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Failure to diagnose bipolar disorder (BD) in time leads to an increase in suicide risk, worse prognosis of the disease, and an increase in the socioeconomic burden.Aim: to assess the incidence of comorbidity of bipolar disorder (BD) and other mental and behavioral disorders, as well as the sequence of formation of this multimorbidity.Patients and methods: in the Affective States Department of the Mental Health Research Institute TNRMC, 121 patients with a diagnosis of bipolar disorder were selected for the study group according to the ICD-10 diagnostic criteria. The predominance of women in the study group was revealed (n = 83; 68.6%; p < 0.01). Median age of male patients was 36 [30; 54] years, for females — 47 [34; 55] years.Results: data were obtained on a high level of comorbidity in the study group: in 46.3% of patients, BD was combined with another mental disorder. It was found that personality disorders as a comorbid disorder in type I bipolar disorder are less common than in type II bipolar disorder. Gender differences were found in the incidence of anxiety-phobic spectrum and substance use disorders in bipolar disorder. The features of the chronology of the development of bipolar disorder and associated mental disorders have been revealed.Conclusion: in the case of bipolar disorder, there is a high likelihood of comorbidity with other mental disorders. Certain patterns in the chronology of the formation of comorbid relationships between BD and concomitant mental and behavioral disorders were revealed.

Background. The comorbid course of Mood Disorders (MD) and Alcohol Use Disorder (AUD) is a problem actively discussed by national and foreign researchers. Scientists pay close attention to clinical and pathodynamic polymorphism of symptoms in their works. Objective of the study: to compare the Clinical-Dynamical characteristics of AUD and MD, taking into account the formation chronology of their comorbidity, in a clinical sample of the specialized psychiatric hospital. Patients and methods: the study enrolled 56 patients under treatment in Department of Affective Disorders or Addictive Disorders of Mental Health Research Institute Clinics with a comorbid diagnosis of AUD (F10.2 according to ICD-10) and MD (F31–F34.1 according to ICD10). The Clinical-Dynamic, Psychometric and Statistical Methods were used in work. Results: according to statistical analysis in the case of the primary onset of AUD a relatively later formation of the comorbidity was shown (p = 0.001, Mann–Whitney test) and a higher frequency of Dysthymia as a Secondary MD (p = 0.043, chi-square test). Inspite of relatively shorter Duration of the Disease (p = 0.001, Mann–Whitney test), Secondary AUD characterized by rapid evolution of clinical and dynamic traits: the Alcohol Tolerance and Duration of Withdrawal Symptoms are comparable to the Primary AUD (p = 0.739, Mann–Whitney test; p = 0.359, Mann–Whitney test), and slightly shorter Duration of Light Gaps (p = 0.087, Mann–Whitney test) and Heavy Drinking Days (p = 0.034, Mann–Whitney test). A Psychometric study of the severity of symptoms of Depression, Anxiety and Craving for alcohol in the dynamics of psychopharmacotherapy demonstrate their comparability both at the beginning of treatment and by the 28th day of therapy (p > 0.05, Mann–Whitney test). Thereby, AUD developed in the background of a formed MD characterized by a prognostically unfavorable course of Disease.

Alcohol dependence (AD) and affective disorders (ADs) are serious medical and socio-economic problems of modern society. It is hypothesized that both disorders share a common neurobiological basis. Phosphatidylinositol-4-phosphate-5-kinase type 2 alpha (PIP5K2A) plays an essential role in neuronal phosphoinositide signaling pathways. Nonsynonymous rs10828317 mutation of the PIP5K2A gene leads to conformational changes of the PIP5K2A protein and a decrease in the functional activity of this enzyme. In this study, we assessed the possibility of using the rs10828317 polymorphic variant of the PIP5K2A gene as a marker of AD and ADs.Objective: to study the associations of the PIP5K2A (rs10828317) polymorphism with AD and ADs clinical course.Patients and methods. We enrolled 255 patients with AD and 325 patients with ADs. 126 patients with AD and 71 patients with ADs underwent a comprehensive clinical, clinical-dynamic, psychodiagnostic assessment using a set of clinical scales and tests, including Structured Interview Guide For The Hamilton Depression Rating Scale, Seasonal Affective Disorders Version (SIGH-SAD), Alcohol Use Disorders Identification Test (AUDIT), The Obsessive-Compulsive Drinking Scale for craving in alcohol (OCDS).Results and discussion. PIP5K2A (rs10828317) polymorphism in patients with AD was associated with the OCDS mean score after the inpatient treatment; in patients with ADs - with the severity of atypical depression symptoms assessed by SIGH-SAD at the time of admission.Conclusion. The results of our pilot study indicate the involvement of PIP5K2A (rs10828317) polymorphism in the AD and ADs pathophysiology.

