Search

Over the past decades, the world has witnessed an increase in the number of vehicles. According to the accident analysis and to the existing transport problems, the development of automated traffic control systems using adaptive management methods is the most optimal way to improve road traffic quality. From the technological point of view, the system must function according to the requirements for the traffic flow level and to the assessment of traffic efficiency, so a clear comparison of systems is impossible under the conditions of various principles for identifying managerial impacts and the designation of management system. The authors’ analysis of the most commonly used traffic management technologies proves that experts choose the system architecture that affects its functions and the ability to implement one or another method of management. In accordance with the ITS approach and management tasks at each hierarchy level, we believe that the traffic management system of the intelligent transport system should be based on the principle of multi-level architecture using ring Ethernet technologies, which corresponds more to the diamond-shaped system structure; it allows to distribute methods of traffic management for purposes and to separate the informational and technological elements of the system.

Objective: To analyze a complex of EEG parameters and quantitative clinical evaluations of depressive-delusional conditions in patients with schizoaffective disorder and to clarify their neurophysiological mechanisms., Material and Methods: A study included 25 female patients, aged 22-40 years, with depressive-delusional conditions. Patients were assessed at baseline and after 4-6 weeks of treatment using HDRS and PANSS. EEG was recorded at each visit., Results: Significant correlations were revealed between the values of pre-treatment background EEG spectral power in narrow frequency bands and quantitative pre-treatment and post-treatment scores of patient's clinical conditions., Conclusion: The results allow clarifying the brain mechanisms of depressive-delusional disorders and reveal possible EEG-predictors of therapeutic response in its treatment.

The study aimed to confirm the association of the schizophrenia genome-wide association study (GWAS) hit rs2514218 located near the DRD2 gene with the risk of the disease and to investigate the relationships between rs2514218 and schizophrenia-related clinical and neuroimaging phenotypes. Genotypes at the rs2514218 site were determined for 2148 schizophrenia spectrum patients and 1273 control subjects from the Russian population. In subsets of subjects, we assessed symptomatic dimensions using the Positive and Negative Syndrome Scale (n = 1651) and Temporal Experience of Pleasure Scale (n = 471). At the brain level, gray matter volumes in striatal structures and cortical thickness in the lateral prefrontal cortical regions were investigated (n = 97). Genotype frequencies did not differ between patients and controls. The allelic association analysis yielded a near-threshold p value (p = 0.054), the magnitude (OR = 0.90), and direction of the minor allele (T) effect being in accord with those in the schizophrenia GWAS. Also, patients homozygous for the risk allele C had more severe consummatory anhedonia and a thinner cortex than controls and patients carrying the T allele. The largest effect size of the genotype with diagnosis interaction was seen in the right pars opercularis area. The findings support the role of rs2514218 in schizophrenia risk and presentation and suggest rs2514218 has an influence on brain morphology and negative symptoms.

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.

Background: Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci., Methods: We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan., Results: Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (P FDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (P FDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system., Limitations: Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients., Conclusions: Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim: To determine a therapeutic effect of agomelatine (valdoxan) on post-schizophrenic depression (PSD), taking into account its psychopathological structure., Material and Methods: A total of 33 patients of both sexes (average age was 32.1 yrs) with symptoms of post-schizophrenic depression (F20.4 according to ICD-10) were examined by using clinical and psychometric methods in the dynamics of shift-like schizophrenia. HAMD-17, PANSS and CGI-S scales were applied. All the patients were subdivided into groups: mild, moderate and severe depressions. Valdoxan was used at a dose of 25-50 mg/day for 28 days along with preceding antipsychotic therapy at maintenance doses. Evaluation of the efficacy of treatment was carried out according to percentage reduction of average total score (ATS) in dynamics., Results: A significant effect of valdoxan, with 73.5% of PANSS score reduction and quicker response to treatment, was identified. Therapeutic effect of valdoxan on separate components of PSD was uneven. The decrease of depressive disorders per se assessed by HAМD-17 and PANSS G-subscale was equally high (78.4 and 78.2%, respectively). Therapeutic reduction of negative disorders according to PANSS N-subscale was the lowest, at the level of 'good' effect (53.6%). In 27.3%, negative disorders were irreversible and were assessed as schizophrenic defect; in 72.7% of patients they were diagnosed as 'secondary' negative symptoms in atypical depression. In the subgroups of mild, moderate, and severe depression, the reduction of negative disorders was 62.4; 44.2 and 60.8%, respectively, and that of total PANSS score were 81.5; 66.1, and 78.6%, i.e. there was no correlation between these variables., Conclusion: Agomelatin (valdoxan) is an effective medication for optimization of methods of PSD treatment, providing the therapeutic effect at the level of significant or complete reduction of symptoms. The quality (depth) and rate of formation of response in the dynamics of course treatment are determined not by the severity of depressive disorders in PSD structure, but by the ratio between negative (deficit) symptoms and 'secondary' symptoms, reflecting the degree of progression of the main disease.

