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Background: insufficient study of heterogeneous delusional disorders in schizophrenia and the role of inflammation in the development of the disease served as the basis for this study. The aim: to establish the role of immune mechanisms in the processes of the interaction of different forms of delusional symptom complexes in schizophrenia. Patients: 60 patients (mean age 38.4 ± 1.11 years) with the diagnosis “paranoid schizophrenia, continuous progressive course” (F20.00, ICD-10) were included in the study. The state of patients was defined by persistent delusional/hallucinatory delusional disorders. Based on the clinical assessment, patients were divided into three groups: 27 patients (group 1) with interpretative delusion, 22 patients (group 2) with delusion of influence based on the phenomena of mental automatism, and 11 examinees (group 3) with mixed forms of delusions (interpretative and delusions of influence with mental automatism). The control group consisted of 17 mentally and somatically healthy people, comparable with the patients by sex and age. Methods: inflammatory and autoimmune markers leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) activity, leukocyte inhibitor index (LII) and antibody (aAb) level to S100B and MBP were determined in the blood. Results: in all groups of patients, an increase in the activity of LE and α1-PI was revealed compared with the control (p < 0.05). In group 2, an increase in aAb level to S100B was also detected (p < 0.05). Intra-group differences in LE activity served as the basis for dividing patients into three clusters. Cluster 1 was characterized by moderate activation of the immune system and was represented mainly by patients with interpretative delusions (54.5% of patients in the corresponding clinical group). Clusters 2 and 3 were distinguished by a higher level of immune system activation. A distinctive feature of cluster 3 was low LE activity against the background of high α1-PI activity and elevated level of aAb to S100B. Clusters 2 and 3 were represented mainly by patients with delusion of influence (74.1%). Сonclusion: the study confirmed the involvement of inflammation in the pathophysiology of delusional disorders in paranoid schizophrenia and allowed us to identify the relationship between the psychopathological structure of these disorders and the features of the spectrum of immune markers. The highest level of activation of the immune system, as well as immunological features presumably indicating impaired permeability of the blood-brain barrier, were associated mainly with delusions of influence with the phenomena of mental automatism.

Background: the significance of the asthenic syndrome as one of the most distressing symptoms affecting the clinical outcome of chronic heart failure (CHF), and insufficient understanding of the pathophysiological aspects of asthenia determines the need to study the clinical and biological features of this syndrome in cardiac pathology. Objective: to determine of a number of inflammatory and autoimmune blood parameters in patients with CHF associated with asthenic disorders in comparison with hypertensive disease in relation to clinical and gender-age characteristics of patients. Patients and methods: 62 patients with CHF (study group; 64.4 ± 9.7 years) and 50 patients with hypertensive disease (HD) (comparison group; 55 ± 9.7 years) were examined. Somatic examination included consultation with a cardiologist. Psychometric assessment was performed using the MFI-20 scale and the MLHFQ questionnaire. In patients' blood, leukocyte elastase (LE) activity, α1-proteinase inhibitor (α1-PI), leukocyte inhibitory index (LII), concentration of CRP, IL-6, and levels of antibodies to S-100B and myelin basic protein were determined. Results: patients with CHF characterized by more pronounced manifestations of all dimensional asthenic disorders compared to patients with HD. The deterioration of CHF patients' quality of life was accompanied by the aggravation of asthenic symptoms on all subscales of the MFI-20 scale. In patients with CHF and HD, multidirectional changes in the leukocyte inhibitory index and significant quantitative differences in other immune parameters compared with the normative values were detected. CHF associated with asthenia was characterized by decreased activity of the blood proteolytic system (decrease in LII), a significant increase in the concentration of IL-6, CRP and antibodies to S-100B in the blood of patients compared to comparison group. Negative correlations between LE activity and several dimensions of the MFI-20 scale, and positive correlations between the severity of general asthenia, patient age, and IL-6 and CRP concentrations indicate the involvement of inflammation in the pathophysiology of asthenic disorders in the cardiac pathology discussed. Conclusion: low activity of blood proteolytic system and high level of inflammation are unfavorable factors in the development of asthenia in chronic heart failure. Qualitative and quantitative features of the spectrum of immunological parameters in patients with CHF are correlated with clinical and genderage characteristics and reflect the severity of both cardiological changes and asthenic symptoms.

