[Activity of enzymes of glutamate, energy and glutathione metabolism in the first juvenile depression with attenuated symptoms of schizophrenia]. / Aktivnost' fermentov glutamatnogo, energeticheskogo i glutationovogo obmena pri pervykh yunosheskikh depressiyakh s attenuirovannymi simptomami shizofrenii.

OBJECTIVE: To reveal clinical and biological correlations in patients with attenuated symptoms of schizophrenia in the first juvenile depression, namely, the correlation between SOPS and HDRS-21 scores and the levels of activities of glutathione, glutamate and energy metabolism enzymes in the blood of patients. MATERIAL AND METHODS: The study included 81 young men, aged 16-25 years, with the first depressive episode (ICD-10 items F32.1, F32.2, F32.38, F32.8), from which the groups with predominantly attenuated positive symptoms (group 1, n=36) and predominantly attenuated negative symptoms (group 2, n=24), and a group without attenuated schizophrenia symptoms (group 3, n=21) were selected. The control group consisted of 20 mentally healthy men aged 19-25 years. Psychometric methods (SOPS and HDRS-21) and psychopathological methods were used. Activities of cytochrome c oxidase (COX), glutamate dehydrogenase (GDH), glutathione reductase (GR), and glutathione S-transferase (GST) enzymes were determined spectrophotometrically in blood cells. RESULTS: When compared with the control group, activities of platelet GDH, GR, and GST (before and after treatment) were significantly reduced in groups 1, 2, 3 (Mann-Whitney U-test, p<0.0002, p<0.001 and p<0.0001, respectively); the activity of erythrocyte GST was reduced in group 1, and the activities of erythrocyte GR and GST were reduced in group 3 (p<0.05). In group 1, baseline COX (before treatment) was positively correlated with post-treatment SOPS-N scores (R=0.580, p=0.0003), while baseline erythrocyte GR was negatively correlated with post-treatment HDRS-21 scores (R=-0.591, p=0.0004). In group 2, baseline GDH levels were positively correlated with post-treatment scores on SOPS-P (R=0.425, p=0.0384), SOPS-N (R=0.500, p=0.0129), SOPS total (R=0.526, p=0.0083) and HDRS-21 (R=0.479, p=0.0180). CONCLUSION: The discovery of clinical and biological correlations in groups of patients with attenuated symptoms of schizophrenia in the structure of juvenile depression contributes to understanding the pathogenetic mechanisms of the formation of a high clinical risk of psychosis and contributes to the search for markers of the initial stages of schizophrenia.

[The activity of enzymes of glutathione metabolism in blood cells of patients with a high risk of manifestation of endogenous psychoses and patients with the first psychotic episode]. / Aktivnost' fermentov glutationovogo obmena v formennykh élementakh krovi u patsientov s vysokim riskom manifestatsii éndogennykh psikhozov i bol'nykh s pervym psikhoticheskim pristupom.

AIM: To assess the activity of glutathione reductase (GR) and glutathione-S-transferase (GST) in blood cells of patients at clinical high-risk (HR) state for psychosis, in first-episode patients with schizophrenia and schizoaffective disorder (SD), and control group, and to seek correlations of these biochemical parameters with clinical assessments in patients. MATERIAL AND METHODS: The study included male patients at HR (n=21, 16-25 years old), first-episode patients with schizophrenia (F20, n=14, 18-25 years old) and SD (F25, n=20, 16-25 years old), and 12 people of the control group (19-25 years old). Psychometric scales (SOPS, HDRS, and PANSS) and psychopathological methods were employed. GR and GST enzymatic activities were determined spectrophotometrically. RESULTS: The activities of platelet GR and GST in all groups of patients both before and after treatment were lower than in controls (p<0.01). The platelet GST activity was lower in patients at HR compared to patients with schizophrenia before treatment and lower than in patients with SD after treatment (p<0.05), it was higher in patients with schizophrenia than in patients with SD before treatment (p<0.05). Erythrocyte GST activity in patients with HR was lower than in patients with SD after treatment, and in the latter it exceeded that in patients with schizophrenia and controls (p<0.05). Complex and different patterns of changes in the activities of erythrocyte and platelet GR and GST in patients with schizophrenia spectrum disorders, occurring both before the first psychotic episode in the initial stage of disease, and in the first-episode patients, were detected. CONCLUSION: The activity of glutathione-converting enzymes in endogenous psychoses of the schizophrenic spectrum, including its early stages, can be used as a biomarker for predicting the development of psychosis, the course of disease, and as criteria for evaluation of therapeutic response to antipsychotic treatment.

