Schizophrenia is a severe mental disorder whose molecular mechanisms remain poorly understood. Investigating brain-derived neurotrophic factor (BDNF)-dependent signaling pathways and their contribution to schizophrenia pathogenesis is a promising research direction in schizophrenia research. BDNF activates multiple intracellular cascades, among which the MAPK/ERK pathway plays a central role. In this study, expression levels of key regulatory proteins of the MAPK/ERK signaling pathway (ERK1/2, STAT3, STAT5, NF-κB, IGF1R, IRS1, IR, TSC2, and CREB1) were examined in lysates of peripheral blood mononuclear cells (PBMCs) from schizophrenia patients using multiplex analysis. The study group included 58 patients diagnosed with schizophrenia (F20); the control group included 60 healthy individuals. The results revealed significantly increased expression of ERK1/2 and STAT3, along with decreased NF-κB levels, in PBMCs from schizophrenia patients compared to controls. Moreover, patients with leading positive symptoms exhibited elevated expression of CREB1 and ERK1/2. These findings suggest that dysregulation of the MAPK/ERK signaling may play a significant role in the pathogenesis schizophrenia. BDNF-dependent signaling pathways may therefore represent promising targets for diagnostics and therapy of this disorder.

OBJECTIVES:Schizophrenia is known to be accompanied by chronic sterile inflammation and elevated circulating cell-free DNA (cfDNA) levels, but the cellular sources have not been fully identified. The aim of this study was to test the hypothesis regarding the contribution of NETosis to the increase in cfDNA and to investigate associations between cfDNA and DNA-associated molecules levels with clinical features and antipsychotic dosage in schizophrenia. METHODS:This case-control study included 63 healthy subjects and 60 patients with schizophrenia. Concentrations in plasma of total, nuclear, and mitochondrial cfDNA, total histone H3, and anti-DNA antibodies as non-specific markers of cell stress/death, and also high-mobility group protein B1 (HMGB1) and citrullinated histone H3 (CitH3) as NETosis-related biomarkers, were analysed using fluorimetric analysis, digital PCR, and ELISA. RESULTS:Total cfDNA levels increased concomitantly with increases in nuclear cfDNA, histone H3, and anti-DNA antibodies, indicating a nuclear origin of plasma cfDNA, while mitochondrial cfDNA decreased in schizophrenia. Correlation analysis revealed a decrease in mitochondrial cfDNA with increasing antipsychotic therapy dosage. NETosis-related markers, CitH3 and HMGB1, did not changed significantly. CONCLUSIONS:These findings did not provide direct evidence linking active NETosis to elevated cfDNA levels, suggesting the involvement of other cell death processes; however, they highlighted the associations between cfDNA and clinical features in schizophrenia.

OBJECTIVES:In light of the frequent co-occurrence of metabolic syndrome (MetS) in schizophrenia and their common links to oxidative stress, the aim of our study was to evaluate glutathione (GSH) metabolism parameters in patients with schizophrenia and MetS. METHODS:The study cohort comprised two groups: (1) 60 patients with schizophrenia and MetS and (2) 70 patients with schizophrenia without MetS,. GSH and its fractions concentration, and GSH-enzymes activity in serum were determined spectrophotometrically. RESULTS:Total GSH and oxidised GSH (GSSG) concentration was significantly higher in schizophrenia patients with MetS (p = 0.003 and p = 0.028 respectively) than in those without MetS. The rGSH/GSSG ratio was significantly reduced in schizophrenia patients with MetS relative to those without MetS (p = 0.022). Glutathione S-transferase (GST) activity was significantly higher in patients with MetS than in those without MetS (p = 0.019). CONCLUSIONS:The findings of this study suggest that MetS in schizophrenia patients is associated with GSH metabolism dysregulation.