Background: the results of previous studies suggest that the level of activation of inflammatory responses in the periphery correlates with the severity of cognitive impairment in patients with neurodegenerative diseases and can serve as an indicator of the activity of the current pathological process in the brain. Epigenetic factors are suggested to influence the regulation of (neuro)inflammation and cognitive recovery in elderly patients, which opens up a wide spectrum of therapeutic strategies for the treatment of age-associated diseases. Objective: to evaluate the possible effects of a comprehensive neurocognitive rehabilitation program on cognitive functioning and blood immunological parameters of elderly patients with mild cognitive impairment (MCI).Patients and methods: 507 participants of the “Memory Clinic” rehabilitation program with signs of MCI (F06.7, F06.78 according to ICD-10) were examined before the start of neurocognitive training and after its completion (after six weeks). Some patients (11.6%) were observed clinically one year after their inclusion in the program. Cognitive status was assessed using the Modified Hachinski Ischemic Scale, the Mini-Mental State Examination, the Montreal Cognitive Assessment, and the Clock Drawing Test. Enzymatic activity of leukocyte elastase (LE), functional activity of α1-proteinase inhibitor (α1-PI), and levels of antibodies to S-100B and myelin basic protein were determined in patients’ blood. The parameters of healthy donors were used as controls.Results: immunological examination of patients before the rehabilitation program revealed increased LE and α1-PI activity in the overall group compared to controls (p < 0.001 and p < 0.05). Using a previously developed regression model to identify a high-risk group for Alzheimer’s disease (AD) among patients with MCI, all subjects were divided into two groups (cut-off value p = 0.65). Group 1 (low-risk of AD, n = 330) was characterized by increased LE activity and α1-PI (p < 0.001), Group 2 (highrisk of AD, n = 177) was distinguished by decreased LE activity (p < 0.001) accompanied by high α1-PI activity (p < 0.001). After neurocognitive training, differently directed variants of the dynamics of immunological parameters associated with the severity of patients’ cognitive impairment on psychometric scales were identified in each group. For the most of the examined patients (61.3%) the training program turned out to be effective, which was confirmed by the positive dynamics of the psychometric scores and relative normalization of the blood inflammatory markers (p < 0.05). The highest effect of the rehabilitation program was typical for patients not included in the high-risk group for AD (p < 0.001). Follow-up examination revealed stabilization of cognitive functioning in 93.2% of those examined, most of whom were patients with an initially low risk of developing the disease (p < 0.01).Conclusion: neurocognitive rehabilitation of patients with MCI carried out in the “Memory Clinic” conditions can be considered as a social epigenetic factor modulating the current pathological process in patients with cognitive disorders, which is confirmed by objective immunological markers.

Special Issue: The ENIGMA Consortium: the first 10 years., 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., European Community's Seventh Framework Programme, Grant/Award Numbers: 278948, 602450, 603016, 602805; US National Institute of Child Health and Human Development, Grant/Award Numbers: RO1HD050735, 1009064, 496682; QIMR Berghofer Medical Research Institute and the Centre for Advanced Imaging, University of Queensland; ICTSI NIH/NCRR, Grant/Award Number: RR025761; European Community's Horizon 2020 Programme, Grant/Award Numbers: 667302, 643051; Vici Innovation Program, Grant/Award Numbers: #91619115, 016-130-669; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433-09-229; Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL); Spinozapremie, Grant/Award Number: NWO-56-464-14192; Biobanking and Biomolecular Resources Research Infrastructure, Grant/Award Numbers: 184.033.111, 184.021.007; Netherlands Organization for Health Research and Development (ZonMW), Grant/Award Numbers: 480-15-001/674, 024.001.003, 911-09-032, 056-32-010, 481-08-011, 016-115-035, 31160008, 400-07-080, 400-05-717, 451-04-034, 463-06-001, 480-04-004, 904-61-193, 912-10-020, 985-10-002, 904-61-090; NIMH, Grant/Award Number: R01 MH090553; Geestkracht programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: NWO/SPI 56-464-14192, NWO-MagW 480-04-004, 433-09-220, NWO 51.02.062, NWO 51.02.061; National Center for Advancing Translational Sciences, National Institutes of Health, Grant/Award Number: UL1 TR000153; National Center for Research Resources; National Center for Research Resources at the National Institutes of Health, Grant/Award Numbers: NIH 1U24 RR025736-01, NIH 1U24 RR021992; NIH Institutes contributing to the Big Data to Knowledge; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Numbers: U54EB020403, G0500092; National Institute of Mental Health, Grant/Award Numbers: R01MH117014, R01MH042191; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; Swedish Research Council, Grant/Award Numbers: 523-2014-3467, 2017-00949, 521-2014-3487; South-Eastern Norway Health Authority; the Research Council of Norway, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Icahn School of Medicine at Mount Sinai; Seventh Framework Programme (FP7/2007-2013), Grant/Award Number: 602450; National Institutes of Health, Grant/Award Numbers: R01 MH116147, R01 MH113619, R01 MH104284; South London and Maudsley NHS Foundation Trust; the National Institute for Health Research (NIHR)

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.

