Serum Growth Factors in Schizophrenia Patients.

Some hypotheses include schizophrenia as a neurodevelopmental disorder, which indicates a special role in growth factors and neuroglia in the development of schizophrenia symptoms. Growth factors are cytokine molecules that play an important role in the regulation of tissue nucleation, cell development, survival, and migration of all tissues in organisms, including the brain and nervous system. The aim of the study was to determine the serum concentration of six growth factors (EGF, VEGF, FGF-2, TGF-α, PDGF-AA, PDGF-AB/BB) in schizophrenia patients and to identify the correlations with clinical characteristics. After signing an informed consent form, 236 schizophrenia patients (F20 according to the ICD-10) and 102 healthy people were recruited in the study. In patients with schizophrenia, we observed a significant elevation in the TGF-α and PDGF-AA serum levels. The duration of schizophrenia was significantly positively correlated with the FGF-2 level. The PANSS total score had a positive correlation with the FGF-2 level and a negative correlation with the TGF-α level. Our results and literature indicate the involvement of growth factors in the mechanisms of development of schizophrenia. Combined biomarker screening seems to be necessary to improve diagnosis and clinical follow-up of patients with severe mental illnesses.

Chemokine Dysregulation and Neuroinflammation in Schizophrenia: A Systematic Review.

Chemokines are known to be immunoregulatory proteins involved not only in lymphocyte chemotaxis to the site of inflammation, but also in neuromodulation, neurogenesis, and neurotransmission. Multiple lines of evidence suggest a peripheral proinflammatory state and neuroinflammation in at least a third of patients with schizophrenia. Therefore, chemokines can be active players in these processes. In this systematic review, we analyzed the available data on chemokine dysregulation in schizophrenia and the association of chemokines with neuroinflammation. It has been shown that there is a genetic association of chemokine and chemokine receptor gene polymorphisms in schizophrenia. Besides, the most reliable data confirmed by the results of meta-analyses showed an increase in CXCL8/IL-8, CCL2/MCP-1, CCL4/MIP-1ß, CCL11/eotaxin-1 in the blood of patients with schizophrenia. An increase in CXCL8 has been found in cerebrospinal fluid, but other chemokines have been less well studied. Increased/decreased expression of genes of chemokine and their receptors have been found in different areas of the brain and peripheral immune cells. The peripheral proinflammatory state may influence the expression of chemokines since their expression is regulated by pro- and anti-inflammatory cytokines. Mouse models have shown an association of schizophrenia with dysregulation of the CX3CL1-CX3CR1 and CXCL12-CXCR4 axes. Altogether, dysregulation in chemokine expression may contribute to neuroinflammation in schizophrenia. In conclusion, this evidence indicates the involvement of chemokines in the neurobiological processes associated with schizophrenia.

Untargeted Plasma Metabolomic Profiling in Patients with Depressive Disorders: A Preliminary Study.

Depressive disorder is a multifactorial disease that is based on dysfunctions in mental and biological processes. The search for biomarkers can improve its diagnosis, personalize therapy, and lead to a deep understanding of the biochemical processes underlying depression. The purpose of this work was a metabolomic analysis of blood serum to classify patients with depressive disorders and healthy individuals using Compound Discoverer software. Using high-resolution mass spectrometry, blood plasma samples from 60 people were analyzed, of which 30 were included in a comparison group (healthy donors), and 30 were patients with a depressive episode (F32.11) and recurrent depressive disorder (F33.11). Differences between patient and control groups were identified using the built-in utilities in Compound Discoverer software. Compounds were identified by their accurate mass and fragment patterns using the mzCloud database and tentatively identified by their exact mass using the ChemSpider search engine and the KEGG, ChEBI, FDA UNII-NLM, Human Metabolome and LipidMAPS databases. We identified 18 metabolites that could divide patients with depressive disorders from healthy donors. Of these, only two compounds were tentatively identified using the mzCloud database (betaine and piperine) based on their fragmentation spectra. For three compounds ((4S,5S,8S,10R)-4,5,8-trihydroxy-10-methyl-3,4,5,8,9,10-hexahydro-2H-oxecin-2-one, (2E,4E)-N-(2-hydroxy-2-methylpropyl)-2,4-tetradecadienamide and 17α-methyl-androstan-3-hydroxyimine-17ß-ol), matches were found in the mzCloud database but with low score, which could not serve as reliable evidence of their structure. Another 13 compounds were identified by their exact mass in the ChemSpider database, 9 (g-butyrobetaine, 6-diazonio-5-oxo-L-norleucine, 11-aminoundecanoic acid, methyl N-acetyl-2-diazonionorleucinate, glycyl-glycyl-argininal, dilaurylmethylamine, 12-ketodeoxycholic acid, dicetylamine, 1-linoleoyl-2-hydroxy-sn-glycero-3-PC) had only molecular formulas proposed, and 4 were unidentified. Thus, the use of Compound Discoverer software alone was not sufficient to identify all revealed metabolites. Nevertheless, the combination of the found metabolites made it possible to divide patients with depressive disorders from healthy donors.

