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Introduction. Associations of disturbances in innate and adaptive immunity during the clinical course of schizophrenia have been found in a number of studies. Yet, the relationship of immune parameters and systemic inflammation in relation to the clinical course of the disease and its prognosis, remains poorly understood, which highlights an interesting topic for further research. The goal of this study was to research the immuno-inflammatory changes in patients with clinical continuous and episodic paranoid schizophrenia, to assess the pathogenetic significance of these changes. Methods. Thirty-six patients with paranoid schizophrenia, of which 20 had episodic symptoms and 16 had continuous symptoms, consented to participate in the study, together with 30 healthy volunteers. In the study we assessed the parameters of innate immune response (serum levels of key pro-inflammatory and anti-inflammatory cytokines, C-reactive protein) and the adaptive immune response, including humoral-mediated immunity (serum immunoglobulins IgA, IgM, IgG, circulating immune complexes), as well as the cell link of adaptive immunity (key lymphocyte subpopulations). Positive and negative symptoms were assessed with the positive and negative symptoms scale; frontal dysfunction was assessed by Frontal Assessment Battery (FAB). Results. Both patient groups had higher than normal levels of C-reactive protein and IL-8. There was a significant elevation of circulating immune complexes among patients with continuous symptoms of schizophrenia, compared to patients with episodic symptoms and healthy controls. Levels of CD45+CD3+ lymphocytes (T-cells) differed between clinical groups, with higher values identified among patients with episodic symptoms and lower values among those with continuous symptoms. In addition, patients with episodic symptoms had significantly increased levels of CD45+CD3+CD4+CD25+CD127- regulatory T-cells. Finally, the level of CD45+CD3-CD19+ B-cells was significantly higher among patients with continuous symptoms vs. patients with episodic symptoms and the control groups. Markers of activation of humoral immunity were associated with the severity of frontal disorders in these patients. Discussion. Comprehensive data on the serum level of cytokines and the parameters of adaptive immunity among individuals with continuous schizophrenia, by comparison with patients with episodic schizophrenia, are practically absent in the literature. We have shown that among those with continuous schizophrenia, there are signs of systemic inflammation and chronic activation of the adaptive humoral immune response, while among patients with episodic symptoms of the disease, there are signs of systemic inflammation and certain activation of cell-mediated immunity, without significant changes in the humoral link of adaptive immunity. Conclusion. More studies are needed, but the data obtained in this study are important for subsequent clinical studies of new treatment methods, based on various immunophenotypes of schizophrenia.

This article addresses the question of the appropriateness of and potential for primary care physicians to diagnose and treat anxious-depressive disorders of nonpsychotic origin in view of their high prevalence for primary care physicians. Arguments are given in favor of a positive answer to this question.

Introduction. Schizophrenia (SZ) increases the level of cell death, leading to an increase in the concentration of circulating cell-free DNA (cfDNA). Ribosomal DNA (rDNA) contains many unmethylated CpG motifs that stimulate TLR9-MyD88-NF-κB signaling and the synthesis of proinflammatory cytokines. The number of rDNA copies in the genomes of SZ patients is increased; therefore, we expect that the concentration of cell-free rDNA in the plasma of the SZ patients also increases. This may be one of the explanations of the proinflammatory cytokine increase that is often observed in SZ. The major research question is what is the rDNA copy number in cfDNA (cf-rDNA CN) and its putative role in schizophrenia? Materials and Methods. We determined cfDNA concentration (RNase A/proteinase K/solvent extraction; fluorescent dye PicoGreen) and endonuclease activity (NA) of blood plasma (radial diffusion method) in the untreated male SZ group (N=100) and in the male healthy control group (HC) (N=96). Blood leukocyte DNA and cfDNA rDNA CN were determined with nonradioactive quantitative hybridization techniques. Plasma concentration of cf-rDNA was calculated. Results. In the subjects from the SZ group, the mean cfDNA plasma concentration was twofold higher and NA of the plasma was fourfold higher than those in the healthy controls. rDNA CN in the blood leukocyte genome and in the cfDNA samples in the SZ group was significantly higher than that in the HC group. cf-rDNA concentration was threefold higher in the SZ group. Conclusion. Despite the abnormally high endonuclease activity in the blood plasma of SZ patients, the circulating cfDNA concentration is increased. Fragments of cf-rDNA accumulate in the blood plasma of SZ patients. Potentially, SZ patients’ cfDNA should be a strong stimulating factor for the TLR9-MyD88-NF-κB signaling pathway.