Objectives. To obtain quantitative assessment of the link between Alzheimer’s disease (AD) and inflammatory markers such as the enzymatic activity of leukocyte elastase (LE) and the functional activity of α1-proteinase inhibitor (α1-PI) using a logistical regression model, which was then applied to predicting the probability of AD in patients with mild cognitive impairment syndrome (MCI). Materials and methods. Mathematical analysis was run using a database containing the results of measurements of these immunological parameters (enzymatic activity of LE and functional activity of α1-PI) in the plasma of 91 patients with verified diagnoses of AD on in-patient or out-patient treatment and 37 healthy subjects of comparable age without clinical indications of somatic or mental pathology. Results and conclusions. A logistical regression model was constructed linking LE and α1-PI with the probability that a patient has AD. The model has favorable statistical properties and high predictive effectiveness. These results allow individual patients’ LE and α1-PI values to be used to generate quantitative probabilities that patients have AD.

Special Issue: The ENIGMA Consortium: the first 10 years.-- Karolinska Schizophrenia Project (KaSP)., 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., National Institute of Mental Health, Grant/Award Numbers: MH104284, MH116147, R01MH113619, R01 MH090553, R01MH117014, R01MH042191; Karolinska Institutet; Stockholm County Council; Southern and Eastern Norway Regional Health Authority; German Centre for Cardiovascular Research; DZHK; Siemens Healthineers; University of Queensland; US National Institute of Child Health and Human Development, Grant/Award Number: RO1HD050735; Australian National Health and Medical Research Council; Eunice Kennedy Shriver National Institute of Child Health & Human Development; National Institute on Drug Abuse, Grant/Award Numbers: UL1 TR000153, 1 U24 RR025736-01, 1 U24 RR021992; Brain Injury Fund Research Grant Program; Indiana State Department of Health Spinal Cord; Parents Against Childhood Epilepsy; Epilepsy Therapy Project, Fight Against Childhood Epilepsy and Seizures; Epilepsy Foundation; American Epilepsy Society; Knut and Alice Wallenberg Foundation; European Community's Horizon 2020 Programme; Vici Innovation Program; NWO Brain & Cognition Excellence Program; Netherlands Organization for Scientific Research; Hersenstichting Nederland; Netherlands Organization for Health Research and Development; Geestkracht Programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; Universiteit Utrecht; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek; National Center for Advancing Translational Sciences; National Institutes of Health; National Center for Research Resources; Consortium grant, Grant/Award Number: U54 EB020403; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Number: G0500092; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; the Research Council, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Swedish Research Council; European Community's Seventh Framework Programme, Grant/Award Number: 602450; King's College London; South London and Maudsley NHS Foundation Trust; Biomedical Research Centre; National Institute for Health Research.

Screening of children 18-48 months of age at risk of mental and developmental disorders in the general population.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.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.Скрининг детей 18—48 мес жизни из общей популяции на выявление риска возникновения нарушений психического развития (НПР).Обследование проводилось сплошным эпидемиологическим методом в учреждениях первичного звена здравоохранения в девяти регионах России. За период 2017—2019 гг. по разработанной авторами анкете (приведена полностью) было проанкетировано 595 691 родителей детей в возрасте 18—48 мес жизни.Определен показатель распространенности риска возникновения НПР — 1307 случаев на 10 000. Показатель распространенности психических расстройств и расстройств поведения (по МКБ-10) составил 151:10 000. Проведен анализ структуры психических расстройств и расстройств поведения. Выявлено увеличение случаев нарушений психического развития (рубрика F84) — расстройств аутистического спектра (РАС) с увеличением возраста детей. Распространенность РАС в возрасте до 48 мес жизни — 18:10 000, по сравнению с данными 2015—2016 гг. — 5:10 000 в возрасте до 24 мес жизни.

