are currently not available for meta-analyses and have never been compared with data from other populations. Most of these problems cannot be solved by individual centers working in isolation but warrant a truly collaborative effort that brings together all the major psychiatric genetic research centers in the Russian Federation in a national consortium. For this reason, we have established the Russian National Consortium for Psychiatric Genetics (RNCPG) with the aim to strengthen the power and rigor of psychiatric genetics research in the Russian Federation and enhance the international compatibility of this research.The consortium is set up as an open organization that will facilitate collaborations on complex biomedical research projects in human mental health in the Russian Federation and abroad. These projects will include genotyping, sequencing, transcriptome and epigenome analysis, metabolomics, and a wide array of other state-of-the-art analyses. Here, we discuss the challenges we face and the approaches we will take to unlock the huge potential that the Russian Federation holds for the worldwide psychiatric genetics community.

The objective of the study was to investigate the association between catatonia in autism spectrum disorder (ASD) and the levels of hair and serum trace elements and minerals in children with ASD. The levels of hair and serum trace elements and minerals of boys suffering from ASD with (n = 30) and without (n = 30) catatonia, as well as 30 age- and sex-matched neurotypical controls were assessed using ICP-MS. Hair calcium (Ca) and selenium (Se) levels were lower in ASD patients as compared to the controls. Hair mercury (Hg) levels in ASD patients were more than 3-fold and 2-fold higher as compared to the controls and children with catatonia in ASD. Hair iodine (I) and manganese (Mn) were the lowest and the highest in ASD + Catatonia, respectively. Serum aluminium (Al) and cadmium (Cd) levels in healthy controls were significantly higher in comparison to the patients of both groups. Serum chromium (Cr), copper (Cu) levels were significantly increased in patients with ASD and catatonia, whereas vanadium (V) levels were elevated in patients both with and without catatonia. Multiple regression analysis demonstrated that hair Hg and serum Al and Cd levels were negatively associated with catatonia in ASD in crude and adjusted models. Although the etiology of catatonia in ASD is unclear, the obtained data demonstrate that catatonic symptoms in ASD may be at least partially mediated by altered trace element levels. Further studies are required to elucidate the role of trace elements in the potential signaling mechanisms of catatonia., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Introduction: At the present time, there is an increased interest in the search for biological predictors of the course and outcome of ischemic stroke (IS). Numerous studies have shown the relationship between neuroinflammation (in the brain) and systemic inflammatory response (in the blood)., Aim: To study the relationship of inflammatory and autoimmune markers in blood serum of patients with acute ischemic stroke (on the 1st day) with the dynamics of the severity of neurological deficit (on the 1st and 10th day) and to assess the predictive ability of these indicators., Material and Methods: Twenty-two patients in the acute period of IS (mean age 60±15.5 years) were examined. The severity of neurological deficit was assessed by ESS and NIHSS. The enzymatic activity of leukocyte elastase (LE), α1-proteinase inhibitor (α1-PI), level of autoantibodies to S-100B and MBP in serum was determined. The control group consisted of 33 healthy subjects. Blood samples were carried out on the 1st day of the post-stroke period, the clinical examination was performed on the 1 st and 10 th day of observation., Results: Depending on the dynamics of neurological symptoms by the 10th day of observation, two subgroups of patients were identified. The1st subgroup was characterized by the normalization of neurological deficit (n=10). In the 2 nd group, the negative dynamics of neurological deficit/lack of any positive changes was observed (n=12). Both subgroups demonstrated the increase in the LE and α1-PI activity as compared to the control (p=0.0019, p=0.00079; p=0.038, p=0.00041, respectively). The highest LE activity was detected in the 1 st subgroup (p=0.035). The high level of autoantibodies to MBP was also observed in the 1st subgroup as compared to the control and the 2nd group (p=0.047, p=0.03, respectively). The 2nd subgroup was characterized by a higher functional activity of acute phase protein α1-PI (p=0.04). Using regression analysis, a model for predicting the course of the early post-stroke period depending on the determined immunological parameters was developed., Conclusion: The results suggest that the studied inflammatory and autoimmune markers may be possible predictors of the course of the early post-stroke period.

