Leukocyte Elastase Activity Research Articles

Risk of Alzheimer’s disease in patients with the syndrome of mild cognitive impairment, amnestic type (cluster analysis)

IntroductionThe creation of mathematical models for determining the risk of Alzheimer’s disease in patients with mild cognitive impairment based on immune markers of blood is important for differential diagnosis of AD, assessment of the clinical state of patients at different stages of the disease, and optimization of therapy.ObjectivesTo assess the risk of AD in patients with amnestic type of mild cognitive impairment (aMCI) 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).MethodsThe object of mathematical analysis on the basis of cluster analysis and logistic regression was the database, including the results of the above immunological parameters (enzyme activity of LE and functional activity of α1-PI.) in plasma of 78 patients with aMCI receiving outpatient treatment in the clinic of FSBSI “Mental Health Research Centre”. Among the examined patients there were 25 men and 53 women aged 44 to 89 years (69.1 ± 9.95).ResultsClustering by k-means and classification by logistic regression indicate the risk of developing 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%.ConclusionsThe high coincidence of the two different methods of grouping confirms the previously stated position on the possibility of identifying patients with a high risk of AD among patients with aMCI in the activity of LE and α1-PI in the blood of patients.DisclosureNo significant relationships.

Association between markers of inflammation and indicators of systemic endotoxemia in endogenous psychosis

IntroductionThe clinical and biological studies indicate the involvement of inflammation in the pathogenesis of endogenous mental disorders. The inflammation markers leukocyte elastase, α1-proteinase inhibitor, and autoantibodies to neuroantigens reflect the severity of the pathological process in the brain. Systemic endotoxemia is a pathological process caused by an excess of endotoxins in the systemic circulation, can be considered as one of the components of the inflammatory process in endogenous psychosis.ObjectivesTo evaluate the association between systemic inflammation markers and indicators of systemic endotoxemia in patients with endogenous psychosis.MethodsThe study included 25 patients aged 23-49 with endogenous psychoses (F20, F25) and 25 healthy people. The severity of symptoms was assessed using PANSS. We detected the activity of leukocyte elastase and a1-proteinase inhibitor, antibodies to neuroantigens, endotoxin (ET) concentration, and antibodies to endotoxin (aEТ) in serum.ResultsIn 24% of cases, an increase of inflammation markers activity, ET concentration, and aET deficiency were observed (p<0.05), which is an unfavorable factor that aggravates the clinical course of the disease. In 76% of cases, ET concentration remained within control values (p>0.05) but associated with different levels of aET, which is likely to be a consequence of previous endotoxin aggression. There were correlations between ET concentration and antibodies to neuroantigens S-100B and MBP. We also revealed the association between the activity of the inflammatory marker with the severity of clinical symptoms in patients.ConclusionsResults suggest the relationship between systemic inflammation markers and indicators of systemic endotoxemia and their involvement in the pathogenesis of endogenous psychosis.DisclosureNo significant relationships.

Innate and acquired immunity indices in assessing the clinical severity of patients with childhood schizophrenia