An analysis of inflammatory and autoimmune markers in schizophrenic patients with- and without catatonic symptoms in comparison to healthy controls.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 was10 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.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.The results suggest that the decrease in leukocyte-inhibitory index is a potential biomarker of catatonic syndrome in schizophrenia.Определение воспалительных и аутоиммунных маркеров у больных шизофренией с кататоническими симптомами и без таковых в сопоставлении с показателями здоровых.Обследованы 170 больных параноидной шизофренией: 66 с кататонической симптоматикой в психическом статусе, 104 без таковой. Критерием включения пациентов в исследование был показатель10 баллов по шкале кататонии Буша—Франциса. Обследование проводилось в условиях стационара с применением психопатологического, психометрического и иммунологического методов.Установлены количественные и качественные различия в спектре иммунологических показателей в выделенных группах пациентов. Более высокий уровень активации иммунной системы был выявлен у пациентов с наличием кататонической симптоматики, что свидетельствует о тяжести патологического процесса. Особенностью иммунологического профиля у больных с симптомами кататонии являлось снижение соотношения между лейкоцитарной эластазой и а1-протеиназным ингибитором (лейкоцитарно-ингибиторного индекса) на фоне повышения других маркеров воспаления, что, предположительно, свидетельствует об истощении фагоцитарного звена воспалительного ответа.Полученные результаты позволяют рассматривать снижение лейкоцитарно-ингибиторного индекса в качестве потенциального биомаркера кататонического синдрома при шизофрении.

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 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.Сравнительный анализ ряда воспалительных маркеров в различных возрастных группах пациентов с эндогенными депрессиями и сопоставление полученных данных с клиническими особенностями проявления депрессий.Обследованы 140 пациентов с эндогенной депрессией (ЭД) (F21, F31—F34 по МКБ-10) от 15 до 82 лет, из них 55 пациентов подростково-юношеского возраста (18,9±2,8 года), 30 больных среднего возраста (38,7±10,3 года) и 55 пациентов пожилого возраста (69,1±7,1 года). Общая длительность заболевания составила от 5 мес до 45 лет. Клинико-психометрическая оценка проведена c помощью шкалы Гамильтона (HDRS). 143 здоровых от 16 до 75 лет составили контрольные группы. В крови обследуемых определяли активность воспалительных маркеров ЛЭ и α1-ПИ, их соотношение (лейкоцитарно-ингибиторный индекс, ЛИИ), уровень антител к белкам S100B и ОБМ.Выявлено три иммунологических кластера, которым соответствуют различные клинические варианты ЭД. Для 52,9% пациентов (1-й кластер) характерен провоспалительный статус с активацией лейкоцитарно-ингибиторной системы, клиническим проявлением которого являются преимущественно «классические» ЭД в виде тревожных, тревожно-меланхолических и тревожно-апатических депрессий без выраженной негативной симптоматики. Два других кластера характеризуются дисбалансом лейкоцитарно-ингибиторной системы, связанным с недостаточной активностью а1-ПИ (2-й кластер) и недостаточной активностью ЛЭ (3-й кластер). Общей чертой таких ЭД является атипичное течение с преобладанием апато-адинамической и дисфорической депрессий в присутствии негативных расстройств, а также неблагоприятный прогноз. Дисбаланс лейкоцитарно-ингибиторной системы, ассоциированный с недостаточной активностью ЛЭ, характерен преимущественно для пациентов пожилого возраста и ассоциирован с большей длительностью заболевания.Статус лейкоцитарно-ингибиторной системы воспаления связан с клиническими особенностями проявления ЭД в разных возрастных группах пациентов. ЛИИ может служить дополнительным параклиническим критерием для дифференциальной диагностики ЭД и прогноза их развития.

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.Two age groups of patients with schizophrenia were examined. The 1In the 1The 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.Определение маркеров воспаления: энзиматической активности лейкоцитарной эластазы (ЛЭ); функциональной активности α1- протеиназного ингибитора (α1-ПИ); аутоантител к нейротрофину S100b и основному белку миелина (ОБМ) в плазме крови больных шизофренией пожилого и молодого возраста в сопоставлении с клиническими особенностями течения шизофренического процесса.Обследованы больные шизофренией двух возрастных групп: в 1-ю группу вошли 19 женщин в возрасте от 60 до 78 лет (средний возраст на момент обследования 67,3±5,4 года) с общей длительностью заболевания от 0,5 мес до 29 лет (9,7±7,6 года); 2-ю группу составили 24 женщины в возрасте от 19 до 42 лет, средний возраст на момент обследования 26,8±6,3 года, с общей длительностью заболевания от 0,15 до 6,6 года (3,3±2,4 года). В контрольные группы входили по 19 здоровых женщин соответствующего возраста. Воспалительные и аутоиммунные маркеры определяли в плазме периферической крови, используя медицинскую технологию «Нейро-иммуно-тест».В группе больных пожилого возраста клнически установлены относительная сглаженность профиля продуктивной симптоматики, снижение темпов прогредиентности заболевания и отчетливая тенденция к формированию негативных расстройств. Для групп пациентов молодого и зрелого возраста были характерны полиморфизм, острота и динамичность продуктивных расстройств, а также большая прогредиентность и лабильность течения шизофренического процесса. Между группами выявлены различия, наиболее выраженные в соотношении активности ЛЭ и ее ингибитора α1-ПИ — протеиназно-ингибиторного индекса (ПИИ). Отмечены разнонаправленные изменения ПИИ по отношению к соответствующим контролю у больных пожилого возраста, что может отражать несбалансированность иммунного ответа и возможную роль этого дисбаланса в формировании особенностей психопатологической симптоматики.