The objective of the present study was to estimate the association between brain inflammatory markers and serum trace element levels as assessed by inductively coupled plasma mass spectrometry at NexION 300D. Leukocyte elastase (LE), α1-proteinase inhibitor (α1-PI) activity, anti-nerve growth factor-antibodies (anti-NGF-Ab), and anti-myelin basic protein-antibodies (anti-MBP-Ab) levels were assessed as inflammatory markers. The obtained data demonstrate that the increase in LE and α1-PI activity is associated with higher serum Cr and Cu levels, respectively. The increase in Anti-NGF-Ab levels was associated with a nearly significant 16% increase in serum Mn levels. Autistic children with high MBP-Ab levels were characterized by 28% higher serum Mn and lower Mg concentration. The results of correlation analysis were generally in agreement with the outcome of group comparisons. Regression analysis demonstrated that serum Mg was significantly negatively associated with LE activity, whereas both serum Fe and V concentrations were characterized by a positive influence on the parameter. In turn, serum Cu was a significant predictor of α1-PI, as well as Cr levels. At the same time, the serum concentrations of Cd and Fe were found to be inversely associated with α1-PI levels. Serum Cd and Mn levels were significant positive predictors of anti-MBP-Ab levels, whereas Mg levels had a negative impact on anti-MBP-Ab values. Generally, the obtained data demonstrate the interrelationship between trace element homeostasis and neuroinflammation in autism. Hypothetically, modulation of trace element status may be used for reduction of neuroinflammatory response, although further studies are required to reveal the underlying mechanisms of the observed associations., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Aim: To determine immunophenotypes of patients with adaptation disorders using cluster analysis. The level of inflammatory markers such as leukocyte elastase (LE) enzyme activity and functional activity of α1-protease inhibitor (α1-PI) were used as a classifying attribute (characteristic)., Material and Methods: The results of evaluation of enzymatic activity of LE and functional activity of α1-PI in 40 patients with adaptation disorders (ICD-10 F43.2) were subjected to cluster analysis. The control group included 23 age- and sex-matched healthy controls., Results: Several algorithms of cluster analysis allow to identify three immunophenotypes in the group of patients with adaptation disorders. Immunophenotypes differed significantly by ratios of LE and α1-PI activity, which were mostly driven by different LE activity. Cluster 1 with the relatively low LE activity and high background α1-PI, is of particular interest because it may reflect the disturbed interaction between the various links of immune response., Conclusion: The obtained results of cluster analysis confirm the hypothesis about the existence of three immunophenotypes in the patients with adaptation disorders, which indicates that a phenotypically similar pattern can be determined by different spectra of immune indices.

Aim: To quantify the relationship of Alzheimer's disease with the inflammatory markers: enzymatic activity of leukocyte elastase (LE) and functional activity of α1-proteinase inhibitor (α1-PI) on the basis of the logistic regression model and to build a model to predict the probability of AD in patients with mild cognitive impairment (MCI)., Material and Methods: The object of the mathematical analysis was the database, which included the results of assays of LE activity and functional α1-PI activity in blood plasma of 91 patients with a verified diagnosis of AD in inpatient or outpatient treatment and 37 age-matched healthy people., Results and Conclusion: The logistic regression model connecting LE and α1-PI with the probability of AD is built. The model has good statistical properties and high predictive efficiency. The results allow to obtain the quantitative estimate of the probability of AD by individual values of LE and α1-PI in patients with MCI.

The authors present a review of literature on the involvement of perinatal and postnatal mercury exposure in the pathogenesis of autistic spectrum disorders (ASD). A number of studies have shown a reliable association between perinatal and postnatal exposure to mercury and ASD development aa well as clinical and laboratory markers of the severity of these disorders. However the association was not confirmed in other studies. Such contradictions may be explained by differences in the composition of study groups, including geographical characteristics, and the influence of the factors related to mercury neurotoxicity.

