[Association study of genetic markers of schizophrenia and its cognitive endophenotypes].

A replicative analysis of associations of 15 SNPs located in the regions of 11 genes (TCF4, VRK2, NOTCH4, ZNF804A, AGBL1, RELN, ZFP64P1, KCNB2, CSMD1, CPVL, NRIP1) and three intergenic regions (SLCO6A1/LINCOO491, LOC105376248/LOC105376249, SPA17/NRGN) with schizophrenia was conducted in the Russian population of the Siberian region. These SNPs were previously identified in genome-wide association studies (GWAS) of schizophrenia and cognitive abnormalities. The present study confirmed associations of KCNB2 rs2247572, CSMD1 rs2616984, and intergenic rs12807809 located in SPA17/NRGN with schizophrenia. It was established that the frequency of the CSMD1 rs2616984 G/G genotype was higher in patients compared to the control group (OR = 1.73; CI: 1.14­2.62; р = 0.0337). The frequencies of the KCNB2 rs2247572 TT genotype (OR = 0.41; CI: 0.20­0.87; р = 0.0485) and intergenic rs12807809 CT genotype located in SPA17/NRGN (OR = 0.70; CI: 0.53­0.94; р = 0.0464) were significantly decreased in patients compared to the control group.

[An effect of quetiapine on the immune system of patients with schizophrenia]. / Vliyanie kvetiapina na nekotorye pokazateli immuniteta u bol'nykh shizofreniei.

AIM: To study an effect of the atypical antipsychotic quetiapine on the immune system of patients with schizophrenia with account for treatment efficacy. MATERIAL AND METHODS: Quetiapine was administered to 27 patients diagnosed with residual schizophrenia (F20.5) for 6 weeks in dose 200-400 mg/day; dynamic of clinical symptoms was evaluated with PANSS и CGI scales before administration of quetiapine and by week 6 of the treatment. Along with clinical assessments, immune indices were determined. RESULTS: At the end of week 6 of treatment, statistically significant changes of PANSS psychopathological symptoms were noted. According to CGI scale, patients were divided into group 1 with high treatment efficacy (n=17) and group 2 with the low efficacy (n=10). Significant between-group differences before treatment were as follows: the decreased number of lymphocytes of CD3+- CD16+-phenotypes, increased number of HLADR+-lymphocytes and IgA level in group 2. The quetiapine therapy led to the positive dynamic of phagocytosis indices, CD16+-lymphocytes, decrease in the level of IgA. CONCLUSION: Possible predictors of treatment efficacy were found including the number of mature T (CD3+) lymphocytes, CD16+ natural killers, HLADR+ lymphocytes and IgA concentrations.

[Antibodies to native and denatured DNA in the serum of patients with schizophrenia depending on the clinical features of the disease].

OBJECTIVE: To study the correlations between the level of antibodies to native and denatured DNA and psychopathological symptoms and illness duration in patients with schizophrenia. MATERIAL AND METHODS: The level of antibodies to native (double-stranded) DNA and denatured (single-stranded) DNA was studied in the serum of 50 patients with schizophrenia, including 12 patients with tardive dyskinesia (TD). The control group consisted of 30 people. RESULTS: A significant twofold increase in antibodies to native DNA was detected in patients with TD. There was no correlation of the amount of antibodies to double-stranded DNA with the duration of disease and leading symptoms both between the groups of patients as well as in comparison with controls. A significant decrease in antibody levels to the denatured (single-stranded) DNA was found in schizophrenic patients compared to the control group (p=0.009). A significant decrease in the concentration of antibodies to single-stranded DNA in patients with increasing duration of the disease, as well as in patients with leading negative symptoms was revealed. CONCLUSION: The results suggest that anti-DNAantibodies may not play a major role in the pathogenesis of schizophrenia.

CYP1A2 and CYP2D6 Gene Polymorphisms in Schizophrenic Patients with Neuroleptic Drug-Induced Side Effects.

Polymorphic variants of CYP1A2 and CYP2D6 genes of the cytochrome P450 system were studied in patients with schizophrenia with drug-induced motor disorders and hyperprolactinemia against the background of long-term neuroleptic therapy. We revealed an association of polymorphic variant C-163A CYP1A2*1F of CYP1A2 gene with tardive dyskinesia and association of polymorphic variant 1846G>A CY2D6*4 and genotype A/A of CYP2D6 gene (responsible for debrisoquin-4-hydroxylase synthesis) with limbotruncal tardive dyskinesia in patients with schizophrenia receiving neuroleptics for a long time.

Serum Glutathione in Patients with Schizophrenia in Dynamics of Antipsychotic Therapy.

Serum concentrations of oxidized and reduced glutathione were measured in 73 patients with schizophrenia at admission and in dynamics of therapy with traditional and atypical antipsychotic drugs. The level of reduced glutathione in patients with schizophrenia with manifest clinical symptoms was lower than in normal subjects. Atypical neuroleptics produced virtually no effects on the glutathione system, while therapy with typical antipsychotics led to further decrease in the levels of reduced glutathione, thus aggravating the imbalance of metabolic processes typical of schizophrenia.

[Lipid spectrum changes and ECG in patients with paranoid schizophrenia in the course of therapy with atypical antipsychotics].

