97 research outputs found

    The functional variant rs334558 of GSK3B is associated with remission in patients with depressive disorders

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    Anastasia Levchenko,1,* Innokentiy S Losenkov,2,* Natalia M Vyalova,2 German G Simutkin,2 Nikolay A Bokhan,2,3 Bob Wilffert,4,5 Anton JM Loonen,4,6 Svetlana A Ivanova2,7 1Institute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg, Russia; 2Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia; 3Department of Psychotherapy and Psychological Counseling, National Research Tomsk State University, Tomsk, Russia; 4Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands; 5University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 6GGZ Westelijk Noord-Brabant, Bergen op Zoom, the Netherlands; 7Division for Control and Diagnostics, School of Non-Destructive Testing & Security, National Research Tomsk Polytechnic University, Tomsk, Russia *These authors contributed equally to this work Purpose: GSK3B and AKT1 genes have been implicated in the pathogenesis of a number of psychiatric and neurological disorders. Furthermore, their genetic variants are associated with response to antidepressant pharmacotherapy. As the evidence is still incomplete and inconsistent, continuing efforts to investigate the role of these two genes in the pathogenesis and treatment of brain disorders is necessary. The aim of our study was thus to evaluate the association of variants of these two genes with depressive disorders and drug treatment response.Patients and methods: In the present study, 222 patients with a depressive disorder who underwent pharmacological antidepressant treatment were divided into remitters and non-remitters following a 28-day course of pharmacotherapy. The association of a depressive disorder and remission rates with polymorphisms rs334558 in the GSK3B gene and rs1130214 and rs3730358 in the AKT1 gene was evaluated with a chi-square test.Results: Neither of the studied genetic variants was associated with a depressive disorder. Furthermore, frequencies of alleles and genotypes for rs1130214 and rs3730358 were not different in the groups of remitters and non-remitters. However, the activating allele T of the functional polymorphism rs334558 was significantly associated with remission, when all types of antidepressant drugs were included. This association continued as a trend when only patients taking selective serotonin reuptake inhibitors were considered.Conclusion: The present study provides support that the functional polymorphism rs334558 of GSK3B may play a role as a useful genetic and pharmacogenetic biomarker in the framework of personalized medicine approach. Keywords: depressive disorder, association study, AKT1, GSK3B, genetic biomarke

    P01-94 - Social Adaptation Level among Inpatients with Atypical and Non-atypical Depression

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    Expansion of depressive disorders and widespread of atypical depression (AD) (by DSM-IV) are the major problems of contemporary psychiatry. The level of social adaptation disturbance may be one of indices of severity depressive impairments.ObjectivesTo compare social adaptation level among psychiatric inpatients with an atypical and non-atypical depression.Methods140 inpatients at the age of 18-65 years were evaluated with SIGH-SAD (Williams J. et al., 1991) and Social Adaptation Self-evaluation Scale (SASS) (Bosc M. et al., 1997). Patients who got more than 7 points by SIGH-SAD atypical features were considered as AD-patients, they formed the main group. Patients who got 7 or less scores by SIGH-SAD atypical features formed the comparison group. Mann-Whitney test was used.Results10 men and 60 women (1:6) at the average age 44.5±11.4 generated the main group. The comparison group was generated by 20 man and 50 women (2:5) at the average age of 48±10.7. Significant difference at the age was not observed. The average age for women of main and comparison groups are 44.6±11.2 and 49.6±10.6 years (p=0.01891). The middle score on SIGH-SAD at admission was 31.4±6.2 in main group and 24.9±6.2 in the comparison group (p=0.0000). The middle score on the SASS in the main and comparison group was 30.4±8 and 33±7.2 properly (p=0.04687). Significant differences in social adaptation level subject to gender among and in the groups were not found.ConclusionsWomen with AD were younger than non-AD women. More severe impairments on SASS were found in a group with AD.</jats:sec