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.Изучение клинико-психопатологических и иммунологических особенностей становления ремиссии после первого психотического приступа в юношеском возрасте для определения закономерностей развития этого этапа и возможности использования полученных результатов для мониторинга, прогноза и оптимизации проведенной терапии.Обследованы 50 пациентов мужского пола юношеского возраста — от 16 до 25 лет (средний возраст 20,8±2,2 года), перенесших первый эндогенный психотический приступ (F20, F25). Контрольная группа состояла из 45 здоровых юношей соответствующего возраста (средний возраст 19,2±3,2 года). Средний возраст манифестации психоза составил 19,8±2,5 дня. Клинико-психопатологическое, психометрическое (шкалы PANSS и HDRS) и иммунологическое обследование (технология Нейро-иммуно-тест) проводилось на высоте психотического состояния, в период редукции приступообразующей симптоматики и далее в течение 1—2 лет до полной редукции/значимого послабления психотических симптомов.В ходе проведенного исследования выделено три основных этапа становления ремиссии: I — этап редукции и модификации ведущей психотической симптоматики, II — этап стабилизации психических функций, III — этап реинтеграции психических функций. Показано, что каждому этапу становления ремиссии соответствуют различные особенности клинической симптоматики, а также определенные спектры иммунных маркеров (активности лейкоцитарной эластазы, α1-протеиназного ингибитора и уровня аутоантител к белку S100-B и основному белку миелина) в крови обследованных пациентов. Различия в спектрах иммунных показателей, наблюдаемые на II этапе становления ремиссии при выявлении у пациентов аффективных расстройств депрессивного полюса, определяют разные закономерности постприступного развития заболевания. Наиболее показательными являются иммунологические особенности III этапа формирования ремиссии. Динамика иммунных маркеров в ходе становления ремиссии может рассматриваться в качестве биологического критерия для оценки исхода первого приступа юношеского эндогенного психоза и полноты достигнутой ремиссии.

Study aim. To develop a highly sensitive method for assaying platelet serotonin concentrations suitable for use in daily clinical practice. Materials and methods. The method was intended for assay of platelet-enriched plasma (PEP). Serotonin was assayed by high performance liquid chromatography (HPLC) with fluorimetric detection and a hematology analyzer. Results and discussion. Investigations of healthy subjects yielded platelet serotonin concentrations consistent with published data: from 2.19 to 4.87 nmol/109 platelets. Investigations of 30 patients with depressive disorders identified decreased platelet serotonin concentrations, with levels ranging from 0.11 to 2.89 nmol/109 platelets, along with a correlation between this value and clinical evaluation of the severity of depression. The authors regard the method developed here as suitable for clinical purposes.

The article discusses the current state of the problem a multidisciplinary approach to the diagnosis of infantile autism and early-onset schizophrenia, differentiation of these diseases. The purpose of this study, which has been conducted at the Mental Health Research Center, is to determine the biological (immunological and physiological), pathopsychological markers of infantile autism and early-onset schizophrenia for potential use as an additional differential diagnostic tool in the clinical evaluation of patients. Allocated to types of cognitive dizontogenezis, which are different and specific for infantile autism and early-onset schizophrenia. Timely early diagnosis of autism in childhood is important for follow-up habilitation. Habilitation of children can be built on the basis of the identification of the zone of proximal development, allowing adequately and correctly pick the individual correction programs for each sick child. In turn, the identification of the zone of proximal development can be performed using multidisciplinario approach.