The aim of the study was to reveal the set of neurobiological parameters informative for individual quantitative prediction of therapeutic response in schizophrenic patients. Correlation and regression analyses of quantitative clinical scores (by Positive And Negative Syndromes Scale - PANSS), together with background EEG spectral power values and four immunological parameters: enzymatic activity of leukocyte elastase and of alpha-1 proteinase inhibitor, as well as serum levels of autoantibodies to common myelin protein and to nerve growth factor, were performed in 50 patients (all females, aged 32.9±10.8 years) with hallucinatory-delusional disorders in the frames of attack-like paranoid schizophrenia. Background neurobiological data obtained before the beginning of syndrome based treatment course (at visit 1) were matched with PANSS clinical scores of the same patients after treatment course at the stage of remission establishment (at visit 2). The multiple linear regression equations were created which contained only 3 to 4 (from initial 80) background EEG parameters and one of four immunological parameters. These mathematical models allowed prediction from 65% to 76% of PANSS scores variance after treatment course (at visit 2). The data obtained may be used for elaboration of methods of individual quantitative prediction of treatment outcome in schizophrenic patients.

Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10-8). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium- and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders., Competing Interests: The authors have declared that no competing interests exist.

Background: Affective syndrome is thought to be a key feature that differentiates schizophrenia from schizoaffective disorder (SA) and bipolar disorder with psychotic features (BDP). However genetic underpinnings of these differences remain unresolved., Objectives: We compared clinical variables of affective psychoses (SA, BDP and schizophrenia with affective symptoms (AFF SCZ)) and schizophrenia without affective symptoms (non-AFF SCZ) and searched for a genetic variant that may differentiate affective psychosis from non-AFF SCZ., Methods: A total of 2677 subjects, including 831 patients with affective psychosis, 785 patients with non-AFF SCZ and 1061 healthy controls, were used. Clinical symptoms were assessed with the PANSS. The sample was genotyped for 5-HTTLPR polymorphism of the serotonin transporter gene., Results: The diagnostic groups differed significantly on demographic and clinical variables. The percentage of men was higher, the current age and age at illness onset were lower in non-AFF SCZ and SA compared to AFF SCZ and BDP. The severity of positive and negative symptoms decreased significantly from group to group in the following manner: non-AFF SCZ>AFF SCZ>SA>BDP. There was the association between 5-HTTLPR polymorphism and affective psychosis (p=0.01). The frequency of the SS genotype was higher in the affective psychosis group compared to non-AFF SCZ and controls. No differences in the genotype distribution were identified between the non-AFF SCZ group and controls., Limitations: Difficulties in the differentiation between non-AFF SCZ and AFF SCZ or SA and between AFF SCZ and SA due to uncertain diagnostic boundaries between these conditions., Conclusions: SA is intermediate between non-AFF SCZ and BDP in the severity of positive and negative symptoms. The first episode patients, carriers of the SS genotype have a higher risk of developing affective psychosis than non-AFF SCZ. This finding carries implications for the prognosis of psychosis outcomes in the first-episode patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Aim: To assess the efficacy and safety of pantogam active (PA) in prevention and correction of neurological side-effects during the course neuroleptic treatment of acute endogenous psychoses., Material and Methods: Eighty schizophrenic patients (mean age 33 years) with acute psychosis were examined. All patients received 28-day course treatment with typical and atypical neuroleptics. Two equal groups were studied: patients of the first group were treated with trihexyphenidyl (THP) in dose of 0,002-0,012 mg and patients of the second group received in addition PA in dose 0,9 mg/day. Clinical-observation, psychometric scales (PANSS, CGI-S, UKU) were administered at baseline and in 1st,3rd,7th, 14th, 21st, 28st day., Results: PA in the combination with THP improved tolerability to neuroleptic therapy in whole and exerted the better correction effect on neuroleptic extrapyramidal disorders (EPD) compared to THP monotherapy. The number of patients with ERD was reduced by 1.5 times and prevention of EPD was observed 3 times more frequent in the group treated with PA. In the THP group, other adverse effects (AE) were 1,7 times more frequent and the total AE score was 2,5 times greater compared to the PA group (131 vs 50). Correction and preventive effects of the combined treatment on the clinically severe symptoms of EPD (akathisia, muscle dystonia) were more frequent in patients treated with typical neuroleptics. A less amount of THP (by 1,2 times) was used to stop EPD in the PA group., Conclusion: PA in the combination with THP has demonstrated the clear neuroprotective effect on the development, frequency and clinical presentations of neurological side-effects. The РА can be recommended as a drug of choice for correction and prevention of neuroleptic side-effects, it promotes their tolerability and improves quality of life during the course treatment.

The present study searched for associations between gene GRIN2B (glutamate receptor, ionotropic, N-methyl-D-aspartate, subunit 2B) and component processes of verbal episodic memory in schizophrenic patients. The Rey Auditory Verbal Learning Test (RAVLT) as a part of a large neuropsychological battery was administered to 302 patients with schizophrenic spectrum disorders (sample PI). Also, 285 patients (sample P2) and 243 healthy controls (sample C2) performed the “10 words” test that measures short-term memory. The GRIN2B rs7301328 (C366G) polymorphism was genotyped for each subject. There were no associations between the polymorphism and any measure of the RAVLT either in the whole PI sample or in a subsample of patients with a severe cognitive deficit. The GRIN2B influenced immediate recall and proactive interference in the “10 words” test in the control group: homozygotes CC recalled fewer words and showed a lower effect of proactive interference than carriers of other genotypes. The results suggest that the C366G polymorphism could influence verbal episodic memory in the general population, but this influence is absent in schizophrenic patients.