[Glutathione reductase and glutathione-S-transferase in blood cells in schizophrenia and schizophrenia spectrum disorders]. / Glutationreduktaza i glutation-S-transferaza v formennykh élementakh krovi pri shizofrenii i rasstroistvakh shizofrenicheskogo spektra.

AIM: To compare glutathione reductase (GR) and glutathione-S-transferase (GST) enzymatic activities in blood cells (erythrocytes and platelets) of patients with schizophrenia spectrum disorders and in the control group and to search for correlations of these biochemical parameters with clinical psychiatric assessments of the patient. MATERIAL AND METHODS: The study included patients (97 men) with schizophrenia spectrum disorder (schizophrenia and schizoaffective disorders) in an acute state of exacerbation of psychotic symptoms and 33 men without mental pathology. Symptom severity was measured with the PANSS before and after antipsychotic therapy. GR and GST activities were determined spectrophotometrically. RESULTS: There were no significant between-group differences in the activities of erythrocyte GR and GST. In platelets, the GR activity was lower in all patients' groups than in controls, whereas the GST activity in patients with schizophrenia relapses and in patients with schizoaffective disorder (SD) was lower than in controls (p<0.05) both before and after treatment. Differences between subgroups of first-episode patients (schizophrenia and SD) and patients with schizophrenia relapses were found not only in the levels of erythrocyte and platelet GR and GST activities, but also in the changes of these enzymatic activity levels under antipsychotic treatment, as well as in links binding these enzymatic activities and PANSS scores. CONCLUSION: The decreased level of GR and GST, the glutathione-dependent enzymes, contributes to the reduction of antioxidant defense in schizophrenia spectrum disorders. The correlations linking the basal levels of GR and GST activities with the results of clinical assessments after treatment allow us to consider these parameters as potential biomarkers for predicting treatment response.

[A differential approach to the improvement of prevention and correction of neuroleptic side extrapyramidal disorders with pantogam activ in patients with schizophrenia]. / Differentsirovannyi podkhod k usovershenstvovaniyu metodov preduprezhdeniya i korrektsii neirolepticheskikh pobochnykh ekstrapiramidnykh rasstroistv preparatom pantogam aktiv u bol'nykh shizofreniei.

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.

MRI Study for the Features of Brain Conduction Pathways in Patients with an Ultra-High Risk of Endogenous Psychoses.

Diffusion parameters of brain tracts (n=18) were studied in 27 men with ultra-high risk of endogenous attack-like psychoses and 27 mentally healthy men of the same age group (fractional anisotropy; and average, radial, and axial diffusion). Correlation analysis was performed between these parameters and severity of mental disorders (SOPS scale). The indexes of radial diffusion and axial diffusion were shown to change in the left anterior thalamic radiation and right posterior cingulum bundle, respectively. Our results are consistent with published data that disturbances in the frontal and temporal lobes play an important role in the pathogenesis of schizophrenia. The degree of mental disorders correlated with diffusion parameters in the left and right anterior cingulum bundle.

[Cognitive insight and dynamics of indicators of ultra-high risk for schizophrenia in young patients with non-psychotic forms of mental disorders]. / Kognitivnyi insait i dinamika simptomov ul'travysokogo riska po shizofrenii u bol'nykh s nepsikhoticheskimi formami psikhicheskikh rasstroistv v yunosheskom vozraste.

