Cortisol and DHEAS Related to Metabolic Syndrome in Patients with Schizophrenia

Background: Both dehydroepiandrosterone (DHEAS) and cortisol are secreted by the adrenal glands and may modulate metabolic syndrome (MetS), which often affects the health of patients with schizophrenia. The relationship between the serum levels of these hormones and MetS has not been established. Purpose: In this pilot study, we investigated the serum levels in schizophrenia patients with and without MetS and compared them with those in healthy volunteers. Patients and Methods: After obtaining informed consent, 110 patients with acute paranoid schizophrenia were recruited directly after admission to the Mental Health Research Institute. The control group consisted of 51 persons reported on questioning to be mentally and somatically healthy. Blood samples to prepare serum were drawn after an 8-h overnight fast during one of the first days of admission. Serum cortisol and DHEAS concentrations were quantified by enzyme-linked immunosorbent assay. Results: A total of 42 patients had MetS and 68 patients were without MetS. The cortisol blood level was significantly (p = 0.012) higher in schizophrenia patients without MetS in comparison to healthy controls, while patients with schizophrenia and a MetS have significantly (p = 0.014) lower DHEAS levels than healthy volunteers. These differences could, however, exclusively be attributed to female participants. Analysis of covariance adjusted for gender and age demon-strated a significant relationship between age and DHEAS levels (F = 9.512, р =0.003). Conclusion: Lower DHEAS serum levels in relationship to MetS become evident in women, but not in men, and have age differences as a confounding factor

Changes in Body Fat and Related Biochemical Parameters Associated With Atypical Antipsychotic Drug Treatment in Schizophrenia Patients With or Without Metabolic Syndrome

Background: Metabolic syndrome (MetS) is a common problem in schizophrenia patients and associated with increased mortality due to cardiovascular disease. Second-generation antipsychotics (SGAs) play an important role in facilitating MetS. Objective: The study aimed to assess weight changes and alterations of indicators of body fat composition and lipid-glucose metabolism induced by reinitiating atypical antipsychotics in patients with schizophrenia when with or without MetS. Methods: After giving informed consent, newly admitted patients with a clinical diagnosis of schizophrenia (ICD-10: F20) and an age between 18 and 55 years were included. MetS was diagnosed according to International Diabetes Federation (IDF) criteria. At entry and after 6 weeks of treatment, anthropometry and biochemical analysis were carried out. Total and visceral fats were measured with the use of non-invasive bioimpedance analysis and subcutaneous fat with calculation of total adipose tissue with the use of caliperometry. Based on biochemical assessments low density (LDL) and very low-density lipoproteins (VLDL), atherogenic index and Homeostatic Model Assessment of Insulin Resistance (IR-HOMA) were calculated. Statistical analysis was conducted using Wilcoxon signed-rank test, Mann-Whitney U-test, and chi-squared test. Differences were considered statistically significant at p < 0.05. Results: A total of 114 patients (59M/55F) with schizophrenia were examined; they were divided into two groups with (n = 43; 37.7%) and without (n = 71; 62.3%) MetS. After a 6-week SGA treatment, only the total fat fold, waist circumference, triglyceride level, and atherogenic index underwent statistically significant changes in patients with MetS. In those without MetS, statistically significant changes across all fat indicators were noted. Also, a significant increase in blood glucose and HOMA-IR parameters, triglyceride, and VLDL levels and atherogenic index was observed in this group. Discussion: The study illustrates the benefits of estimating both anthropometric and biochemical parameters shortly after (re)installing treatment of schizophrenia in order to minimize the risk of MetS development

Adipocytokines and Metabolic Syndrome in Patients with Schizophrenia

The adipokines leptin, adiponectin, tumor necrosis factor-alpha (TNF-alpha), and interleukin 6 (IL-6) might be associated with metabolic syndrome (MetS) in patients with schizophrenia. In the present study, we attempted to confirm the results of previous reports and assessed their MetS-related correlation with body fat composition and biochemical parameters. We measured in 46 patients with schizophrenia and MetS serum levels of adiponectin insulin, leptin, TNF-alpha and IL-6 and compared these levels to those of patients with schizophrenia without MetS. The MetS patients had significantly increased leptin levels and leptin/adiponectin ratios, as well as decreased adiponectin levels. Leptin levels correlated with several metabolic parameters, both in patients with and without MetS, including body fat percentage, total fat fold, and body mass index (BMI). Patients without abnormal MetS components had lower levels of leptin and leptin/adiponectin ratios compared with patients who had one or two MetS components. Leptin/adiponectin ratios were higher in patients who had four rather than three MetS components. Multiple regression analysis revealed multiple associations for leptin but only one for adiponectin, TNF-alpha, and IL-6. Our results support an important pathophysiological role for leptin more than adiponectin in patients with schizophrenia with MetS

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-alpha 2 (p = 0.010), IL-1 alpha (p = 0.024) and IL-7 (p = 0.017) levels in patients with MetS, whereas the same treatment led to decreased levels of IFN-gamma (p = 0.011), IL-1 beta (p = 0.035), IL-12p40 (p = 0.011), IL-17A (p = 0.031), IL-6 (p = 0.043) and TNF-alpha (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

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

Body Fat Parameters, Glucose and Lipid Profiles, and Thyroid Hormone Levels in Schizophrenia Patients with or without Metabolic Syndrome

In this study, we aim to investigate associations between body fat parameters, glucose and lipid profiles, thyroid-stimulating hormone (TSH), and thyroid hormones (THs) levels in Tomsk-region schizophrenia patients depending upon the presence or absence of metabolic syndrome (MetS). A total of 156 psychiatric inpatients with schizophrenia who had been treated with antipsychotics for at least six months before entry were studied: 56 with and 100 without MetS. Reference groups consisted of general hospital inpatients with MetS and without schizophrenia (n = 35) and healthy individuals (n = 35). Statistical analyses were performed using the Mann-Whitney U-test, chi-square test, Spearman's rank correlation coefficient, multiple regression analyses, and descriptive statistics. Patients with schizophrenia and MetS had significantly higher levels of free triiodothyronine (FT3) and thyroxine (FT4) compared to schizophrenia patients without MetS (3.68 [3.25; 5.50] vs. 3.24 [2.81; 3.66], p = 0.0001, and 12.68 [10.73; 15.54] vs. 10.81 [9.76; 12.3], p = 0.0001, in pmol/L, respectively). FT3 maintained an association with MetS (p = 0.0001), sex (p = 0.0001), age (p = 0.022), and high-density lipoproteins (p = 0.033). FT4 maintained an association with MetS (p = 0.0001), sex (p = 0.001), age (p = 0.014), and glucose (p = 0.009). The data obtained showed body fat parameters, glucose and lipid profiles, and THs levels in Western-Siberian schizophrenia patients depending on MetS presence or absence

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

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

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