[Oxidative stress, rRNA genes, and antioxidant enzymes in pathogenesis of schizophrenia and autism: modeling and clinical advices].

Ribosomal genes (RG), or genes for rRNA, are represented by multiple tandem repeats in eukaryotic genomes, and just a part of them is transcriptionally active. The quantity of active copies is a stable genome feature which determines the cell's capability for rapid synthesis of proteins, necessary to cope with stress conditions. Low number of active RG copies leads to reduced stress resistance and elevated risk of multifactorial disorders (MFD). Oxidative stress (OS) in the brain cells is believed to be involved in the pathogenesis of infantile autism (IA) and schizophrenia, i.e., MFDs with a manifested genetic predisposition. With autism, OS markers are found almost in every research, whilst with schizophrenia, the OS data are contradictory. Earlier, in a sample of patients with schizophrenia, we have found significantly higher quantity of active RG copies than at the average in healthy population. Here we have estimated the number of active RG copies in a sample of patients with IA (n = 51) and revealed significantly lower mean value than in healthy population. A novel mathematical model of the dynamic pattern of OS has been proposed. The model is realized as an ordinary differential equation system, supposing induction of antioxidant protection enzymes being mediated by reactive oxygen species (ROS), with the subsequent decrease of ROS content in a cell. The rate of synthesis of antioxidant protection enzymes is limited by the ribosome synthesis rate which depends on the number of active RG copies. Analysis of the model showed that the system always approaches a single stable equilibrium point along a damped oscillation trajectory, which in some degree resembles the dynamics of 'predator-prey' interaction in Lotka-Volterra model. The stationary ROS level inversely depends on the number of active RG copies. Our study explains the inconsistency of clinical data of OS in schizophrenia and suggests a novel criterion for discriminative cytogenetic diagnostics of schizophrenia and IA, as well as allows to assume that antioxidant therapy should be effective only for children with low number of active RG copies.

[Differences in the EEG synchrony between healthy children and adolescents and patients with schizophrenia].

In this paper, we have used a method for EEG synchrony estimation (an analysis of correlation synchrony of EEG. EEG recording was performed in a group of children and adolescents, aged 8-15 years, normal group (n=40) and schizophrenic group (n=30). One of the basic features of the integrated EEG picture is the presence of a pathology of extended zones of sharply lowered EEG-synchrony dividing the local and isolated areas in frontal and occipital regions, mainly of normal or sometimes raised synchrony. Also, there were significant correlations of synchrony estimates with memory and attention. The results obtained are in line with the theory of disintegration of cortical electrical activity in schizophrenia spectrum disorders. It is important that the used method provides the high reliability (up to 100%) of the differentiation between normalcy and a pathology.

[The importance of biological and social factors in school success].

Three groups of children with learning difficulties (a total of 62 children) are dealt with in this study according to their cognitive and psychological special features. In the first group the difficulties are a symptom of the FMR1-gene dysfunction. In the second group the poor school performance is associated with social interaction problems and high intelligence level. In the third group of gifted children with low verbal intelligence parameters the poor school performance occurred because of unevenly developed verbal and non-verbal abili-ties. We demonstrate the importance of complex neurophysiological, neuropsychological and clinical psychological investigation for establishing the reasons for school difficulties.

[Variations of heterochromatic chromosomal regions and chromosome abnormalities in children with autism: identification of genetic markers in autistic spectrum disorders].

In the present study, the cytogenetic and molecular cytogenetic analysis of 90 children with autism and their mothers (18 subjects) was carried out. Chromosome fragility and abnormalities were found in four cases: mos 47,XXX[98]/ 46,XX[2]; 46,XY,r(22)(p11q13); 46,XY,inv(2)(p11.2q13),16qh-; 46Y,fra(X)(q27.3)16qh-. Using C-banding and quantitative fluorescent in situ hybridization (FISH), the significantly increased incidence of heterochromatic region variation was shown in autism as compared to the controls (48 and 16%, respectively). Pericentric 9phqh inversion was not characteristic of the patients with autism whereas heterochromatic variations 1phqh, 9qh+ and 16qh- were more frequent in autism (p<0,05). Basing on the data obtained, a possible role of position effect in autism pathogenesis as well as a potential of heterochromatic region variation analysis for the search of biological markers of autistic spectrum disorders are discussed.

[Segmental structure of the EEG alpha activity in adolescents with disorders of schizophrenic spectrum].

The EEG records of 39 healthy adolescents and 45 age-matched schizophrenic patients were analyzed. The broad-band EEG spectral analysis and segmental analysis of the alpha-activity revealed significant differences between the groups. Schizophrenics differed in a decreased spectral power for the alpha2 and betal frequency bands and increased power for the delta and theta bands. Also, in schizophrenic adolescents, quasi-stationary alpha-rhythm segments were longer, and within-segmental EEG amplitudes were higher than in the healthy subjects; the amplitude variability and the steepness of transitions between neighbor segments were increased. The results of the EEG segmental analysis suggest a disintegration of local cortical neuronal ensembles in schizophrenia.