Objective: To search for the association between the GRIN2B gene and signs of thought and speech disorders which may be the result of decreased accessibility to the mental lexicon., Material and Methods: The association between the GRIN2B polymorphism rs7301328 with semantic verbal fluency and five symptoms of thought and speech disorders, as assessed with the PANSS, was studied in 552 patients with schizophrenia-spectrum disorders., Results and Conclusion: There was the association of the GRIN2B gene with verbal fluency and the PANSS item «Difficulty in Abstract Thinking». The association was not modified by verbal fluency. The results suggest that the GRIN2B gene may modify the linguistic processes involved in the retrieval of information from the mental lexicon on the basis of semantic traits and, moreover, contribute to the variability of clinical symptoms of impairment of abstract thinking in patients with schizophrenia. The heterozygous genotype may be protective against the development of thought and speech disorders.

Objective: To study neurophysiologic correlates of the severity of clinical conditions and to search for possible predictors of therapeutic response in attack-like schizophrenic patients with delusional disorders., Material and Methods: During the treatment of 40 attack-like schizophrenic patients (all females, right-handed, aged 20--50 years old) with delusional disorders, clinical symptoms were quantitatively assessed using PANSS. Resting EEG was recorded with the consequent spectral-coherent analysis. Correlation analysis was performed at the beginning of treatment and at the stage of the development of remission., Results: Significant (p<0.05) correlations between some initial (before treatment) resting EEG parameters and PANSS scores before treatment and at the stage of remission were revealed. The reduction in psychopathologic symptoms after treatment course was associated with the decrease in alpha-3 spectral power in occipital zones and increase of theta-1 and theta-2 spectral power in frontal-central regions. Besides, the number of statistically significant intra-hemispheric and inter-hemispheric links was increased in theta-1 and theta-2 frequency bands in frontal and central regions compared to initial levels., Conclusion: These EEG changes reflected the facilitation of cortical inhibitory processes as well as recovery of impaired intra-cortical links i.e. the normalization of the brain integrative activity.

Objective: to identify a complex of neurobiological parameters informative for the assessment of severity of patient's initial clinical state and for individual prognosis of therapeutic response., Material and Methods: Correlation and regression analyses of clinical scores measured by the PANSS scale, resting EEG spectral parameters and immunological parameters have been performed in 45 patients (mean age 31.3±11.4 years with manic-delusional conditions in attack-like schizophrenia., Results: Neurobiological data obtained before the treatment course were matched with clinical scores of the same patients at the stage of remission establishment after treatment course. The multiple linear regression equations, which contained only 3 to 4 (from 80) initial EEG parameters and one of four immunological parameters, allowed to explain with high significance from 89 to 92% of clinical scores variance before treatment course, and to predict from 72 to 87% of clinical scores variance after treatment course at the stage of remission establishment, as well., Conclusion: The data obtained emphasize the role of neurophysiological inhibition deficit and processes of neuroinflammation and neuroplasticity in the pathogenesis of manic-delusional conditions and may be used in practice for elaboration of methods of prediction of treatment efficacy in patients with manic-delusional disorders.

Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD.

The purpose of this work was to search for associations between the serotonin receptor 2C gene (HTR2C) and the peculiarities of social behavior and social cognition in schizophrenia. To do this, patients with schizophrenia spectrum disorders and healthy control subjects were genotyped for the Cys23Ser HTR2C marker and underwent psychological examination, including assessment of Machiavellianism, recognition of emotions in facial expression, and theory of mind. In addition, we estimated the trait anxiety level as a potential factor affecting the relationship between the gene HTR2C and social behavior. We found a significant association between the Ser allele and a reduction of estimates on the Mach-LV Machiavellianism scale in the total sample of patients (n = 182) and control subjects (n = 189), which did not reach the confidence level in either of the groups. A tendency towards a HTR2C gene influence on the trait anxiety level was also revealed. The association between HTR2C and Machiavellianism was retained if the anxiety level was taken into account. The results suggest a pleiotropic effect of HTR2Con anxiety and Machiavellianism.

Objective: To determine clinical and pathopsychological parameters of negative personality changes, their diagnostic and predictive significance based on the variant of neuroleptic treatment in the dynamics of remissions in shift-like schizophrenia., Material and Methods: Twenty-nine female patients diagnosed with ICD-10 schizophrenia (items F20.01 and F20.02) were examined. The patients were treated with typical neuroleptics (TN) or atypical (ATN) neuroleptics in the hospital and then as outpatients. Patient's state was assessed clinically and psychometrically with the PANSS at admission, at the beginning of remission and after one and two years of remission. Mean score of positive (PS) and negative (NS) symptoms was determined differentially in the dynamics basing on the neuroleptic used. Twenty-seven patients underwent experimental/pathopsychological examination., Results and Conclusion: In different stages of the dynamics of shift-like schizophrenia, NS had different capacity of «reversibility» and were distinctly associated with the illness-shaping influence of PS severity and activity and characteristics of psychotropic effect of the neuroleptics. The highest severity of NS was noted in the stage of active psychosis (up to 3.6 and 4.2 scores), with the following decrease in the beginning of remission (up to 2.3 and 2.8 scores). The most distinct trend towards the reduction of NS in the first and second years of remission (up to 2.0-1.0 scores), along with a trend to the complete reduction of PS, was identified in patients treated with ATN. In patients treated with TN, the severity of NS was relatively stable in all stages of remission, with a trend towards the increased severity (up to 2.8 and 3.2 scores) with the stable reduction of PS to1.6 scores. The distinct property of ATN to exert the reducing psychotropic effect on NS and the lack of antinegative effect in the antipsychotic spectrum of TN is discussed.