The results of previous studies suggest pathogenetic role of immune system in the development of schizophrenia. Examination of adolescent and young adult schizophrenic patients showed that the activity/ level of distinct parameters of innate and acquired immunity correlates with acuity and severity of pathological process in the brain. Presumably, evaluation of immune system characteristics in patients with childhood schizophrenia, concerning severity of their clinical symptoms, along with potential therapeutic aspect, may be the basis for early diagnosis of these conditions, and monitoring and prognosis of the further progression of the disease. The objective of our study was to compare clinical and immunological indices in children with schizophrenia to analyze the possibility of using these parameters for determination of the degree of activity of the pathological process. Sixty-two patients (39 boys and 23 girls) from 4 to 17 years of age with childhood schizophrenia were examined. Psychopathological and psychometric methods (PANSS and CGI-S scales) were used to assess mental state of the patients. Immunological parameters were determined in blood serum taken by fingerprick. Activity of leukocyte elastase (LE) and a1-proteinase inhibitor (a1-PI) was determined by spectrophotometric method. To determine the level of autoantibodies to S-100B and MBP, we used enzyme immunoassay. The study revealed activation of innate (by activity of LE and a1-PI) and acquired (by the level of autoantibodies to S-100B and MBP neuroantigens) immunity markers in blood serum of children with schizophrenia. Correlation analysis showed the significant positive correlation between complex evaluation of activation level of the immune system and severity of the patients’ state on the CGI-S scale (r = 0.64, p < 0.0001), as well as severity of negative symptoms according to the PANSS scale (r = 0.34, p = 0.0077). The revealed correlations suggest an opportunity for using immunological parameters (LE and a1-PI activity, and antibodies to neuroantigens), as the additional laboratory criteria for the assessment of clinical state in patients with childhood schizophrenia.

Вплив багатокомпонентної терапії на діастолічну функцію лівого шлуночка в пацієнтів з резистентною артеріальною гіпертензією

The aim – to determine prognostic factors of improving left ventricular diastolic function (LV DF) in resistant hypertension (RH) patients (pts) treated with multicomponent antihypertensive therapy during three years.Materials and methods. 102 patients with true RH were included. Patients received triple fixed combination (blocker of the renin-angiotensin-aldosterone system / calcium antagonist / diuretic), to which has been added a fourth drug (spironolactone, eplerenone, moxonidine, torasemide or nebivolol). The state of LV DF was studied at the beginning and at the end of the study. Office and 24-h ambulatory blood pressure (BP) measurements, echocardiography, clinical characteristics, neurohumoral and proinflammatory status were assessed.Results and discussion. Impairment LV DF was detected in 75.5 % of pts. The first degree of LV diastolic dysfunction (DD) was observed in 63.7 %. The patients were divided into 2 groups: the first group included persons without initial impairment of LV DF (n=25), the second – pts with LV DD (n=77). Patients with LV DD were older, had a longer duration of hypertension, higher body mass index, 24-h urinary albumin excretion, office BP and 24-h ambulatory BP, more often (in 2 times) disorders of circadian BP rhythm and concomitant diabetes mellitus (DM). Left ventricular DD in 100 % of cases was associated with severe LV hypertrophy (LVH), increased plasma concentration of inflammatory proteins (CRP, fibrinogen), cytokines (IL-6, TNF-α), increased activity of leukocyte elastase, macrophage matrix metalloproteinase-12. The concentration in the blood of aldosterone, active renin, 24-h urinary excretion of metanephrines did not differ between the groups.Conclusions. Improvement and stabilization of LV DF occurred in parallel with regression of LVH (normalization of LVMI in 35.1 % of pts and significant decrease of LVMI in 64.9 %) against the background of decrease of BP and in the proportion of pts with disturbed circadian BP rhythm. The independent factors of the E/E’ ratio were the initial plasma concentrations of aldosterone (β=0.556; р=0.0001), glucose (β=0.366; р=0.0001), active renin (β=–0.223; р=0.004), 24-h urinary albumin excretion (β=0.188; р=0.016), age (β=0,192; р=0,023). The odds of an improvement in LV DF increased by 3.7 times, if the patient with RH had no DM, LVH regression occurred.