NOS1AP Gene Variants and Their Role in Metabolic Syndrome: A Study of 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.

Cell Adhesion Molecules in Schizophrenia Patients with Metabolic Syndrome.

Metabolic syndrome (MetS) is a common comorbidity of schizophrenia and significantly shortens life expectancy of the patients. Intercellular (ICAM), vascular (VCAM), and neural (NCAM) cell adhesion molecules (CAMs) mediate neuroinflammatory processes, and their soluble forms (e.g., sICAM) in plasma are present in parallel with their cell-bound forms. In this study, their serum levels were examined in 211 white Siberian patients with paranoid schizophrenia (82 patients with and 129 without MetS according to the 2005 International Diabetes Federation criteria). Serum levels of CAMs were determined with Magpix and Luminex 200 (Luminex, Austin, TX, USA) using xMAP Technology. The level of sICAM-1 was significantly higher and that of sVCAM-1 significantly lower in patients with MetS compared to patients without MetS. Levels of NCAM did not differ between the groups. More pronounced Spearman's correlations between CAMs, age, duration of schizophrenia, and body-mass index were observed among patients without MetS than among patients with MetS. Our results are consistent with MetS's being associated with endothelial dysfunction along with other components of inflammation. Through these endothelial components of peripheral inflammatory processes, MetS might induce intracerebral neuroinflammatory changes, but further investigation is needed to confirm this.

Building Predictive Models for Schizophrenia Diagnosis with Peripheral Inflammatory Biomarkers.

Machine learning and artificial intelligence technologies are known to be a convenient tool for analyzing multi-domain data in precision psychiatry. In the case of schizophrenia, the most commonly used data sources for such purposes are neuroimaging, voice and language patterns, and mobile phone data. Data on peripheral markers can also be useful for building predictive models. Here, we have developed five predictive models for the binary classification of schizophrenia patients and healthy individuals. Data on serum concentrations of cytokines, chemokines, growth factors, and age were among 38 parameters used to build these models. The sample consisted of 217 schizophrenia patients and 90 healthy individuals. The models architecture was involved logistic regression, deep neural networks, decision trees, support vector machine, and k-nearest neighbors algorithms. It was shown that the algorithm based on a deep neural network (consisting of five layers) showed a slightly higher sensitivity (0.87 ± 0.04) and specificity (0.52 ± 0.06) than other algorithms. Combining all variables into a single classifier showed a cumulative effect that exceeded the effectiveness of individual variables, indicating the need to use multiple biomarkers to diagnose schizophrenia. Thus, the data obtained showed the promise of using data on peripheral biomarkers and machine learning methods for diagnosing schizophrenia.

The Influence of Antipsychotic Treatment on the Activity of Abzymes Targeting Myelin and Levels of Inflammation Markers in Patients with Schizophrenia.

Catalytic antibodies, or abzymes, are capable of not only binding but also hydrolyzing various proteins. Previously, an increase in the level of myelin basic protein (MBP)-hydrolyzing activity of antibodies was shown in patients with a number of neurological and mental disorders, including schizophrenia. Furthermore, antipsychotic therapy is known to induce a change in cytokine levels in patients with schizophrenia, which affects regulation of the immune response and inflammatory status. This study investigated the influence of typical and atypical antipsychotics on catalytic antibody activity and the 10 major pro- and anti-inflammatory serum cytokine levels. The study included 40 patients with schizophrenia: 15 treated with first-generation antipsychotics and 25 treated with atypical antipsychotics for 6 weeks. It was found that treatment with atypical antipsychotics changed the levels of some pro-inflammatory cytokines. Antipsychotic therapy also caused a significant decrease in MBP-hydrolyzing activity in patients with schizophrenia (p = 0.0002), and associations of catalytic activity with interleukins were observed.

Cytokine level in patients with mood disorder, alcohol use disorder and their comorbidity.