AIM: To determine characteristics of cognitive insight and its relationship with the severity and dynamics of symptoms in patients with ultra-high risk for schizophrenia during treatment. MATERIAL AND METHODS: The study included 76 young patients with subpsychotic symptoms corresponding to criteria of ultra-high risk for psychosis and 55 healthy subjects. Patients were examined using psychopathological analysis and a battery of psychological tests. RESULTS AND CONCLUSION: Cognitive insight, although not linked to objective indicators of ultra-high risk for schizophrenia, predicts a decline in both total score of SOPS, and in the Positive symptoms subscale during the treatment of patients with personality disorders. In the groups with mood disorders and schizotypal disorder, cognitive insight reflects more anxiety and uncertainty related to patients' experience rather than the true conscious criticism. In the group with schizotypal disorder, it is also closely related to the severity of subjective psychopathological symptoms.

[The dynamics of psychopathological symptoms of ultra high risk for psychosis in young patients with non-psychotic mental disorders].

OBJECTIVE: Based on the results of 5-year follow-up study, to describe the dynamics of psychopathological symptoms in young patients with non-psychotic forms of mental diseases met the criteria of ultra-high risk for schizophrenia who received preventive psychopharmacotherapy. MATERIAL AND METHODS: The study included 32 young men, aged 16--25 years, presented with the symptoms of ultra-high risk of schizophrenia during the first hospitalization in 2009--2011. Follow-up was carried out in 2014--2015 (mean follow-up 5.79±0.36 years). According to ICD-10, patients were stratified into 3 groups: mood disorders, personality disorders and schizotypal disorders. RESULTS AND CONCLUSION: According to the characteristics of subsequent development of these disorders, four types were singled out: mechanisms of the development of acute sensitive delusions (I), interpretative delusions (II), catatonic disorganization (III) and cognitive disorders pathognomonic for schizophrenia spectrum disorders (IV). Correlations between these types and nosologic disorders and their different reversibility under treatment were found. These types can be considered as predictors of outcome over the follow-up period.

[Risk of manifestation of endogenous psychosis in patients with nonpsychotic mental disorders of juvenile age].

OBJECTIVE: To identify people at high risk of endogenous psychosis in patients of juvenile age with nonpsychotic mental disorders. MATERIAL AND METHODS: Authors examine 49 patients of juvenile age with symptoms of nonpsychotic mental disorders (ICD-10 diagnoses of mood disorder, personality disorder or schizotypal disorder). RESULTS: In all cases, symptoms related to signs of the premorbid stage of endogenous psychosis (schizophrenia and schizoaffective psychosis) were identified. After psychopharmacological treatment, an incomplete (<30%) reduction of psychopathological disorders recorded at admission was found in 24.5% of patients. Based on the response of patients to treatment, family history (having a first-degree relative with psychosis) and the diagnosis of mental disorder, it was singled out "high-risk" (20.4% patients) and "ultra-high risk" (18.4%) states for psychosis. CONCLUSION: In light of these findings, the necessity of a longitude prospective study of these patients and pharmacological interventions in outpatient conditions is discussed.

[Features of the immune system and the risk of endogenous psychosis at juvenile age].

OBJECTIVE: To study an immunological profile at prodromal and manifesting stages of endogenous juvenile psychosis. METHODS: Authors studied 77 patients, aged from 16 to 25 years. Patients were stratified into 2 groups. The first group included 39 patients without psychotic symptoms (prodromal group) and the second one -- 38 patients with the first episode of psychosis (psychotic group). A complex of immunological parameters included phagocyte activity, cytotoxic activity, natural killer lymphocytes, production of interleukins (IL-1, IL-4, IL-10 and γ-interferon), content of circulating immune complexes. These parameters were measured at baseline and after treatment. RESULTS: The changes in the immune system emerged at the very early stages of the disease. There was the activation of proinflammatory and anti-inflammatory interleukins, decrease in the phagocyte index and cytotoxic activity of natural killer lymphocytes. The high activity of IL-10 production, decreased levels of the cytotoxic activity of natural killer lymphocytes and reduced phagocyte index as well as the accumulation of circulating immune complexes are maintained during psychosis. CONCLUSIONS: The authors recommend to use immunomodulating drugs, along with psychotropics, at the very early stages of the disease to prevent poor outcome.

[Glutamine synthetase-like protein, glutamate dehydrogenase, and cytochrome c-oxidase in platelets of patients with the first episode psychosis in the course of treatment].