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 (Проверка рабочей гипотезы: тромбодинамические показатели гиперкоагуляции и показатели нейроиммунотеста коррелируют с тяжестью кататонии у больных c расстройствами аутистического спектра (РАС), а комбинация этих показателей может с высокой точностью предсказывать тяжесть кататонии.Была сформирована группа из 24 больных с РАС (22 мальчика и 2 девочки) с инфантильным психозом при детском аутизме (F84.02). Медианный возраст больных был равен 5,5 года. Проводили нейроиммунотест и тест тромбодинамики.Было установлено, что при изучаемой патологии тромбодинамические показатели скоростей роста сгустка от активатора (V, Vi и Vst) статистически значимо выше их нормальных значений. Значения показателя времени появления спонтанных сгустков (Tsp) статистически значимо меньше нижних предельных значений для нормы (30 мин). Показатели активности лейкоцитарной эластазы и функциональной активности α1 протеинового ингибитора статистически значимо выше их нормальных значений. Уровни аутоантител к белку S100 (аАТS100Б) и основному белку миелина (аАТОБМ) находятся в пределах нормальных значений. Показатели инициальной скорости роста сгустка (Vi) и времени появления спонтанных сгустков (Tsp) статистически значимо коррелируют с тяжестью кататонии: корреляция по Спирмену R для показателя Vi=0,55

To determine factors of innate and acquired immunity in adaptation disorders with a predominance of asthenic or anxiety-depressive syndrome.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.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.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.Определение особенностей врожденного и приобретенного иммунитета при расстройствах адаптации с преобладанием в клинической картине астенического или тревожно-депрессивного синдрома.Обследовали 25 пациентов, поступивших на стационарное лечение с диагнозом по МКБ-10 «расстройства адаптации» (F43.2). Из них 9 больных с астеническим синдромом и 16 больных с тревожно-депрессивным. Контрольную группу составили 23 здоровых. Определяли относительное содержание фенотипов лимфоцитов методом проточной цитометрии; концентрацию IgM, IgG, IgA, аутоантитела (аАТ) к S100b и общему белку миелина методом иммуноферментного анализа; уровень циркулирующих иммунокомплексов методом селективной преципитации с полиэтиленгликолем-6000; фагоцитарную активность нейтрофилов в тест-системе с меламиноформальдегидным латексом; активность лейкоцитарной эластазы и α1-протеиназного ингибитора (α1-ПИ) спектрофотометрическим методом.Изменения показателей приобретенного иммунитета были установлены в группе пациентов с астеническим синдромом, врожденного — в группе пациентов с тревожно-депрессивным синдромом. При тревожно-депрессивном синдроме по сравнению с астеническим установлено повышение активности α1-ПИ, увеличение достоверных связей между различными иммунологическими показателями, усиление вовлеченности в интеграцию приобретенного и врожденного иммунитета α1-ПИ. Особенностями реакции на стресс у пациентов с ведущим тревожно-депрессивным синдромом является высокая активность α1-ПИ, что наряду с усилением корреляционных межсистемных ассоциаций и вовлеченности данного белка в интеграцию адаптивного и врожденного иммунитета позволяет рассматривать α1-ПИ в качестве критерия, повышающего точность диагностики характера течения этого расстройства.

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.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.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 (p0.0000). Immunophenotype A includes patients with complex depressions, comorbid with anxiety and senesto-hypochondriac disorders. In immunophenotype B, patients with prolonged apatic/adynamic depressions (p0.05), with an earlier onset and longer duration of the disease, with incomplete remissions and more burdened with cardiovascular diseases were more common (p0.05).Цель исследования. Поиск иммунологических особенностей депрессии при у пожилых больных, выделение определенных иммунофенотипов и анализ возможной их связи с клинико-психопатологическими особенностями депрессий позднего возраста. Материал и методы. Исследуемая выборка состояла из 55 госпитализированных больных позднего возраста (медиана 68 лет) с депрессивным эпизодом легкой или умеренной выраженности. Контрольную группу составил 41 человек пожилого возраста (медиана 67 лет) без депрессивных расстройств. Обследование больных проводили c использованием клинического, психометрического, иммунологического и статистического методов. Оценочными шкалами являлись шкала депрессии Гамильтона (HAMD-17) и краткая шкала оценки когнитивных функций (MMSE). В сыворотке крови больных и лиц контрольной группы определяли активность воспалительных и аутоиммунных маркеров: энзиматическую активность лейкоцитарной эластазы (ЛЭ), α1-протеиназного ингибитора, уровень аутоантител к нейроспецифическим антигенам S-100B и основному белку миелина. Результаты и заключение. В группе депрессивных больных пожилого возраста выявлен разброс изучаемых иммунологических показателей как в сторону превышения средних значений, так и их снижение по отношению к контролю. С помощью кластерного анализа было выявлено два иммунофенотипа больных пожилого возраста с депрессией. Иммунофенотип А - группа пациентов, у которых активность ЛЭ была повышена, и иммунофенотип В - группа пациентов с понижением активности ЛЭ (р0,0000). В иммунофенотипе А преобладали больные со сложными депрессиями, коморбидными с тревожными и сенесто-ипохондрическими нарушениями. В иммунофенотипе В чаще встречались больные с затяжными апатико-адинамическими депрессиями (p0,05), более ранним началом и большей продолжительностью заболевания, неполными ремиссиями и большей отягощенностью сердечно-сосудистыми заболеваниями (p0,05).