To study the prevalence of somatic diseases in patients with mental disorders based on the results of medical examination in Moscow mental health clinics in 2018.A retrospective analysis of the results of the clinical examinations of 6492 outpatients, which accounted for 79.5% of patients who underwent medical examination in this time period.Comorbid somatic diseases were found in 4883 (75%) patients. Hypertension and non-insulin-dependent diabetes mellitus were most frequent with the prevalence higher than in the general population of the Russian Federation. Patients with diagnosed schizophrenia, along with hypertension and diabetes mellitus, have found to be at increased risk of diseases of the endocrine system and metabolic disorders. The incidence of the mentioned diseases is not higher than that reported in literature.The higher prevalence of socially relevant diseases (hypertension, diabetes mellitus) among patients with mental disorders demands the development of strategies for prevention, early detection and treatment of these diseases in psychiatric patients.Изучение распространенности соматических расстройств у пациентов с психическими заболеваниями на основании анализа сплошной выборки по результатам диспансеризации больных в лечебных учреждениях Москвы в 2018 г.Проведен ретроспективный анализ результатов диспансеризации 6492 человек, что составило 79,5% пациентов, подлежавших диспансеризации.Коморбидные соматические расстройства выявлены у 75% пациентов, страдающих психическими заболеваниями. Преобладали в общей выборке гипертоническая болезнь и инсулиннезависимый сахарный диабет, распространенность которых была значительно выше, чем в общей популяции РФ. У больных шизофренией наряду с указанными двумя заболеваниями были выявлены другие нарушения со стороны эндокринной системы, обмена веществ, при этом их распространенность соответствовала данным литературы. Наличие таких социально-значимых заболеваний, как гипертоническая болезнь и диабет, обусловливает целесообразность разработки стратегии по предупреждению, раннему выявлению и лечению данных заболеваний у психически больных.

Circular RNAs (circRNAs) are endogenous, single-stranded, most frequently non-coding RNA (ncRNA) molecules that play a significant role in gene expression regulation. Circular RNAs can affect microRNA functionality, interact with RNA-binding proteins (RBPs), translate proteins by themselves, and directly or indirectly modulate gene expression during different cellular processes. The affected expression of circRNAs, as well as their targets, can trigger a cascade of events in the genetic regulatory network causing pathological conditions. Recent studies have shown that altered circular RNA expression patterns could be used as biomarkers in psychiatric diseases, including schizophrenia (SZ); moreover, circular RNAs together with other cell molecules could provide new insight into mechanisms of this disorder. In this review, we focus on the role of circular RNAs in the pathogenesis of SZ and analyze their biomarker and therapeutic potential in this disorder.

Background.Psychosocial (PS) risk factors (RF) make a substantial contribution in populational burden of cardio-vascular diseases (CVD) and their complications.Purpose.The KOMETA (Comet) study was directed to obtaining actual information on PSRF among ambulatory patients with arterial hypertension (AH) and / or ischemic heart disease (IHD) in 30 cities of Russian Federation.Materials and methods.This multicenter cross-sectional study was conducted in 2016–2017. Doctors participating in the study (n=325) recruited in state polyclinics 2775 patients aged ≥55 years with AH and / or IHD. Information collected from these patients comprised social-demographic and clinical characteristics, data on RF, adherence to therapy. Assessment of PSRF was carried out with consideration of levels of anxiety, depression and stress, presence of personality type D. Results. Population of patients studied (72 % women) was characterized by considerable prevalence of PSRFs. Low levels of education and income were found in 24.5 and 44.2 % of patients, respectively; 25.2 % of patients reported living alone, 6.3 % – felt social isolation. Elevated, extremely high levels of stress, type D personality were detected in 67.8, 10, and 37.6 % of patients, respectively; clinically significant symptoms of anxiety and depression were found in 25.5 and 16.3 %, respectively. Most RFs were significantly more often detected in women, and older people. One third of patients (33.1 %) during a year preceding inclusion took some psychotropic drugs mainly herbal or barbiturate-containing (27.1 %). Moreover, 30 % of patients had lowering of cognitive functioning.Conclusion.In this large-scale study we revealed high prevalence of PSRFs among ambulatory patients with AH and / or IHD in Russia. Despite positive dynamics of prevalence of states of anxiety and depression relative to earlier studies in this country their negative impact on prognosis of CVD and quality of life of affected patients requires optimization of efforts for organization of adequate care and directed to timely diagnosis and correction of these states.

