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We aimed to screen children aged 18-48 months in the general population of nine Russian regions for risk of mental, behavioral and developmental disorders (MBDDs) including autism spectrum disorders (ASD) using an original screening tool. The prevalence of the risk for MBDDs is 1307:10,000 (13.07%), the prevalence of clinically verified cases of MBDDs is 151:10,000 (1.51%), whereas the prevalence of ASD among them is 18:10,000 (0.18%). Basing on our results, the screening procedures are already integrated into the Russian primary care system since the end of 2019. Screening of the risk for MBDDs including ASD in Russia among children in the general pediatric population is a promising area of preventive medicine.

Introduction: While chronic inflammation and enhanced imbalance of pro- and antioxidant, including glutathione-dependent, systems contribute substantially to pathogenesis of mental disorders in old age, extent of oxidative stress and degree of inflammatory processes severity are varying among patients with late onset schizophrenia. Objectives: Revealing various phenotypes in patients with late onset schizophrenia basing on measurement of activity levels for blood glutathione-dependent enzymes and inflammation markers and analysis of their links with clinical features of the patients. Methods: Of 59 studied women patients 34 were with late onset (after 40 years) and 25 with very late onset (after 60 years) schizophrenia or schizophrenia-like psychoses (F20; F22.8; F25; F23; F06.2 by ICD-10). 34 mentally healthy women elder than 50 years comprised controls. Glutathione reductase (GR), glutathione-S-transferase (GST), neutrophil elastase (NE), and α1-roteinase inhibitor (α1-PI) activities were measured in blood. PANSS, CDSS and CGI-S were used to assess the severity of psychotic symptoms, depression and treatment effectiveness. Results: In the whole group of patients, GR was lower (p <0.05), and α1-PI was higher (p <0.0001) than in control group. Clustering the patients by their biochemical and immunological signs revealed two clusters (C1, n=34, and C2, n=25) significantly differing by GST (p <0.0001), NE (p <0.0001), and α1-PI (p <0.001) activities. As compared with controls, GST and α1-PI were higher (p <0.05 and p <0.0001), and NE was lower (p <0.05) in C1. As compared with controls, GR activity was lower (p <0.05), NE activity was higher (p <0.001), and α1-PI activity was much higher (p <0.001) in C2. Patients of C1 and C2 did not differ in age, diagnosis, severity of the disease, but differed in clinical features of the course of the disease: significantly more patients with very late onset schizophrenia (76%) were met in C1 (χ2=13.41, p <0.001). Also, different clinical-biological correlations were found in these clusters. Particularly, negative correlations of baseline NE activity with PANSS general psychopathology subscale scores (R=-0.39, p <0.05) and with total PANSS scores (R=-0.39, p <0.05) were found in C1. Positive correlation of GST activity with PANSS positive subscale score was found in C2 (R=0.43, p <0.05). Conclusions: The revealed clusters differ in the extent of the glutathione antioxidant system impairment and in levels of the immune response markers. The revealing of the patient subgroups on the basis of biological markers reflecting impairments in metabolic and immune systems can represent interest in the search for individual treatment approaches. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: The studies on various groups of patients with schizophrenia revealed impairments in immune system, glutamatergic, and antioxidant systems contributing substantially in schizophrenia pathogenesis. Objectives: To search for links between the activities of platelet enzymes involved in glutamate and glutathione metabolism and monocytes' subpopulation compositions in patients with schizophrenia and to identify possible correlations of the biomarkers with clinical data. Research objectives: determination of subpopulation ratio of monocytes; measurement of the activity levels of glutamate dehydrogenase (GDH), phosphate-activated glutaminase (PAG), glutathione reductase (GR) and glutathione S-transferase (GST) in blood platelets; search for correlations between these parameters and the scores by psychometric scales. Methods: The study included 36 women aged 16-45 years with acute schizophrenia hospitalized in the Mental Health Research Centre with their current condition assessed as depressive-delusional. The control group consisted of 17 women 18-45 years old without somatic or mental pathology. GDH, PAG, GR and GST activities were measured by spectrophotometric methods, and numbers of monocyte subpopulations - "classical", "intermediate", "non-classical" - by flow cytometry. The Hamilton Depression Rating Scale (HAMD-17) was used to assess depression severity. The data was processed using the Statistica 8.0 software. Results: The detected changes in monocyte subpopulations' composition towards the increase in the proportion of cells having a pro-inflammatory phenotype (CD14++CD16+ "intermediate") indicated the activation of inflammatory reactions. Also, the activities of platelet enzymes of glutathione metabolism (GR and GST) were significantly decreased (p<0.05). Moreover, GDH and GST activities significantly correlated with the scores by HAMD-17 (r=0.40, p=0.022 and r=0.45, p=0.030, respectively). The results indicate the presence of pathological inflammatory process, the decrease in activities of glutathione antioxidant metabolism enzymes and a link to glutamate metabolism involvement (GDH) in the studied patient group. Conclusions: The identified redistribution in the monocyte subpopulations' composition and decrease in the activity of enzymes involved in glutamate metabolism and antioxidant system indicate the involvement of the immune, glutamate and antioxidant systems in the pathogenesis of schizophrenia and may reflect a functional interaction between these systems. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: Impairments in energy metabolism, glutamate neurotransmitter and antioxidant systems contribute substantially in development of schizophrenia spectrum disorders, especially in late-onset psychosis (LOP). Objectives: Revealing subgroups of patients with LOP by determining activity of platelet enzymes of energy, glutamate, and glutathione metabolism. Methods: 62 women of 52-89 years old were studied, with late onset schizophrenia spectrum disorders (F20.0, F25, F22.0, F06.2 by ICD-10). PANSS with its subscales was used to assess the severity of psychotic symptoms. Scores by PANSS and activity levels of platelet cytochrome c -oxidase (COX), glutamate dehydrogenase (GDH), glutathione reductase (GR) and glutathione-S-transferase (GST) were evaluated twice: before and on the 28-th day of antipsychotic treatment. Activities of COX, GDH, GR, and GST were measured in 37 women of 50-84 years old comprising the control group. Results: Clustering of patients by the enzymatic activities resulted in 2 clusters (C1 and C2) significantly different by COX and GST (p<0.001). In C1 (n=40), as compared with control, reduced level of GDH activity before and after treatment (p=0.049 and p=0.032, respectively) and a reduced level of GR activity before treatment (p=0.026) were revealed. In C2 (n=22), as compared with the control, COX activity was increased before and after treatment (p=0.0001), GDH activity was decreased before and after treatment (p=0.0002 and p=0.0001, respectively), and GST activity was decreased before and after treatment (p=0.029 and p=0.0029, respectively). GR activity was not significantly changed in both clusters. Significant correlations were found between enzymatic activities and scores by psychometric scales: in C1, GR activity positively correlated with the score reduction (delta) by PANSS-Pos (R=0.45, p=0.004), by PANSS-Psy (R=0.44, p=0.005), and by PANSS (R=0.47, p=0.002), and GST activity – with the score reduction by PANSS-Psy (R=0.315, p=0.048). In C2 (n=22), GDH activity negatively correlated with the score reduction by PANSS-Pos (R=-0.41, p=0.050) and by PANSS (R=-0.49, p=0.021). Conclusions: The different correlations revealed in two separated clusters between enzymatic activity levels and clinical measures characterizing the antipsychotic treatment efficacy will allow us to approach differentiated predicting the effectiveness of pharmacotherapy using the biochemical parameters. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: Basing on our previous findings of significant additional gain obtained from usage of adjunctive antioxidant medicine added to antipsychotic+antidepressant therapy in late-onset schizophrenia-like psychoses (LOP), the group often suffering of comorbid pathologies and experiencing substantial side-effects of drugs, we spred our approach to try "metabolic" medicines as adjunctives in LOP. Objectives: To reveal biochemical parameters of the blood cells which might be used for distinguishing subgroups of patients suffering with LOP for whom various adjunctive therapy (antioxidant, metabolic) would be advantageous. Methods: The study included 59 patients 50-89 years old, with LOP (onset after 40 years), and 38 healthy peoples 51 – 84 years old. The activities of glutamate dehydrogenase (GDH), glutathione reductase (GR), and glutathione S-transferase (GST) were determined spectrophotometrically in erythrocytes and platelets. Scores by PANSS were evaluated twice: before and on the 28-th day of antipsychotic treatment. Results: Samples from control group were used for determination of the control ranges for levels of studied enzymatic activities. Enzymatic activity levels were analyzed in three groups of patients: group Gr1 (n=16) treated without adjunctive therapy, and two other groups (Gr2 and Gr3) treated with adjunctive medicines: antioxidant 2-ethyl-6-methyl-3-hydroxypyridine succinate (Gr2, n=20), or "metabolic" medicines citicoline/cerebrolysin/cortexin/actovegin/gliatilin (Gr3, n=23). As compared with controls, activity of erythrocyte GR was decreased at baseline and after the treatment course in all patients' groups (p<0.01); in Gr2 significant decreases in baseline platelet GDH and GST activities were observed (p=0.005). Different significant links between biochemical parameters and scores by clinical scales before treatment were observed: in Gr1, erythrocyte GST activity positively correlated with scores by PANSS-Neg (R=0.61, p=0.012), by