[Features of inflammatory reactions in patients with juvenile depression with a clinically high risk of psychosis]. / Osobennosti vospalitel'nykh reaktsii u patsientov s yunosheskimi depressiyami s klinicheski vysokim riskom psikhoza.

OBJECTIVE: To determine the levels of pro-inflammatory and anti-inflammatory cytokines and inflammatory markers such as C-reactive protein, leukocyte elastase, α1-proteinase inhibitor, autoantibodies to neuroantigens in the blood of patients with adolescent depression with clinical high risk for psychosis (CHR-P) and to study the relation of these biological markers to the features of psychopathological symptomatology of the patients. MATERIAL AND METHODS: Eighty young adults, aged 16-24 years, with the first depressive episode (F32.1-2, F32.38, F32.8) were studied. Based on the presence of attenuated positive symptoms in the structure of depression, all patients were divided into two groups: with CHR-P (clinical group, n=58) and without CHR-P (comparative group, n=22). The HDRS-21, SOPS, and SANS were used for psychometric assessment of the patients. Serum levels of cytokines TNF-α, IL-6, IL-8, IL-10, and concentration of C-reactive protein (CRP) were determined. Leukocyte elastase (LE) activity, α1-proteinase inhibitor (α1-PI) activity, and plasma levels of autoantibodies to S100B protein and myelin basic protein (MBP) were assessed. RESULTS: Both groups of patients were characterized by the high levels of inflammation as assessed by LE (250.5 (226.2-280.8) nmol/min·ml vs 248.3 (226.8-284.5) nmol/min·ml) and α1-PI activity (44.4 (37.5-50.1) IE/ml vs 45.2 (36.4-49.9) IE/ml). Higher levels (p<0.05) of IL-6 (1.22 (0.64-2.2) pg/ml), CRP (0.93 (0.18-3.18) mg/l), and TNF-α/IL-10 (0.34 (0.2-0.47)) were detected in the group with CHR-P. This group was also characterized by higher levels of antibodies to the S100B protein 0.78 (0.69-0.84 units of opt.density) compared with the group without CRH-P (p<0.05). In each clinical group, different correlations between clinical, psychometric and biological parameters were revealed. CONCLUSIONS: The results confirm the involvement of inflammation in the development of depression in youth and indicate a different role of the inflammatory markers analyzed in the formation of CHR-P. The differences in the spectrum of inflammatory markers in depressed patients suggest a more pronounced pro-inflammatory potential in the group with CHR-P.

[Therapeutic drug monitoring of antipsychotic drugs in routine psychiatric practice]. / Terapevticheskii lekarstvennyi monitoring antipsikhoticheskikh preparatov v povsednevnoi psikhiatricheskoi praktike.

OBJECTIVE: To evaluate the relationship between daily doses of antipsychotic drugs, their serum concentrations, and characteristics of patients treated for schizophrenia or schizophreniform disorder in day-to-day clinical practice. MATERIAL AND METHODS: A total of 187 patients were included in the study, 77 (41.1%) patients were on monotherapy, and 110 (58.9%) patients received two or more antipsychotics. Patients age was 27.8±8.1 years, and their body weight was 79.8±15.6 kg. The sample was represented mainly by young men (93.0%). The proportion of smokers was 37.4%. The appropriate HPLC-MS/MS method was used for the simultaneous analysis of 8 antipsychotics and its active metabolites. Serum concentrations of the drugs aripiprazole (ARI), chlorpromazine (CPZ), haloperidol (HAL), zuclopenthixol (ZUC), clozapine (CLO), risperidone (RIS), quetiapine (QUE), olanzapine (OLA), norclozapine (N-desmethylclozapine, NOR), 9-hydroxyrisperidone (9-OH-RIS), dehydroaripiprazole (DGA) were measured. The serum concentration/dose ratio (C/D) was employed as the primary outcome measure, as doses were not kept constant during the study. The active antipsychotic fraction (drug+active metabolite, active moiety - AM) was also evaluated for RIS and ARI. In addition, the metabolite/parent ratio (MPR) was evaluated for RIS and ARI. RESULTS: A total of 265 biological samples were obtained, 421 and 203 measurements of the concentration of drugs and their metabolites were carried out, respectively. Overall, 48% of antipsychotics levels were in the expected therapeutic ranges, 30% were below therapeutic ranges, and 22% were above them. A total of 55 patients underwent dose adjustments or drug changes due to ineffectiveness or side-effects. It has been found that smoking reduces the level of C/D for CLO (p<0.01, Mann-Whitney test). We have established that comedication with CLO significantly increases the C/D ratio of QUE (p<0.05, Mann-Whitney test). We have not revealed any influence of weight and age of the subjects on the C/D. The dose-concentration regression relationships are formalized for all AP. CONCLUSION: Therapeutical drug monitoring (TDM) is an essential tool to personalize antipsychotic therapy. Careful analysis of TDM data can contribute significantly to the study of the impact of individual patient characteristics on systemic exposure to these drugs.