Отдаленные неврологические последствия у детей от матерей с гестационным сахарным диабетом

Objective. To improve the early diagnosis of neurological pathology in children from mothers with GSD by studying their neuroimmune interactions using the “Neuro-test” technology. Patients and methods. 74 children aged 4–12 years from mothers with GSD were examined clinically: The control group consisted of 72 children born to mothers without endocrine pathology during pregnancy. A number of indicators of innate and acquired immunity were determined in the blood serum (activity of leukocyte elastase, alpha-proteinase inhibitor and autoantibodies to the proteins of the nervous tissue MBM, S100, GFAP and FRN). Results. Neuropsychiatric pathology was significantly more often detected in children from mothers with GSD at the age of 4–12 years compared with the control group (43.2% and 16.7%, p < 0.001). Moreover, at the age of 4–7 years, this pathology was more common in the study group, compared with children aged 8–12 years (66.7% and 31.7%, p = 0.003). It was noted that heart abnormalities were significantly more often detected in the study group (33.8% and 13.9%, p = 0.004). In children from mothers with GSD, elevated levels of AAT to nerve tissue proteins are more often detected (25.7% and 8.3%, p = 0.006). The possible mechanisms of the influence of the diabetic state of the mother on the embryo/fetus, leading to the development of pathology of the nervous system in children, are discussed. Conclusion. children born to mothers with GSD in the long-term period are characterized by a high incidence of pathology of the nervous system. Key words: gestational diabetes mellitus, neuropsychiatric pathology, leukocyte elastase, autoantibodies

Clinical-neurobiological correlations in young depressive patients with a history of suicidal attempts

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. 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). 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. 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.

Immunological and clinical aspects of the long-term stages of youth schizophrenia

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. 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. 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. 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).

Clinical and immunological correlates in endogenous psychoses developed after COVID-19

The clinical and immunological study of the potential impact of coronavirus infection on the course of endogenous psychosis. 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. 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. 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 Indicators of Infl ammation in Late-Life Bipolar Disorder

The aim of the study was to determine the immune markers of infl ammation in the blood plasma of the elderly patients with bipolar affective disorders (BD) in relation to the clinical specifi cities of the disease. Patients and methods: 134 blood samples from the elderly patients aged from 52 to 88 years old (mean age 66.7 ± 7.7 years) with diagnose of bipolar disorder were examined. Infl ammatory markers in the blood plasma were determined as follows: the enzymatic activity of leukocyte elastase (LE) and the functional activity of the D1-proteinase inhibitor (D1-PI), as well as the level of autoantibodies (aAB) to S100b and myelin basic protein (MBP), and the protease inhibitor index (PII), which was the ratio of LE and D1-PI activity and characterized the activity of the proteolytic system as the most important component of infl ammation. Cluster analysis was used to reveal immunotypes. Results and discussion: а signifi cant increase in D1-PI and the level of aAB to S100b was revealed in elderly patients diagnosed with bipolar disorders, as well as low proteolytic activity of infl ammation (according to PII). Immune markers of infl ammation in different types of affective episodes (depressions, manias, mixed affective states) and in therapeutic remission did not differ from each other. Immunological parameters in elderly patients with bipolar disorders depended on the severity degree of the affective disorder. A relationship was found between the severity of depression and the level of aAB to S100b; the difference between mania and hypomania in terms of LE and PII activity was shown; in mixed affective states immunological parameters differed from the control only in moderate disorders. Remission with residual symptoms differed from asymptomatic therapeutic remission in terms of LE and PII activity. The two identifi ed clusters (immunotypes) differed in the activity of LE and PII. Conclusion: the results indicated the participation of infl ammation in the pathogenesis of bipolar disorder, and the isolated immunotypes confi rmed the clinical diversity of the disease. The study of the pathogenetic signifi cance of infl ammation and the identifi cation of various immunotypes was aimed at search for new therapy targets, taking into account the contribution of infl ammation.