OBJECTIVES: Because alcohol use disorder (AUD) is often accompanied by mood disorder (MD) and both alcoholism and depression result in activation of the immune system, this study compares serum cytokine levels in the presence of co-morbidity with those in either AUD or MD alone. METHODS: In this naturalistic prospective study the levels of 15 different cytokines were measured in serum samples of patients with MD (n = 43), participants with combined AUD-MD (n = 44) and AUD without MD (n = 42). The levels were compared cross-sectionally among themselves and with those in 50 healthy volunteers. RESULTS: Pro-inflammatory IFN-2α levels were consistently significantly higher and anti-inflammatory IL-1RA significantly lower in all study groups in comparison to healthy volunteers. In the MD only group we found increased IL-6 (p = 0.001), IL-7 (p = 0.001) and IL-13 (p = 0.006) levels, and decreased TNFα (p = 0.0001), IL-1RA (p = 0.012), IL-10 (p = 0.002) compared with group MD + AUD. Patients with AUD only showed elevated levels of IL-1ß (p = 0.046), IL-2 (p = 0.004), IL-7 (p = 0.0001), IL-4 (p = 0.049) and IL-13 (p = 0.015) in contrast with MD + AUD group. CONCLUSIONS: Because the interactions of alcohol with peripheral and cerebral immune systems are multifaceted, the pertinent connection to the mechanism how alcohol consumption contributes to the development of mood disorders cannot be properly explored.

Levels of Acylcarnitines and Branched-Chain Amino Acids in Antipsychotic-Treated Patients with Paranoid Schizophrenia with Metabolic Syndrome.

Several studies have shown that patients with schizophrenia are at high risk for metabolic syndrome (MetS) and bioenergetic dysfunction. Because acylcarnitines are involved in bioenergetic pathways and reflect the functioning of mitochondria, we hypothesized that these compounds are biomarkers of MetS in schizophrenia. The aim of this work was to quantify acylcarnitines and branched-chain amino acids in patients with schizophrenia comorbid with MetS. The study included 112 patients with paranoid schizophrenia treated with antipsychotics. Among them, 39 subjects met criteria of MetS. Concentrations of 30 acylcarnitines and three amino acids in dry serum spots were measured by liquid chromatography coupled with tandem mass spectrometry. MetS patients were found to have higher levels of valeryl carnitine (C5), leucine/isoleucine, and alanine as compared with patients without MetS, indicating possible participation of these compounds in the pathogenesis of metabolic disorders in schizophrenia. In patients with paranoid schizophrenia with or without MetS, lower levels of carnitines C10, C10:1, C12, and C18 were recorded as compared with the healthy individuals (n = 70), implying deterioration of energy metabolism. We believe that this finding can be explained by effects of antipsychotic medication on an enzyme called carnitine-palmitoyl transferase I.

Cytokines as Potential Biomarkers of Clinical Characteristics of Schizophrenia.

Immune activation plays a major role in the pathogenesis of schizophrenia, as confirmed by many studies, systematic reviews, and meta-analyses. The important role of neuroinflammation in the formation of the relation between impaired neurobiological processes and schizophrenia psychopathology is being actively discussed. We quantified serum concentrations of 22 cytokines in 236 patients with schizophrenia and 103 mentally and somatically healthy individuals by a multiplex assay. We found higher TGF-α (p = 0.014), IFN-γ (p = 0.036), IL-5 (p < 0.001), IL-6 (p = 0.047), IL-8 (p = 0.005), IL-10 (p <0.001), IL-15 (p = 0.007), IL-1RA (p = 0.007), and TNF-α (p < 0.001) levels in patients with schizophrenia than in healthy individuals. Subgroup analysis revealed a much greater number of statistically significant differences in cytokine levels among females than among males. Patients with a continuous course of schizophrenia showed statistically significantly higher levels of IL-12p70 (p = 0.019), IL-1α (p = 0.046), and IL-1ß (p = 0.035) compared with patients with an episodic course. Most cytokines were positively correlated with positive, general, and total PANSS scores. In patients with a duration of schizophrenia of 10 years or more, the level of IL-10 was higher than that in patients with a disease duration of 5 years or less (p = 0.042). Thus, an imbalance in cytokines was revealed in patients with schizophrenia, depending on sex and clinical characteristics of the disease.

Metabolic Hormones in Schizophrenia Patients with Antipsychotic-Induced Metabolic Syndrome.