Aim: To identify clinical, psychopathological, and immunological features of the asthenic symptom-complex in patients with schizophrenia and to analyze the possibility of optimizing complex therapy of these conditions using the immunotropic drug bestim., Material and Methods: Forty-three male patients, aged 20-55 years, were examined. Clinical examination of patients (PANSS, MFI-20) was performed before, and 5, 30 days after the end of treatment. The activity of inflammatory markers (leukocyte elastase (LE) and a1-proteinase inhibitor (a1-PI)) was determined in blood serum., Results: The affective-asthenic (32.5%) and asthenic-negative (67.5%) variants of the asthenic symptom-complex in schizophrenia characterized by different immune reactions (depending on LE activity) were revealed. Complex therapy with bestim contributed to a statistically significant reduction in the main clinical manifestations of endogenous asthenia in the majority of patients. More significant regression at a remote stage of the study was observed in the astheno-negative group of patients (p<0.001)., Conclusion: LE and a1-PI reflect the clinical and biological features of the asthenic symptom-complex which develops within the endogenous process. Normal/reduced activity of LE accompanied by the increased activity of a1-PI is the best predictor of bestim efficacy in terms of reduction of asthenic symptoms.

Aim: The evaluation of the risk of Alzheimer disease (AD) in patients with cognitive impairment, amnestic type (aMCI) on the basis of cluster analysis and logistic regression with the use of such markers of inflammation as enzymatic activity of leukocyte elastase (LE) and the functional activity of α1-proteinase inhibitor (α1-PI)., Material and Methods: The study object of statistical analysis was the database, including the results of LE activity and functional α1-PI activity in blood plasma of 78 outpatients with aMCI (25 men and 53 women, aged 44 to 89 years (69.1±9.95)., Results and Conclusion: Clustering by k-means and classification by logistic regression indicate a high probability of AD in patients with aMCI depending on the activity of LE and α1-PI in blood plasma. The total coincidence of objects included in the clusters and in the AD risk group was 94%. The high coincidence of two different methods of grouping confirms the previously stated notion of the possibility of identifying patients with the high risk of AD among patients with aMCI by the activity of LE and α1-PI in the blood.

The aim of the study was to reveal the set of neurobiological parameters informative for individual quantitative prediction of therapeutic response in schizophrenic patients. Correlation and regression analyses of quantitative clinical scores (by Positive And Negative Syndromes Scale - PANSS), together with background EEG spectral power values and four immunological parameters: enzymatic activity of leukocyte elastase and of alpha-1 proteinase inhibitor, as well as serum levels of autoantibodies to common myelin protein and to nerve growth factor, were performed in 50 patients (all females, aged 32.9±10.8 years) with hallucinatory-delusional disorders in the frames of attack-like paranoid schizophrenia. Background neurobiological data obtained before the beginning of syndrome based treatment course (at visit 1) were matched with PANSS clinical scores of the same patients after treatment course at the stage of remission establishment (at visit 2). The multiple linear regression equations were created which contained only 3 to 4 (from initial 80) background EEG parameters and one of four immunological parameters. These mathematical models allowed prediction from 65% to 76% of PANSS scores variance after treatment course (at visit 2). The data obtained may be used for elaboration of methods of individual quantitative prediction of treatment outcome in schizophrenic patients.

