[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.

[Anxiety-phobic disorders in the early childhood stage].

The complex of such phenomena as anxiety and fear in children of the early age and their relationship with risk factors for psychic pathology were investigated. Eighty cases of anxiety-phobic disorders in children of the first five years of life were studied. The types of behavioral and somatic reactions that allowed to reveal not only the clinically expressed phenomena of anxiety and fear but the higher readiness to them were described. The first anxiety-phobic reactions appeared at the age when emotional functions were not completely formed and might be considered as the presentations of emotional dysontogenesis. The authors assume that characteristics of fear expression in the early age allow to suspect a mental disease which might be timely diagnosed in case of its manifestation. The conclusions made in the paper may be useful for clinical practice of pediatricians, children neurologists, psychologists and psychiatrists.

[Dynamics of immunological and clinical parameters in the treatment of childhood schizophrenia].

A state of innate and adaptive immunity (leukocyte elastase (LE) activity, alpha(1)-proteinase inhibitor (alpha(1)-PI), the level of autoantibodies to nerve growth factor (Aab-NGF) and to basic myelin protein), have been studied in the blood serum of children with schizophrenia and compared to the changes of their clinical-psychopathological state. It has been shown that the exacerbation of schizophrenic process with early onset is accompanied by the activation of some parameters of innate immunity. But the higher activity of LE and alpha(1)-PI before the treatment cannot be considered as a predictive marker of therapeutic efficacy. At the same time, the decrease of LE activity during the treatment is a significant predictor of favorable therapeutic response. The unchanged level of Aab-NGF comparing to controls is also a favorable factor associated with therapeutic efficacy.

[Specific disturbances of psychomotor development in children with thymomegaly].

Ninety children, aged from 2 month to 3 years, with thymomegaly and 25 aged-matched controls were studied. Most children with thymomegaly had disturbances of psychomotor development. Depending on their types, the cohort of children was stratified into 4 subgroups: 1st - 36 patients (40%) with schizotypal signs; 2nd - 30 hyperactive children (33%); 3rd - 19 children with hyperthymia signs (21%); 4th - 5 normal children (6%). The deviations of locomotion and psychiatric development were correlated with the extent of thymus enlargement and activation of innate and adaptive immunity.

[Mental disorders in children after the sexual abuse].

Consequences of intrafamily noncontact abuse (40 children aged from 3 to 13 years) and out-of-family contact abuse (15 children aged from 7 to 15 years) have been studied. The intrafamily abuse was long-term and demanded from a child the immersion into situation of "secrecy". The out-of-family abuse had a character of the extreme influence upon a victim. Independently of the abuse character, border-line mental disorders were found in all children. A character of these disorders was determined by the specifics of psychogenic factor, its duration and child's age. A decreased mood, different levels of autism and disturbances of cognitive function were common features of border-line disorders. In cases of intrafamily abuse, uncontrolled drives, sexual character of games and fantasies, elements of depersonalization and age-specific transformation of affective disorders from depressiveness to dysphoric aggressive reactions were observed. In the out-of-family contact abuse, especially in teenagers, the main appearances approached to posttraumatic stress syndrome. In all cases, there was a trend to stronger differentiation of affective disorders, intensification of drives and formation of characteristic pathologic changes as children get older.

[Depressive states in early childhood].

A group of 75 children of early age with depressive states of different origin comprising 25 children at high risk for schizophrenia, 30 orphans and 20 children with consequences of perinatal encephalopathy were examined. Clinical symptoms of these disorders had a number of peculiarities caused by depression origin, risk factors and the age. The most common features are the presence of somatic depression masks, somato-autonomic disturbances and signs of mental and physical retardation.

[A state of innate and adaptive immunity in children with schizophrenia and in the high-risk group for the disease].

Leukocyte elastase (LE) activity, alpha1-proteinase inhibitor (alpha1-PI), C-reactive protein (CRP) as the indices of innate immunity and the level of autoantibodies to nerve growth factor (Aab-NGF) and to basic myelin protein (Aab-BMP) as the indices of adaptive immunity have been studied in the blood serum of 40 children at high risk for schizophrenia and in 32 children with schizophrenia. In the high-risk group, an increase both of the LE activity, CRP content and variance of alpha1-PI concentrations, indicating the activation of innate immunity, was found. LE activity correlated with severity of schizotypal diathesis. The development of schizophrenic process is accompanied by generalization of the immune response: along with activation of the innate immunity, there was activation of immunity acquired as an increase of the level of autoantibodies to neuroantigenes. It is suggested that activation of innate and adaptive immunity is related to the processes determining the disturbances of the nervous system development.