The mechanisms underlying the recently discovered catalase activity of immunoglobulin G (IgG) in patients with schizophrenia remain unclear. Using a series of rigorous criteria, it has been demonstrated that this activity is an intrinsic property of antibodies themselves. The present study shows that classical catalase inhibitors also suppress the catalase activity of IgG. Specifically, inhibitor analysis revealed a dose-dependent reduction in the IgG catalase activity following addition of sodium azide (IC50 = 140 μM) and 3-aminotriazole (IC50 = 16.06 μM), suggesting that the catalytic mechanism of IgG shares similarities with that of classical catalase and may be due to the ability of antibodies to bind metalloporphyrin complexes, including heme. IgG catalase activity in patients with schizophrenia during therapeutic remission was significantly reduced, being fourfold lower than in healthy controls (p = 0.0004) and twofold lower than in patients during disease exacerbation (p = 0.002). A moderate positive correlation was observed between the total Positive and Negative Syndrome Scale (PANSS) score and IgG catalase activity (R = 0.32, p = 0.01). Therefore, IgG catalase activity in patients with schizophrenia depends on the disease clinical state and may contribute to the regulation of reactive oxygen species (ROS) metabolism and the severity of oxidative stress in affected individuals.

Введение. Шизофрения – хроническое эндогенное психическое расстройство, которое относится к социально значимым заболеваниям в связи с высокой проградиентностью и тяжестью социальных последствий. Генетическая составляющая может быть одним из механизмов, лежащих в основе патогенеза заболевания и клинической гетерогенности шизофрении. Цель. Выявить полиморфные варианты генов нейропластичности и протеинкиназ, ассоциированные с неблагоприятным течением шизофрении. Материалы и методы. В исследовании принимали участие 430 пациентов с шизофренией (F20 согласно МКБ-10). Диагностическая оценка и клиническая квалификация расстройства осуществлялись с применением клинико-психопатологического, клинико-динамического, клинико-катамнестического и психометрического методов. Было проведено генотипирование 10 полиморфизмов 5 генов (BDNF (rs6265, rs11030104), GSK3β (rs13321783, rs6805251, rs334558), AKT1 (rs1130233, rs3730358), MAPK (rs8136867, rs3810608), CREB1 (rs6740584)) методами ПЦР на амплификаторах StepOnePlus Real-Time PCR System и QuantStudio 3D Digital PCR System (Applied Biosystems, США) (ЦКП «Медицинская геномика», Томский НИМЦ). Статистическую обработку данных проводили с использованием ПО SPSS и скриптового языка программирования R 3.6.1 с использованием специальных пакетов. Результаты. На основании клинических и психометрических данных был выделен и проанализирован неблагоприятный вариант течения шизофрении, который характеризуется ранним дебютом, непрерывным типом течения и стабильной негативной симптоматикой. В результате проведенного исследования впервые продемонстрировано участие полиморфных вариантов генов нейропластичности и протеинкиназ (rs8136867 гена MAPK, rs11030104 гена BDNF, rs334558 гена GSK3β и rs1130233 гена AKT1) в формировании клинических фенотипов шизофрении, связанных с неблагоприятным прогнозом заболевания. Заключение. Полученные данные в перспективе можно использовать для разработки технологий ранней диагностики неблагоприятного течения шизофрении и разработки персонализированной терапии данного контингента пациентов. Introduction. Schizophrenia is a chronic endogenous mental disorder, which is classified as a socially significant disease due to its high prevalence, progression and severity of social consequences. The genetic component may be one of the mechanisms underlying the pathogenesis of the disease and the clinical heterogeneity of schizophrenia. Purpose. To identify polymorphic variants of genes of neuroplasticity and protein kinases associated with the unfavorable course of schizophrenia. Materials and methods. The study involved 430 patients with schizophrenia (F20 according to ICD-10). Diagnostic assessment and clinical qualification of the disorder was carried out using clinical-psychopathological, clinical-dynamic, clinical-follow-up and psychometric methods. We genotyped 10 polymorphisms of 5 genes (BDNF (rs6265, rs11030104), GSK3β (rs13321783, rs6805251, rs334558), AKT1 (rs1130233, rs3730358), MAPK (rs8136867, rs3810608), CREB1 (rs 6740584) by PCR using amplifiers StepOnePlus Real-Time PCR System and QuantStudio 3D Digital PCR System (Applied Biosystems, USA) (Center for Collective Use "Medical Genomics", Tomsk National Research Medical Center). Statistical data processing was carried out using SPSS software and the scripting programming language R 3.6. using special packages. Results. Based on clinical and psychometric data, an unfavorable variant of the course of schizophrenia was identified and analyzed, which is characterized by an early onset, a continuous type of course and stable negative symptoms. As a result of the study, the participation of polymorphic variants of genes of neuroplasticity and protein kinases (rs8136867 MAPK, rs11030104 BDNF, rs334558 GSK3β and rs1130233 AKT1) in the formation of clinical phenotypes of schizophrenia associated with an unfavorable prognosis of the disease was demonstrated for the first time. Conclusion. The data obtained, in the future, can be used to develop technologies for early diagnosis of the unfavorable course of schizophrenia and the development of personalized therapy for this group of patients.