[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.

[Youth-onset schizophrenia: psychopathology, clinical presentation and therapy]. / Yunosheskaya shizofreniya: osobennosti psikhopatologii, kliniki i terapii.

The paper reviews the clinical presentations and pathogenetic features of youth-onset schizophrenia with onset at the age of 16-25 years old. The clinical presentation of the disease in young people is different in comparison to adult patients. Psychopathological and biological characteristics of the first episode, the course of «progressive¼ schizophrenia and «malignant youth schizophrenia¼ in the pubertal period are described. Early diagnosis and prevention of disease manifestation are discussed. Recommendations on therapeutic measures at different stages of the endogenous process in this age are presented. The most important future goals of research in this field are formulated.

[The cytotoxic activity of natural killer cells in patients with the first episode of endogenous psychosis (a comparative study of test methods)].

Authors studied the cytotoxic activity (CA) of natural killer cells (NK) in 16 schizophrenic patients, aged from 18 to 25 years, with the first episode of psychosis. A significant decrease in CA NK was found in the total group of patients compared to healthy controls that suggested the dysregulation of natural immunity at this stage of disease. The addition of serotonin to the cell culture in vitro in concentrations 10-9 M stimulated the NK activity while the elimination of monocytes resulted in the significant reduction of CA NK. The parallel use of two methods for assessment of CA NK (a radioactive method and an easy and safe method using multifunctional particle size analyzer Multisizer MS-4) revealed similar results.

[The effect of serotonin on the cytotoxic activity of natural killer lymphocytes in patients with the first episode of endogenous psychosis].

Authors studied the level of cytotoxic activity of natural killer lymphocytes (NKCA) and the effect of monocytes, serotonin, rate of serotonin reuptake by lymphocytes and psychotropic therapy on NKCA levels in 59 male patients, aged 18-30 years, with the first episode of attack-like progressive schizophrenia (33 patients) and schizoaffective psychosis (26 patients). All patients were examined at baseline, 4 and 8 weeks after the beginning of treatment with haloperidol and clozapine. Before the treatment, the decrease of NKCA was found in a half of patients compared to controls. In other patients, the NKCA levels were high and did not differ from those in controls. The treatment resistance was estimated as 70,6% in patients with schizophrenia with initially low NKCA levels and 30,8% in patients with schizoaffective psychosis with initially low NKCA levels. During the treatment, the initially high NKCA level decreased while the initially low level increased but remained lower compared to controls. These changes suggest the active reaction from the immune system of the patient to treatment with neuroleptics. The changes of NKCA values during the treatment were reciprocally related to the maximal rate of serotonin reuptake by lymphocytes. Serotonin added to the cell culture in vitro normalized the NKCA level in cultures with- and without monocytes. This effect was revealed in both pathologies only in responders, regardless of the presence or absence monocytes, that may be explained by the presence of active serotonin receptors on the NK cell surface in these 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 characteristics of cognitive functions in patients with first episodes of endogenous psychosis.

This report presents studies of the neurophysiological correlates of the characteristics of cognitive disorders in patients with first psychotic episodes of endogenous psychosis at juvenile age. Three groups of patients were studied: those with a predominance of catatonic symptomatology (22 patients), those with a predominance of hallucinatory-delusional symptomatology (22 patients), and those with a predominance of affective-delusional symptomatology (24 patients), along with a group of psychologically healthy subjects (15 subjects). Parameters of auditory evoked potentials were analyzed using the oddball paradigm. The group with a predominance of catatonic disorders showed the greatest differences in the latent periods (LP) of the N200 and P300 components as compared with the other groups; patients with a predominance of hallucinatory-delusional symptomatology showed the most localized anomalies in the latent period of the P300 component; the group of patients dominated by affective-delusional symptomatology showed almost no increase in the latent period of the N200 component, though the extents of anomalies in the N100 component in responses to non-target signals and deviations in the P300 component were more marked than in the other groups. These characteristics of the neurophysiological correlates of cognitive functions in each group of patients supported the significance of evaluating the psychopathological structure of manifest psychotic episodes for determining the clinical typology.