G. Simutkin

Signs of apoptosis of immunocompetent cells in patients with depression

A total of 26 patients with depression and 20 healthy subjects were studied. Measures of apoptosis of peripheral blood lymphocytes and serum cortisol concentrations were determined. A significant increase in lymphocyte apoptosis was found in patients with depression, resulting in an increase in the proportion of lymphocytes expressing the FAS receptor; cells with morphological signs characteristic of apoptosis (nuclear condensation, vacuolization) were also seen. Changes in cellular immunity were observed on the background of clinical depressive symptomatology, with decreases in the total numbers of T-lymphocytes (CD3+), T-helpers (CD4+), and natural killer cells (CD16+) as compared with numbers in healthy subjects. Serum cortisol levels were elevated. Correlation analysis revealed an interaction between high cortisol levels and decreases in T-helper cells (CD4+) and increases in apoptosis receptor expression in patients with depressive disorder.

Proteins of the Akt1/GSK-3β signaling pathway in peripheral blood mononuclear cells of patients with affective disorders

The Akt1/GSK-3β signaling pathway is involved in the regulation of biological processes in nerve cells. Here we studied the intracellular proteins Akt1 and GSK-3β and their phosphoforms in patients with affective disorders. Sixty patients with diagnoses of depressive episodes, major depressive disorder, and bipolar affective disorder (BAD) and 34 mentally and somatically healthy subjects were examined. Proteins of the Akt1/GSK-3β signaling pathway (total glycogen synthase kinase 3β (GSK-3β), phospho-serine-9-GSK-3β, total protein kinase Akt1, phospho-serine-473-Akt1) were measured in peripheral blood mononuclear cells using the immunoblotting technique. High levels of total GSK-3β were found in groups of patients with affective disorders. Patients with recurrent depressive disorder had an increased level of total GSK-3β as compared with the level in depressive episode. The level of total Akt1 in patients decreased as compared with the control group. Patients with depressive disorder had decreased levels of phospho-serine-473-Akt1. Our results confirm the hypothesis of the involvement of glycogen synthase kinase-3β in the pathogenesis of affective disorders.

Association of polymorphic variants of PIP5K2A and HTR2C genes with response to antidepressant therapy of patients with a current depressive episode

AIM To study the association between polymorphisms of PIP5K2A and HTR2C genes and response to antidepressant therapy in patients with a current depressive episode. MATERIAL AND METHODS The study included 222 patients (168 women and 54 men) with a current depressive episode. The assessment of the severity of the current depressive episode and the efficacy of treatment was performed using the Hamilton depression scale (HDRS-17) and the Clinical global impression scale (CGI-S, CGI-I). The association of treatment efficacy with PIP5K2A polymorphisms rs10430590, rs10828317 and HTR2C polymorphisms rs6318, rs569959, rs3813929, rs12858300 was studied. RESULTS AND CONCLUSION Polymorphisms rs10828317 and rs10430590 in the PIP5K2A gene were associated with the CGI-S total score at day 28 of therapy. Polymorphism rs6318 in the HTR2C gene was associated with response to antidepressant therapy followed by clinical improvement of patients with current depressive episode on the 28th day of antidepressant therapy.

An association of AKT1 gene polymorphism with antidepressant treatment response

Abstract Objectives: Nowadays it is considered that protein kinase Akt1 could be involved in pathogenesis of affective disorders. We have examined whether AKT1 gene polymorphisms are associated with antidepressant treatment response. Methods: The study included 106 Caucasian patients with depressive disorders from Siberia and 103 healthy control donors. The frequencies of single nucleotide polymorphisms rs1130214 and rs3730358 of AKT1 gene were examined. Results: A comparison of genotypic or allelic frequencies between the groups of healthy donors and depressive patients showed no statistically significant difference. No association between the polymorphisms under study and the scores according to Hamilton Depression Rating Scale 17 was found. However, an association between treatment response assessed by the Clinical Global Impression – Improvement scale and rs1130214 polymorphism was observed. Conclusions: AKT1 gene polymorphism rs1130214 is associated with antidepressant treatment response in patients with depressive disorders.

Serum Levels of Neurosteroids in Patients with Affective Disorders

According modern biological hypotheses of the pathogenesis of affective disorders, hypothalamic–pituitary–adrenal axis dysfunction play a special role in the pathogenesis of this condition. Our study shows that the range of neuroprotective neurosteroids is gender- and nosology-dependent. Patients with affective disorders have reduced levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate; the most pronounced defi ciency of neuroprotective neurosteroids is typical of patients with a single depressive episode. Reduced levels of neurosteroids producing an anabolic effect probably indicate depletion of adaptive capacities of the hypothalamic–pituitary–adrenal system in affective disorders.

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

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.

LED-technologies for bright light therapy

The significance of the LED-based medical equipment design is caused by the need to make up for the sunshine shortfall in many areas of Russia (Siberia, the Far East, the Extreme North) that will allow reducing dramatically the risk of seasonal affective disorders. The sunshine is the essential synchronizer of the human biological rhythms, the abnormality of which plays an important role in the seasonal affective disorder nature. The study allows proving the object database development able to meet the human demand for a comfortable and high-quality placemaking as well as the health potential recoverability.

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

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.

Brain-derived Neurotrophic Factor in Patients with Affective Disorders

Currently new biological models of the pathogenesis of affective disorders are developed which give crucial irregularities in neurotrophic factors. Objectives of the study was to investigation of brain-derived neurotrophic factor (BDNF) with study the polymorphisms of locus rs6265 of gene BDNF and the content of BDNF in the serum of patients with affective disorders and healthy persons. We studied the patients with a current depressive episode (F32, F33, ICD-10, 218 persons) and 94 mentally healthy persons. Genotyping was performed with TaqMan® SNP Genotyping Assay and StepOnePlus Real-Time PCR System (Applied Biosystems, USA). The concentrations of BDNF was determined by enzyme immunoassay using reagent kits Human BDNF Immunoassay (R&D Systems) and automatic microplate spectrophotometer Epoch BioTek Instruments (USA). Statistical analysis was performed using the program SPSS, version 20.0. Statistical analysis of the results revealed a significant increased frequency of the allele T of gene BDNF in patients compared with healthy people (p=0,0003). Frequency of genotypes CT and TT in patients with affective disorders were significantly higher than in control (OR=1,62, 95% CI=0,94-2,78, p=0,003). The study of concentration of BDNF in patients showed slightly reduced level of neurotrophin in patients compared with healthy individuals (4852,02 (4052,7-4985,15) pg/ml and 4950,33 (4625,03-5003,58) pg/ml). Thus, patients with current depressive episode characterized by changes in the neurotrophic system, increased frequency of the allele T of locus rs6265 and reduced content of BDNF in serum. The investigation is supported by grant of President RF N14.120.14.3854-MK and project of RFBR N14-04-01157 and N14-04-31925.

P01-94 - Social adaptation level among inpatients with atypical and non-atypical depression

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. Objectives To compare social adaptation level among psychiatric inpatients with an atypical and non-atypical depression. Methods 140 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. Results 10 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. Conclusions Women with AD were younger than non-AD women. More severe impairments on SASS were found in a group with AD.