[Polymorphism C366G of gene GRIN2B and verbal episodic memory: No association with schizophrenia].

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.

[The estimation of selen content in blood serum and the diet correction in patients with acute Q-wave myocardial infarction].

The use of selenium-containing specialized food products in prophylactic and therapeutic diets is based on hypothesis that selenium as antioxidant can potentially decrease the risk of oxidative stress induced diseases. There is a hypothesis, which is strongly supported during last 10-15 years that the reactive oxygen species are generated during ischemic myocardium reperfusion and cardiomyocyte damage. In addition selenium as an important component of glutationperoxidaze, it promotes protection against ischemic damage, improvement of functional regeneration and reduction of morphological changes in cardiomyocytes. We established a low serum selenium level in patients with acute and subacute stage of Q-wave myocardial infarction (75.5±1.8 mcg/L). New dietary product - jam made of seaweed with dried apricot enriched with selenium - was included in patient diet. We observed 72 persons (40-75 years old) who were randomized in a control group (30 patients) on standard treatment and a main group (42 patients) that received the dietary product (80 mcg Se) in addition to the standard treatment. Critical serum selenium level was found initially in 16 main group patients (38%), in 2 patients (7%) 2 weeks later and in none of patients in a month of dietary jam treatment. Selen concentration in blood serum increased from basal value 78.3±3.1 mcg/L after 2 weeks of treatment by 16% and after one month of treatment by 20% (p <0.05). In the control group the serum selenium level remained on critical and selenium-deficient levels during a month on standard treatment without dietary compensation. No adverse events were revealed in patients of main group, the investigated product was well tolerated.

Common variant at 16p11.2 conferring risk of psychosis.

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).

[Association between serotonin receptor 2C gene Cys23Ser polymorphism and social behavior in schizophrenia patients and healthy individuals].

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.

[Association of kynurenine-3-monooxygenase gene with schizophrenia].

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.

[Influence of enzymatic hydrolyzate of mussel meat on growth and some indicators of general adaptation syndrome in rats].

The impact of the 15-day consumption of enzymatic hydrolyzate of the mussels meat as a part of semi-synthetic diet on some stress biomarkers and apoptosis activity in various organs of growing male Wistar rats have been studied. Enzymatic hydrolyzate of the mussels meat (EMM) was obtained in pilot conditions using the enzyme preparation "Protozim". The animals of control group 1 (n = 8 with initial body weight of 179.4 ± 5.9 g) and experimental group 2 (n = 8, 176.3 ± 4.5 g) received a semi synthetic diet; the animals of the experimental group 3 (n = 8, 177.6 ± 4.0 g) received the same semi synthetic diet in which 50% of the casein was replaced by the peptides of EMM. On the penult day of the experiment animals of groups 2 and 3 were subjected to stress exposure by electric current on their paws (current 0.4 mA for 8 seconds) and were placed in metabolic cages for the collection of daily urine. At the 15th day of the study, all control and test animals were killed by decapitation under ether anesthesia and necropsied. The content of prostaglandin E2 and ß-endorphin in blood plasma was determined by ELISA test. The concentration of urine corticosterone was measured by HPLC. DNA damage and percentage of apoptotic cells (apoptotic index) were calculated in thymus by single-cell gel electrophoresis assay (Comet assay). The relative body weight increase of animals treated with EMM was significantly (p < 0.05) higher (68.2 ± 3.0%) than those in animals of groups 1 and 2 (57.2 ± 4.0 and 59.7 ± 2.8%, respectively). The apoptotic index in thymus cells of tested groups of animals (2 and 3) was significantly (p < 0.05) higher (1.13 ± 0.09 and 1.09 ± 0.01%) compared to intact animals of control group (1.04 ± 0.01%). Determination of ß-endorphin and prostaglandin E2 levels did not shown any significant differences between the groups. Significantly (p < 0.05) lower concentrations of corticosterone was found in the daily urine of stressed animals from group 3 (452 ± 78 ng/ml), treated with EMM, compared to stressed animals of group 2 that received a casein diet (834 ± 167 ng/ml). It has been shown that consumption of EMM with a high content of short and medium peptides has an impact on effectiveness of body weight gain of growing laboratory animals, and restrict the increase of corticosterone level in rats blood, which is typical for general adaptation syndrome.

[Auditory event-related evoked potentials in dynamics of treatment of affective-delusional conditions].

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.

[Clinical assessment of dietary correction of metabolic syndrome by using specialized food product enriched with chrome].