Serum samples were collected from children suffering from psychotic forms of autistic disorders – childhood autism (F84.02) and atypical childhood psychosis (F84.11) – and measures of innate and acquired immunity were assessed, i.e., leukocyte elastase activity, α1-proteinase inhibitor, C-reactive protein, and antibodies to nerve growth factor and myelin basic protein. Activation of innate immunity (increases in acute-phase inflammatory protein levels and activities) were seen in childhood psychosis. In more severe mental disorders such as atypical endogenous childhood psychoses, activation of both innate and acquired immunity was seen (increases in anti-neuroantigen antibody levels). A correlation between immunological and clinical measures was seen, which provided grounds for suggesting the involvement of innate and acquired immunity in the development of autistic and cognitive impairments in these children.

Proteins diffusing from tobacco pollen grains into external medium, being inactivated by low temperature (0°C), were shown to stimulate pollen germination in vitro. Fractionation of these proteins by affinity chromatography using α-D-methylmannopyranoside (MMP) immobilized on agarose resulted in the isolation of lectins stimulating germination. The mol wts of these lectins were estimated by SDS-PAGE as 58, 69, and 74 kD. A stimulatory effect of these lectins was determined by their specific interaction with carbohydrate determinants because a competitive sugar (0.3 M MMP) suppressed completely lectin effect on germination. Polyvalent lectins capable of erythrocyte agglutination were also found among diffused proteins. These lectins are glycoproteins with Glu/Man carbohydrate determinants. MMP did not affect their capability of agglutination. This finding permits a conclusion that pollen grain wall contains lectins differing in their carbohydrate specificity.

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).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.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.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.Цель исследования. Определение иммунофенотипов пациентов с расстройствами адаптации при помощи кластерного анализа с использованием в качестве классифицирующих признаков уровня таких функционально связанных воспалительных маркеров, как энзиматическая активность лейкоцитарной эластазы (ЛЭ) и функциональная активность α1-протеиназного ингибитора (α1-ПИ). Материал и методы. Объектом математического анализа (кластерный анализ) служила база данных 40 пациентов с расстройствами адаптации (по МКБ-10 F43.2), включающая результаты определения энзиматической активности ЛЭ и функциональной - α1-ПИ. Контрольную группу составили 23 здоровых, сопоставимых по возрасту и полу с пациентами. Результаты и заключение. Использование нескольких алгоритмов кластерного анализа экспериментальных данных позволило получить устойчивые решения из трех кластеров анализируемых воспалительных маркеров. Выявленные иммунофенотипы характеризуются различными соотношениями активности ЛЭ и α1-ПИ, и эта вариативность определяется прежде всего различной активностью ЛЭ. Особого внимания заслуживает кластер 1, характеризующийся достоверно низкими показателями активности ЛЭ на фоне высокой активности α1-ПИ, что, вероятно, является отражением нарушения связи между различными звеньями иммунного ответа. Полученные результаты кластерного анализа подтверждают гипотезу о существовании в группе пациентов с расстройствами адаптации трех иммунофенотипов, фенотипическая картина которых может определяться различными спектрами иммунных показателей.

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).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).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.Цель исследования. Оценка риска развития болезни Альцгеймера (БА) у пациентов с синдромом мягкого когнитивного снижения амнестического типа (аМКС) на основе кластерного анализа и логистической регрессии с использованием маркеров воспаления - энзиматической активности лейкоцитарной эластазы (ЛЭ) и функциональной активности α

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).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.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.Цель исследования. Количественная оценка связи болезни Альцгеймера (БА) с такими маркерами воспаления, как энзиматическая активность лейкоцитарной эластазы (ЛЭ) и функциональная активность α