    Association of polymorphic variants of serotonin receptor genes, serotonin synthesis and metabolism enzymes genes with depressive disorder and clinical remission

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    The article presents the results of studies of associations of polymorphic variants of serotonin receptor genes and serotonin synthesis and metabolism enzymes genes with depressive disorders and the presence of clinical remission. The associations of polymorphic variants rs130058 of HTR1B gene and rs1176744 of HTR3B gene with depressive disorders was shown. Clinical remission assessed according to the CGI-S scale on the 28th day of therapy, associated with the polymorphic variant rs6298 of HTR1B gene, with remission in women, evaluated according to the HDRS-17 scale, associated polymorphic variants rs3813929 and rs1737429 of HTR2C gene. The data obtained confirm the participation of the serotonergic system in the pathogenesis of depressive disorders

    C/O Kerma coefficient ratio for 96 MeV neutrons deduced from microscopic measurements

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    Double-differential cross sections for neutron-induced light-ion production at 96 MeV have been measured for a variety of nuclei at The Svedberg Laboratory. Using the measured cross-section data, we deduce the Kerma coefficient from carbon and oxygen for p, d, t, He-3 and alpha particles. In order to get the total Kerma for C and O, we add GNASH calculation values where experimental data are not available and obtain a Kerma coefficient of 7.85 +/- 0.63 fGy m(2) for carbon and 7.09 +/- 0.57 fGy m(2) for oxygen. The C/O Kerma coefficient ratio then becomes 1.11 +/- 0.11. In addition we determine the Kerma ratio between ICRU muscle and A-150, again adding calculations with the GNASH code where no experimental data are available, and obtain a value of 0.98 +/- 0.05. While the Kerma coefficients for carbon and oxygen do not agree with the prediction in ICRU Report 63, the ratio values are in good agreement with existing predictions.</p

    Analysis of Mass Spectrometric Data of Proteins from Serum in Patients with Bipolar Disorder and and ealthy Individuals Using the PeptideShaker Software