Effectiveness of Laminaria jam enriched with chromium has been investigated in ambulatory patients with metabolic syndrome. 50 patients ranging in age from 30 to 65 years (mean age 53.4 +/- 7.5) were under observation during 6 months. 30 patients from comparison group were given recommendations on modeling of lifestyle (diet, reduced and controlled dosed physical loading) and they received medical treatment. Main group of patients (20 people) in addition received dietary product--Laminaria jam, enriched with chromium, which daily dose (20 g) contain 280 microg of iodine and 66 microg of chromium. In both groups declines of overweight, improving clinical and laboratory parameters, adaptive organism reserves and quality of life has been registered. Patients from the main group referred good organoleptic properties of dietary product, it was well tolerated by patients without causing unwanted side effects. After 6 months of a dietary correction mean relative body mass reduction in the main group amounted to 5.0% while in the comparison group--3.0%. Positive dynamics of the circumference of the waist in patients accounted for 5.9% in main group and 3.1% in comparison group. Systolic and diastolic blood pressure decreased in the main group, an average of 20.5 and 24.2%; in the comparison group--10.5 and 13.3% respectively. The average reduction in LDL-C reached 28.3% in the main group and 18.3% in the comparison group. Triglyceride levels decrease was an average of 18.9% in the studied group, that was significantly higher than in the control group (3.7%). The dynamics of OGTT in main group amounted to 13.1% while in the comparison group--8.6%. Differences between group indices were statistically significant for most of the variables. The inclusion of the dietary product in a range of therapeutic and preventive activities under metabolic syndrome has been shown to improve clinical and metabolic indicators (body mass, arterial pressure, lipid and carbohydrate metabolism parameters) compared with standard therapy.

[Comparative evaluation of the influence of homogenate and enzymatic hydrolyzate of mussels' meat in the growth rats and their protein assimilation].

The experiment in vivo by a comparative assessment of the biological value of peptide fractions in structure of enzymatic hydrolyzates of mussels' meat and protein in structure of homogenate of mussels' meat (raw material) was carried out. The experiment was made in growing male rats of Wistar line, who got semi-synthetic diet with a source of protein presented by homogenate of mussels meat and enzymatic hydrolyzate of mussels meat. Throughout the study were defined the individual parameters of palatability of feed and increase of body weight of each animal; during the so-called exchange period, besides the listed parameters, were taken into account the quantity of nitrogen removed with excrement. Biological value of protein in structure of homogenate of mussels meat and peptide fractions in structure of enzymatic hydrolyzate of mussels meat was evaluated by determining the coefficient of efficiency of the protein and true digestibility of the protein. The findings show a high biological value of new source of protein - enzymatic hydrolyzate of mussels meat, the prospectivity of the further researches by evaluating a possible antistress properties of enzymatic hydrolyzate of mussels meat, as well as the opportunity of its use as a component of preventive food product of a broad spectrum of action.

Expanding the range of ZNF804A variants conferring risk of psychosis.

A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P<5 × 10(-8)) associated with schizophrenia earlier. However, one variant, rs1344706[T], had come very close. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 × 10(-7), and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 × 10(-8). In this study, using 5164 schizophrenia cases and 20,709 controls, we replicated the association with schizophrenia (odds ratio OR = 1.08, P = 0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N = 609, OR = 1.09, P = 0.00065). Furthermore, as it has been proposed that variants such as rs1344706[T]-common and with low relative risk-may also serve to identify regions harboring less common, higher-risk susceptibility alleles, we searched ZNF804A for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients with other psychiatric disorders and 39,481 controls. We identified two CNVs including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in controls (P = 0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P = 0.0016 for association with the larger set of psychiatric disorders).

[Possibilities of using MIGI-K protective activity under conditions of radionuclide contamination].

Experimental studies of the mussel hydrolyzate (MIGI-K) have shown that this preparation can enhance both general and radiation resistance of the organism. Moreover, MIGI-K promotes elimination of incorporated radionuclides from the organism. Some properties of this preparation, in particular, the absence of toxicity or harmful side effects, have made it possible to apply MIGI-K as an adaptogen, that is, a food supplement oftherapeutic and preventive action used to increase radionuclide excretion in the Chernobyl emergency clean-up workers.

[New sources of organic form zinc].

The Comparative analysis of the efficiency of the enzymatic hydrolysis of the mussels meat has been carried out, using enzymatic preparations with proteolytic action called "Protozim", "Flavoenzyme" and "Pancreatine". Complexes of fermentolyzates of the mussels meat with zink have been obtained by the reaction of chelating. Prepared fermentolyzates and their complexes with zink have been determined by physicochemical methods. Composition of amino acids has been determined in fermentolyzates and in their complexes with zink has been characterized the content of zink. The valuation of molecular-mass distribution of peptide fractions of fermentolyzates and their complexes with zink has been given.

