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.

Multiplex Analysis of Serum Cytokine Profiles in Systemic Lupus Erythematosus and Multiple Sclerosis.

Changes in cytokine profiles and cytokine networks are known to be a hallmark of autoimmune diseases, including systemic lupus erythematosus (SLE) and multiple sclerosis (MS). However, cytokine profiles research studies are usually based on the analysis of a small number of cytokines and give conflicting results. In this work, we analyzed cytokine profiles of 41 analytes in patients with SLE and MS compared with healthy donors using multiplex immunoassay. The SLE group included treated patients, while the MS patients were drug-free. Levels of 11 cytokines, IL-1b, IL-1RA, IL-6, IL-9, IL-10, IL-15, MCP-1/CCL2, Fractalkine/CX3CL1, MIP-1a/CCL3, MIP-1b/CCL4, and TNFa, were increased, but sCD40L, PDGF-AA, and MDC/CCL22 levels were decreased in SLE patients. Thus, changes in the cytokine profile in SLE have been associated with the dysregulation of interleukins, TNF superfamily members, and chemokines. In the case of MS, levels of 10 cytokines, sCD40L, CCL2, CCL3, CCL22, PDGF-AA, PDGF-AB/BB, EGF, IL-8, TGF-a, and VEGF, decreased significantly compared to the control group. Therefore, cytokine network dysregulation in MS is characterized by abnormal levels of growth factors and chemokines. Cross-disorder analysis of cytokine levels in MS and SLE showed significant differences between 22 cytokines. Protein interaction network analysis showed that all significantly altered cytokines in both SLE and MS are functionally interconnected. Thus, MS and SLE may be associated with impaired functional relationships in the cytokine network. A cytokine correlation networks analysis revealed changes in correlation clusters in SLE and MS. These data expand the understanding of abnormal regulatory interactions in cytokine profiles associated with autoimmune diseases.

Association between 8 P-glycoprotein (MDR1/ABCB1) gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia.

INTRODUCTION: Hyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P-glycoprotein. Genetic variants of P-glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland. AIMS: To investigate possible associations between MDR1/ABCB1 gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia in Russian patients with schizophrenia and to determine possible differences between risperidone/paliperidone and other antipsychotics. METHODS: In total, 446 patients with schizophrenia were included from 3 psychiatric hospitals in Siberia. Blood samples were obtained in a cross-sectional study design for DNA extraction and prolactin measurement. Associations between hyperprolactinaemia and 8 MDR1/ABCB1 gene-polymorphisms were assessed using logistic regression analysis accounting for covariates. The analysis was repeated in a patient subgroup using risperidone or paliperidone. RESULTS: We did not observe an association between any of the 8 single nucleotide polymorphisms and the prevalence of antipsychotic-induced hyperprolactinaemia in the total patient population. However, in the risperidone/paliperidone subgroup, the single nucleotide polymorphism rs2032582 (G2677T) was found to be negatively associated with risperidone/paliperidone-induced hyperprolactinaemia. CONCLUSION: This study revealed a significant association between the ABCB1 gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone-induced hyperprolactinaemia.

Association of ANKK1 polymorphism with antipsychotic-induced hyperprolactinemia.

OBJECTIVE: Schizophrenia is a severe highly heritable mental disorder. Genetic polymorphisms of dopaminergic pathways are related to pathogenesis of drug response. Hyperprolactinemia (HPRL), a common adverse effect of antipsychotics, is attributed to blockade of dopamine D2 receptors. Ankyrin Repeat and Kinase Domain containing 1 (ANKK1) gene is closely related to Dopamine Receptor D2 type (DRD2) gene functioning. We examined whether the functional polymorphism rs2734849 in the ANKK1 gene is associated with antipsychotic-induced HPRL. METHODS: We recruited 446 patients with schizophrenia from among the Russian population of the Siberian region. The polymorphism rs2734849 in the ANKK1 gene was genotyped with The MassARRAY® Analyzer 4 by Agena Bioscience™, using the kit SEQUENOM Consumables iPLEXGold 384. Genotype and allele frequencies were compared between groups of schizophrenia patients with and without HPRL using the χ2 test. RESULTS: A comparison between schizophrenia patients with and without HPRL revealed significantly higher frequency of the C allele of the polymorphic variant rs2734849 in the ANKK1 gene in patients with HPRL as compared to the patients without it (χ2 = 3.70; p = .05; odds ratio [OR] = 1.30 [0.99-1.69]). CONCLUSION: The functional polymorphism rs2734849 in the ANKK1 gene was associated with HPRL in patients with schizophrenia.

A pharmacogenetic study of patients with schizophrenia from West Siberia gets insight into dopaminergic mechanisms of antipsychotic-induced hyperprolactinemia.