In this study, for the first time, data were obtained on the architecture of effective connections in extended default neural network in patients with schizophrenia and the healthy controls. Also, a determination of the immunological status of patients was performed. At rest, the effective connectomes of the patients and healthy subjects had significant differences in the strength of connections. Immunological data analysis showed that despite clinical improvement after inpatient treatment, most patients had elevated levels of markers of systemic inflammation and activation of humoral immunity. At the next stage of work, a comprehensive analysis of neurophysiological and immunological data is planned.

Schizophrenia is a complex chronic disease. The molecular determinants and neuropathology of schizophrenia are multifaceted; an important role in the pathogenesis is played by the dysregulation of molecular and epigenetic mechanisms. However, the molecular mechanisms of the development of the disease have not yet been studied.An important task is the accumulation and systematization of “OMICS”-knowledge of the molecular profiles (transcriptome, proteome, metabolome) of blood specific to pathology. Thereby the development and improvement of mass spectrometric methods for the detection of biological molecules has become increasingly important in biomedical research. In the field of applied problems in biomedical research, the most prevalent issue involves the identification of serological protein markers associated with the development of schizophrenia, which account for the diseases that cause the a life-shortening illness, disability, decreased of functioning and quality of life and wellbeing or health status.OMICS approaches are designed to detect genes (genomics), mRNA (transcriptomics), proteins (proteomics) and metabolites (metabolomics) in a specific biological sample.We report the proteomic datasets on the serum samples from patients with schizophrenia (series “SCZ”) and healthy volunteers (series “CNT”). Data were acquired using shotgun ultra-high resolution mass spectrometry. Keywords: Serum, Schizophrenia, Proteomics, Tandem mass spectrometry

The review is devoted to the analysis of the current state of pharmacogenetic research and their use in psychiatric practice. The main genes responsible for the pharmacodynamics and pharmacokinetics of drugs used in psychiatry are listed. Foreign pharmacogenetic clinical recommendations and progress on their implementation in medical practice in various countries of Europe and the USA are analyzed. The need to create Russian clinical guidelines on pharmacogenomics to improve the effectiveness of patient care and to implement a personalized approach to therapy is discussed.Статья представляет собой обзор, посвященый современному состоянию фармакогенетических исследований и возможностям их применения в области психиатрии. Перечислены основные гены, ответственные за фармакодинамику и фармакокинетику лекарственных средств, применяемых в клинической психиатрии. Представлен анализ соответствующих зарубежных фармакогенетических клинических рекомендаций и результатов их внедрению в медицинскую практику в различных странах Европы и США. Поставлен вопрос о необходимости создания российских клинических рекомендаций по фармакогеномике для повышения эффективности лечения пациентов и осуществления персонифицированного подхода к терапии.

Objective. The aim of this study was (1) to examine the leukocyte mtDNA copy number (CN) in unmedicated (SZ (m−)) and medicated (SZ (m+)) male patients with paranoid schizophrenia (SZ) in comparison with the healthy male controls (HC) and (2) to compare the leukocyte mtDNA CN with the content of an oxidation marker 8-oxodG in lymphocytes of the SZ (m−) patients. Methods. We evaluated leukocyte mtDNA CN of 110 subjects with SZ in comparison with 60 male HC by the method qPCR (ratio mtDNA/nDNA (gene B2M) was detected). SZ patients were divided into two subgroups. The patients of the subgroups SZ (m+) (N=55) were treated with standard antipsychotic medications in the hospital. The patients of the subgroup SZ (m−) (N=55) were not treated before venous blood was sampled. To evaluate oxidative DNA damage, we quantified the levels of 8-oxodG in lymphocytes (flow cytometry) of SZ (m−) patients (N=55) and HC (N=30). Results. The leukocyte mtDNA CN showed no significant difference in SZ (m+) patients and HC. The mtDNA CN in the unmedicated subgroup SZ (m−) was significantly higher than that in the SZ (m+) subgroup or in HC group. The level of 8-oxodG in the subgroup SZ (m−) was significantly higher than that in HC group. Conclusion. The leukocytes of the unmedicated SZ male patients with acute psychosis contain more mtDNA than the leukocytes of the male SZ patients treated with antipsychotic medications or the healthy controls. MtDNA content positively correlates with the level of 8-oxodG in the unmedicated SZ patients.

Because of the high prevalence of nonpsychotic anxiety-depressive disorders, the authors discuss the necessity and possibility of their diagnosis and treatment by primary care physicians. Arguments supporting this suggestion are presented.В статье обсуждается вопрос о целесообразности и возможности доверить диагностику и лечение тревожно-депрессивных расстройств непсихотического уровня в связи их широким распространением врачам первичного звена медицинской помощи. Приводятся аргументы в пользу положительного решения этого вопроса.