PANSS-Psy (R=0.54, p=0.032), and by PANSS (R=0.62, p=0.010), in Gr2, erythrocyte GST activity positively correlated with scores by PANSS-Pos (R=0.53, p=0.016), by PANSS-Psy (R=0.52, p=0.015), and by PANSS (R=0.60, p=0.005), in Gr3, platelet GR activity positively correlated with PANSS-Pos (R=0.50, p=0.014). Conclusions: We have confirmed the additional favor (decrease in side-effect severity) obtained by distinct patient groups when treated with adjunctive antioxidant or "metabolic" therapy. Moreover, correlations revealed in the patient subgroups between enzymatic activities and scores by psychometric scales enable revealing those biochemical markers measurement of which facilitate differentiating the patients for whom the adjunctive medicines to antipsychotic+antioxidant treatment can positively influence the treatment outcome. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: The data of current research indicate the participation of systemic inflammation in the pathogenesis of endogenous psychoses. Changes in the level of peripheral immune markers are associated with the development of neuroinflammation and correlate with the severity of psychopathological symptoms detected in patients. However, the association between individual components of the immune system involved in the development of endogenous psychosis remains poorly understood. Objectives: To study the connection between molecular and cellular components of the immune system in women with endogenous psychoses with depressive-delusional symptoms. Methods: 32 female patients aged 23 [17; 36] years with endogenous psychoses within different nosologies (F20, F21, F31, depressive-delusional conditions) and 17 women without clinical signs of psychiatric pathology were examined. The activity of leukocyte elastase (LE), α1-proteinase inhibitor (α1-PI), the proportion of four subpopulations of monocytes (classical CD14++CD16-, intermediate CD14++CD16+, nonclassical CD14+CD16+ and transitional CD14+CD16-) in plasma, activity of cytochrome-c oxidase (COX), glutamate dehydrogenase (GDH), glutathione s-transferase (GST) and glutathione reductase (GR) in platelets and functional activity of complement system (faCS) in serum were determined. The PANSS scale was used to assess the severity of psychopathological symptoms. Results: Increased activity of the inflammatory markers LE (p=0.033) and α1-PI (p=0.02) was found in the plasma of the patients. Increased percentage of pro-inflammatory monocytes (intermediate and transient) in plasma (p=0.003) was confirmed by negative correlations between CD14++CD16- and CD14++CD16+ (R=-0.685, p=0.00002), CD14++CD16- and CD14+CD16- (R=-0.608, p=0.0002), CD14++CD16- and CD14+CD16+ (R=-0.424, p=0.002). A decrease in GDH activity (p=0.0079), GST activity (p=0.002) and GR activity (p=0.0006) was observed in patient platelets, which can reflect changes in the activity of intracellular metabolic pathways. A positive correlation was found between COX activity and α1-PI (R=0.51, p=0.025). A significant decrease in faCS compared to control (p=0.0003) and a negative correlation between faCS and GST activity (R=-0.496, p=0.011) were observed. faCS was positively correlated with the degree of reduction in the PANSS score (R=0.416, p=0.038). Conclusions: The revealed connection between molecular and cellular components of the immune system in patients with endogenous psychoses reflect activation of the systemic inflammatory response accompanied by changes in the ratio of monocyte subpopulations and impaired regulation of the complement system. The data obtained can be used to develop methods of monitoring patients taking into account their immunological features. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Background: Evaluation of possible relationship between platelet glutamate dehydrogenase (GDH) activity and mental state of schizophrenia patients after antipsychotic pharmacotherapy. Methods: Patients (n = 50) with chronic paranoid schizophrenia (F20.0) initially in acute psychotic state were examined before and after a treatment course with antipsychotics. When assessing the patients' states using PANSS, the "responder" category was attributed to those patients who had not less than 30% reduction in the score for the corresponding PANSS "subscale". The control group (n = 48) was ageand gender-matched with the patient group. Platelet glutamate dehydrogenase (GDH) activity was measured in patients twice, before and after the treatment course, and once in controls. Results: Significantly reduced GDH activity was found in patients compared with controls. The patient group was divided into two subgroups according to median GDH activity at baseline: above and below the median GDH, subgroup 1 and subgroup 2, respectively. GDH activity significantly increased from its level at baseline after antipsychotic treatment in subgroup 2. Distribution of non responders / responders to antipsychotic treatment (by PANSS scores) was significantly uneven among subgroups 1 and 2. In subgroup 1, GDH activity levels significantly correlated with PANSS scores after the treatment course. Conclusions: Baseline platelet GDH activity might serve as a predictor of antipsychotic therapy efficacy in schizophrenia patients.