The authors searched for correlations between amounts of platelet proteins and results of psychometric tests in patients with the first episode psychosis (schizophrenia, schizoaffective psychosis) in the course of their combined antipsychotic treatment with haloperidol and clozapine. Psychometric evaluations (PANSS, BPRS) and analyses of platelet enzymes - glutamine synthetase-like protein (GSLP), glutamate dehydrogenase (GDH), and cytochrome c-oxidase (COX) - were carried out before, during, and after the treatment. These proteins were also analyzed in matched controls. All the parameters comprised a database, followed by statistical data processing using Statistica 6.0 (StatSoft) software, nonparametric statistics module. The patients before the treatment, when compared with controls, demonstrated significantly decreased COX activity (p=0,0000001) and increased GSLP amount (p=0,006) with a positive correlation between GSLP amount and PANSSneg (R=0,34, p<0,01). Those patients who displayed initially low COX activity (below median) demonstrated significant increase in COX activity after the treatment. Negative correlations were revealed between COX activity and PANSS, PANSSpsy scores during the treatment, i.e. the lower was COX activity, the more severe syndromes were observed. Negative correlations were found between the initial COX activity and PANSS, PANSSpsy, BPRS scores after the treatment, i.e., the higher was COX before the treatment, the less prominent syndromes were observed after the treatment. Significantly more "non-responders" by PANSSneg were found among the patients with low GSLP level (below median) than their calculated expected amount. The COX activity measured before the treatment was significantly lower in patients with schizophrenia than in patients with schizoaffective disorder (SAD) (p=0,038). In SAD patients, the initial COX activity was negatively correlated with PANSSpsy and BPRS scores after the treatment (R=-0,5, p=0,02), i.e. the lower was the COX the activity before the treatment, the more prominent syndromes were observed after the treatment.

[The state of the immune system in endogenous mental diseases with pronounced affective disorders].

Parameters of innate and adaptive immunity were studied in the blood serum of 180 patients, aged 15-25 years, with different endogenous mental diseases with depressive and mania disorders in the clinical picture (affective psychoses (29 patients), schizoaffective psychoses (106 patients) , slow-progressive schizophrenia (23 patients) and intermittent-progressive schizophrenia (22 patients)). The activation of innate immunity (the increase in the degranulation activity of leukocyte elastase (LE) and functional activity of alpha-1-proteinase inhibitor (α1-PI) were found in all the diseases. The increase in disease severity (from affective disorders to intermittent-progressive schizophrenia) was correlated with the significant elevation of LE activity. The LE activity did not depend on the polarity and severity of affective pathology in each diagnostic group. The mean levels of autoantibodies to the nerve growth factor and the myelin basic protein did not differ from the control values in all the groups of patients.

Dynamics of cognitive anomalies in patients with first episodes of juvenile endogenous psychosis.

The therapeutic dynamics of neuropsychological and neurophysiological markers of impairments to cognitive functions were studied in groups of patients with first episodes of juvenile endogenous psychosis (90 patients). At the initial stage of remission, subjects were found to show improvements in processes associated with voluntary regulation of cognitive functions (due to the activity of extensive networks of cortical and subcortical structures), while more automatic processes (associated mainly with the temporal areas of the brain) remained abnormal. Changes in neurocognitive anomalies during the onset of remission were also identified in groups of patients in whom episodes had different syndromal structures - catatonic, hallucinatory-delusional, and affective-delusional.

[The dynamics of neurocognitive functions in patients with the first psychotic episode of endogenous psychosis manifested in the juvenile age].

The dynamics of neuropsychological and neurophysiological markers of cognitive functions was analyzed in the groups of the first-episode young male patients. Totally 90 patients have been studied. At the early stage of remission, the improvement of the processes associated with voluntary regulation of cognition caused by the activity of the wide circuit of cortical and subcortical structures was found. At the same time, the more automated processes related mostly with the temporal brain areas remained abnormal. The peculiarities of neurocognitive dynamics during the development of the remission were revealed in the groups of patients with different syndrome structure of the first episode (catatonic, delusion/hallucination, affective-delusion).

[Neurophysiological abnormalities in the P300 paradigm as endophenotypes of schizophrenia].

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.