[Speech and motor disorders in Rett syndrome]. / Rechevye i motornye rasstroistva pri sindrome Retta.

Rett syndrome (RS) is a severe genetically conditioned disorder of an early childhood with an definite clinical phenotype in girls. Motor and speech disturbances are noted as the essential part of RS clinical picture. The variability of motor dysfunction and degree of speech deterioration were noted at different stages of the illness. The aim of the present investigation was to study dynamics of both speech and motor disturbances during 2-5 years of the course of the illness and to analyze a correlation of motor and speech functions' disorders. The study was performed in 50 girls with classical RS aged from 12 months to 14 years. The data obtained show a gradual involvement of different brain cortex structures in pathological process during the course of RS (especially of frontal and temporal-parietal regions) at the early stage of the illness and subsequent spread of the pathological process with successive involvement of subcortical structures, cerebellum, brain stem and eventually spinal cord. The neurophysiological investigation showed a strong correlation of speech and motor disturbances' degree with the EEG parameters. The level of theta-activity was significantly lower and the level of alpha- and beta-activity was significantly higher in EEGs of RS patients with more preserved speech and motor functions. In discussion mechanisms of motor and speech disturbances in RS were considered.

[Quantitative EEG correlates of the human frontal lobe dysfunction]. / Kolichestvennye EEG-korreliaty disfunktsii lobnykh dolei kory golovnogo mozga cheloveka.

Increased central-parietal EEG theta-2 activity (about 6.5 per sec) was found in children with cognitive disorders (in Rett's syndrome, fragile X-syndrome, infantile autism) and in elderly patients with Alzheimer-type dementia (with prevalence of neuropsychological "frontal" disorders) in the presence of suppressed alpha rhythm. This theta-activity was closely associated with cognitive deficits and possessed a specific functional topography, namely it focused in the parietal region and suppressed by both visual stimulation and motor tests. The similar EEG pattern was observed in some patients treated with neuroleptics and/or during hyperventilation. By taking into account the data available in the literature on motor, oculomotor, regional cerebral blood flow and the probability prediction in frontal lobar dysfunction, it is suggested that the theta-activity described appears in the visuomanual coordination system and is a physiological correlate of decreased functional status of frontal lobes.

[An elevation in the level of autoantibodies to nerve-growth factor in the blood serum of schizophrenic children]. / Povyshenie urovnia autoantitel k faktoru rosta nervov v syvorotke krovi detei, bol'nykh shizofreniei.

The level of autoantibodies (AAB) to nerve growth factor (NGF) was examined in blood of mentally healthy children, children with early children schizophrenia as well as with Kanner's and Asperger's syndromes too. The elevated titer of AAB to NGF was determined in blood of children with acute, active state of disease; meanwhile the same titer wasn't changed in the state of stable remission or steady defective state as compared with control group. The correlation was found between the level of AAB to NGF and the degree of disease progression. The correlations which were revealed between AAB to NGF level and peculiarities of the clinical state of patients permitted to use this index as the objective marker of both the acuteness and the severity of the patient's state.

[Brain bioelectrical activity in patients with the fragile X-chromosome syndrome and in their mothers]. / Bioélektricheskaia aktivnost' mozga u bol'nykh s sindromom lomkoi X-khromosomy i ikh materei.

30 patients (4-22 years old) and their 12 mothers were examined by means of method of electroencephalography (EEG). Healthy individuals of corresponding age were included in the control group. EEG changes of the same type were observed in all the patients with syndrome of fragile X-chromosome: reduction of occipital alpha-rhythm, prevalence of theta-rhythm in central-parietal and central frontal regions as well as epileptoid activity in parietal and central-parietal cortical regions. These peculiarities could be considered as the markers in syndrome's diagnostics. EEG of mothers (heterozygous carriers of mutant gene) were characterised by considerable variations: increase of rolandic rhythm's presentation in central cortical zones, accumulation of hypersynchronous EEG, increase of rhythmical theta-activity, etc. EEG of mother with shift-like schizophrenia resembled one of proband in one case.

[The clinical, neurophysiological and differential diagnostic aspects in a study of severe forms of early childhood autism]. / Klinicheskie, neirofiziologicheskie i differentsial'no-diagnosticheskie aspekty izucheniia tiazhelykh form rannego detskogo autizma.

Clinical, pathopsychological and neurophysiological studies have been carried out in 85 children with infantile autistic psychosis and in 38 girls with Rett's syndrome. New improved differential diagnostic criteria between these two forms of early childhood autism have been suggested. EEG spectral density values in alpha-1, alpha-2, beta and theta subbands are established to be their neurophysiological markers. Special attention was paid to close relationship between ontogenetic neuromorphogenesis of the brain cortical structures (e.g. physiological lysis of cortical cell populations at the age 8-30 months of the child's life) and the defect severity in the onset of illness at the same age range in patients with the studied forms of early childhood autism. The data obtained are discussed in terms of new approaches to understanding pathogenesis of different forms of early childhood autism.