Objective: To specify clinical action of venflaxine during the course treatment of patients with different depressive states of endogenous nature., Material and Methods: An open naturalistic study of 32 patients with different nosological forms of endogenous depression (manic-depressive psychosis, cyclothymia, schizophrenia) was carried out. Duration of the course treatment with venflaxine (velaxin) administered in daily dose of 37,5-300 mg was 56 days. Clinical and psychometric methods were used., Results: Venflaxine was a highly effective antidepressant. In the end of treatment, a "good" therapeutic effect with >50% reduction in total scores on the Hamilton scale (HAMD-D) was achieved in 84,4% of patients, a "marked" effect up to complete recovery with >80% reduction in HAMD-D scores was in 78,1% of cases., Conclusion: Due to its clinical characteristics, venflaxine may be regarded as a multiprofile antidepressant with the distinct balanced action. In the spectrum of its antidepressant activity, a thymoleptic effect is most pronounced compared to anxiolytic and stimulating effects. This provides a high efficacy of the drug in different types of endogenous depression (anxiety, apatho-adynamic and, in particular, melancholic).

Objective: To analyze the therapeutic effect of valdoxan on symptoms of anhedonia in patients with endogenous depressions and to develop indications for its use., Material and Methods: Authors examined 30 women, mean age 35,9 years with anhedonic depression (ICD-10 items F31.3-4, F33.1-2, F20.4). Valdoxan was administered in average daily dose from 25.8 to 45.8 mg during 30 days. Patient's status was assessed on 0, 7, 14 and 30th days, using clinical and psychometric (HAMD-21, HADS, SHAPS and UKU scales) methods. The reduction of scores was used as a measure of therapeutic effect designated as «mild», «moderate», «good» and «marked»., Results: Antianhedonic effect of valdoxan on 30th day was superior to thymoleptic and anxiolytic effects of this drug (91.5 versus 82.2 and 76.9%). The marked effect was identified already on 14th day and enhanced to 30th day. The best effect was seen in depression of moderate severity. Single autonomic side-effects of the treatment were observed., Conclusion: The course treatment of anhedonic depressions with valdoxan should be considered as preferable and highly effective method that provides a dominative antianhedonic effect in the spectrum of antidepressive properties of the drug. Good and marked effects have been achieved in 96.7% of patients. The intensity and rate of its formation, good tolerability allow to tailor indications of valdoxan basing on the psychopathological characteristics of gedonic disorders.

With the aim to study neurophysiologic correlates and to search for some possible predictors of therapeutic response correlation analysis has been carried out of links between temporal parameters of components of auditory event-related potentials (AERPs) and dynamics of quantitative clinical assessments of mental state conditions in two groups of patients--with depressive-delusional conditions (group 1) and with manic-delusional conditions (group 2) in the frames of attack-like schizophrenia. Statistically significant correlations have been revealed between values of peak latencies of main AERPs components and severity of psychopathologic symptoms before beginning of treatment course, as well as between initial (before treatment course) AERPs temporal parameters and quantitative clinical assessments at the stage of remission establishment. Larger severity of residual positive, negative and common psychopathologic symptoms of schizophrenia (and also of depression and anxiety in group 1) after course of treatment was associated with smaller initial (before treatment course) values of peak latencies of "early" (P1 and N1) and with larger initial values of "late" (P2, N2 and P3) AERPs components in both groups of patients. The data obtained allow to justify basic views on brain mechanisms of affective-delusional disorders, and to reveal possible neurophysiologic predictors of treatment efficacy in such disorders.

Neurotoxic products produced during tryptophan metabolism via the kynurenine pathway could be involved in schizophrenia pathogenesis. It has been shown that kynurenine-3-monooxygenase (KMO) is indirectly involved in these products' formation. KMO polymorphic loci rs2275163 (C/T) and rs1053230 (A/G) were examined in 187 schizophrenia patients and 229 healthy subjects. A genetic combination of allele T and genotype GG was observed more often in a patient group compared with healthy controls (p = 0.003, OR 2.0 (95% CI 1.2-2.9). In the latter group, this combination was associated with schizophrenia endophenotype (p = 0.04), which manifested in a higher expression of schizotypal personality traits assessed using the MMPI test.

Bipolar disorder (BD) is a common and highly heritable mental illness and genome-wide association studies (GWAS) have robustly identified the first common genetic variants involved in disease aetiology. The data also provide strong evidence for the presence of multiple additional risk loci, each contributing a relatively small effect to BD susceptibility. Large samples are necessary to detect these risk loci. Here we present results from the largest BD GWAS to date by investigating 2.3 million single-nucleotide polymorphisms (SNPs) in a sample of 24,025 patients and controls. We detect 56 genome-wide significant SNPs in five chromosomal regions including previously reported risk loci ANK3, ODZ4 and TRANK1, as well as the risk locus ADCY2 (5p15.31) and a region between MIR2113 and POU3F2 (6q16.1). ADCY2 is a key enzyme in cAMP signalling and our finding provides new insights into the biological mechanisms involved in the development of BD.