—Studies on the pathophysiology of mental disorders indicate the involvement of neurobiological processes, including the neuroinflammatory response, neurogenesis, and neuronal degeneration, in the mechanisms of development of these disorders. We examined 135 patients with addictive and affective disorders (51 patients with alcohol dependence syndrome, 41 patients with a current depressive episode and 43 patients with comorbidity of alcohol dependence syndrome and affective disorder) and 46 mentally healthy donors. The content of neurospecific proteins (NSE, MBP, and GFAP) in the blood serum of patients and healthy people was determined by enzyme-linked immunosorbent assay. The study of peripheral markers of nerve tissue damage showed that all patients are characterized by signs of neuronal and glial distress. The results of analysis of variance and ROC analysis indicate the contribution of NSE and MBP to the development of affective disorders, while GFAP has a greater predictive efficiency in the case of addictive pathology. The tendency towards imbalance in the secretion of neurospecific proteins in the blood serum of patients with comorbidity of alcohol dependence and affective disorders is enhanced, which probably indicates a greater defect in neurobiological processes and neurodegeneration, and is also confirmed by data showing more severe clinical symptoms of patients in these cases of comorbidity.

Objectives. To identify the characteristics of impairments to spatial working memory and their neurophysiological correlates in patients with mild depressive disorders. Materials and methods. A total of 30 patients (right-handed) with ICD-10 diagnoses of Mood Disorder (F31.3, F32.0, F33.0, F34.1) were studied before treatment started. Mean age was 37 ± 8 years. The control group consisted of 30 mentally and somatically healthy subjects (mean age 32 ± 7 years). Spatial working memory was investigated using the Corsi Block-Tapping test. Electroencephalography (EEG) studies were also run for analysis of spectral power in the θ, α, and β ranges. Results and conclusions. Decreases in spatial working memory were seen in mild depressive disorders and this corresponded to high EEG θ-rhythm power in the frontal and occipital areas and α-rhythm power in the frontal cortex.

Comorbidity of affective disorders (AD) and alcohol dependence (AlD) worsens prognosis and efficiency of therapy, exacerbates non-compliance in patients, and lowers their level of social adjustment. To study the influence of AlD on clinical-dynamic characteristics of AD, two groups of patients were examined and compared. The study group included 32 patients with AD and comorbid AlD. The comparison group included 31 AD patients without comorbid addictive pathology. The patients of compared groups did not have statistical differences (p > 0.05) according to sex, age, and AD. The Clinical Global Impression scale (CGI), Hamilton Depression Rating Scale (HDRS-17), Hamilton Anxiety Rating Scale (HARS), and Social Adaptation Self-evaluation Scale (SASS) were used. Compared to the group without comorbidity, the group of patients with comorbid AD and AlD had more frequent suicide attempts in their medical history, a high level of anxiety according to HARS, severe disorders according to CGI-S, and difficult and impaired social adaptation according to SASS; patients with recurrent depressive disorder (RDD) and bipolar disorder (BD) also experienced a larger number of affective episodes per year. AlD comorbid with AD affects clinical-dynamic indicators and levels of social adjustment in patients.

Background: Brain-derived neurotrophic factor (BDNF) is associated with response to antidepressant drugs in mood and anxiety disorders. Prolactin (PRL) is a pituitary hormone with behavioural effects, acting as a neurotrophic factor within the brain and may be involved in antidepressant response.Objectives: To investigate the relationship between BDNF and PRL genotypes with antidepressant drug response.Methods: Prospective inception cohort of 186 Russian treatment-free participants (28 men and 158 women) between 18 and 70 years clinically diagnosed with depressive disorder who initiated antidepressant medication. DNA polymorphisms were genotyped for PRL rs1341239, BDNF rs6265 and rs7124442. Primary outcome was measured by differences in Hamilton Depression Rating Scale (Delta HAM-D) scores between baseline/week two, week two/week four, and baseline/week four. Linear regression and independent t-test determined the significance between polymorphisms and Delta HAM-D.Results: Comparisons between genotypes did not reveal any significant differences in scores during the first two weeks of treatment. In the latter two weeks, BDNF rs7124442 homozygous C patients responded significantly worse in comparison to homozygous T patients during this period. Further analysis within women and in postmenopausal women found a similar comparison between alleles.Limitations: Study lasted four weeks, which may be considered short to associate genuine antidepressant effects.Conclusions: Patients taking tricylic antidepressants were noted to have a significant improvement in Delta HAM-D compared to patients taking SSRIs. Homozygous C BDNF rs712442 patients were found to respond significantly worse in the last two weeks of treatment.