A comprehensive study of the contribution of dysfunction AKT/mTOR signaling to the pathogenesis of schizophrenia is needed. The aim of the study is to determine the expression of the protein kinase AKT/mTOR signaling pathway in peripheral mononuclear cells (PMCs) of patients with schizophrenia. Determination of AKT1, mTOR, p70S6K, GSK3-α, and GSK3-β in mononuclears was performed on multiplex analyzers. Statistical data processing was carried out using SPSS. The critical significance level for the differences was 0.05. The study included 58 patients with schizophrenia (F20) and 60 healthy individuals. We found an increase in the expression of AKT1 and p706SK in PM׳s of patients (p = 0.006, p = 0.001). Analysis of kinase expression was carried out depending on clinical characteristics (type of course, leading symptoms and duration of the schizophrenia). Increased expression of GSK3-α and GSK3-β was detected in patients with a duration of disease more than 5 years (p = 0.019, p = 0.018). The AKT/mTOR signaling cascade may play a significant role in the pathogenesis of schizophrenia. We can assume that signaling pathways are involved in neurobiological processes and can be targets for new methods of pharmacotherapy, prognosis and diagnosis of mental disorders.

OBJECTIVE:To study the associations of NOS1AP gene polymorphisms with the duration of the QT interval (QTc) in patients with schizophrenia receiving antipsychotics. MATERIAL AND METHODS:One hundred and sixty-eight patients (78 men and 90 women) with an established diagnosis of schizophrenia were examined. The patients received basic antipsychotic therapy. At the time of admission to the hospital, a standard 12-lead electrocardiogram recording was performed. The calculation of the QTc interval was carried out using the Bazett formula. Three NOS1AP polymorphisms (rs12029454, rs10494366 and rs12143842) were selected for genotyping. RESULTS:Spearman's correlation revealed a significant relationship between CPZeq and the duration of the QTc interval in the group of men (rs=0.262; p=0.021; pBonf=0.042). CPZeq was positively correlated with the duration of the QTc interval in men with AA and AG rs12029454 (rs=0.717; p=0.00025; pbonf=0.0015), GG and GT rs10494366 (rs=0.381; p=0.008; pbonf=0.048), TT and CT rs12143842 (rs=0.389; p=0.003; pbonf=0.018) genotypes. We did not find any significant correlations in the group of women. CONCLUSION:Genetic variants rs12029454, rs10494366 and rs12143842 of the NOS1AP gene are associated with the duration of the QTc interval in men with schizophrenia in response to antipsychotics. The AA/AG rs12029454, GG/GT rs10494366 and TT/CT rs12143842 genotypes in men contribute to the prolongation of the QTc interval and the development of undesirable cardiovascular disorders against the background of antipsychotic therapy.

OBJECTIVE:To analyze the factor structure of PANSS in a sample of patients with schizophrenia receiving inpatient treatment and to compare the factors with the data of neuropsychological evaluation of their cognitive functions. MATERIAL AND METHODS:The study included 110 patients (50 females and 60 males) diagnosed with schizophrenia. The psychopathological symptoms were assessed using the PANSS scale in the adapted Russian version - SCI-PANSS. Cognitive functioning was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) scale. RESULTS:A six-factor PANSS model was constructed using the principal components method, which included a negative factor, a positive factor, a depressive factor, an excitement factor, a disorganized factor, and a cognitive factor. The cognitive factor was the only one associated with some subtests, as well as the overall BACS score.Negative correlations were found with memorization of a sequence of numbers (r=-0.184, p=0.045), a motor test with chips (r=-0.250, p=0.019), a test for speech fluency (r=-0.186, p=0.043), an Encoding test (r=-0.291, p=0.002), and an overall BACS score (r=-0.228, p=0.017). CONCLUSION:It is advisable to use a six-factor model with differentiation of a disorganized and cognitive factor to increase the value of PANSS as an assessment tool for the severity of cognitive impairment in patients with schizophrenia.