Metabolic syndrome (MetS) is a common complication of schizophrenia that is quite exacerbated by long-term use of (atypical) antipsychotics. The mechanism of MetS has neuronal, neuroendocrine, and neuroimmunological components and shows some overlap with those of aspects of schizophrenia. We examined 195 patients with schizophrenia (90 with and 105 without MetS) for the association of serum levels of ghrelin, insulin, and leptin with metabolic abnormalities. Serum glucose levels and lipid profiles were routinely measured with colorimetric enzymatic methods and hormone levels with multiplex analyzers. Leptin levels were highly significantly increased (p < 0.001) in people with MetS (9.966 [5.882; 21.496] vs. 6.35 [2.005; 11.753], Me [Q1; Q3]) and ghrelin levels were actually significantly decreased (p = 0.045). Insulin levels did not differ significantly between those with and without MetS (p = 0.162). In Spearman's correlation analysis between the hormone levels, body characteristics, and biochemical parameters, significant correlations were seen somewhat more often in people without MetS than in those with MetS and also less often for ghrelin than for the other hormones. We conclude that evidence exists for a role in the development of MetS especially for leptin, but that less is supporting a role for ghrelin.

Immunoglobulins G of Patients with Schizophrenia Protects from Superoxide: Pilot Results.

This study aimed to evaluate the superoxide dismutase (SOD) activity of IgG in patients with schizophrenia. After signing informed consent, we included 67 patients with schizophrenia (34 people with acute schizophrenia and 33 individuals were on outpatient treatment in therapeutic remission) and 14 healthy volunteers. IgGs from blood serum were isolated by affinity chromatography. SOD activity of antibodies was determined spectrophotometrically. We have shown for the first time that IgGs from patients with schizophrenia have SOD activity and this activity is an intrinsic property of antibodies. The maximum increase in SOD activity was registered in the group of patients in therapeutic remission compared with acute schizophrenia (p = 0.005) and in healthy individuals (p = 0.001). Based on the data of inhibitory analysis using a specific SOD inhibitor enzyme, triethylenetetramine (TETA), we can assume that the mechanism of the SOD activity of IgG is similar to the mechanism of classical enzyme catalysis. According to the kinetic analysis, the affinity of the IgGs to the substrate is higher than that of the classical SOD enzyme.

Gene Polymorphisms of Hormonal Regulators of Metabolism in Patients with Schizophrenia with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a common complication of long-term treatment of persons with schizophrenia taking (atypical) antipsychotics. In this study, we investigated the existence of an association with polymorphisms of genes for four hormones that regulate energy metabolism. METHODS: We recruited 517 clinically admitted white patients (269M/248F) with a verified diagnosis of schizophrenia (ICD-10) and with a stable physical condition. Participants were classified for having or not having MetS and genotyped for 20 single-nucleotide polymorphisms (SNPs) in the genes encoding insulin-induced gene 2 (INSIG2), ghrelin (GHRL), leptin (LEP), and leptin receptor (LEPR). RESULTS: The 139 patients (26.9%) with MetS were significantly more likely to be women, older, and ill longer, and had a larger body mass index (BMI). Four polymorphisms (rs10490624, rs17587100, rs9308762, and rs10490816) did not meet the Hardy-Weinberg equilibrium (HWE) criterion and were excluded. Only genotypes and alleles of the rs3828942 of LEP gene (chi2 = 7.665, p = 0.022; chi2 = 5.136, p = 0.023) and the genotypes of the rs17047718 of INSIG2 gene (chi2 = 7.7, p = 0.021) had a significant association with MetS. CONCLUSIONS: The results of our study suggest that the LEP and INSIG2 genes play a certain causal role in the development of MetS in patients with schizophrenia.

The Gender-Specific Association of DRD2 Polymorphism with Metabolic Syndrome in Patients with Schizophrenia.

BACKGROUND: Metabolic syndrome is widespread in patients with schizophrenia receiving long-term antipsychotic therapy. Dopamine D2 receptors play an important role in mediating both the therapeutic actions of antipsychotics and their side effects. The present study examined the association of two polymorphisms of the DRD2 gene with metabolic syndrome in patients with schizophrenia. METHODS: We examined 517 patients from several regions of Siberia (Russia) with a clinical diagnosis of schizophrenia. Genotyping of two single nucleotide polymorphisms rs1799732 and rs4436578 of the dopamine D2 receptor gene (DRD2) was performed in a population of 471 patients. The results were analyzed using chi-square tests. RESULTS: Functional polymorphism rs1799732 of the DRD2 gene is associated with drug-induced metabolic syndrome in women with schizophrenia. CONCLUSIONS: Our results show that the DRD2 gene may be involved in the pathogenesis of metabolic disorders in patients with schizophrenia. Further analysis of possible genetic markers will allow for personalized treatment with minimal side effects and optimal efficacy. This which seems relevant in light of the recent focus on improving the quality of life and ensuring a high level of social adaptation of patients with schizophrenia.