Background Many antidepressants are substrates of P-glycoprotein, an efflux transporter in the blood-brain-barrier encoded by the ABCB1 gene. Genetic variations might influence the transport rate of antidepressants and hence their pharmacological effects. This study investigates the influence of eight polymorphisms in the ABCB1 gene on antidepressant treatment response. Method 152 patients were included from psychiatric departments of the Mental Health Research Institute in Tomsk. The difference in Hamilton-Depression-Rating-Scale (HAMD-17)-scores between baseline and week two, week two and four, and baseline and week four was used to estimate timing of improvement of depression. Associations between the ABCB1 gene-polymorphisms and reduction in HAMD-17 score were assessed using independent t-test and multiple linear regression. Results Tricyclic antidepressants were associated with a higher reduction of HAMD-17 score when compared to SSRIs. The SNP rs2235040 A-allele had a significant positive influence on the Delta HAMD-17((0 -> 2W)) score but a significant negative influence on the Delta HAMD-17((2 -> 4W)) score. The rs4148739 G-allele had a significant negative influence on the Delta HAMD-17((0 -> 2W)) score but a significant positive influence on the Delta HAMD-17((2 -> 4W)) score. The SNP rs2235015 T-allele is significant negatively related to the Delta HAMD-17((2 -> 4W)) score. Conclusion ABCB1 Genetic variations appear to affect speed but not magnitude of antidepressant drug response.

Background: There is sufficient evidence that interference of dopaminergic neurotransmission contributes to the therapeutic effects of antidepressants in unipolar and bipolar depression. Methods: Hamilton depression rating scale (HAMD 17) scores of 163 at least moderately ill patients with major depressive disorders were used to establish treatment response. HAMD 17 score status was measured before initiation, after two weeks, and after four weeks of treatment with various antidepressants. The possible association between response and genotype in a total of 14 variants of dopamine neurotransmission-related proteins was investigated. Results: DRD4 rs11246226 CA heterozygous patients were found with a greater improvement of HAMD 17 score when compared to homozygous C patients during 0–2 weeks and 0–4 weeks. Patients with MAOB rs1799836 heterozygous GA and homozygous A also demonstrated improved scores during 2–4 weeks and 0–4 weeks. Conclusions: The results are preliminary due to the limited population size and the small number of variants. Further research into the involvement of habenular dopamine D4 receptors in the antidepressant response is desirable.

We provide an overview of the recent achievements in psychiatric genetics research in the Russian Federation and present genotype-phenotype, population, epigenetic, cytogenetic, functional, ENIGMA, and pharmacogenetic studies, with an emphasis on genome-wide association studies. The genetic backgrounds of mental illnesses in the polyethnic and multicultural population of the Russian Federation are still understudied. Furthermore, genetic, genomic, and pharmacogenetic data from the Russian Federation are not adequately represented in the international scientific literature, are currently not available for meta-analyses and have never been compared with data from other populations. Most of these problems cannot be solved by individual centers working in isolation but warrant a truly collaborative effort that brings together all the major psychiatric genetic research centers in the Russian Federation in a national consortium. For this reason, we have established the Russian National Consortium for Psychiatric Genetics (RNCPG) with the aim to strengthen the power and rigor of psychiatric genetics research in the Russian Federation and enhance the international compatibility of this research.The consortium is set up as an open organization that will facilitate collaborations on complex biomedical research projects in human mental health in the Russian Federation and abroad. These projects will include genotyping, sequencing, transcriptome and epigenome analysis, metabolomics, and a wide array of other state-of-the-art analyses. Here, we discuss the challenges we face and the approaches we will take to unlock the huge potential that the Russian Federation holds for the worldwide psychiatric genetics community.