Objective: To analyze background EEG parameters correlated with frontal lobe dysfunction, that might be considered, prospectively, as individual predictors of relative pharmacoresistance (or relatively lower treatment efficacy) in different forms of endogenous affective disorders., Material and Methods: An analysis of a set of several EEG parameters and quantitative clinical assessments has been carried out during the treatment in patients with endogenous depression (group 1), depressive-delusional conditions in the frames of attack-like schizophrenia (group 2), and manic-delusional conditions in the frames of attack-like schizophrenia (group 3)., Results and Conclusion: Statistically significant correlations have been revealed between initial (before treatment course) values of narrow-band EEG spectral power (mainly of beta activity reflected the frontal lobe dysfunction and hyper-activation of brain stem structures) and quantitative clinical assessments of patient's conditions at remission stage. The data obtained allow to justify the basic considerations on the brain mechanisms of different affective disorders, and to reveal possible neurophysiologic predictors of relative pharmacoresistance (or relatively lower treatment efficacy) in patients with endogenous affective disorders.

The 5-HTTLPR SLC6A4 and catechol-o-methyltransferase (COMT) Val158Met polymorphisms are reported to be associated with processing of facial expressions in general population. Impaired recognition of facial expressions that is characteristic of schizophrenia negatively impacts on the social adaptation of the patients. To search for molecular mechanisms of this deficit, we studied main and epistatic effects of 5-HTTLPR and Val158Met polymorphisms on the facial emotion recognition in patients with schizophrenia (n=299) and healthy controls (n=232). The 5-HTTLPR polymorphism was associated with the emotion recognition in patients. The ll-homozygotes recognized facial emotions significantly better compared to those with an s-allele (F=8.00; p=0.005). Although the recognition of facial emotions was correlated with negative symptoms, verbal learning and trait anxiety, these variables did not significantly modified the association. In both groups, no effect of the COMT on the recognition of facial emotions was found.

To analyze the possibility of using immunological parameters for the assessment of the activity of the process and prediction of the quality and completion of remission, we compared the dynamics of clinical and immunological parameters in 76 patients with endogenous attack-like psychoses during pharmacotherapy of a psychotic episode. Authors confirmed evidence for the activation of innate and adaptive immunity in the acute stage of psychosis as well as the correlation between immunological parameters (leukocyte elastase (LE) activity, alpha(1)-proteinase inhibitor (alpha(1)-PI), the level of autoantibodies to nerve growth factor (Aab-NGF)) and clinical symptoms assessed with the PANSS. The improvement of the clinical state assessed by the reduction in PANSS total score was noted in all patients though there were variations in the dynamics of immunological parameters. The increase of immunological parameters, along with the absence of changes at the discharge from the hospital, suggests that the remission was of low quality and the pathological process did not attenuate. Outpatient examination revealed the different dynamics of psychopathological disorders: stable state in 50% patients, moderate worsening of psychological state in 50% patients. Worsening of clinical symptoms after the discharge and in the outpatient stage was correlated with the elevation of the activity/level of immunological parameters. The changes in LE activity and Aab-NGF level precede the changes in mental state of patients in the following 1-2 months. These parameters may be used for monitoring of patients and prediction of quality and completion of remission.

Cognitive reserve (CR) postulates that individual differences in the cognitive processes or neural networks underlying task performance allow some people to cope better than others with brain damage. An aim of the study was to search for candidate genes for CR in schizophrenia. We propose that higher frequencies of low risk alleles is observed in healthy relatives of schizophrenic patients compared to patients and controls and in patients without neurocognitive deficit and with less severity of the disease compared to other patients and controls. Besides, frequencies of these alleles in patients should be similar to those in general population. Authors studied SNAP-25 and DTNBP1 genes. The polymorphism T1065G of SNAP-25 was genotyped in 278 patients with schizophrenia, 126 their relatives and 207 controls and the polymorphism P1763 of DTNBP1 was genotyped in 202 patients, 229 relatives and 262 controls. There was a trend towards the increase in the frequency of an G allele of SNAP-25 in siblings of patients. The frequency of this allele was higher in patients without neurocognitive deficit compared to patients with cognitive deficit (p=0.003) and controls (p=0.002). The allele was associated with index of cognitive functioning in patients (p=0.012) and controls (p=0.006) and with the severity of negative symptoms in patients (p=0.023). At the same time, the polymorphism T1065G was not associated with schizophrenia. Therefore, an allele G may be considered as a marker for higher CR.

To evaluate a role of dopamine transmission in the theory of mind (ToM) dysfunction in schizophrenia, authors studied the association of ToM with COMT and DRD2 gene polymorphisms in 209 patients with schizophrenia and 172 healthy people. All subjects performed second-order false belief (FB2) and faux pas stories. The association between the COMT Val158Met polymorphism and performance on FB2 was found. The association was sex-specific. The worse performance was associated with a Met allele in female patients and with the ValVal genotype in male ones. A correlation analysis of the COMT Val158Met polymorphism, performance on FB2 task, neurocognitive and clinical symptoms suggests that in female patients the association was modified, in part, by the higher stress sensitivity caused by the severity of clinical symptoms and its consequences for cognitive functioning.