OBJECTIVE: To study correlations between parameters of lipid metabolism and ECG in patients with schizophrenia in light of therapy with atypical antipsychotics. MATERIAL AND METHODS: We examined 42 patients with paranoid schizophrenia. All patients received atypical neuroleptics - seroquel, zyprexa, and rispolept. A group of controls included 25 healthy people. RESULTS: There was a significant increase (p=0.0002) in body mass (in average by 1.5 kg) in 88% patients. A significant increase in the concentration of serum triglycerides was identified as well. The concentration of VLDL in the patients with schizophrenia was 2 times higher compared to controls. After treatment, VLDL concentration increased even more considerably An increase in atherogenic index (AI) was up to 3.1 in patients with schizophrenia compared to 2.2 in controls. After treatment, Al increased up to 4 that demonstrated the high risk of development of atherosclerosis. A significant increase in QT interval in the ECG and heart rate (p=0.03) was revealed only in patients receiving rispolept. In patients receiving zyprexa and seroquel only heart rate was increased. CONCLUSION: The antipsychotics studied increase the risk of development of cardiovascular pathology.

[Association of (N251S)-PIP5K2A with schizophrenic disorders: a study of the Russian population of Siberia].

The phosphatidylinositol-4-phosphate-5-kinase type IIa (PIP5K2A) gene has been proposed as a putative susceptibility gene for schizophrenia on both positional and functional grounds. The association between the (N251S)-PIP5K2A (rs10828317) variant and schizophrenia was found in German and Dutch populations but was not replicated in several other populations. The purpose of the study was to examine whether the previously implicated (N251S)-PIP5K2A variant influences susceptibility to schizophrenia in the Russian population of Siberia. Authors studied 355 patients with schizophrenic disorders from the Russian population of Siberia. The control group consisted of 100 healthy. Results confirm the association of the (N251S)-PIP5K2A (rs10828317) polymorphism with schizophrenia (p=0.04, OR=2.48, 95%CI=1.19--5.17 for the CC genotype). The association can be explained by the inability of mutant kinase to activate the phosphatidylinositol-4,5-biphosphate dependent proteins, including neuronal KCNQ channels and glutamate EAAT3 transporters, which leads to the lack of dopaminergic and glutamatergic control in schizophrenic patients carriers of this mutation.

NMDA receptor genotypes associated with the vulnerability to develop dyskinesia.

Dyskinesias are involuntary muscle movements that occur spontaneously in Huntington's disease (HD) and after long-term treatments for Parkinson's disease (levodopa-induced dyskinesia; LID) or for schizophrenia (tardive dyskinesia, TD). Previous studies suggested that dyskinesias in these three conditions originate from different neuronal pathways that converge on overstimulation of the motor cortex. We hypothesized that the same variants of the N-methyl-D-aspartate receptor gene that were previously associated with the age of dyskinesia onset in HD were also associated with the vulnerability for TD and not LID. Genotyping patients with LID and TD revealed, however, that these two variants were dose-dependently associated with susceptibility to LID, but not TD. This suggested that LID, TD and HD might arise from the same neuronal pathways, but TD results from a different mechanism.

[Clinical and experimental research of immunomodulatory effect of amisulpride].

Study of immunomodulatory effect of atypical antipsychotic amisulpride has revealed a positive clinical effect after 6-week therapy of schizophrenic patients regarding both positive and negative symptoms. A decrease in activity of humoral immunity factors (B lymphocytes, immunoglobulins, HLADR(+)-cells) identified among schizophrenic patients in the process of amisulpride therapy can be attributed to a positive effect optimizing the ratio Th1/Th2. Amisulpride when used under experimental conditions produced a suppression of IgM-immune response in mice of the C57BL/6J strain. This effect was more expressed in animals with aggressive behavior pattern.

[The social and occupational adaptation of schizophrenia patients with different clinical structures of the negative disorders in remission]. / Sotsial'no-trudovaia adaptatsiia bol'nykh shizofreniei s razlichnoi klinicheskoi strukturoi negativnykh rasstroistv v remiaaiiakh.

The authors examined 171 patients suffering from shift-like schizophrenia taking its course with remissions free of psychotic disorders. Negative symptoms were studied by means of an original three-dimensional scale taking into account the severity, sphere and characteristics of the mental disturbance. New data were obtained on development and time course of negative disorders at different stages of the illness. The most frequent patterns of the defects observed in remission were characterized in accordance with combination of quantitative and qualitative disorders. The basic types of compensatory-adaptation defenses were described and the structural and clinico-dynamic effects of the negative disorders on their forming was shown. The data obtained may help improve the effectiveness of rehabilitation of patients suffering from schizophrenia.

[Comparative clinical, social and work characteristics of patients with schizoaffective variants of schizophrenia]. / Sravnitel'naia klinicheskaia i sotsial'no-trudovaia kharakteristika bol'nykh s shizoaffektivnymi variantami shizofrenii.

On the basis of clinico-epidemiological, clinico-dynamic and clinico-catamnestic study of 184 patients with schizoaffective variants of schizophrenia (cyclothymia-like, affective-paranoid, hallucinatory-delirious, and with catatonic symptomatology) the authors come to the conclusion on the relative homogeneity of this cohort of patients and on the considerably frequent favourable outcomes of this disease. The variants of the disease and structure of remissions of each of the clinical variants have been compared. Assessment of inter-attack clinical characteristics and the degree of social and occupational adaptation has made it possible to divide the patients into 3 groups differing by adaptational parameters. The results obtained may be used in the development of the system of rehabilitative measures in any of the aforesaid variants of schizophrenia.