GSK3B, BDNF, NGF, NRG1, HTR2C, and PIP4K2A play important roles in molecular mechanisms of psychiatric disorders. GSK3B occupies a central position in these molecular mechanisms and is also modulated by psychotropic drugs. BDNF regulates a number of key aspects in neurodevelopment and synaptic plasticity. NGF exerts a trophic action and is implicated in cerebral alterations associated with psychiatric disorders. NRG1 is active in neural development, synaptic plasticity, and neurotransmission. HTR2C is another important psychopharmacological target. PIP4K2A catalyzes the phosphorylation of PI5P to form PIP2, the latter being implicated in various aspects of neuronal signal transduction. In the present study, the six genes were sequenced in a cohort of 19 patients with bipolar affective disorder, 41 patients with recurrent depressive disorder, and 55 patients with depressive episode. The study revealed a number of genetic variants associated with antidepressant treatment response, time to recurrence of episodes, and depression severity. Namely, alleles of rs35641374 and rs10508649 (NRG1 and PIP4K2A) may be prognostic biomarkers of time to recurrence of depressive and manic/mixed episodes among patients with bipolar affective disorder. Alleles of NC_000008.11:g.32614509_32614510del, rs61731109, and rs10508649 (also NRG1 and PIP4K2A) seem to be predictive biomarkers of response to pharmacological antidepressant treatment on the 28th day assessed by the HDRS-17 or CGI-I scale. In particular, the allele G of rs10508649 (PIP4K2A) may increase resistance to antidepressant treatment and be at the same time protective against recurrent manic/mixed episodes. These results support previous data indicating a biological link between resistance to antidepressant treatment and mania. Bioinformatic functional annotation of associated variants revealed possible impact for transcriptional regulation of PIP4K2A. In addition, the allele A of rs2248440 (HTR2C) may be a prognostic biomarker of depression severity. This allele decreases expression of the neighboring immune system gene IL13RA2 in the putamen according to the GTEx portal. The variant rs2248440 is near rs6318 (previously associated with depression and effects of psychotropic drugs) that is an eQTL for the same gene and tissue. Finally, the study points to several protein interactions relevant in the pathogenesis of mood disorders. Functional studies using cellular or animal models are warranted to support these results.

Objective: to study clinical-biological features of affective disorders including their comorbidity with coronary artery disease and personality disorders and efficacy of psychopharmacotherapy in these patients.Material and Methods. In the first group at a heart station 290 patients with chronic coronary artery disease and affective disorders (209 men and 81 women) were fully examined. The second group included 120 patients (40 men and 80 women) of a psychiatric hospital with affective disorder comorbid with personality disorders. The third group included the study of 29 patients with depressive disorders and a control group (n=21).Results. Data on significant clinical-dynamic, biological and therapeutic features of affective disorders comorbid with coronary artery disease were obtained. It was revealed that presence of a comorbid personality disorder in the case of affective disorders causes the necessity to use a combined psychopharmacotherapy more frequently, worsens indicators of the efficacy of the psychopharmacotherapy of current episode of depression, and increases negative estimation of their social adaptation by these patients. Dysregulation of the processes of programmed cell death in patients with depressive disorders was found.Conclusion. Obtained data testified to the high degree of comorbidity of affective disorders with coronary artery disease and personality disorders which worsened the prediction of the course and indicators of the efficacy of psychopharmacotherapy of these disorders. In patients with depressive disorders the specific weight of mononuclears of peripheral blood was increased in the state of apoptosis.

Depressive disorder is considered as an important medico-social problem due to its severity, chronic nature, and high level of clinical polymorphism. The precise biological mechanism of this pathology is still unknown. The latest data confirms the role of the glutamatergic system in the pathogenesis of depression. Here, 79 patients with depressive disorders (50 diagnosed with a “single depressive episode” and 29 with “recurrent depressive disorder”) who were treated with selective serotonin reuptake inhibitors (SSRIs) and 27 healthy control donors underwent complex clinical and biochemical examinations. The depression severity at the baseline and on the 14th and 28th days of treatment, as well as during remission, was evaluated using the 17-item Hamilton Depression Rating Scale (HDRS-17). The therapy response was evaluated using the CGI-I scale. The blood serum glutamate concentration was measured at the baseline. The concentration of glutamate was significantly higher in the group of patients compared to the controls. No difference in this parameter was observed between groups of patients. A positive correlation between the severity of depression at the 28th day and the glutamate concentration was found in the groups of patients with recurrent depressive disorder. No association between glutamate concentration and the CGI-I scale score, as well as remission, was found. A high glutamate level in blood serum of patients with depressive disorders could be an indicator of glutamatergic system dysregulation. This value in the future may be used as a predictor of the effectiveness of SSRI treatment in patients with recurrent depressive disorder.