Background: Common genetic polymorphisms at chromosome 3p21.1, including rs2251219 in polybromo 1 (PBRM1), have been implicated in susceptibility to bipolar affective disorder (BP) through genome-wide association studies. Subsequent studies have suggested that this is also a risk locus for other psychiatric phenotypes, including major depression and schizophrenia., Methods: To replicate the association, we studied 2562 cases with BP and 25,439 control subjects collected from seven cohorts with either genome-wide association or individual genotyping of rs2251219 and tagging single nucleotide polymorphisms across the PBRM1 gene. Results from the different case-control groups were combined with the inverse variance weighting method., Results: In our dataset, rs2251219 was associated with BP (odds ratio [OR] = .89, p = .003), and meta-analysis of previously published data with our nonoverlapping new data confirmed genome-wide significant association (OR = .875, p = 2.68 × 10(-9)). Genotypic data from the SGENE-plus consortium were used to examine the association of the same variant with schizophrenia in an overall sample of 8794 cases and 25,457 control subjects, but this was not statistically significant (OR = .97, p = .21)., Conclusions: There is strong evidence of association of rs2251219 with BP. However, our data do not support association of this marker with schizophrenia. Because the region of association has high linkage disequilibrium, forming a large haplotype block across many genes, it is not clear which gene is causally implicated in the disorder., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Growing evidence suggest that interleukin-1beta (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) are involved in the pathogenesis of schizophrenia. The objective of this study was to test the association of the functional promoter polymorphism 511T>C of the IL-1B gene and the VNTR polymorphism of the IL-1RN gene with clinical symptoms of schizophrenia. We studied 758 patients, 415 men and 343 women, with the ICD-10 diagnosis of schizophrenia. Symptoms of schizophrenia were measured using the Positive and Negative Symptome Scale (PANSS). The sample was stratified by gender and type of schizophrenia (chronic or episodic). We found the association between the VNTR IL-1RN polymorphism and PANSS negative symptoms (p = 0.02) in men. Male patients with the genotype 2*2 had lower scores than those with 1*2 and 1*1 genotypes. The genotype 2*2 was associated with a more severe illness course (shorter illness duration and smaller number of hospitalizations) as well. The results suggest that the VNTR polymorphism in the IL-1RN gene may be a predictor of outcome of schizophrenia in men.

We conducted a genome-wide association study (GWAS) and a follow-up study of bipolar disorder (BD), a common neuropsychiatric disorder. In the GWAS, we investigated 499,494 autosomal and 12,484 X-chromosomal SNPs in 682 patients with BD and in 1300 controls. In the first follow-up step, we tested the most significant 48 SNPs in 1729 patients with BD and in 2313 controls. Eight SNPs showed nominally significant association with BD and were introduced to a meta-analysis of the GWAS and the first follow-up samples. Genetic variation in the neurocan gene (NCAN) showed genome-wide significant association with BD in 2411 patients and 3613 controls (rs1064395, p = 3.02 × 10(-8); odds ratio = 1.31). In a second follow-up step, we replicated this finding in independent samples of BD, totaling 6030 patients and 31,749 controls (p = 2.74 × 10(-4); odds ratio = 1.12). The combined analysis of all study samples yielded a p value of 2.14 × 10(-9) (odds ratio = 1.17). Our results provide evidence that rs1064395 is a common risk factor for BD. NCAN encodes neurocan, an extracellular matrix glycoprotein, which is thought to be involved in cell adhesion and migration. We found that expression in mice is localized within cortical and hippocampal areas. These areas are involved in cognition and emotion regulation and have previously been implicated in BD by neuropsychological, neuroimaging, and postmortem studies., (Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

NRG1 is a strong candidate for schizophrenia though its role in the pathogenesis of the disease remains unknown. One of the approaches to study mechanisms underlying the association between NRG1 and schizophrenia is to investigate the association between a gene and an endophenotype of schizophrenia, e.g., cognitive dysfunctions. Authors looked for the association of 478B14-848 и 420M9-1395 microsatellites with semantic verbal fluency, working and episodic memory in 338 patents with schizophrenia, 162 their unaffected relatives and 316 healthy controls from the Russian population. It was found associations between allele 0 at 478B14-848 (220 bp) and long-term episodic memory and between allele 0 at 420M9-1395 (274 bp) and short-term memory in schizophrenic patients. The frequency of homozygotes for 420M9-1395 was higher in the group of patients as compared to controls. In conclusion, the risk allele 0 at 420M9-1395 is associated with the short-term memory deficit while allele 0 at 478B14-848 is protective for long-term memory deficits.

Associations between polymorphisms in the T102C and A-1438G loci of the 5-HTR2A and the P1763 and P1578 markers of the DTNBP1 gene with the overall productivity and individual subprocesses of shortterm verbal memory were studied in 4-5 patients with schizophrenia and 290 healthy subjects. Subjects were asked to reproduce immediately two lists of 10 words. The overall productivity of reproduction was assessed, along with the reproduction productivity of the first list (immediate memory or general attention), the effect of proactive interference, and the number of intrusions. Patients were significantly different from controls on all measures. Patients showed decreases in overall task performance productivity, in immediate memory productivity, and in the effect of proactive interference; fewer intrusions were seen. Both markers of the 5-HTR2A gene were associated with short-term memory productivity in the combined cohort: assessments were worse in T102C CC and A-1438G GG homozygotes. The P1763 marker of the DTNBP1 gene, conversely, had significant influences on the memory subprocesses reflected in the levels of interference and intrusions but had insignificant influence on overall productivity. Homozygotes for P1763G GG had the worst parameters. Overall, these data are consistent with the concept that these polymorphic genes are involved in different subprocesses of short-term memory both in normal subjects and in patients with schizophrenia.

