Effect of Neurotropic and Immunotropic Drugs on Leukocyte Elastase Activity In Vitro.

Leukocyte elastase is a marker of inflammation. Previously, a relationship was found between the severity of mental disorders in patients and elastase-like activity of blood plasma. The effect of various neurotropic drugs on leukocyte elastase activity was analyzed in an in vitro experiment. We revealed an inhibitory effect of the benzodiazepine tranquilizers diazepam and bromodihydrochlorophenylbenzodiazepine and immunomodulators aminodihydrophthalazinedione and diclofenac on the plasma elastase-like activity of healthy donors and pure human neutrophil elastase. The antipsychotics chlorpromazine and alimemazine, as well as the nootropic vinpocetine increased elastase-like activity in a dose-dependent manner. The activating effect of chlorpromazine and vinpocetine, but not alimemazine, was reproduced in neutrophil elastase. We hypothesized that these drugs can affect the development of inflammatory reactions in the complex therapy of mental disorders.

[Functional hypercortisolism in mental disorder - association with psychopathological manifestations and course of the disease]. / Funktsional'nyi giperkortitsizm pri psikhicheskom rasstroistve ­ assotsiatsiya s psikhopatologicheskimi proyavleniyami i techeniem zabolevaniya.

The article presents a case of a long-term mental disorder in a 35-year-old woman with a persistent laboratory-confirmed increase in cortisol levels, without clinical manifestations of hypercortisolism. The first signs of mental illness appeared at the age of 14; over the past 8 years, the disease has been continuous and manifests itself in the form of a predominantly depressive state with increasing severity and complication of symptoms. Throughout all the years of the disease, active psychopharmacotherapy was carried out, combinations of antidepressants with antipsychotics and mood stabilizers were used, but no pronounced effect was achieved. Inpatient treatment in the clinic of the Mental Health Research Center for 5 months using several methods of enhancing antidepressant therapy had a good therapeutic effect and made it possible to achieve complete remission of the disease. There was a normalization of laboratory parameters of cortisol along with a decrease in the severity of pathopsychological symptoms, which indicates the genesis of hypercortisolism secondary to mental illness and its functional nature. It is assumed that hypercortisolism in this patient contributed to the formation of atypical clinical symptoms and resistance to antidepressant therapy. The discussion substantiates the need to consult a psychiatrist in case of persistent hypercortisolism in the absence of clinical manifestations of Cushing's syndrome. The detection of persistent hypercortisolism in patients with depression determines the advisability of active therapy using several tactics to enhance the effect of antidepressants.

[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.

[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).

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.

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.

Neurotropic peptide HLDF-6-amide reduces age-related decline in sexual activity in old male rats.

Aging is associated with a decline in the erectile capacity and sexual motivation. Emerging new therapy for the treatment of these age-related pathologies in men is the use of the regulatory peptides. We validated the use of HLDF-6-amide (Thr-Gly-Glu-Hse-His-Arg-NH2) as a potential modulator of sexual performance in aged male rats. Behavioral tests, including the standard parameters of sexual behavior, were performed longitudinally at 20 and 26 months of age. The effects of HLDF-6-amide administered daily at 300 µg/kg for 3 week on the levels of sex hormones and the activity of antioxidant enzymes and indicators of inflammation were evaluated. HLDF-6-amide administration increased the copulative activity of the 20-month-old male rats. This effect of HLDF-6-amide was more pronounced in the 26-month-old rats. Although HLDF-6-amide did not have the effect on the levels of circulating testosterone and estradiol, it reduced the activity of leukocyte elastase and glutathione-S-peroxidase, suggesting that the peptide has anti-inflammatory and antioxidant properties. Therefore, this study shows that HLDF-6-amide has the positive impact on sexual activity in this rodent model, representing a new therapeutic approach for improving sexual performance in older men.

[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.

[A combined marker of catatonia severity including autoimmune and thrombodynamic parameters in patients with autism spectrum disorder]. / Kombinirovannyi marker tyazhesti katatonii, vklyuchayushchii immunnye i trombodinamicheskie pokazateli, u bol'nykh s rasstroistvami autisticheskogo spektra.

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.

[The association of aromatic microbial metabolites, inflammatory and autoimmune biomarkers with clinical dynamics in severe diseases of the central nervous system]. / Svyaz' aromaticheskikh mikrobnykh metabolitov, vospalitel'nykh i autoimmunnykh biomarkerov s klinicheskoi dinamikoi pri tyazhelykh zabolevaniyakh tsentral'noi nervnoi sistemy.

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.

[Features of the immune profile of schizophrenic patients with catatonic syndrome]. / Osobennosti immunnogo profilya bol'nykh shizofreniei s katatonicheskim sindromom.

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.