The life expectancy of patients with psychotic disorders is significantly shorter than that of the general population; antipsychotic-induced metabolic disorders play a significant role in reducing life expectancy. Both metabolic syndrome (MetS) and schizophrenia are multifactorial conditions. One area where the two conditions overlap is oxidative stress, which is present in both diseases. The glutathione-S-transferase (GST) system is a major line of defense against exogenous toxicants and oxidative damage to cells. The aim of our study was to perform an association analysis of gene polymorphisms with metabolic disorders in patients with schizophrenia treated with antipsychotic therapy. Methods: A total of 639 white patients with schizophrenia (ICD-10) from Siberia (Russia) were included in the study. Genotyping was carried out using real-time polymerase chain reaction for two single-nucleotide polymorphisms (SNPs) in the GSTP1 (rs614080 and rs1695) and one SNP in the GSTO1 (rs49252). Results: We found that rs1695*GG genotype of GSTP1 is a risk factor for the development of overweight (OR 2.36; 95% CI: 1.3–4.29; p = 0.0054). In the subgroup of patients receiving first-generation antipsychotics as basic therapy, the risk of overweight was associated with carriage of the rs1695*GG (OR 5.43; 95% CI: 2.24–13.16; p < 0.001) genotype of GSTP1 in a recessive model of inheritance. In contrast, an association of rs1695*G GSTP1 with obesity (OR: 0.42; 95% CI: 0.20–0.87; p = 0.018) was shown in the dominant model of inheritance in patients receiving second-generation antipsychotics. Conclusions: The pilot results obtained confirm the hypothesis of a violation of the antioxidant status, in particular the involvement of GSTP1, in the development of antipsychotic-induced metabolic disorders in schizophrenia. Further studies with larger samples and different ethnic groups are needed to confirm the obtained results.

ObjectivesThe search for the genetic basis of the leading symptom domains of schizophrenia is of interest. BDNF is a universal neurotrophin that promotes brain development and neuroplasticity. Our aim was to study polymorphisms of the BDNF gene and serum levels of BDNF in schizophrenia and to analyze the concentration of this marker depending on clinical and genetic characteristics.MethodsA clinical and biological examination of 123 patients with paranoid schizophrenia (F20.0, ICD-10) was conducted. The control group consisted of 193 healthy individuals. Genotyping of polymorphisms (rs6265 and rs11030104) was performed by RT-PCR. BDNF concentration was determined using xMAP technology. Statistical data processing was performed in SPSS software.ResultsA lower BDNF concentration was found in schizophrenia patients than in healthy individuals. Clinical characteristics of the disease, such as duration of the disease and leading clinical symptoms do not affect the level of BDNF. The continuous type of course is characterized by a tendency to decrease the BDNF serum concentration compared to the episodic type. The distribution of rs6265 genotypes differed significantly between the groups of schizophrenia patients and healthy individuals. The TT genotype was more common among the patients and had a predisposing effect on schizophrenia. Serum levels of BDNF did not differ between the patients with different genotypes.ConclusionsOur results support a potential value of studied BDNF protein and gene as a neurobiological marker for schizophrenia pathogenesis and clinical characteristics. Further case-control studies on the BDNF gene and peripheral BDNF levels with larger sample sizes and different ethnic groups are needed to better understand the pathogenesis of the schizophrenia.

Dopamine receptor inhibition underlies both the therapeutic and adverse effects of antipsychotics, but the mechanisms modulating these effects in patients with schizophrenia remain incompletely understood. Hyperprolactinemia (HPRL), a direct consequence of D2 dopamine receptor blockade, provides a unique clinical model to investigate how genetic variation in glutamatergic signaling influences the downstream effects of dopaminergic disruption. We hypothesized that polymorphisms in GRIN2A and GRIN2B, encoding NMDA glutamate receptor subunits, modify the neuroendocrine consequences of dopamine receptor inhibition. By studying antipsychotic-induced HPRL, we aimed to demonstrate that NMDA receptor genetic variants shape the functional outcomes of dopaminergic perturbation. In a cross-sectional analysis of 536 schizophrenia patients, we measured prolactin levels-a sensitive biomarker of D2 receptor inhibition-and genotyped 23 GRIN2A/GRIN2B variants. Logistic regression assessed gene-drug relationships while controlling for clinical covariates. NMDA receptor genetic variation significantly influenced susceptibility to HPRL, with distinct effects observed between antipsychotic classes with the highest effect for the typical antipsychotics, which are D2 dopamine receptor antagonists. This demonstrates that glutamatergic genotypes predict interindividual variability in the neuroendocrine response to dopamine receptor blockade. These results provide the first clinical evidence in support of the hypothesis that NMDA receptor polymorphisms modulate the effects of dopaminergic inhibition in schizophrenia. Beyond HPRL, this dopamine-glutamate relationships paradigm may extend to other clinical outcomes of antipsychotic treatment, including therapeutic response and neurological side effects. Our findings underscore the importance of glutamatergic pathways in determining the functional consequences of dopamine receptor targeting.

