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.

Introduction: It was shown that copy number variations (CNVs) of human satellite III (1q12) fragment (f-SatIII) reflects the human cells response to stress of different nature and intensity. Patients with schizophrenia (SZ) experience chronic stress. The major research question: What is the f-SatIII CNVs in human leukocyte as a function of SZ? Materials and Methods: Biotinylated pUC1.77 probe was used for f-SatIII quantitation in leukocyte DNA by the non-radioactive quantitative hybridization for SZ patients (N = 840) and healthy control (HC, N = 401). SZ-sample included four groups. Two groups: first-episode drug-naïve patients [SZ (M-)] and medicated patients [SZ (M+)]. The medical history of these patients did not contain reliable confirmed information about fetal hypoxia and obstetric complications (H/OCs). Two other groups: medicated patients with documented H/OCs [hypoxia group (H-SZ (M+)] and medicated patients with documented absence of H/OCs [non-hypoxia group (NH-SZ (M+)]. The content of f-SatIII was also determined in eight post-mortem brain tissues of one SZ patient. Results: f-SatIII in human leukocyte varies between 5.7 to 44 pg/ng DNA. f-SatIII CNVs in SZ patients depends on the patient’s history of H/OCs. f-SatIII CN in NH-SZ (M+)-group was significantly reduced compared to H-SZ (M+)-group and HC-group (p < 10-30). f-SatIII CN in SZ patients negatively correlated with the index reflecting the seriousness of the disease (Positive and Negative Syndrome Scale). Antipsychotic therapy increases f-SatIII CN in the untreated SZ patients with a low content of the repeat and reduces the f-SatIII CN in SZ patients with high content of the repeat. In general, the SZ (M+) and SZ (M-) groups do not differ in the content of f-SatIII, but significantly differ from the HC-group by lower values of the repeat content. f-SatIII CN in the eight regions of the brain of the SZ patient varies significantly. Conclusion: The content of f-SatIII repeat in leukocytes of the most patients with SZ is significantly reduced compared to the HC. Two hypotheses were put forward: (1) the low content of the repeat is a genetic feature of SZ; and/or (2) the genomes of the SZ patients respond to chronic oxidative stress reducing the repeats copies number.

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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.

Introduction. The COVID-19 pandemic is associated with the spread of conspiracy theories, which are heterogeneous in terms of the structure of their views. The hypothesis is that the substrate for the spread of conspiracy trend is an increased level of anxiety, reduced due to the paralogical (conspiracy) interpretation of events. The purpose of this research was to study the prevalence of conspiracy trends during the preparation for the COVID-19 pandemic in Moscow (before the introduction of strict restrictive measures). Methods: 320 people, randomly selected from the general population, were asked if they agree or disagree with 9 statements regarding the conspiracy interpretation of events, compared with the level of anxiety/depression (using the HADS scale). There are 3 trends (COVID-conspiracy, COVID-skepticism, COVID-obscurantism). Results: 45.7% of respondents were ready to agree with one or the other conspiracy idea. I The level of anxiety in all adherents of conspiracy theory was found to be higher than in the rest of the sample. Differences in sociodemographic characteristics of adherents of different conspiracy tendencies are revealed. Among COVID skeptics, there are significantly fewer students and pensioners, and among COVID conspiracy theorists, the level of education received is lower, with unstable labor and family status. Discussion. Conspiracy trends were universal for all social groups in the background of increased anxiety among the population of Moscow in preparation for the COVID-19 pandemic. It is suggested that the mechanism for the development of conspiracy tendencies may be the process of rationalization of an increased level of anxiety as a protective response during a crisis.