[Selenium provision in heart failure of different aetiology].

Determination of selenium status of patients with chronic heart failure of various etiologies showed reduced provision of selenium compared with the control group. Statistically significant increased serum levels of selenium have occurred on average 35,9% after the correction. Intake of sea cabbage jam led to a significant increase in the level of selenium in serum only at patients with deficiency of this trace constituent.

[Clinical-neurophysiological correlations in patients with depressive-delusional conditions]. / Kliniko-neirofiziologicheskie korrelyatsii u bol'nykh s depressivno-bredovymi sostoyaniyami.

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.

[Clinical efficiency of using laminaria jam enriched with selenium].

Effectivity was studied of a new dietary product enriched with organic form of selenium--laminaria gel in patients with ischemic heart disease and hypertonia. Functional condition of nervous and cardiovascular systems improved after intake of testing product. There were no any adverse changes in biochemical indices of patients receiving studied product. Intake of the product gave reliable increase in the selenium levels of blood serum only in patients with low content of this trace element.

The modulatory influence of polymorphism of the serotonin transporter gene on characteristics of mental maladaptation in relatives of patients with endogenous psychoses.

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.

[Association between the Val66Met polymorphism of brain-derived neurotrophic factor gene and schizophrenia in Russians].

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.

[Clinical-psychopathological aspects of therapeutic effects of agomelatine (valdoxan) and its place in perfection of methods of therapy of postschizophrenic depressive disorders]. / Kliniko-psikhopatologicheskie aspekty osobennostei terapevticheskogo deistviia agomelatina (val'doksana) i ego mesto v usovershenstvovanii metodov terapii postshizofrenicheskikh depressii.

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.

Supportive evidence for the association between the T102C 5-HTR2A gene polymorphism and schizophrenia: a large-scale case-control and family-based study.

Serotonin type 2A receptors (5-HTR2A) have long been implicated in schizophrenia pathology. A decreased number of these receptors were found in postmortem brain studies of schizophrenic patients as well as in experiments using neuroimaging techniques. Molecular genetic studies revealed that the T102C polymorphism of the 5-HTR2A gene is associated with schizophrenia, with the CC genotype frequency being higher in patients compared to healthy controls. However the association was not confirmed in all studies. We carried out a replication study, which aimed at searching for association between this polymorphism and schizophrenia in a large samples of patients (n=919), their psychiatrically well first-degree relatives (n=330) and screened controls (n=500). The C allele and the CT+CC genotype frequencies were significantly higher in patients than in controls (chi2=5.1; df=1; p=0.02; OR 1.2, 95% CI 1.0-1.4) and chi2=5.4; df=1; p=0.02; OR 1.4, 95% CI 1.1-1.8 respectively). In a family-based study, the transmission disequilibrium test (TDT) and the family-based association test (FBAT) did not show a preferential transmission of any allele. In conclusion, our replication study provides further evidence for association between the 5-HTR2A receptor T102C polymorphism and schizophrenia.

Interaction of dopamine system genes and cognitive functions in patients with schizophrenia and their relatives and in healthy subjects from the general population.

Linkage between the DRD4 and COMT genes and cognitive measures characterizing verbal memory, executive functions, and associative processes was studied in 150 patients with schizophrenia, 83 of their relatives, and 118 mentally healthy subjects without any family history of psychoses, with the aim of detecting the main effects of the polymorphic markers -809G/A and -521C/T (DRD4) and Val158Met (COMT) when present individually and together. The group of patients showed a main effect for polymorphism -521C/T on verbal fluency and an effect of the interaction of this polymorphism and the COMT gene on this cognitive trait. The highest level of verbal fluency was seen among carriers of the Val/Val+CC and Met/Met+TT genotypes. In the combined group of unaffected individuals, the interaction of the COMT and DRD4 -521C/TT genotypes had an effect on the standardness of speech associations due to a decrease in the standardness of associations in carriers of the Met/Met+CC genotype. Finally, both patients and unaffected individuals showed an effect for the interaction between the COMT and DRD4 -809G/A genotypes on working memory. Patients and healthy subjects showed similar features: the highest values were seen in subjects homozygous for the Val and G alleles, while the lowest values were seen in homozygotes for the Met and A alleles. These data provide evidence for a relationship between the DRD4 and COMT genes and different aspects of executive functions and the absence of such a relationship in relation to verbal memory.