[Mental development of children in condition of chronic physical abuse: methodical aspect].

Mental dysfunction of 130 children aged 0-14 years with a history of family physical abuse was studied using a number of known methods adapted for early aged children including an original scale of mental dysfunction assessment, which has been elaborated in Mental Health Research Center (Moscow). A battery of clinico-psychopathological and clinico-psychological methods allowed comprehensive assessment of mental state, with 95% cases of mental dysfunction being found in the group studied. The most pronounced were depression spectrum disorders.

[Leaf proteins in transgenic tobacco plants, expressing dual-stranded RNA in viral infection]. / Issledovanie belkov list'ev v transgennykh rasteniiakh tabaka, ékspressiruiushchikh dvunitevuiu RNK, pri virusnoi infektsii.

Generation of transgenic tobacco plants, producing double-stranded RNA with no homology to tobacco genome sequences is reported. The RNA synthesis is mediated by a construct containing an inverted repeat of the pBR322 tetracycline-resistance gene fragment under control of the 35S CaMV promoter. Analysis of the resistance of transgenic plants to the tobacco mosaic virus revealed the changes in the protein spectra of the infected plants. The 25- and 30-kDa proteins found were not detected in the extracts of normal plants. Amino acid sequencing of the 30-kDa peptide with subsequent computer database search revealed the homology of this protein to the hydrolases belonging to the group of plant beta-glucanases. The role of the novel polypeptides in an increase of the resistance of transgenic plants to TMV, and also the possibility of the regulation of their expression by nonhomologous dsRNA are discussed.

[Nerve growth factor auto-antibodies in children with various forms of mental dysontogenesis and in schizophrenia high risk group]. / Autoantitela k faktoru rosta nervov u detei s razlichnymi formami psikhicheskogo dizontogeneza i iz gruppy vysokogo riska po shizofrenii.

The level of autoantibodies (AAb) to nerve growth factor was evaluated in blood serum of 163 children with different forms of mental dysontogenesis of endogenic, residual-organic, psychogenic and deprivative origin. Significant elevation of the level of AAb was found in all forms of psychic dysontogenesis. The most significant elevation of the level of AAb (p < 0.01), as compared with the controls (45 children), was characteristic for endogenic forms of dysontogenesis (schizophrenia, early children's autism, schizotypic diathesis). The level of AAb was also found as an indicator of the acuteness of the pathologic state. Besides, its elevation was observed 1-2 weeks prior to the onset of the clinical exacerbation. Elevation of AAb level was also found in psychic dysontogenesis of residual-organic nature (children with perinatal encephalopathy), but it was not so significant as compared with the controls (p < 0.05%). The analysis in the age dynamics of children from this group revealed, that AAb level may serve as some prognostic index of the severity of psychic dysontogenesis. The level of AAb differs some states in schizotypic diathesis and deprivative dysontogenesis, which are clinically quite similar. The method for the estimation of serum AAb level may be proposed as screening in prophylactic medical examination of children from the first year of life under conditions of pediatric outpatient service for identification of risk-groups by psychic dysontogenesis to perform early special psychoprophylaxis.

[Electroencephalographic correlates of schizophrenic type mental disorders at an early age in childhood]. / Elektroéntsefalograficheskie korreliaty psikhicheskikh narushenii shizofrenicheskogo spektra v rannem detskov vozraste.

Electroencephalographic study was performed in 30 children of 1-3 years old from the group with the high risk of schizophrenia. Clinical observation of the patients was performed in the period of EEG recording and follow-up study was also made during 10-12 years. Three groups of patients were picked out with the differences in both clinical and electrophysiologic indices. Bundle beta-activity was registered on EEG in the cases of an active schizophrenic process. A presence of the spindles of the sleep and their dominance on EEG were characteristic for children with nonprocessual disorders of psychopathic-like type with disinhibition of the drives. Hypersynchronism of delta- and theta-activities were observed in the cases of schizotypic diathesis and an early children's autism with the predominance of paroxysmal somato-autonomic disorders.

