Cytokine Production in Whole Blood Cells Culture of Patients with Alcohol Dependence and Autologous Plasma Oxidative Stress Markers.

We studied spontaneous production of a spectrum of proinflammatory cytokines by cultured whole blood cells from men with alcohol dependence at the stage of withdrawal syndrome and oxidative stress markers (carbonylated proteins and TBA-reactive substances) in the plasma of these blood samples. Enhanced production of cytokines by blood cells and increased concentrations of oxidative stress markers in the autologous plasma were revealed in comparison with the corresponding parameters in the control (blood from healthy men). Direct correlations were found between the levels of spontaneous cytokine production by blood cells from subjects with alcohol dependence and the concentration of oxidized proteins and lipids in autologous plasma.

Correlation of Antibodies to Neurotransmitters in the Sera of Women with Alcohol Dependence and Depressive Disorders.

Comparative analysis of blood sera from women with alcohol dependence and depressive disorders or from conditionally healthy women revealed reduced level of antibodies to dopamine, norepinephrine, serotonin, glutamate, and GABA in blood serum in women with dysthymic disorder and a depressive episode and their increased content in women with alcohol dependence in combination with depressive disorders.

[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.

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.

Cytokine mediated changes of pain sensitivity in predisposition to substance dependence.

The purpose of study was evaluation of extra and intracellular cytokine production in blood cultures and cytokine-pain relationship at different stages od addiction. Methods: Classic and multiplex enzyme immunoassay, flow, cytometry, algometry, visual analogue scale were used in 34 abusers, 12 users and 20 control subjects. Results: Cytokine profile correlated with clinical parameters and pain sensitivity in abusers (mostly IL-6 and IL-1ß). IL-10 production is increased in episodic and systematic users. Activation of intracellular IL-6 synthesis was found in users. Both parameters are expected to affect the emotional evaluation of pain. Conclusion: To assess the predisposition to substance dependence most informative are balance of extra and intracellular production of IL-6 and IL-10 and algometry.

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.

Serum levels of neurosteroids in patients with affective disorders.

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

Association of Cytokine Production with Hormone Level and Sensory Responses during the Formation of Psychoactive Drug Addiction in Men.

We performed immunophysiological examination of 144 men aged 17-25 years, patients with psychoactive substance dependence, episodic psychoactive drug users, and conditionally healthy individuals. Associations of proinflammatory cytokine production with age, sex, hormone levels, and olfactory and nociceptive indices were revealed in cases of psychoactive drug use and formation of addiction. Predictive models based on the use of androstenone aversion, pressure algometry testing, and immunological parameters were proposed.

[Influence of Adamantilbromphenylamine on Parameters of Immunity and Symptoms of Asthenia in Patients with Non-Psychotic Mental Disorders].

OBJECTIVE: Our aim was to assess effect of antiasthenic drug adamantilbromphenylamine on the immune system and symptoms of asthenia in patients with non-psychotic mental disorders and to reveal possible criteria for prediction of treatment efficiency. METHODS: Uncontrolled study with interrupted time series was carried out. According to efficiency of treatment patients were divided into two groups (group 1 (n=21)--very much improved and much improved; group 2 (n=9)--minimally improved). Adamantilbromphenylamine was administered to patients as a monotherapy 100 mg a day for 28 days. Examination was conducted before and after therapy. Severity of asthenic symptoms according to MFI-20 scale was identified; cellular and humoral immunity parameters, mitogen-induced production of interleukins (IL) 1ß and IL 4 by immunocompetent cells of patients were assessed. RESULTS: 30 patients with non-psychotic mental disorders with predominance of asthenic symptomatology in clinical picture of the disease were examined. Before therapy every proband had over 60 points across 5 items of MFI-20 scale. As compared with control decrease of number of lymphocytes of CD3+-, HLA-DR+, CD16+-phenotypes; increase in the ratio of CD4+/CD8+; concentration of serum IgM; phagocytic activity of neutrophils were revealed. In the end of therapy in group 1, sum total of points of asthenia decreased up to 26(23-37) (p<0.001); in group 2--up to 57(47-61). Only in group 1 positive dynamic of immune parameters was revealed. It was shown that baseline level of proinflammatory cytokine IL 1ß in group with apparent therapeutic effect of the drug was reliably lower, than in group with minimal improvement (p=0.005). These differences remained also after course of therapy (p=0.042). CONCLUSION: Interrelationship of clinical-immunological effect of adamantilbromphenylamine has been revealed; intensity of production of IL 1ß may be considered as a criterion of prognosis of efficiency of treatment with adamantilbromphenylamine in patients with non-psychotic mental disorders.