The role of the genetic component in the development of schizophrenia and the formation of its clinical heterogeneity has been proven. To conduct a pilot associative analysis between positive and negative schizophrenia symptoms and polymorphic variants of the Transcription Factor 4 (TCF4) gene. The study included 373 patients with schizophrenia of Caucasian ethnicity, who underwent a comprehensive clinical examination, and a control group consisted of 194 mentally and somatically healthy individuals. Genotyping of three polymorphic variants of the TCF4 gene was carried out in the studied samples (rs2958182, rs8766, and rs9636107). Statistical analysis of the results was performed using Statistica for Windows V.12.0. Association analysis in SNPs was conducted using the chi-square criterion and Bonferroni correction. Groups of schizophrenia patients and healthy individuals were compared for selected TCF4 gene polymorphisms. No statistically significant differences in genotype and allele frequencies were found. The AA genotype and the A allele of the rs2958182 polymorphic variant, as well as the A allele of the rs9636107 polymorphic variant, had an effect predisposing to the predominance of negative symptoms. The TT genotype and the T allele of the rs2958182 polymorphic variant, as well as the G allele of the rs9636107 polymorphic variant, were statistically significantly more common among patients with leading positive symptoms. As a result of the study, associations of the polymorphic variant TCF4 rs2958182 and TCF4 rs9636107 with the leading symptoms of schizophrenia were discovered for the first time in Caucasian populations of the Siberian region. The obtained data confirm the contribution of the genetic component to the formation of clinical heterogeneity of schizophrenia and open up prospects for further search for genetic markers in order to prevent an unfavorable outcome of the disease.

Objective. To identify the relationship between functional changes in the brain in patients with schizophrenia and the clinical manifestations of the disease and their constitutional and morphological features. Materials and methods. A total of 118 patients with schizophrenia (64 men and 54 women) aged 33 [29; 40] years were examined. The following clinical and dynamic parameters were used: age of disease onset, disease duration, and severity of clinical and psychopathological symptoms on the PANSS. Anthropometric examination of patients was performed by the Bunak method modified by Chtetsov for adult samples, with calculation of the Rees–Eysenck and Tanner indexes. EEG traces were recorded and analyzed in a state of quiet, relaxed wakefulness with the eyes closed, with calculation of absolute spectral power for the θ (4–7 Hz), α (8–13 Hz), and β (14–30 Hz) rhythms. Statistically significant (p < 0.05) direct correlations were found between the age of disease onset and the spectral power of the β rhythm in the frontal leads (Fp1, Fp2, F3, and F4). Inverse correlations (p < 0.05) were found between disease duration in schizophrenia patients and the spectral power of the α rhythm in the left temporal (T3) and right central (C4) leads, the β rhythm in the parieto-occipital (P3, P4, O1, O2) and temporal (T3, T4, T5) leads, and the θ rhythm in the left occipital (O1) and posterior temporal (T5) leads. Statistically significant (p < 0.05) inverse correlations were also found between the Tanner index and the spectral power of the α rhythm in the frontal and temporal leads, as well as between the Rees–Eysenck index and the spectral power of the θ rhythm in the frontal leads. Conclusions. The data obtained here indicate that there are correlations between functional changes in the brain in schizophrenia patients and the clinical manifestations of the disease and their constitutional and morphological features. Thus, assessment of the functional state of the central nervous system in patients with schizophrenia is an important component of the diagnostic search.