The olfactory epithelium (OE) is an accessible source of neural stem cells and progenitor cells. The objective of the study was to compare the effectiveness of various biopsy sites to isolate and propagate neural progenitor cells from the olfactory epithelium (OE). The authors assessed OE cell count in OE in different sites of the nasal cavity and showed the possibility of isolation neurospheres from nasal biopsies. In total, 45 inpatinets were included in the study. Biopsy specimens were obtained from 30 patients undergoing septoplasty and/or turbinate surgery. Three areas of OE were biopsied: lower third section of the nasal septum (A), anterior part of the middle turbinate (B), upper third of the nasal septum (C). Immunocytochemistry and fluorescence-activated cell sorting showed that OE cells were NCAM-positive. Mean percentage of NCAM+ cells was 7.8% for A, 42.7% for B and 18.2% for C. The difference was significant between A and B (p=0.0001) and B and C (p=0.01). Therefore, the anterior part of the middle turbinate was an easily accessible and safe site to obtain neural cells. To confirm this, neurospheres were obtained in 15 patients with schizophrenia who underwent in-office endoscopy.Обонятельный эпителий (ОЭ) является доступным источником для получения нейральных стволовых и прогениторных клеток. Цель исследования состояла в определении наиболее оптимального локуса полости носа для забора биологического материала, служащего источником прогениторных нейрональных клеток, в условиях местной анестезии. Авторы оценили концентрацию клеток ОЭ в различных участках полости носа и доказали возможность получения нейросфер из биопсийного материала. В исследование были включены 45 стационарных пациентов без нарушения обоняния. Исследование проводили в 2 этапа. У 30 пациентов во время септопластики и вазотомии брали биопсию слизистой оболочки (размер 2 мм) из трех локусов. В результате иммуноцитохимического анализа и проточной цитометрии было установлено, что на медиальной поверхности средней носовой раковины в месте ее крепления к латеральной стенке полости носа процентное содержание NCAM+ клеток составило 42,7%, в верхнем отделе перегородки носа напротив места прикрепления средней носовой раковины - 18,2%, с перегородки носа на уровне прикрепления нижней носовой раковины - 7,8% (подсчет вели на 10 000 выращенных клеток). У 15 пациентов, больных шизофренией, забор биопсийного материала производили из аналогичного локуса средней носовой раковины в условиях местной анестезии. Во всех случаях были получены нейросферы, пригодные для дальнейшего анализа (положительный ответ на маркер βIII-tubulin и MAP2).

Background. More than 10 years passed since conduction of the first clinical-epidemiological study of prevalence of psychosocial risk factors (PSRF) in patients with arterial hypertension (AH) an/or ischemic heart disease in Russian Federation. Purpose: to assess current prevalence of PSRF in patients with AH/CHD and their relationship with traditional risk factors. Materials and methods. Patients with verified AH and/or CHD aged ≥55 years were included into this cross-sectional study in 30 cities of Russia representing 7 federal districts according to the following procedure. In each city we selected 2-5 federal clinics - providers of primary medical care; in each of these clinics we at random invited 2-5 physicians to take part in this study. Each of these physicians for 1-2 days included 10 consecutive patients with AH and/ or CHD. Information collected from patients comprised social demographic and clinical characteristics, risk factors, adherence to therapy; Hospital Anxiety and Depression Scale (HADS) was applied for detection of symptoms of anxiety and depression. Obtained information was used for analysis of prevalence of cardiovascular risk factors and their association with symptoms of depression and anxiety in a framework of Pearson linear and Kendall rank correlation analysis. Results. Symptoms of anxiety of various severity (HADS-A≥7) were detected in 42.2% of patients with AH and/or CHD, in 25.5% they were clinically significant (HADS-A>11). Symptoms of depression of various severity (HADS-D ≥7) were detected in 42.5% of patients with AH and/or CHD, in 16.3% they were clinically significant (HADS-D≥11). We also observed several significant associations of symptoms ofdepression and anxiety with traditional cardiovascular risk factors: low level of physical activity, elevated systolic and diastolic arterial pressure, level of total cholesterol, abdominal obesity; some unhealthy nutritional habits. Conclusions. Prevalence of symptoms of anxiety and depression was found to be high among ambulatory patients with AH and/or CHD. However, in this study it was lower compared with that reported by previous studies in Russia.