[Characteristics of Membrane-Bound Pool of Leukocyte Lactate Dehydrogenase in Healthy Men of Different Age].

The study of isoenzymes of leucocyte lactate dehydrogenase (LDH) in healthy men of different age showed a decrease in the membrane-bound pool of LDH-1 and LDH-4 in 40-year-old males as compared with 20-year-old males. The results indicate an age-related reduction of the reserve membrane-bound pool of several LDH isoforms.

[Relationship between sex hormones, pheromones, interleukine production and risk of drug dependence].

Serum steroid hormones and production of proinflammatory cytokines in 109 individuals with substance dependence, 34 occasional users and 78 control subjects were examined. Immaturity of gender as a risk factor for the formation of drug dependence associated with infectious and inflammatory processes was estimated by olfactory pheromone tests.

Neurophysiological patterns of search and creative behavior in patients with psychoactive substance-induced disorders.

The correlation between search and creative behavior with parameters of bioelectric brain activity was observed in patients with addictive disorders. The prevalence of α- and θ-activities in the parietal-temporal-occipital areas of the cortex and increased θ-activity in the right hemisphere in addiction patients with high search and creative activities were associated with enhanced high-frequency activity in these brain areas. These changes can reflect the formation of a focus of pathologically increased excitation related to the pathogenic mechanisms of addictive disorders.

Ratio of antibodies to neurotransmitters in the serum of students, occasional drug users.

The survey included volunteer students of secondary and higher educational institutions. Two groups have been formed based on the results of clinical and laboratory studies. Group 1 comprised students occasionally using cannabinoids and amphetamines (risk group for psychoactive substances addiction) and group 2 included students who do not use drugs. The serum level of autoantibodies to norepinephrine, dopamine, and serotonin was reduced in the risk group.

[Prevalence and risk factors of non-suicidal self-injury behavior]. / Rasprostranennost' i faktory riska nesuitsidal'nogo samopovrezhdayushchego povedeniya.

The prevalence of non-suicidal self-injury (NSSI) behavior in adolescents has increased significantly in the early 21st century. The phenomenon of NSSI behavior has become one of the key health problems in the field of adolescent psychiatry and psychology over the past decade worldwide. However, the social characteristics and factors influencing NSSI are very different in different regions of the world. Studies of self-harming behavior indicate that the upward trend is almost equally relevant for developing and developed countries. To date, the methodological basis for the diagnosis of NSSI has not been sufficiently developed in the Russian Federation, there are only some studies of NSSI both from an empirical perspective and in the context of the search for risk factors, causes and functions, models of comorbidity with mental disorders.

[Cerebral hemodynamic disorders in patients with schizophrenia with concomitant metabolic syndrome]. / Tserebral'nye gemodinamicheskie narusheniya u bol'nykh shizofreniei s metabolicheskim sindromom.

OBJECTIVE: To identify the differences or comparability of parameters of cerebral hemodynamics between patients with schizophrenia with or without concomitant metabolic syndrome (MS). MATERIAL AND METHODS: The study included 94 patients with schizophrenia (48 men and 46 women). A control group consisted of 40 mentally and somatically healthy individuals (17 men and 23 women) comparable in sex and age to the main group of patients. The diagnosis of metabolic syndrome was carried out according to the criteria of the International Diabetes Federation (IDF). Assessment of cerebral hemodynamics was carried out by 4 - channel rheoencephalography (REG) at rest with closed eyes. Data analysis was carried out using the Kraskel-Wallis ANOVA criterion with the procedure of automatic a posteriori pairwise comparison, the χ2 criterion and Spearman correlation analysis. RESULTS: According to the IDF criteria, 37 (39.4%) patients were diagnosed with MS. REG results revealed significantly (p<0.05) lower indicators of blood filling in the carotid basin, elasticity of the wall of the main arteries, the tone of small-caliber arteries and arterioles, as well as higher values of the tone of medium-caliber arteries in the carotid and vertebrobasilar basins, in both groups of patients with schizophrenia compared with the control group. In patients with schizophrenia with MS, compared with patients without MS, there were lower indicators of blood filling (p=0.044 and p=0.016) and elasticity of the wall of the main arteries (p=0.044 and p=0.028) in the carotid basin on the left and right sides. CONCLUSION: The presence of MS in patients with schizophrenia was accompanied by more pronounced disorders of cerebral blood flow in the form of a decrease in blood filling and elasticity of the wall of the main arteries in the carotid basin. The results indicate that patients with schizophrenia with MS should be considered as a group at increased risk of cerebrovascular diseases.