[Nerve growth factor auto-antibodies in the sera of mothers of schizophrenic children and children from high risk group]. / Autoantitela r faktory rosta vervov v syvorotke krovi materei bol'nykh shizofreniiei detei and detei gruppy vysokogo riska.

A level of autoantibodies (aAB) to nerve growth factor (NGF) was measured in blood serum of children from 4 groups: 1) schizophrenic patients; 2) children from the families, in which one of the parents suffered with schizophrenia (high risk groups of schizophrenia); 3) children with residual-organic damages of CNS; 4) control group. This index was also determined in their mothers. Significant elevation of a titer of aAB to NGF was observed in blood of children from groups 1 and 2 as well as in their mothers, as compared with 3 and 4 groups. Among the mothers of the children from 1 and 2 groups there were met women with different endogenous mental disorders, with the disorders of personality as well as mentally healthy women. An increase of a level of aAB to NGF was found in all the women from groups 1 and 2, independently of their mental status including mentally healthy women. Such results allow to consider elevated level of aAB to NGF as a risk factor of mental pathology.

[A method for determining the mental development of children up to 3 years old--the Schedule for the Neuropsychological Examination of Infants]. / Metodika opredeleniia psikhicheskogo razvitiia detei do 3 let--GNOM.

GNOM--is standard method of estimation of health state in babies and infants with determination of coefficient of mental development. Method's basis appears to be tasks and tests allowing to evaluate (in scores) the state of the main neuropsychiatric spheres, namely: sensory, motor, emotional, cognitive and social-communicative. Method exists both in ordinary and computer variations. It was approved in process of observation of 500 children. GNOM permits to perform the screening of children in big children's contingents. It may be used by either the physicians or other medical personnel as well as by the parents too.

[Depressive states at an early age]. / Depressivnye sostoianiia v rannem vozraste.

100 children of 1-3 years old were observed. In 50 of them depressive states developed in conditions of total deprivation--the situation of orphanhood. In other 50 children the depressions were caused by partial deprivation--upbringing by schizophrenic mother (children from group with high risk of schizophrenia). Three variations of depression were found in the first group: autonomic, somatizated, and regressive-apathetic. Depressions in the second group were presented either by infantile depression or by infantile distress-syndrome in frames of schizotypic diathesis.

[Clinical computed tomographic correlations in children from a group at high risk for schizophrenia]. / Kliniko--komp'iuterno-tomograficheskie korreliatsii u detei iz gruppy vysokogo riska po shizofrenii.

Computed tomography (CT) was performed in 189 individuals: in 44 children of schizophrenic parents (high risk group, HRG), in 39 parents with schizophrenia or with schizophrenic disturbance, in 56 children with schizophrenia, in 50 children with consequences of early organic damages of central nervous system (mental retardation syndrome and generalized tic syndrome). The frequency of CT changes was equal in the mentioned groups but their character was quite different. The widening of brain's liquor system (89.7%), the signs of frontal and temporal atrophia (31%), foci of decreased density of cerebral brain's matter, closer in subcortical ganglia and periventricular zone, and different anomalies of brain were observed in HRG children.

[Micropsychiatry and the possibilities for correcting mental disorders in infancy]. / Mikropsikhiatriia i vozmozhnosti korrektsii psikhicheskikh rasstroistv v mladenchestve.

The investigations of authors concerning infants and their families were generalized on the basis of the observations of infants and their parents with some psychological problems in families. The principles of psychotherapeutic work in above-mentioned groups were formulated. Besides the methods of the diagnosis of psychical deviations development in first year infants as well as peculiarities of alterations in mother-baby system and the main forms of psychic disturbances correction in infants were also described.

[The prevention of mental pathology at an early age]. / O profilaktike piskhicheskoi patologii v rannem vozraste.

New principles of family medical-psychological and psychotherapeutic correction of infants and their parents are presented. Main approaches to prevention of psychic disorders in early childhood are formulated and main tasks for different specialists are specified. Organizational structures such as primary preventive centers based on joint activities of physicians, psychologists and pedagogues are offered.