Cytokine Level Changes in Schizophrenia Patients with and without Metabolic Syndrome Treated with Atypical Antipsychotics.

The present study aims at comparing the change in cytokine levels in schizophrenia patients treated with atypical antipsychotics, with or without metabolic syndrome (MetS). The study included 101 patients with schizophrenia, 38 with and 63 without MetS, who received risperidone, quetiapine, olanzapine or aripiprazole for six weeks. We analyzed the concentration of 21 cytokines in the serum patients. The treatment with atypical antipsychotics changed some proinflammatory cytokine levels. It led to increased IFN-α2 (p = 0.010), IL-1α (p = 0.024) and IL-7 (p = 0.017) levels in patients with MetS, whereas the same treatment led to decreased levels of IFN-γ (p = 0.011), IL-1ß (p = 0.035), IL-12р40 (p = 0.011), IL-17A (p = 0.031), IL-6 (p = 0.043) and TNF-α (p = 0.012) in individuals without MetS. Our results demonstrated the effects of atypical antipsychotics on the immune-inflammatory parameters, depending on the metabolic disturbances in schizophrenia patients.

Comparative Characteristics of the Metabolic Syndrome Prevalence in Patients With Schizophrenia in Three Western Siberia Psychiatric Hospitals.

Objective: The purpose of this study was to compare the prevalence of MetS and the associated sociodemographic, clinical, and pharmacotherapeutic characteristics of patients with schizophrenia in three psychiatric hospitals in the West Siberian region. Methods: Patients with a clinical diagnosis of schizophrenia (ICD-10: F20) and an age between 18 and 60 years were included in the study after giving informed consent. Metabolic syndrome was diagnosed according to the International Diabetes Federation criteria. This research was carried out at three Western Siberian psychiatric hospitals in Kemerovo, Tomsk, and Omsk. The study population included respectively 94, 131, and 91 inpatients with schizophrenia. We carried out schizophrenia symptoms assessment by PANSS, antipsychotic therapy evaluation, anthropometry, and biochemical analysis. Statistical Analysis included the Shapiro-Wilk test, non-parametric Kruskal-Wallis H-test for independent samples, Mann-Whitney U-test for independent samples, the chi-square test, stepwise multiple regression analyses. The level of significance was p < 0.05. Results: The metabolic syndrome prevalence was higher among patients in Tomsk (36.6%), compared with Kemerovo (20.2%, p = 0.008) or Omsk (18.7%, p = 0.004), mainly due to the high prevalence of abdominal obesity, while men from Tomsk were more susceptible to this condition than men from other regions (p < 0.05). Patients from Omsk had the highest severity schizophrenia symptoms according to PANSS, and patients from Tomsk had the lowest severity of positive symptoms according to PANSS. Patients from Tomsk had the minimum duration of antipsychotic therapy compared with the patient from Kemerovo (p = 0.017) and from Omsk (p = 0.000019), but most patients from Tomsk received second-generation atypical antipsychotics, while patients from Omsk received mainly conventional antipsychotics (p = 0.0001). Multiple regression analysis showed that metabolic syndrome associated with schizophrenia duration and body mass index, although the association was not so strong (adjusted R 2 = 0.2435, p < 0.0001). Discussion: The study illustrates that in different psychiatric hospitals within the same region, the prevalence of metabolic syndrome in patients with schizophrenia can vary significantly, which dictates the need to look for opportunities to minimize the risk of its occurrence, taking into account the experience of each hospital.

Search for Possible Associations of FTO Gene Polymorphic Variants with Metabolic Syndrome, Obesity and Body Mass Index in Schizophrenia Patients.