[Electroencephalographic differences in patients with paranoid schizophrenia with or without a history of suicide attempts]. / Elektroentsefalograficheskie razlichiya u bol'nykh paranoidnoi shizofreniei s nalichiem ili otsutstviem suitsidal'nykh popytok v anamneze.

OBJECTIVE: To identify differences in electroencephalographic parameters in schizophrenia patients with and without a history of suicide attempts. MATERIAL AND METHODS: Eighty-seven inpatients (50 men and 37 women) with paranoid schizophrenia were examined. Suicidal attempts in the anamnesis of patients were verified by a psychiatrist on the basis of clinical interviewing. The severity of psychopathological symptoms was assessed using The Positive and Negative Syndrome Scale (PANSS) based on a five-factor model. Electroencephalogram (EEG) parameters were recorded and evaluated using a 16-channel encephalograph. A clinical and quantitative analysis of the recordings was carried out with the calculation of absolute spectral power indicators for theta, alpha and beta rhythms, as well as the severity of the activation reaction (Berger effect). RESULTS: Significantly higher rates of the PANSS depression factor were revealed in patients with a history of suicide attempts (p=0.016). Clinical analysis of EEG changes did not reveal any significant differences between the groups (p>0.05). The spectral analysis of the EEG showed significant differences only in the spectral power of the beta rhythm in the central (p=0.048) and occipital (p=0.021) leads with closed eyes, which was lower in the group with a history of suicide attempts. The degree of alpha rhythm depression in the occipital leads was also significantly lower in this group (p=0.016). The regression analysis showed that significant correlates of suicidal attempts in patients with paranoid schizophrenia are the PANSS depressive factor (t=2.784; p=0.016) and a deficiency in the activation response to EEG (t=-2.035; p=0.045). CONCLUSION: The results complement previous studies on the relationship between suicidal attempts, clinical symptoms and neurophysiological features of the functioning of the brain of patients with paranoid schizophrenia.

[Growth factors PDGF-AA, PDGF-BB and BDNF as potential differentiating biomarkers of unipolar and bipolar depression]. / Faktory rosta PDGF-AA, PDGF-BB i BDNF kak potentsial'nye differentsiruyushchie biomarkery monopolyarnoi i bipolyarnoi depressii.

OBJECTIVE: To establish the differences and identify the prognostic value of biological markers - platelet growth factors PDGF-AA, PDGF-BB and brain-derived neurotrophic growth factor (BDNF) - for the differential diagnosis of patients with unipolar and bipolar depression using machine learning. MATERIAL AND METHODS: The study included 79 patients aged 48 [34; 57] years, including 35 people with bipolar depression (ICD-10. F31) and 44 people with unipolar depression (F32-33). Clinical assessment of the patients' condition was carried out using the Hamilton Depression Rating Scale (HDRS-17) and the Hamilton Anxiety Rating Scale (HARS). The concentration of growth factors in the blood serum of patients was determined using multiplex analyzers Magpix and Luminex 200 (Luminex, USA). To build a predictive model, the support vector machine was used. RESULTS: Patients with bipolar depression showed statistically significant higher concentrations of PDGF-AA and PDGF-BB, as well as lower concentrations of BDNF. When constructing a predictive model, it was possible to separate patients with unipolar and bipolar depression according to all three biomarkers; the sensitivity and specificity of the model were 0.96±0.06 and 0.95±0.05, respectively. CONCLUSIONS: The study of concentrations of BDNF and platelet-derived growth factors shows statistically significant differences in indicators in the case of unipolar and bipolar depression, which can potentially be used as prognostic biomarkers for differential diagnosis in appropriate clinical cases.