Features of Inflammatory Response in Juvenile Depression with Attenuated Symptoms of Schizophrenic Spectrum

Background: early nosological qualification of juvenile depression and detection in its structure of specific phenomena of schizophrenic spectrum makes it possible to identify the onset of an endogenous process and to provide timely therapeutic intervention. This becomes possible using an integrated approach based on a psychopathological assessment of patients and the determination of individual immunological indicators of blood. The objective: to determine the inflammation markers in patients with juvenile depression with attenuated symptoms of schizophrenic spectrum (ASSS) in relation to features of their clinical manifestation and response to therapy. Patients and methods: 50 patients aged 16 to 25 years with fi rst depressive episode with ASSS (F32.1, F32.2, F32.28, F32.8), of which 26 patients with attenuated psychotic symptoms (APS) and 24 ones with attenuated negative symptoms (ANS). The control group consisted of 19 mentally healthy volunteers. The leukocyte elastase (LE) and D1-proteinase inhibitor (D1-PI) activity and the level of autoantibodies (AB) to S100E and MBP were measured in blood plasma. The ratio of LE to D1-PI activity was defined as a leukocyte-inhibitory index (LII). Clinical and psychometric assessment (HDRS, SOPS, SANS scales) as well as immunological examination were carried out at admission to the hospital and at discharge. Results: the differences revealed in profiles of immunological parameters in patients with juvenile depression with ASSS reflect the different variants of the inflammatory response to pathological process. Regardless of the identified clinical group, only 24% of patients were characterized by a balanced immune response. The inflammatory response in 76% of cases was accompanied by varying degrees of insufficiency of neutrophils functional activity and an increase in D1-PI activity, i.e. reduced LII. In 44% of cases, a decrease in LII was also accompanied by an increase in the level of AB to S100E. The relationship between immunological profiles and clinical severity of depression with APS and ANS was confirmed. The patients with balanced immune response without an autoimmune component have the best therapeutic response. Conclusions: the results extend the concepts of the pathogenetic mechanisms of juvenile depression with ASSS and indicate various variants of inflammatory response associated with this pathological condition. Immunological analysis complements the clinical examination of patients in terms of assessing the severity of condition, prediction of the disease course and response to therapy.

Features of infllammatory reactions and clinical picture in elderly and young patients with schizophrenia

IntroductionIt is known that the intensity of inflammation weakens with age, and therefore it is of interest to study the clinical features of schizophreniс process in relation to the level of inflammatory markers.ObjectivesTo determine the level of inflammatory markers (the activity of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI), autoantibodies (aAB) to neurotrophin S100b and myelin basic protein) in plasma in different years old groups of patients with schizophrenia.MethodsTwo groups of patients with schizophrenia were examined: the 1st group - 19 women aged 60 to 78 years; the 2nd group - 24 women aged 19 to 42 years.ResultsAn increase in activity both of LE and α1-PI was found in young patients. This characterizes a balanced inflammatory response. Elderly patients showed a similar increase in the activity of α1-PI, however, LE activity did not exceed the control values. Insufficient LE activity probably characterizes a decrease in the functional activity of neutrophils. The negative correlation was revealed between the activity of LE and TotPsy (PANSS) in the group of elderly patients (r=-0.62, p<05) and positive correlation between aAB to S100b and TotNeg in both groups (r=0.56 and r=0.49, p<05 respectively). There is relationship between age, the activity of psychopathological symptoms and the rate of development of schizophrenia: the rapid course and variety of disorders at a young age, against the poverty of symptoms and a slow rate in the elderly.ConclusionsThere is relationship between the features of inflammatory reactions and clinical picture in elderly and young patients with schizophrenia.