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    In this work, the sera of patients with bipolar disorder and healthy people were purified by affinity chromatography from 14 major proteins and separated using 1D SDS-PAGE. After trypsinolysis, the resulting samples were identified by HPLC/mass spectrometry using an Ultimate 3000 Nano LC HPLC system (Thermo Scientific, Rockwell, IL, USA) coupled to a Q Exactive HF-X hybrid quadrupole - Orbitrap (Thermo Fisher Scientific).Peptide separation was performed on a C18 column with an inner diameter of 75 μm and a length of 150 mm (Acclaim® PepMap™ RSLC, Thermo Fisher Scientific, Rockwell, IL, USA). One microliter of sample, equivalent to one microgram of peptides, was loaded directly onto the column and equilibrated isocratically with mobile phase C (2% acetonitrile, 0.1% formic acid). The peptides were then eluted using a linear gradient of 5 to 55% buffer B (0.1% formic acid and 80% acetonitrile) at a flow rate of 0.3 μl/min. for 75 minutes, then for another 6 minutes to reach 99% buffer B. Before the next sample was loaded, a 10-minute wash with 99% buffer B and a 7-minute re-equilibration of the column with buffer A (0.1% formic acid) was performed.Then, the eluting peptides were loaded into the mass spectrometer through a capillary at a temperature of 240°C and an emitter voltage of 2.1 kV.Samples were analyzed in triplicate in Full MS mode followed by a single DDA MS2. Mass spectra were obtained in the mass range 320–1500 m/z with a resolution of 120,000 (MS). Precursor ions were fragmented in the HCD mode (Higher-Energy Collision Dissociation). Tandem mass spectra of the fragments were obtained at a resolution of 15,000 (MS/MS) in the range from 140 m/z to the m/z value determined by the charge state of the precursor, but not more than 2000 m/z. The maximum accumulation time of precursor ions was 50 ms, and that of fragment ions was 100 ms. The target fill value of the automatic gain control (AGC) for precursor and fragment ions was set to 1 x 106 and 2 x 105, respectively.An isolation intensity threshold of 50,000 arbitrary units was defined for precursor selection, and up to 20 of the best precursors were selected for fragmentation at a normalized collision energy (NCE) of 30. The precursor ion isolation width was 2 m/z. Precursors with a charge state of 1+ and more than 5+ were rejected, and all measured precursors were dynamically excluded from the launch of the subsequent MS/MS for 20 s.Data processing was performed using the search algorithms Peptide Shaker version 2.1.9, OMSSA, X!Tandem, Andromeda, and the UniProtKB database. The search was carried out using SearchGUI version 3.3.12.Protein identification was conducted against a concatenated target/decoy version of the UniProtKB (version of v04/2019; 20303 (target) sequences) database considering the species Homo sapiens (40606 sequences). The decoy sequences were created by reversing the target sequences in SearchGUI. The identification settings were as follows: Trypsin, Specific, with a maximum of 1 missed cleavages 10.0 ppm as MS1 and 0.5 Da as MS2 tolerances; variable modifications: deamidation of N (+0.984016 Da), deamidation of Q (+0.984016 Da), oxidation of M (+15.994915 Da), oropionamide of C (+71.037114 Da); variable modifications during the refinement procedure: acetylation of protein N-term (+42.010565 Da), pyrolidone from E (-18.010565 Da), pyrolidone from Q (-17.026549 Da), pyrolidone from carbamidomethylated C (-17.026549 Da). The rest of the parameters were set by default.Peptides and proteins were inferred from the spectrum identification results using PeptideShaker version 2.2.9. Peptide Spectrum Matches (PSMs), peptides, and proteins were validated at a 1.0% False Discovery Rate (FDR) estimated using the decoy hit distribution. Proteins were considered as reliably identified if at least two of their peptides could be identified. Post-translational modification localizations were scored using the D-score and the phosphoRS score with a threshold of 95.0 as implemented in the compomics-utilities package. A phosphoRS score above this threshold was considered a confident localization.An unlabeled analysis based on an exponentially modified protein abundance index was used to detect differences in the relative abundance of detected proteins between study groups, e.g., emPAI (emPAI = 10 PAI -1). This index showed good specificity and sensitivity for samples with low protein content, which may be useful for determining minor proteins in blood serum The emPAI intensities for proteins were taken log2 and normalized to ensure equal mean protein content in all samples. Statistically significant differences in mean emPAI for each protein in the study group were assessed using a two-tailed unpaired Student's t-test (p=0.05).</p

    Neurohumoral markers that predict the efficiency of pharmacologic therapy of depressive disorders

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    We present a comprehensive clinical and biological study of 46 patients with depressive disorder (F32-F33: depressive episode and recurrent depressive disorder) during pharmacotherapy. Neurohumoral factors (cortisol, brain-derived neurotrophic factor, serotonin, DHEA and its sulfated form) were determined in serum by ELISA. The severity of the current depressive episode was evaluated using the 17-point Hamilton Depression Rating Scale (HDRS-17); the pharmacotherapy efficacy was evaluated using the scale of the Clinical Global Impression (CGI Scale). We showed that before prescription of pharmacotherapy peripheral blood neurohumoral markers that characterize the state of stress-realizing and stress-limiting systems of the body may be considered as biological predictors of the effective pharmacotherapy of a current depressive episode and used as additional paraclinical examination methods. At higher concentrations of cortisol and serotonin associated with a decrease in the content of neurosteroid dehydroepiandrosterone, the high efficiency of the pharmacotherapy of depressive episode is predicted

    A CAMAC-USB crate controller

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    79-83A controller providing communication between a computer and a CAMAC crate via the USB bus is described. For this purpose, the controller includes a DLP-USB245M module, which allows a programmer to work with the controller through a virtual COM port and, at the same time, provides all the advantages of the USB standard. We consider versions of interactions of the DLP-USB module with controller registers on a programmable logic array and on the microcontroller.</p
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