[The relationship between the functional state of the brain and clinical and constitutional factors in schizophrenia]. / Svyaz' funktsional'nogo sostoyaniya golovnogo mozga s klinicheskimi i konstitutsional'nymi faktorami pri shizofrenii.

OBJECTIVE: To establish the relationships of functional changes of the brain of patients with schizophrenia with clinical manifestations of the disease and their constitutional and morphological features. MATERIAL AND METHODS: One hundred and eighteen patients with schizophrenia (64 men and 54 women), aged 33 [29; 40], years were examined. The following clinical and dynamic parameters were used: age of manifestation of the disease, duration of the disease, severity of clinical and psychopathological symptoms according to the PANSS. The anthropometric examination of patients was carried out according to V.V. Bunak's method in V.P. Chitetsov's modification for adult samples with calculation of Rees-Eysenk and Tanner indices. The EEG was recorded and analyzed in a state of calm, relaxed wakefulness with closed eyes with the calculation of the absolute spectral power for theta (4-7 Hz), alpha (8-13 Hz) and beta (14-30 Hz) rhythms. RESULTS: Significant (p<0.05) direct correlations between the age of the disease manifestation and the spectral power of the beta rhythm in the frontal leads (Fp1, Fp2, F3 and F4) were revealed. Inverse correlations (p<0.05) were found between the duration of the disease in patients with schizophrenia and the spectral power of the alpha rhythm in the left temporal (T3) and right central leads (C4), the spectral power of the beta rhythm in the parietal-occipital (P3, P4, O1,O2) and temporal leads (T3, T4, T5), the spectral power of the theta rhythm in the left occipital (O1) and posterior temporal leads (T5). Significant inverse correlations were also found between the Tanner index and the spectral power of the alpha rhythm in the frontal and temporal leads, between the Rees-Eysenk index and the spectral power of the theta rhythm in the frontal leads. CONCLUSION: The results indicate the presence of the conjugation of functional changes in the brain of patients with schizophrenia with clinical manifestations of the disease and their constitutional and morphological features. Thus, the assessment of the functional state of the central nervous system in patients with schizophrenia is an important component of the diagnostic search.

[Associations between components of metabolic syndrome and cognitive impairment in patients with schizophrenia]. / Svyazi mezhdu komponentami metabolicheskogo sindroma i kognitivnymi narusheniyami u bol'nykh shizofreniei.

OBJECTIVE: To study the relationship between the individual components of the metabolic syndrome and cognitive dysfunction in patients with schizophrenia. MATERIAL AND METHODS: A total of 133 patients with schizophrenia were examined. To assess cognitive functioning, the Brief Assessment of Cognition in Schizophrenia (BACS) was used. The components of the metabolic syndrome were determined in accordance with the criteria of the International Diabetes Federation. RESULTS: Hyperglycemia in patients with schizophrenia led to a decrease in cognitive functioning in two domains: verbal fluency (ß=-10.67; p=0.019) and attention stability (ß=-9.519; p=0.043). Abdominal obesity was associated with lower indicators of executive functions (ß=-8.856; p=0.026). CONCLUSION: It is assumed that drug treatment of some components of the metabolic syndrome may affect cognitive functions in patients with schizophrenia.

[EEG features during olfactory stimulation in drug dependence persons].

Power spectra analysis EEG was used for baseline interval and during olfactory stimulation in drug dependence and healthy persons. Intergroup differences of EEG spectra were related with enhancement of cortex biopotential power in narcological patients at parietal and temporal sites. Interhemispheres features of frequency bands contribution in EEG spectra were identified. Increased biopotential power in drug dependence persons was observed at left temporal hemisphere in high-frequency bands in baseline interval and during olfactory stimulation. Increased power of alpha activity was typical for right temporal hemisphere in narcological patients as compare to healthy persons. Detected neurophysiological patterns may be related with psychological and behavioral features of addictive disorders.