The role of inflammation in pathogenesis of juvenile schizophrenia

IntroductionInflammation is now known to be a key factor in the development of schizophrenia. In this regard, the study of the pathogenic role of inflammation in the early stages of schizophrenic process is of particular importance, making it possible to assess its activity and to predict the development of the disease.ObjectivesTo compare the dynamics of inflammatory markers in blood of first-episode psychosis (FEP) patients and people at risk signs for schizophrenia in the course of the treatment. Juvenile depression (JD) with attenuated symptoms of schizophrenic spectrum (ASSS) was investigated as a risk group.MethodsThe patients aged 17-25 years (20 people, of which 10 FEP patients (F20) and 10 JD with ASSS ones (F32.1-2, F32.38, F32.8)) were examined at admission to the hospital and at discharge. The controls consisted of 10 healthy volunteers. Symptom severity was collected using PANSS, SOPS, SANS, HDRS. The inflammation markers (TNF-α, IL-6, IL-10, leukocyte elastase (LE), CRP, α1-proteinase inhibitor (α1-PI), anti-S100-beta antibodies) were determined in blood.ResultsAn increase of inflammatory markers in both groups compared to controls was found (p<0,05). The highest values of IL-6, LE, CRP, α1-PI and anti-S100-beta antibodies in FEP patients were revealed (p=0,03). After the treatment, the positive trend of inflammatory markers in FEP patients (p<0,05), but not in JD with ASSS patients was detected (except LE activity, p<0,05).ConclusionsThe results confirm the pathogenic role of inflammation in the development of endogenous mental disorders. The inflammatory markers studied reflect the activity of the pathological process in the early stages of schizophrenia.DisclosureNo significant relationships.

Immune heterogeneity of non-psychotic mental disorders

IntroductionCurrent studies indicate the involvement of inflammation in the pathogenesis of chronic non-infectious diseases, and therefore it is of interest to study the role of inflammation markers in non-psychotic mental disorders (NPMD).ObjectivesTo identify a number of inflammatory markers in serum of patients with NPMD.Methods73 patients with NPMD were examined (F43.2; F06.6). The comparison group consisted of 76 patients with endogenous psychosis (EGP) (F20.0; F25.0). The control group included 80 healthy people. The serum activity of leukocyte elastase (LE), α1-proteinase inhibitor (α1-PI) and the level of autoantibodies (aAb) to neuroantigens were determined.ResultsThree groups of patients with different variants of inflammatory response to the pathological process were identified. In group 1 (23.3%), all indices corresponded to the control values, which indicated the absence of the pathological process in brain. In group 2, there was a significant increase in activity both LE and α1-PI compared to control (p<0.05). This type of immune reaction characterized a balanced inflammatory response. It was found in 52% of patients with NPMD and in all patients with EGP. The aAb level also exceeded the control values (p<0.05). Group 3 (24.7%) showed an increase in α1-PI activity (p<0.05), but not in LE activity compared to control. Insufficient LE activity reflects a decrease in the functional activity of neutrophils.ConclusionsThe immune heterogeneity of NPMD according to the level of inflammatory markers was identified. 52% of patients with NPMD have a pronounced activation of inflammatory reactions accompanied by increased levels of aAb to neuroantigens.

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 26months of age. The effects of HLDF-6-amide administered daily at 300μg/kg for 3week 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.

Combined Diagnostic Accuracy of Total Leukocyte Count, Neutrophil Count, and Ultrasonography for the Diagnosis of Acute Appendicitis.

Acute appendicitis is a common surgical emergency that classically presents with right lower abdominal pain and tenderness on palpation. The diagnosis is often based on clinical examination in order to avoid the complications of surgery delay, yielding a high rate of negative appendectomies. Ultrasonography is a regularly used modality for establishing the diagnosis, whereas abdominal computed tomography (CT) is often used in sonologically equivocal cases. Other parameters include total leukocyte count, granulocytes, C-reactive protein (CRP), leukocyte elastase activity, D-lactate, phospholipase A2, and interleukin-6 (IL-6). We conducted a prospective study to assess the combined accuracy of total leukocyte count, neutrophil count, and ultrasound as an integrated diagnostic tool. The results of these investigations were tabulated and compared to histopathological evidence of acute appendicitis on biopsy (taken as the gold standard) to calculate sensitivity, specificity, positive predictive value, and negative predictive value. Combined sensitivity and specificity were calculated using cross-tabulation, whereas diagnostic accuracy was estimated from the receiver operating curve (ROC) at the optimal cut-off point. The results showed that the absence of inflammatory findings on ultrasound and normal blood parameters (total leukocyte count and neutrophil count) have a high combined diagnostic accuracy and appendicitis may be ruled out.