PURPOSE: Metabolic syndrome (MetS) is characterized by abdominal obesity, hyperglycaemia, dyslipidaemia and hypertension. FTO gene has been implicated in the pathogenesis of obesity, but the available scientific data concerning their relationship to antipsychotic drug-induced obesity and metabolic syndrome is still incomplete and inconsistent, which indicates that continuing the investigation of this gene's role is necessary. PATIENTS AND METHODS: In the present study, 517 patients with schizophrenia underwent antipsychotic drug treatment, and two groups were identified: patients with MetS and without MetS. Genotyping of 6 SNPs in the FTO gene was performed, and the results analyzed using R-programme. RESULTS: We performed a statistical analysis to identify possible associations of the frequencies of genotypes and alleles of the studied polymorphisms with the presence of metabolic syndrome in schizophrenia patients, with the presence of abdominal obesity, and with an increased body mass index. The rs7185735 polymorphism did not meet the Hardy-Weinberg criterion and was excluded. After correcting for differences in age, gender and duration of illnesses, none of the variants was shown to be related to metabolic syndrome or abdominal obesity, but rs9939609, rs1421085, rs3751812 and rs8050136 were associated with body mass index. CONCLUSION: The present study provides additional support for these SNP's roles as a pharmacogenetic biomarker that may become useful in the framework of the personalized medicine approach.

Amino Acid and Acylcarnitine Levels in Chronic Patients with Schizophrenia: A Preliminary Study.

Amino acids and acylcarnitines play an important role as substrates and intermediate products in most of pathways involved in schizophrenia development such as mitochondrial dysfunction, inflammation, lipid oxidation, DNA damage, oxidative stress, and apoptosis. It seems relevant to use an integrated approach with 'omics' technology to study their contribution. The aim of our study was to investigate serum amino acid and acylcarnitine levels in antipsychotics-treated patients with chronic schizophrenia compared with healthy donors. We measured serum levels of 15 amino acids and 30 acylcarnitines in 37 patients with schizophrenia and 36 healthy donors by means of tandem mass spectrometry. In summary, patients with chronic schizophrenia had an altered concentration of a few amino acids and acylcarnitines in comparison to the healthy probands. Further research is needed to assess and understand the identified changes.

Genetic Polymorphisms of 5-HT Receptors and Antipsychotic-Induced Metabolic Dysfunction in Patients with Schizophrenia.

BACKGROUND: Antipsychotic-induced metabolic syndrome (MetS) is a multifactorial disease with a genetic predisposition. Serotonin and its receptors are involved in antipsychotic-drug-induced metabolic disorders. The present study investigated the association of nine polymorphisms in the four 5-hydroxytryptamine receptor (HTR) genes HTR1A, HTR2A, HTR3A, and HTR2C and the gene encoding for the serotonin transporter SLC6A4 with MetS in patients with schizophrenia. METHODS: A set of nine single-nucleotide polymorphisms of genes of the serotonergic system was investigated in a population of 475 patients from several Siberian regions (Russia) with a clinical diagnosis of schizophrenia. Genotyping was performed and the results were analyzed using chi-square tests. RESULTS: Polymorphic variant rs521018 (HTR2C) was associated with higher body mass index in patients receiving long-term antipsychotic therapy, but not with drug-induced metabolic syndrome. Rs1150226 (HTR3A) was also associated but did not meet Hardy-Weinberg equilibrium. CONCLUSIONS: Our results indicate that allelic variants of HTR2C genes may have consequences on metabolic parameters. MetS may have too complex a mechanistic background to be studied without dissecting the syndrome into its individual (causal) components.

IgG-Dependent Dismutation of Superoxide in Patients with Different Types of Multiple Sclerosis and Healthy Subjects.

This work is the first to demonstrate that class G immunoglobulins (IgGs) in patients with multiple sclerosis and healthy individuals have the ability to catalyze the dismutation reaction of the superoxide anion radical. Thus, superoxide dismutase (SOD) activity is an intrinsic property of antibodies, which is confirmed by a number of stringent criteria. SOD activity of IgGs in patients with multiple sclerosis statistically significantly exceeds such activity in healthy individuals by 2-4 times. Moreover, the maximum activity has been registered in patients with relapsing remitting multiple sclerosis. The kinetic characteristics of the SOD reaction of IgGs are several orders of magnitude lower than those for the SOD enzyme but do not differ between patients with multiple sclerosis and healthy individuals. Consequently, abzymes with SOD activity have a lower catalysis rate than that of the enzymes and form a stronger complex with the substrates. Inhibitory analysis showed that this activity is inhibited by classical metal-dependent SOD inhibitors. The activity of IgGs was inhibited by classical metal-dependent inhibitors EDTA and TETA (triethylenetetramine). Also, high catalase activity of IgGs was detected in these patients. We suggest that these abzymes help protect the body from oxidative stress.