Introduction The development of oxidative stress in patients with schizophrenia is associated with changes in the level of activity of antioxidant enzymes. It is likely that catalytically active antibodies (abzymes) can take on these functions. Abzymes are antibodies with enzymatic activity. Catalase and SOD activity of abzymes was previously detected in patients with schizophrenia. But NADPH-dependent peroxidase activity has not been studied. The present work discusses the protective role of abzymes against reactive oxygen species within the pathogenesis of schizophrenia. Objectives The aim of the study was to investigate the NADPH-dependent peroxidase activity of IgG in patients with paranoid schizophrenia in the exacerbation phase and in the remission phase. Methods A total of 124 patients were examined during the work. Of them, 82 patients with paranoid schizophrenia (F20.0) had a mean age of 33.6±5.12 years (52 males, 30 females), disease duration averaged 8.9± 4.62 years. Patients with schizophrenia included 42 patients with acute schizophrenia and 40 patients with schizophrenia in therapeutic remission. The control group included 42 sex- and age-matched patients. IgG was purified by affinity chromatography on columns with proteinsepharose on an AKTA purifier chromatograph (GE). The homogeneity of isolated IgG preparations was checked by Lemilly electrophoresis in a gradient of 4-18% PAAG. Gel filtration under pH-shock conditions was performed on a Superdex-200 HR 10/30 column. NADPH-dependent peroxidase activity of IgG was determined on a SPECORD M-40 spectrophotometer (Carl Zeiss) at 340 nm by NADPH oxidation in the conjugated glutathione reductase reaction of tertiary butyl hydroperoxide reduction. Statistical processing of data was performed in Statistica 12.0 program. Results It was proved that IgG from patients with schizophrenia had NADPH-dependent peroxidase activity, and this activity is an intrinsic property of the investigated antibodies. The NADPH-dependent peroxidase activity in IgG patients in the exacerbation stage was increased 3-fold (p=0.0001) compared to the studied activity in the group of healthy individuals, and it was increased 2-fold (p=0.017) in the group of patients in therapeutic remission compared to the activity in healthy individuals. Also NADPH-dependent IgG peroxidase activity in patients in remission was 1.7 times lower than in patients during the exacerbation period (p=0.012). Conclusions It was established for the first time that abzymes from patients with schizophrenia and healthy individuals have NADPH-dependent peroxidase activity and can decompose lipo and hydroperoxides. We hypothesize that these abzymes help cope with generalized oxidative stress. Under the influence of neuroleptic therapy in patients in remission, the level of oxidative stress and NADPH-dependent peroxidase activity of abzymes decrease. Disclosure of Interest None Declared

Background Antipsychotic-associated metabolic abnormalities are widespread among patients with schizophrenia and are the risk factors for cardiovascular disease, type 2 diabetes mellitus, and premature mortality. However, not all patients experience this side effect, and therefore new data are emerging indicating a certain genetic predisposition of patients with schizophrenia to metabolic disorders. Cardiovascular risk factors such as hypertriglyceridemia increase the production of reactive oxygen species and thereby lead to the development of oxidative stress and oxidative modification of proteins. Enzymes from the classes of oxidases, reductases and dehydrogenases take part in maintaining the prooxidant/antioxidant balance in the body. The purpose of our study was to investigate the association of NAD(P)H dehydrogenase (quinone 1) (NQO1), catalase (CAT) and superoxide dismutase (SOD) gene polymorphisms with hypertriglyceridemia in patients with schizophrenia receiving long-term antipsychotic therapy. Methods The study sample consisted of 444 inpatients with chronic schizophrenia from the Siberian region. Blood was taken from the ulnar vein in the morning after a 12-hour fast. Serum triglyceride concentrations were measured using a colorimetric method. Genomic DNA was isolated using the phenol-chloroform micromethod. Genotyping of NQO1 (rs1800566), CAT (rs1001179) and SOD2 (rs4880) genes was done by real-time PCR on a QuantStudio 5 amplifier (Applied Biosystems, USA). Statistical analyzes were performed using R version 4.0.4. Differences were considered statistically significant at a significance level of p<0.05. Results One hundred twenty-eight (28.8%) patients with schizophrenia had hypertriglyceridemia (triglyceride concentration > 1.7 mmol/L). Logistic regression including sex and age as covariates showed statistical significance of the NQO1 rs1800566 polymorphism (p = 0.042) in relation to hypertriglyceridemia. Allele A had a predisposing (OR=1.45, 95 % CI 1.02–2.06), and allele G had a protective (OR=0.69, 95 % CI 0.49–0.98) effect on risk hypertriglyceridemia (p = 0.04). No association was found between the CAT (rs1001179) and SOD2 (rs4880) gene polymorphisms and the risk of antipsychotic-induced hypertriglyceridemia in patients with schizophrenia. Discussion Our results indicate that the NQO1 gene may be involved in the pathogenesis of antipsychotic-induced dyslipidemias in patients with schizophrenia. An analysis of the literature data showed that our findings may be due to the low transcriptional activity of the NQO1 gene in carriers of this polymorphism. Further search for genetic markers will contribute to the development of effective methods for diagnosing and correcting antipsychotic-induced metabolic abnormalities in patients with schizophrenia.This research was funded by Russian Science Foundation, grant number 23-75-10088. https://rscf.ru/en/project/23-75-10088/