Aim: To identify inflammatory and autoimmune markers (enzymatic activity of leukocyte elastase (LE), functional α1-proteinase inhibitor (α1-PI), the level of autoantibodies to neurospecific antigens S100b and myelin basic protein (MBP)) as well as phagocytic activity of blood neutrophils of patients with disorders of adaptation, to determine certain immunophenotypes and analyze their possible relationships with disease characteristics., Material and Methods: The study included 40 patients with adaptation disorders, mostly women. Diagnostic evaluation and clinical qualification of patients was carried out in accordance with ICD-10: 'Adjustment disorder' (F43.2). The control group consisted of 23 individuals matched for age and sex with patients. The activity of LE and α1-PI was determined by spectrophotometry, and the levels of autoantibodies to S100b and MBP by ELISA, phagocytic activity by the absorptive capacity of neutrophils of peripheral blood of melamine-formaldehyde latex particles., Results: In the total group of patients with adaptation disorders, increased enzymatic activity of LE and functional α1-PI was shown compared to controls (p<0.001 and p<0.0001, respectively). There were no differences in the level of autoantibodies to neuroantigens, and changes in phagocytic index (PhN) compared with the control, however the tendency to reduction of phagocytic number (PhN) was observed. Patients were stratified by leading psychopathological symptoms (predominance of asthenic-depressive or anxious-depressive symptoms, polymorphic symptomatology) and by immunophenotype: (A) inflammatory markers - in the range of control values, (B) - the increase compared to the control activity of both LE and α1-PI, (C) preferential increase in the activity of α1-PI only. The frequency of these immunophenotypes was similar within each of the clinical subgroups., Conclusion: The results suggest the involvement of inflammation in the pathogenesis of adjustment disorders due to stress factors. Various immunological variants differed by proportion of inflammatory markers were not associated with clinical symptoms.

The primary objective of the present study was to investigate the levels of essential trace elements in hair and serum in children with autism spectrum disorder (ASD) and investigate the age and gender effects. Children with ASD were characterized by significantly higher levels of copper (Cu) (+8%), iron (Fe) (+5%), and selenium (Se) (+13%) levels in hair and only 8% higher serum Cu levels. After stratification for gender, ASD boys were characterized by significantly increased hair Cu (+ 25%), Fe (+ 25%), and Se (+ 9%) levels, whereas in girls only Se content was elevated (+ 15%). Boys and girls suffering from ASD were characterized by significantly higher serum manganese (Mn) (+20%) and Cu (+18%) as compared to the control values, respectively. In the group of younger children (2-5 years), no significant group difference in hair trace element levels was detected, whereas serum Cu levels were significantly higher (+7%). In turn, the serum concentration of Se in ASD children was 11% lower than that in neurotypical children. In the group of older children with ASD (6-10 years), hair Fe and Se levels were 21% and 16% higher, whereas in serum only Cu levels were increased (+12%) as compared to the controls. Correlation analysis also revealed a different relationship between serum and hair trace element levels with respect to gender and age. Therefore, it is highly recommended to assess several bioindicative matrices for critical evaluation of trace element status in patients with ASD in order to develop adequate personalized nutritional correction.

The existing data demonstrate a significant interrelation between ASD and essential and toxic trace elements status of the organism. However, data on trace element homeostasis in particular ASD forms are insufficient. Therefore, the objective of the present study was to assess the level of trace elements and electrolytes in serum of children with childhood and atypical autism. A total of 48 children with ASD (24 with childhood and 24 with atypical autism) and age- and sex-adjusted controls were examined. Serum trace elements and electrolytes were assessed using inductively-coupled plasma mass spectrometry. The obtained data demonstrate that children with ASD unspecified are characterized by significantly lower Ni, Cr, and Se levels as compared to the age- and sex-matched controls. At the same time, significantly decreased serum Ni and Se concentrations were detected in patients with childhood autism. In turn, children with atypical autism were characterized by more variable serum trace element spectrum. In particular, atypical autism is associated with lower serum Al, As, Ni, Cr, Mn, and Se levels in comparison to the control values. Moreover, Al and Mn concentration in this group was also lower than that in childhood autism patients. Generally, the obtained data demonstrate lower levels of both essential and toxic trace elements in atypical autism group, being indicative of profound alteration of trace elements metabolism. However, further detailed metabolic studies are required to reveal critical differences in metabolic pathways being responsible for difference in trace element status and clinical course of the disease., (Copyright © 2016 Elsevier GmbH. All rights reserved.)