BACKGROUND: Hyperprolactinemia (HPRL) is a classical side effect of antipsychotic drugs primarily attributed to blockade of dopamine D2 receptors (DRD2s) on the membranes of lactotroph cells within the pituitary gland. Certain antipsychotic drugs, e.g. risperidone, are more likely to induce HPRL because of relative accumulation within the adenohypophysis. Nevertheless, due to competition for pituitary DRD2s by high dopamine levels may limit antipsychotic-induced HPRL. Moreover, the activity of prolactin-producing lactotrophs also depends on other hormones which are regulated by the extra-pituitary activity of dopamine receptors, dopamine transporters, enzymes of neurotransmitter metabolism and other factors. Polymorphic variants in the genes coding for these receptors and proteins can have functional significance and influence on the development of hyperprolactinemia. METHODS: A set of 41 SNPs of genes for dopamine receptors DRD1, DRD2, DRD3, DRD4, the dopamine transporter SLC6A3 and dopamine catabolizing enzymes MAOA and MAOB was investigated in a population of 446 Caucasians (221 males/225 females) with a clinical diagnosis of schizophrenia (according to ICD-10: F20) with and without HPRL who were treated with classical and/or atypical antipsychotic drugs. Additive genetic model was tested and the analysis was carried out in the total group and in subgroup stratified by the use of risperidone/paliperidone. RESULTS: One statistically significant association between polymorphic variant rs1799836 of MAOB gene and HPRL in men was found in the total group. Furthermore, the rs40184 and rs3863145 variants in SLC6A3 gene appeared to be associated with HPRL in the subgroup of patients using the risperidone/paliperidone, but not with HPRL induced by other antipsychotic drugs. CONCLUSIONS: Our results indicate that genetic variants of MAOB and SLC6A3 may have consequences on the modulation of prolactin secretion. A further search for genetic markers associated with the development of antipsychotic-related hyperprolactinemia in schizophrenic patients is needed.

No evidence so far of a major role of AKT1 and GSK3B in the pathogenesis of antipsychotic-induced tardive dyskinesia.

OBJECTIVE: AKT1 and GSK3B take part in one of the intracellular cascades activated by the D2 dopamine receptor (DRD2). This receptor is antagonized by antipsychotics and plays a role in the pathogenesis of antipsychotic-induced tardive dyskinesia (TD). The present study investigated association of several polymorphisms in the two candidate genes, AKT1 and GSK3B, with TD in antipsychotic-treated patients with schizophrenia. METHODS: DNA samples from 449 patients from several Siberian regions (Russia) were genotyped, and the results were analyzed using chi-squared tests and analyses of variance. RESULTS: Antipsychotic-induced TD was not associated with either of the tested functional polymorphisms (rs334558, rs1130214, and rs3730358). CONCLUSIONS: Despite regulation of AKT1 and GSK3B by DRD2, we found no evidence that these two kinases play a major role in the pathogenesis of antipsychotic-induced TD. These results agree with previously published data and necessitate further exploration of other pathogenic mechanisms, such as neurotoxicity due to excessive dopamine metabolism.

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.

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.

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.

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.

Association of Peripheral Inflammatory Biomarkers and Growth Factors Levels with Sex, Therapy and Other Clinical Factors in Schizophrenia and Patient Stratification Based on These Data.

Multiple lines of evidence are known to confirm the pro-inflammatory state of some patients with schizophrenia and the involvement of inflammatory mechanisms in the pathogenesis of psychosis. The concentration of peripheral biomarkers is associated with the severity of inflammation and can be used for patient stratification. Here, we analyzed changes in serum concentrations of cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-21, APRIL, BAFF, PBEF/Visfatin, IFN-α, and TNF-α) and growth/neurotrophic factors (GM-CSF, NRG1-ß1, NGF-ß, and GDNF) in patients with schizophrenia in an exacerbation phase. IL-1ß, IL-2, IL-4, IL-6, BAFF, IFN-α, GM-CSF, NRG1-ß1, and GDNF increased but TNF-α and NGF-ß decreased in schizophrenia compared to healthy individuals. Subgroup analysis revealed the effect of sex, prevalent symptoms, and type of antipsychotic therapy on biomarker levels. Females, patients with predominantly negative symptoms, and those taking atypical antipsychotics had a more pro-inflammatory phenotype. Using cluster analysis, we classified participants into "high" and "low inflammation" subgroups. However, no differences were found in the clinical data of patients in these subgroups. Nevertheless, more patients (17% to 25.5%) than healthy donors (8.6% to 14.3%) had evidence of a pro-inflammatory condition depending on the clustering approach used. Such patients may benefit from personalized anti-inflammatory therapy.

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.

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.

Serum Cytokine Levels of Systemic Lupus Erythematosus Patients in the Presence of Concomitant Cardiovascular Diseases.

BACKGROUND: Systemic lupus erythematosus (SLE) is known to be associated with an increased risk of cardiovascular diseases (CVD). SLE patients suffer from CVD 3.5 times more often than healthy people. Cytokine-mediated inflammation is actively involved in the development of cardiovascular pathology. OBJECTIVE: Here, we analyzed serum levels of nine cytokines of steroids-treated SLE patients depending on the presence of concomitant CVD. METHODS: The levels of interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-10, IL-21, tumor necrosis factor α (TNFα), B-cell activating factor (BAFF), and a proliferation-inducing ligand (APRIL) were analyzed using multiplex immunoassay. RESULTS: In the total group of SLE patients (n=29), the concentrations of IL-6 and IL-10 were higher, and the APRIL level decreased compared to healthy donors (n=39, p<0.05). The same changes were observed in the group of patients without CVD (n=15); the levels of IL-6 and IL- 10 were found to be increased, and the level of APRIL was lower than in healthy individuals (p<0.05). In the group of SLE patients with CVD (n=14), the concentrations of IL-4, IL-6, IL- 10, and TNFα were found to be increased (p<0.05). Interestingly, the levels of TNFα and BAFF in SLE patients with CVD were higher than in patients without cardiovascular pathology. Thus, TNFα and BAFF levels were significantly altered in SLE with concomitant CVD compared to SLE without CVD. CONCLUSION: These findings suggest that cytokine profiles in SLE with concomitant CVD and SLE without CVD are different, which should be considered in further research with large samples.

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.

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.

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.