Abstract—Many individuals with schizophrenia also suffer from metabolic syndrome (MetS), which is a major risk factor for the development of cardiovascular disroders associated with a heavy burden of disease, as well as with premature death of patients. This study investigated the expression of 7 genes potentially important for the development of metabolic syndrome. QuantiGene Plex 2.0 technology was used to measure how 7 studied genes (DRD3, GHRL, FTO, LEPR, INSIG2, GSTP1, and ABCB1 (MDR1)) were expressed in leukocytes in 60 recently admitted patients with schizophrenia who had been on treatment with antipsychotic drugs. The preliminary results of our study show a change in the expression of the FTO gene in schizophrenic males with metabolic disorders, however, further studies are needed to determine the role of disturbances in the expression of this gene in the development of the metabolic syndrome in patients with schizophrenia.

Metabolic syndrome (MetS) is common among schizophrenia patients, and one of MetS’s causes may be an imbalance in nitric oxide regulation. In this study, we examined associations of three polymorphic variants of the nitric oxide synthase 1 adapter protein (NOS1AP) gene with MetS in schizophrenia. NOS1AP regulates neuronal nitric oxide synthase, which controls intracellular calcium levels and may influence insulin secretion. The aim of the investigation was to study polymorphic variants of the NOS1AP gene as possible markers of MetS in patients with schizophrenia. A total of 489 Caucasian patients with schizophrenia (ICD-10) from Siberia (Russia) were included in the study, and 131 (26.8%) patients had MetS (IDF classification, 2007). The participants were genotyped for three single-nucleotide polymorphisms in NOS1AP (rs12143842, rs10494366, and rs12029454). Logistic regression was used for association analysis. Single-nucleotide polymorphisms, sex, and age served as covariates; the dependent variable was the coded parameter of the presence/absence of MetS. Polymorphisms rs12143842 and rs10494366 showed a stable association even after Bonferroni’s correction for multiple comparisons (p = 0.005 and 0.002, respectively), indicating a statistically significant contribution of these polymorphic variants to the pathogenesis of MetS. Our results suggest that in patients with schizophrenia, NOS1AP may be involved in MetS pathophysiology.

OBJECTIVE:To identify the differences or comparability of parameters of cerebral hemodynamics between patients with schizophrenia with or without concomitant metabolic syndrome (MS).MATERIAL AND METHODS:The study included 94 patients with schizophrenia (48 men and 46 women). A control group consisted of 40 mentally and somatically healthy individuals (17 men and 23 women) comparable in sex and age to the main group of patients. The diagnosis of metabolic syndrome was carried out according to the criteria of the International Diabetes Federation (IDF). Assessment of cerebral hemodynamics was carried out by 4 - channel rheoencephalography (REG) at rest with closed eyes. Data analysis was carried out using the Kraskel-Wallis ANOVA criterion with the procedure of automatic a posteriori pairwise comparison, the χ2 criterion and Spearman correlation analysis.RESULTS:According to the IDF criteria, 37 (39.4%) patients were diagnosed with MS. REG results revealed significantly (p<0.05) lower indicators of blood filling in the carotid basin, elasticity of the wall of the main arteries, the tone of small-caliber arteries and arterioles, as well as higher values of the tone of medium-caliber arteries in the carotid and vertebrobasilar basins, in both groups of patients with schizophrenia compared with the control group. In patients with schizophrenia with MS, compared with patients without MS, there were lower indicators of blood filling (p=0.044 and p=0.016) and elasticity of the wall of the main arteries (p=0.044 and p=0.028) in the carotid basin on the left and right sides.CONCLUSION:The presence of MS in patients with schizophrenia was accompanied by more pronounced disorders of cerebral blood flow in the form of a decrease in blood filling and elasticity of the wall of the main arteries in the carotid basin. The results indicate that patients with schizophrenia with MS should be considered as a group at increased risk of cerebrovascular diseases.