To assess spatial working memory disorders in patients with mild depressive disorders and determine their neurophysiological correlates.Thirty patients (right-handed) with ICD-10 diagnosis Mood Disorders (F31.3, F32.0, F33.0, F34.1), aged 37±8 years, were examined before treatment. A control group included 30 mentally and somatically healthy individuals (32±7 years old). The study of spatial working memory was carried out using the Corsi Block-Tapping test. EEG was recorded and the values of the spectral power of theta, alpha and beta rhythms were analyzed.A decrease in the level of working memory that was correlated with higher values of theta rhythm power in the frontal and occipital regions and alpha rhythm in the frontal cortex was observed in affective disorders with mild depressive symptoms.Цель исследования. Определение особенностей нарушения пространственной рабочей памяти и их нейрофизиологических коррелятов у пациентов с депрессивными расстройствами легкой степени. Материал и методы. Обследовали 30 пациентов (правшей) с диагнозом по МКБ-10 'Расстройства настроения' (рубрики F31.3, F32.0, F33.0, F34.1) до начала лечения. Средний возраст пациентов - 37±8 лет. В качестве группы контроля были обследованы 30 психически и соматически здоровых (средний возраст - 32±7 лет). Исследование пространственной рабочей памяти осуществляли при помощи теста Корси (Corsi Block-Tapping). Проводили также электроэнцефалографию (ЭЭГ). На ЭЭГ анализировали спектральную мощность тета-, альфа- и бета-ритмов. Результаты и заключение. При легких депрессивных расстройствах наблюдали снижение уровня пространственной рабочей памяти, на ЭЭГ этому соответствовали более высокие значения мощности тета-ритма во фронтальных и затылочных отделах и альфа-ритма в лобной коре.

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.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.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.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.

IntroductionStudies of the pathophysiology of mental disorders indicate the involvement of neurobiological processes, including the release of neurospecific proteins in biological substances.ObjectivesThe purpose of this study was to research the level of neuron-specific enolase in patients with alcohol use disorder and mood disorders during the therapy.MethodsThe studied groups included patients with alcohol use disorder (AUD, F10.2, ICD-10; n=41), patients with mood disorders (MD, F32, F33, ICD-10; n=39), patients with co-morbidity of AUD and MD (n=31) and 20 healthy controls. Severity of depressive symptoms was assessed with HDRS-17 and CGI-S scales. The concentration of NSE were measured in serum by enzyme immunoassay. Рarticipants of the study were examined with clinical scales and laboratory analysis at baseline and on the 28th day of treatment. For statistical analysis we used the SPSS software.ResultsThe results of the study showed that all patients are characterized by an increased level of NSE (p>0.005 compared with control). Patients with AUD characterized by changes in the concentration of NSE during therapy (p>0.005 compared with patients after therapy). In patients with MD revealed correlation between the level of NSE on the 28th day of antidepressive therapy and the HDRS-17 score before treatment (r=0,421; p=0,018). In patients with co-morbidity correlation between the level of NSE and the CGI-S score before therapy was found (r=-0,537; p=0,001).ConclusionsThe revealed correlations indicate the relationship between the severity of depressive symptoms and the level of NSE. Disclosure statement: This study was supported by the Russian Science Foundation, grant No. 19-15-00023.Conflict of interestDisclosure statement: This study was supported by the Russian Science Foundation, grant No. 19-15-00023.