Immune-inflammatory markers in remission after a first-episode psychosis in young patients

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. 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. 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. 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.

The status of leukocyte-inhibitory system of inflammation in different age groups of patients with endogenous depression

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. 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. 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. 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.

Predicting the Risk of Depression in the Elderly by Immunological Indicators Research

Objective: to construct a mathematical model that predicts the state of depression by immunological parameters in the blood plasma of older people to further predict the development of the disease.Patients and methods: 55 hospitalized patients of late age (mean age 69.2 ± 6.9 years) with a depressive episode were included in the study. The control group consisted of 41 elderly people (average age 66.6 ± 6.2 years) without depressive disorders. The activity of inflammatory and autoimmune markers in the blood plasma of patients and control groups was determined: the enzymatic activity of leukocyte elastase (LE), the functional activity of the α1-proteinase inhibitor (α1-PI), the level of autoantibodies to neuro-specific antigens S100B and the myelin basic protein (MBP). Statistical data processing was performed using the R (R version 3.2.4) and STATA (version 12.1) programs. We used point-bead-correlation to measure the strength and direction of the relationship between the binary variable and continuous variables and logistic regression to predict the probability of occurrence of events of interest by the values of one or more independent variables (predictors).Results: in patients with depressive disorders, a statistically significant increase in the functional activity of α1-PI (p ≤ 0.05) and the level of autoantibodies to the neurospecific S100B antigen (p ≤ 0.05) was revealed compared with the control. LE activity and MBP level did not differ from the control (p = 0.12 and p = 0.1, respectively). Based on immunological parameters in elderly patients with depression, a mathematical model is constructed. The accuracy of the correct prediction of outcomes using the model as a whole was 83.33%, which indicates a high predictive efficiency of this model.Conclusion: the results of mathematical analysis obtained in this work indicate that immunological parameters such as the functional activity of α1-PI and S100B are statistically significantly associated with the likelihood of depression in the elderly. Indicators such as enzymatic activity of LE and the level of autoantibodies to MBP did not have a statistically significant effect on the desired probability.

Evidence-Based Psychiatry: Paraclinical Diagnostics of Asthenic Syndrome in Schizophrenia Based on the Determination of Leukocyte-Inhibitory Index

A leukocyte-inhibitory index (LII) is the ratio of the proteolytic enzyme leukocyte elastase (LE) to its inhibitor, an α1- proteinase inhibitor (α1-PI). LII characterizes the activity of the proteolytic system and can be considered as a potential objective criterion that determines both the course and the outcome of the disease. The changes of LII in schizophrenia patients with clinically diagnosed asthenia (schizoasthenia) and patients with schizophrenia without clinical signs of this syndrome were revealed. The objective: to study the possibility of the 95% confidence intervals for a comparative assessment of LII in patients with schizoasthenia and patients with schizophrenia without clinical signs of asthenic syndrome to obtain correct statistical conclusions. Patients and methods: Overall, 95 patients aged 20–55 years with paroxysmal-progressive (F20.x1) and paranoid (F20.00) schizophrenia were examined: 61 patients in the total sample were clinically diagnosed with asthenic symptom-complex. The enzymatic activity of LE and the functional activity of α1-PI were determined in blood serum. LII was calculated according to the formula. The confidence intervals were built using 4 different methods: Fieller’s theorem, delta method, regression methods and bootstrap method. Results: the statistical analysis indicates that the 95% confidence intervals of these indicators for the examined patient groups do not overlap. Therefore, these indicators relate to different populations, which mean the examined groups are characterized by different variants of the ratio of the proteolytic system components. Conclusion: the assessment of LII can serve as an objective statistically correct criterion for presence or absence of asthenic disorder in patients with schizophrenia in addition to clinical examination.

A combined marker of catatonia severity including autoimmune and thrombodynamic parameters in patients with autism spectrum disorder

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. 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. 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.