Synaptosomal protein SNAP-25 is involved in the process of transmitting nerve spikes in the CNS and in the consolidation of memory traces in the hippocampus. Two independent studies have demonstrated associations between SNAP-25 gene polymorphisms and intellectual functions in a group of mentally healthy subjects and patients with schizophrenia. The aim of the present work was to perform a comparative study of the association between the MnlI polymorphism of SNAP-25 and cognitive functions (verbal memory, attention/executive functions) in 66 patients with endogenous psychoses, 75 of their mentally healthy relatives, and 136 healthy control subjects. Statistical analysis showed that the effectiveness of performing cognitive tests was significantly affected by group assignment (p = 0.00001) and genotype (p = 0.012). The interaction between genotype and group assignment also had an influence (p = 0.02). In all groups, carriers of the TT genotype had worse measures than carriers of other genotypes. The similar nature of the influences of the MnlI polymorphism on variations in measures in all groups indicates that this gene is related to overall intellect.

The aim of the study was to find molecular-genetic variants associated with nosologically independent schizoaffective disorder (SAD) which clinical presentations had been specified earlier. Authors studied a sample of 230 patients including 39 with "nuclear" (nosologically independent) and marginal (intermediate) variants of SAD, 53 with schizophrenia with schizoaffective states and 81 with schizophrenia with affective disorders in the structure of psychotic attacks. In these groups, authors studied the following polymorphisms: 5-HTTLPR, Val66Met BDNF, T102C 5-HTR2a and С677Т MTHFR. Frequencies of genotypes were compared to those in a sample of healthy controls (328 people). It has been shown that the "nuclear" variant has a genetic profile represented by a combination of genetic variants (SS*ValVal*TT*CC) that distinguishes this clinical entity from other groups and controls. The results may be used as an additional criteria for clinical and nosological differentiation of SAD from schizophrenia.

The elevated level of homocysteine has been repeatedly observed in patients with schizophrenia. Molecular-genetic studies revealed the association between schizophrenia and polymorphisms of two genes - methylenetetrahydrofolate reductase (MTHFR) and cystathionine-beta-synthase (CBS) involved in the conversion of homocysteine to methionine and cysteine, respectively. Authors have studied the association of C677T MTHFR and 844ins68 CBS polymorphisms with attention in 105 schizophrenic patients (56 women and 49 men) by measuring auditory evoked potentials and concentration of attention. Women with a genotype containing an insertion (Ins+) had the shorter latency of N100 in the frontal leads compared to those with the Ins- genotype. The results of the neuropsychological study revealed that women with Ins+ genotypes performed better on the test as well. In conclusion, the 844ins68 CBS polymorphism is associated with attention in patients with schizophrenia.

Caregiving of a family member with psychotic disorder is considered among the most significant stressors and relatives of a sufferer experienced psychological and physical burden that may be the cause of neurotic states. There is growing evidence that sensitivity of individuals to depressogenic effects of stressful factor is moderated by genetic variants of serotonin transporter (SERT) and brain-derived neurotrophic factors (BDNF). We examined the association of the 5-HTTLPR SERT and Val66Met BDNF polymorphisms with signs of depression and anxiety measured with the Minnesota Multiphasic Personality Inventory (MMPI) in 235 unaffected parents of patients with major psychosis and 102 age-matched controls. A significant effect of the SERT-BDNF interaction on Depression and Psychasthenia scales was found in the group of parents, but not in the control group. Carriers of the Val/Val x SS variant scored higher as compared to other allelic combinations. The results obtained revealed that the SERT-BDNF interactions might moderate the level of anxiety and depression caused by caregiving status in parents of psychotic patients.

The aim of this study was to investigate the possibility that affect recognition impairments are associated with genetic liability to schizophrenia. In a group of 55 unaffected relatives of schizophrenia patients (parents and siblings) we examined the capacity to detect facially expressed emotions and its relationship to schizotypal personality, neurocognitive functioning, and the subject's actual emotional state. The relatives were compared with 103 schizophrenia patients and 99 healthy subjects without any family history of psychoses. Emotional stimuli were nine black-and-white photos of actors, who portrayed six basic emotions as well as interest, contempt, and shame. The results evidenced the affect recognition deficit in relatives, though milder than that in patients themselves. No correlation between the deficit and schizotypal personality measured with SPQ was detected in the group of relatives. Neither cognitive functioning, including attention, verbal memory and linguistic ability, nor actual emotional states accounted for their affect recognition impairments. The results suggest that the facial affect recognition deficit in schizophrenia may be related to genetic predisposition to the disorder and may serve as an endophenotype in molecular-genetic studies.

An association study of variations in the DTNBP1 (P1763 and P1578) and 5-HTR2A (T102C and A-1438G) genes with short-term verbal memory efficiency and its component process variables was carried out in 405 patients with schizophrenia and 290 healthy controls. All subjects were asked to recall immediately two sets of 10 words. Total recall, List 1 recall, immediate recall or attention span, proactive interference and a number of intrusions were measured. Patients significantly differed from controls by all memory variables. The efficiency of test performance, efficiency of immediate memory, effect of proactive interference as well as number of intrusions were decreased in the group of patients. Both 5-HTR2A polymorphisms were associated with short-term verbal memory efficiency in the combined sample, with the worst performance observed in carriers of homozygous CC (T102C) and GG (A-1438G) genotypes. The significant effect of the P1763 (DTNBP1) marker on the component process variables (proactive interference and intrusions) was found while its effect on the total recall was non-significant. The homozygotes for GG (P1763) had the worst scores. Overall, the data obtained are in line with the conception of DTNBP1 and 5-HTR2A involvement in different component process variables of memory in healthy subjects and patients with schizophrenia.