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.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.In the total group of patients with adaptation disorders, increased enzymatic activity of LE and functional α1-PI was shown compared to controls (p0.001 and p0.0001, 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.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.Цель исследования. Определение воспалительных и аутоиммунных маркеров (энзиматическая активность ЛЭ, функциональная - α1-ПИ, уровень аутоантител к нейроспецифическим антигенам S100b и основному белку миелина (ОБМ)), а также фагоцитарной активности нейтрофилов крови пациентов с расстройствами адаптации, выделение определенных иммунофенотипов и анализ возможной их связи с особенностями течения заболевания. Материал и методы. Обследовали 40 пациентов с расстройствами адаптации (по МКБ-10 F43.2). Контрольную группу составили 23 здоровых. Активность лейкоцитарной эластазы (ЛЭ) и α1-протеиназного ингибитора (α1-ПИ) определяли спектрофотометрическим методом, уровни аАТ к S100b и ОБМ - иммуноферментным методом, фагоцитарную активность - по поглотительной способности нейтрофилов периферической крови частиц меламиноформальдегидного латекса. Результаты. В общей группе пациентов с расстройствами адаптации выявлено повышение энзиматической активности ЛЭ и функциональной - α1-ПИ; не выявлено различий в уровне аутоантител к нейроантигенам, а также изменения фагоцитарного индекса (ФИ); установлена тенденция к снижению фагоцитарного числа (ФЧ). При разделении пациентов на подгруппы в зависимости от ведущей психопатологической симптоматики установлено, что выявленные иммунофенотипы встречаются с равной частотой. Заключение. Констатирована вовлеченность реакций воспаления в патогенез расстройств адаптации и отсутствие связи между иммунологическими вариантами по соотношению воспалительных маркеров с клиническими особенностями симптоматики.

We studied physical development, behavioral characteristics, and learning capacity in the offspring of mice immunized with nerve growth factor and bovine serum albumin. High titer of antibodies to these factors in the blood of pregnant females determines high levels of these antibodies in the blood of their pups. These changes modulate physical development, behavior, and learning capacity of rat pups. The effects of these antibodies differed in the strength and directionality. Antibodies to nerve growth factor more markedly retarded physical development, reduced learning capacity, and considerably increased pain thresholds in animals.

Biolan containing carnosine and delta sleep-inducing peptide produced a protective effect on cerebellar granular cells from 7-day-old rats exposed in culture to ischemia (oxygen and glucose deprivation) and cytotoxic influence of glutamate. These results indicate that Biolan holds much promise for correction of ischemic brain damages in clinical practice.

Studies were performed using 80 children aged 1–3 years with lesions to mental development. Patients were divided into three groups according to the severity and structure of lesions of mental development: those most strongly characterized by delayed speech development (group 1), those with delayed mental development due to organic CNS lesions (group 2), and those with abnormal mental development and high levels of psychopathological symptoms (group 3). There were significant increases (p < 0.001) in blood levels of autoantibodies to nerve growth factor (NGF) in children in each of these groups as compared with a control group (0.75 ± 0.24 OD units). The levels of anti-NGF autoantibodies increased from group 1 to group 3 (0.95 ± 0.24 OD units in group 1, 1.13 ± 0.27 OD units in group 2, and 1.24 ± 0.4 OD units in group 3). These correlations suggest that the level of anti-NGF autoantibodies can, taken in conjunction with a number of other parameters, be regarded as a potential molecular marker demonstrating abnormal development of the nervous system.

Autoimmune reactions resulting in the production of autoantibodies to nerve tissue are relevant to many mental diseases, including schizophrenia [4, 10, 14]. However, there are currently no generally accepted concepts of the role of these autoantibodies in the pathogenesis of the corresponding diseases. We have previously demonstrated increases in the level of humoral autoantibodies to nerve growth factor (NGF) in schizophrenia; this is a neurotrophic factor required for the maturation and development of neurons in the central and peripheral compartments of the nervous system [2]. The present work describes an attempt to identify the role of autoantibodies to NGF in the pathogenesis of schizophrenia. Serum levels of antibodies to NGF were measured in children with schizophrenia and were compared with the levels of antibodies to three other nerve tissue antigens--water-soluble astrocyte protein S-100, glial fibrillar acid protein (GFAP), and nerve cell membrane protein from the integrin MP-65 superfamily. Proteins S-100, GFAP, and MP-65 belong to the class of so-called neurospecific proteins and are involved in supporting specific brain functions [3, 7, 13]. This comparison allowed us to identify the antigen involved in producing the strongest immune response as determined by the level of serum antibodies in patients. Studies were also made of the relationships

Titers of autoantibodies to nerve growth factor, water-soluble astrocytic protein S-100, glial fibrillary acidic protein, and MP-65 membrane protein of the nervous cell superfamily of integrins was determined by solid-phase immunoenzyme assay in healthy children and in children with the Romano-Ward and sick sinus syndromes. Immunoreactivity to these antigens was either increased or decreased in 20% of sick children in comparison with that of healthy children of the same age.