Background Purpose of study is revealing significant differences in serum proteomes in schizophrenia and bipolar disorder (BD). Results Quantitative mass-spectrometry based proteomic analysis was used to quantify proteins in the blood serum samples after the depletion of six major blood proteins. Comparison of proteome profiles of different groups revealed 27 proteins being specific for schizophrenia, and 18 – for BD. Protein set in schizophrenia was mostly associated with immune response, cell communication, cell growth and maintenance, protein metabolism and regulation of nucleic acid metabolism. Protein set in BD was mostly associated with immune response, regulating transport processes across cell membrane and cell communication, development of neurons and oligodendrocytes and cell growth. Concentrations of ankyrin repeat domain-containing protein 12 (ANKRD12) and cadherin 5 in serum samples were determined by ELISA. Significant difference between three groups was revealed in ANKRD12 concentration (p = 0.02), with maximum elevation of ANKRD12 concentration (median level) in schizophrenia followed by BD. Cadherin 5 concentration differed significantly (p = 0.035) between schizophrenic patients with prevailing positive symptoms (4.78 [2.71, 7.12] ng/ml) and those with prevailing negative symptoms (1.86 [0.001, 4.11] ng/ml). Conclusions Our results are presumably useful for discovering the new pathways involved in endogenous psychotic disorders. Electronic supplementary material The online version of this article (10.1186/s12864-019-5848-1) contains supplementary material, which is available to authorized users.

Major depressive disorder (MDD) is a clinically and biologically heterogeneous disorder with a heavy personal and socio-economic burden [1]. The neurotrophic theory of the development of depression most fully explains the morphological changes that occur in the brain of patients [2,3]. Among the various neurotrophic factors brain-derived neurotrophic factor (BDNF) and prolactin play an important role in pathogenesis of depression [4]. Objective of the study was to investigate the association of genes polymorphisms of BDNF and prolactin with responsiveness to therapy in patients with MDD. Methods The study group included 185 MDD patients (F32,F33,ICD-10) and 134 healthy persons. Severity of depressive symptoms on the baseline and on the 14th and 28th day of therapy was assessed using Hamilton Depression Scale (HDRS-17) and Clinical Global Impression – Severity scale (CGI-S). Antidepressive therapy response on the 14th and 28th day of therapy was evaluated using Clinical Global Impression – Improvement scale (CGI-I). Genotyping was carried out on polymorphic variants of BDNF genes (rs6265, rs7124442, rs11030104) and PRL gene (rs1341239). The SPSS software was used for statistical analysis. The Hardy-Weinberg equilibrium (HWE) of genotypic frequencies was tested by the chi-square test. Results The study found no deviation of genotype frequencies from HWE (р > 0.05), except for the SNP rs11030104 in the group of patients (χ2 = 37.540; p = 0.001). Important differences in frequency of genotypes and alleles of SNPs rs11030104 of BDNF and rs1341239 of PRL genes between patients and healthy persons at entry have been found. The final multivariate binary logistic regression analysis shows that the A/A genotype of SNP rs11030104 has a more than 6 times higher risk of developing depression than G/G or G/A genotype (p = 0.009). Allele G of SNP rs1341239 gene was more common in patients (63%) compared to control (59%) (p

To study the association between polymorphisms of PIP5K2A and HTR2C genes and response to antidepressant therapy in patients with a current depressive episode.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.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.Цель исследования - выявление ассоциаций полиморфных вариантов гена PIP5K2A киназы и гена HTR2C рецептора 2С серотонина с эффективностью терапии текущего депрессивного эпизода. Материал и методы. Обследованы 222 пациента, 168 женщин и 54 мужчины, с текущим депрессивным эпизодом. Оценку тяжести текущего депрессивного эпизода и эффективности терапии проводили с применением шкал депрессии Гамильтона (HAM-D-17) и общего клинического впечатления (CGI-S) при поступлении в стационар, а также на 14-й и 28-й дни терапии. Оценивали ассоциации полиморфных вариантов генов PIP5K2A (rs10430590, rs10828317) и HTR2C (rs6318, rs569959, rs3813929, rs12858300) с эффективностью терапии текущего депрессивного эпизода. Результаты и заключение. Пациенты с депрессивным эпизодом с генотипом С/С по rs10828317 гена PIP5K2A имели более низкий балл по шкале CGI-S (1,64±0,64) на 28-й день терапии, чем пациенты с генотипами С/Т (2,23±0,96) и Т/Т (2,18±0,79) (р=0,038), а носители генотипа Т/Т по rs10430590 гена PIP5K2A - более низкие значения балла по шкале CGI-S (1,53±0,87) по сравнению с генотипами А/А (2,18±0,79) и А/Т (2,24±0,96) (р=0,043). У женщин rs3813929 ассоциирован с тяжестью текущего депрессивного эпизода, оцененной по шкале CGI-S до начала терапии (р=0,019), a rs6318 гена HTR2C ассоциирован с клиническим улучшением, оцененным по шкале Гамильтона, на 28-й день терапии (р=0,050).