The DRD2 Ser311Cys polymorphism was studied in a sample which included 366 patients with schizophrenia and 387 healthy controls. The frequency of the Cys allele was significantly higher (p<0,009) in the group of patients compared to the controls (8,5% and 3,9%, respectively). Sustained attention assessed by P300 parameters was studied in 66 patients with the SerSer and SerCys genotypes (the CysCys genotype was not observed in the sample studied). A significant effect (p=0,01) of the SerCys genotype on P300 latency in frontal, central and temporal regions was found. Patients with the at-risk allele presented delayed latencies that reflected the lower speed of mental processes related to activation of attention resources. In conclusion, our data support the evidence of association between the Cys allele and schizophrenia obtained earlier for other populations and revealed that carriers of the genotype containing the at-risk allele had delayed P300 latencies.

The synaptosomal-associated protein (SNAP-25) plays an integral role in synaptic transmission and in memory consolidation in the hippocampus. Recently an association between SNAP-25 gene polymorphism and cognitive ability has been reported in two independent studies of healthy people and patients with schizophrenia. Authors carried out an association study of MnlI SNAP-25 polymorphism and performance on neurocognitive tests measuring verbal memory, attention/executive functions in 66 patients with major psychosis, 75 their relatives and 136 controls. MANCOVA revealed a significant effect of group (small er, Cyrillic=0,00001) and genotype (small er, Cyrillic=0,012) as well as an interaction effect between group and genotype (small er, Cyrillic=0,02) on the performance on neurocognitive tests. Carriers of the TT genotype performed worse on the most tasks compared to other genotypes. The similar character of the MnlI SNAP-25 polymorphism effect on the variability of neurocognitive traits in all groups suggests the relationship between this gene and general cognitive ability.

Recent studies have demonstrated a role of the brain-derived neurotrophic factor (BDNF) in schizophrenia. An association between the Val66Met BDNF polymorphism has been reported but the results of different studies are inconsistent. An aim of the present article is to study the allele and genotype distribution in patients with schizophrenia (783) and mentally healthy controls (633). No statistically significant between-group differences have been found. When the group of patients has been stratified by sex and form of schizophrenia, the higher frequency of the Val/Val genotype is observed in the subgroup of men with continuous (chronic) schizophrenia as compared to men with attack-like form (p = 0.047). Clinical symptoms assessed with the PANSS were more severe in male patients with the Val/Val genotype. The Val66Met polymorphism was not associated with forms of schizophrenia or clinical symptoms in female patients. The results obtained suggest that the association between the BDNF gene and schizophrenia may be related to sex and clinical heterogeneity of disease. The Val/Val genotype is associated with severer form of schizophrenia in men.

A number of studies have reported an association between 5-HTTLPR, a polymorphism of the serotonin transporter gene, and the development of depressive states in response to a variety of distal and proximal stressors. We report here studies of the effects of the 5-HTTLPR polymorphism on the probability that an individual will develop mental maladaptation in 224 close relatives of patients with severe chronic mental disorders - schizophrenia and schizoaffective and affective psychoses. The ss genotype of the serotonin transporter gene contributes to the formation predominantly of manifestations of distress, reflected by increases on the hypochondriasis scale of the MMPI scale of factors such as the extent of the autonomic component of anxiety reactions and increased attention to own health, as well as increases in sensitivity. At the same time, the ss genotype was less likely to influence the appearance of depression and anxiety, as determined on the depression scale. These tendencies were more marked in males than females. Furthermore, males with the ss genotype were characterized by some increase in tension, suspicion, detachment, and attention difficulty (on the paranoia and schizophrenia scales). These data can be regarded as supporting the role of the short allele of the serotonin transporter gene in enhancing and modulating psychopathological reactions to chronic stress situations in relatives of mental patients.

To investigate the effect of Val66Met BDNF and 5-HTR2A T102C polymorphisms on the characteristics of voluntary and involuntary visual attention, 89 patients with schizophrenia, 91 their well relatives and 163 controls have been studied. Attention was assessed using a modified version of the Munsterberg test. The significant interaction effect of the BDNF, 5-HTR2A and diagnosis on attention characteristics was found (p=0,04). Carriers of the Val/Val genotype demonstrated higher scores of both voluntary and involuntary attention and those with the A1 (T) allele needed more time for the performance of the test. The combination of the A1 allele with a Met BDNF allele was associated with lower scores of voluntary attention and higher scores of involuntary attention. The study confirmed the impairment of selective attention in patients with schizophrenia and their relatives while any pathological changes in involuntary attention were not observed. The effect of genotypes was presented irrespective of diagnostic group studied. The data obtained suggest that carriers of the Val/Val genotype are able to allocate more attentional resources to process external stimuli. At the same time, the possibility that this polymorphism is likely associated with specific visual-spatial abilities than with attention as such or general cognitive resources can not be excluded.

The aim of the study was to discriminate the auditory event-related potentials (ERP) abnormalities in the P300 paradigm as the possible neurophysiological endophenotypes (pathogenetic predisposition markers) of schizophrenia. Deviations of the parameters of different waves of auditory ERP were determined in a sample of patients as compared to the controls, the influence of patient's clinical state (measured by PANSS) upon ERP abnormalities was studied. The comparison of neurophysiological characteristics was carried out also in mentally healthy parents from the families with so-called "sporadic" cases of schizophrenia and in parents from the families, in which the other spouse was either affected with mental disorder or had relatives with schizophrenia. The data obtained suggest that two neurophysiological abnormalities of auditory ERP - the decrease of N100 amplitude in ERP to non-target stimuli and reduction of P300 amplitude, fulfill the "endophenotype" criteria.