Glutamate Concentration in the Serum of Patients with Schizophrenia

Glutamate is the major neurotransmitter with multiple functions in the central nervous system. Glutamate-mediated excitotoxicity is involved in the pathophysiological processes in schizophrenia. The purpose of this study was to determine the concentration of glutamate in the serum of patients with paranoid schizophrenia compared with healthy individuals, and depending on the duration of the schizophrenic process and leading clinical symptoms. We investigated the level of glutamate in the serum of 158 patients with paranoid schizophrenia and 94 healthy persons. Higher concentrations of glutamate in schizophrenic patients compared with healthy persons have been found. The maximum concentrations of glutamate were detected in patients with disease duration of more than ten years. Glutamate level in the serum does not depend on the prevailing negative or positive clinical symptoms. The increased concentration of glutamate can hypothetically contribute to dopaminergic and glutamatergic imbalance, leading to the development of psychotic symptoms and cognitive dysfunction

СОВРЕМЕННЫЕ ВОПРОСЫ И ПЕРСПЕКТИВЫ ИЗУЧЕНИЯ ШИЗОФРЕНИИ С ВЕДУЩЕЙ НЕГАТИВНОЙ СИМПТОМАТИКОЙ

Basic contemporary trends in schizophrenia studies with leading negative symptoms in the clinical picture has been presented. There were mainly overviewed the works resulted from original research as well as the papers clinical dynamics, the study of constitutional factors, adjustment as well as schizophrenia therapy with predominant negative symptoms. There was shown interdisciplinary character of the discussed problem in the plane of a biopsychosocial approach. There was demonstrated the priority of updating of clinical patterns phenomenology and schizophrenia dynamics with predominance of negative symptoms in connection with the upcoming transition to the new revision of the international classification of diseases and the need for profound studies of the influence of constitutional factors on the clinical dynamics and prognosis of the disorder in terms of patients adjustment and therapy.Представлены основные современные направления изучения шизофрении с ведущей негативной симптоматикой в клинической картине. Преимущественно рассмотрены работы, являющиеся результатами оригинальных исследований, а также проблемные публикации по вопросам клинической динамики, изучения конституциональных закономерностей, адаптации и терапии шизофрении с преобладающей негативной симптоматикой. Показан междисциплинарный характер обсуждаемой проблемы, лежащей в плоскости биопсихосоциального подхода. Продемонстрирован приоритет уточнения феноменологии клинических паттернов и динамики шизофрении с преобладанием негативной симптоматики в связи с предстоящим переходом на новый пересмотр Международной классификации болезней, а также необходимость углубленных исследований влияния конституциональных факторов на клиническую динамику и прогноз заболевания в аспекте адаптации больных и проводимой терапии

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

Climate Change, Growth, and California Wildfire

Large wildfire occurrence and burned area are modeled using hydroclimate and landsurface characteristics under a range of future climate and development scenarios. The range of uncertainty for future wildfire regimes is analyzed over two emissions pathways (the Special Report on Emissions Scenarios [SRES] A2 and B1 scenarios); three global climate models (Centre National de Recherches Météorologiques CM3, Geophysical Fluid Dynamics Laboratory CM21 and National Center for Atmospheric Research PCM2); a mid‐range scenario for future population growth and development footprint; two model specifications related to the uncertainty over the speed and timing with which vegetation characteristics will shift their spatial distributions in response to trends in climate and disturbance; and two thresholds for defining the wildland‐urban interface relative to housing density. Results were assessed for three 30‐year time periods centered on 2020, 2050, and 2085, relative to a 30‐year reference period centered on 1975. Substantial increases in wildfire are anticipated for most scenarios, although the range of outcomes is large and increases with time. The increase in wildfire area burned associated with the higher emissions pathway (SRES A2) is substantial, with increases statewide ranging from 57 percent to 169 percent by 2085, and increases exceeding 100 percent in most of the forest areas of Northern California in every SRES A2 scenario by 2085. The spatial patterns associated with increased fire occurrence vary according to the speed with which the distribution of vegetation types shifts on the landscape in response to climate and disturbance, with greater increases in fire area burned tending to occur in coastal southern California, the Monterey Bay area and northern California Coast ranges in scenarios where vegetation types shift more rapidly.National Oceanic and Atmospheric Administration (NOAA) Regional Integrated Science and Assessment Program for California, United StatesCalifornia Climate Change Center/[CEC-500-2009-046-F]//Estados UnidosUnited States Department of Agriculture (USDA) Forest Service Pacific Southwest Research Station///Estados UnidosNational Oceanic and Atmospheric Administration (NOAA) Regional Integrated Science and Assessment Program for California///Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI

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

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

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

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

Dehydroepiandrosterone sulphate as a putative protective factor against tardive dyskinesia

AbstractBackgroundTardive dyskinesia (TD) is a potentially irreversible consequence of long term treatment with antipsychotic drugs which is according to a well-known theory believed to be related to oxidative stress induced neurotoxicity. Dehydroepiandrosterone (DHEA) is an endogenous antioxidant with neuroprotective activity. The biosynthesis of DHEA depends upon the activity of cytochrome P450c17α (CYP17). The gene that encodes for CYP17 has a (T34C) single nucleotide polymorphism which enhances CYP17 transcription and expression.ObjectiveTo test the hypothesis that carriership of a more active CYP17 variant would result in higher DHEA(S) levels and protect against neurotoxicity which results in orofaciolingual TD (TDof), limb-truncal TD (TDlt) or both (TDsum).MethodTardive dyskinesia was assessed cross-sectionally in 146 Caucasian psychiatric inpatients from Siberia.ResultsPatients who are carriers of the Cyp17 genotype CC have less chance of developing TD compared to patients who are carriers of the Cyp17 genotypes TC or TT (p<0.05). However, these carriers have significant lower circulating DHEAS levels compared to carriers of the Cyp17 genotypes TC and TT (p<0.05). Conversely, carriers of the CYP17 T-allele have significant elevated DHEAS levels. After correcting for gender and age no significant relationship between Cyp17 genotype CC, the T-allelle and the C-allele and the DHEAS concentration of patients was observed.ConclusionsAlthough an association between the CYP17 CC genotype and TD is indicated, our findings do not support the hypothesis that this is mediated through increased DHEA(S) levels. We believe that the relationship between this polymorphism and neuroprotective effects of steroids is more complex and cannot be elucidated without taking the posttranslational regulation of the enzyme into account