Depressive disorders are a great burden for individual patients and society. Blood-based biomarkers are regarded as a feasible option for investigation of depressive disorders. Several potential biomarkers for depression were selected. We studied the following serum markers: cortisol, melatonin, brain-derived neurotrophic factor (BDNF), prolactin, insulin-like growth factor 1 (IGF-1), β-endorphin, orexin A. The patient sample consisted of 78 persons with depressive disorders. Patients were divided into two groups: 46 patients with a first depressive episode and 32 patients with recurrent depressive disorder. Control group consisted of 71 healthy individuals of corresponding age and sex. All markers were measured in serum using MILLIPLEX® MAP panels (Merck, Darmstadt, Germany) by analyzer MAGPIX (Luminex, USA). Statistical analyses were performed using SPSS software. Results were expressed as median and quartile intervals [Q1–Q3]. There was a significant increase of serum concentrations of cortisol (663.69 [467.5–959.49] nmol/L, Р < 0.001) and melatonin (66.31 [33.6–132.59] pg/mL, P = 0.029) in patients compared with the control group (526.1 [367,24–654,7] nmol/L and 45.11 [27.47–73.47] pg/mL). In addition, correlations were found between potential biomarkers, clinical indicators and treatment response measured by applying the Hamilton Depression rating scale and the Clinical Global Impression rating scales. A significant correlation was found between the concentration of prolactin and high response to pharmacotherapy (r = –0.267, P = 0.029). Identifying biomarkers that can be used as diagnostics or predictors of treatment response in people with depressive disorders will be an important step towards being able to provide personalized treatment.Disclosure of interestThe work is supported by the project of Russian Foundation of Basic Research No 14-04-01157a.

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.

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.

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 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.

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.

The contribution of comorbid with coronary artery disease (CAD) mood disorders (MD) into total mortality is contradictory.ObjectiveTo study frequency and time until death due to general causes in groups of patients with comorbid MD, and without them as well as interrelationship of these indicators with comorbid MD and therapy with antidepressants.MethodsInpatients with chronic CAD (n = 333) under conservative therapy were investigated (31% females (n = 103), 69% males (n = 230), mean age 61.8 ± 9.8 years). Team of cardiologists and psychiatrists followed up patients for 7 years (2008–2014). Survival frequency was evaluated by method of life tables.ResultsAmong patients under conservative therapy of CAD the death frequency due to general causes did not differ significantly in presence (n = 80) and absence of MD (n = 253) and was 18.8% and 16.6%, respectively. Correlation of deaths with hypomanic and mixed episodes was revealed (rs = 0.3). The groups differed according to function of immediate risks: patients with MD were at high risk of death during the year after detection of affective symptoms, and in group without MD it increased over the time of observation (Р = 0.0000).Duration of antidepressant therapy was 5.5 ± 0.5 months. Among patients receiving antidepressants (n = 20), during therapy and after one month after discontinuation there were not deaths. Difference of function of immediate risks in these subgroups was not significant (Р = 0.09).ConclusionsPatients with affective disorders and chronic CAD under conservative therapy are at high risk of death within affective episode and therapy with antidepressants did not influence change of risk of death.Disclosure of interestThe authors have not supplied their declaration of competing interest.

A comprehensive evaluation of biological indices has been carried out in 26 patients with depressive disorders and in 20 age- and sex-matched controls. Indices of programmed cell death (apoptosis) in subpopulations of blood lymphocytes and concentration of cortisone in blood serum were determined. Significantly enhanced apoptosis was observed in the lymphocytes of depressive patients as shown by increased percentage of lymphocytes expressing FAS-receptor and cells with morphological changes characteristic of apoptosis (nuclear condensation, vacuolation. Clinical symptoms of depression were concomitant with alterations of cellular link of immunity expressing in the decrease of the total T-lymphocytes (CD3+) number, T-helpers (CD4+) and natural killers (CD16+) as compared to healthy persons. The level of blood serum cortisone was increased in patients with depression. High cortisone values correlated with suppression of cellular CD4+ population and an increase of FAS-receptors expression in patients with depression.