Background: Autism is a common childhood neurodevelopmental disorder with a possible genetic background. About 5-10% of autism cases are associated with chromosomal abnormalities or monogenic disorders. However, the role of subtle genomic imbalances in autism has not been delineated. This study aimed to investigate a hypothesis suggesting autism to be associated with subtle genomic imbalances presenting as low-level chromosomal mosaicism. Methods: We surveyed stochastic (background) aneuploidy in children with/without autism by interphase three-colour fluorescence in situ hybridisation. The rate of chromosome loss and gain involving six arbitrarily selected autosomes and the sex chromosomes was assessed in the peripheral blood cells of 60 unaffected children and 120 children with autism. Results: Of 120 analysed boys with autism, 4 (3.3%) with rare s t r u c t u r a l c h r o m o s o m a l a b n o r m a l i t i e s ( 4 6, X Y , t ( 1; 6) ( q 42 . 1 ; q 2 7 ) ; 4 6 , XY , i n v ( 2 ) ( p 1 1q 13 ) ; 4 6 , X Y , d e r ( 6 ) , i n s ( 6 ; 1 ) ( q 2 1 ; p 1 3 . 3 p 2 2 , 1 ) p a t ; a n d 46,XY,r(22)(p11q13)) were excluded from further molecular cytogenetic analysis. Studying ,420 000 cells in 60 controls and 116 children with idiopathic autism, we determined the mean frequency of stochastic aneuploidy in control and autism: (1) autosome loss 0.58% (95% CI 0.42 to 0.75%) and 0.60% (95% CI 0.37 to 0.83%), respectively, p = 0.83; (2) autosome gain 0.15% (95% CI 0.09 to 0.21%) and 0.22% (95% CI 0.14 to 0.30%), respectively, p = 0.39; and (3) chromosome X gain 1.11% (95% CI 0.90 to 1.31%) and 1.01% (95% CI 0.85 to 1.17%), respectively, p = 0.30. A frequency of mosaic aneuploidy greater the background level was found in 19 (16%) of 116 children with idiopathic autism, whereas outlier values were not found in controls (p = 0.0019). Conclusions: Our findings identify low-level aneuploidy as a new genetic risk factor for autism. Therefore, molecular cytogenetic analysis of somatic mosaicism is warranted in children with unexplained autism.
Cytogenetic and molecular cytogenetic analysis of children with autism (90 subjects) and their mothers (18 subjects) is presented. Anomalies and fragility were found in chromosome X in four cases of autism: mos 47,XXX[98]/46, XX[2]; 46,XY,r(22)(p11q13); 46,XY,inv(2)(p11.2q13),16qh-; and 46,Y,fra(X)(q27.3),16qh-. C staining and quantitative fluorescent in situ hybridization (FISH) were used to demonstrate a significant increase in the frequency of variations in the heterochromatin regions of chromosomes in children with autism as compared with a control group (48% and 16% respectively). Pericentric chromosome inversion 9phqh was not characteristic of patients with autism, while variation in heterochromatin regions 1phqh, 9qh+, and 16qh-were found significantly more frequently in children with autism. These data provide the basis for discussing the possible role of the gene position effect in the pathogenesis of autism and the possible search for biological markers of autistic disorders.
Schizophrenia falls into the small category of diseases that impair the total psychic activity rather than particular brain systems and functions. It is not surprising that researchers have long been interested in the integrative activity of the human brain in schizophrenia. They have reported considerable data on histological and physiological changes in the human brain, providing evidence for disturbance of interrelationships and functional association between different parts of the brain at different stages of schizophrenia [1][2][3]. The most conspicuous data have been obtained for the brain electrical activity [4][5][6][7][8][9][10]. Based on these data, a hypothesis of disintegration of cortical functions (the disconnection hypothesis) has been advanced [11] to explain the schizophrenic disorders [11][12][13].In EEG studies, spectral and correlation analyses are a common method for investigating the integrative activity of the human brain, yielding evidence for the impairment of local and distant synchronies of neuronal networks in schizophrenia [4,5,7,8,14]. However, a number of limitations typical of spectral methods, specifically, of the coherence function [7,[15][16][17], have motivated the development of new techniques to examine the interdependences of EEG paired time series data in schizophrenia, including nonlinear interdependence [9], mutual information transmission measure [18], and phase locking [10], which reflect nonlinear and, in the last case, also in-phase components of the interdependence of cortical electrical processes.The results of the above studies are also in line with Friston's hypothesis of disintegration of neuronal networks in schizophrenia [11].Yet, cortical bioelectrical processes associated with ontological nonstationarity of the EEG signal [19][20][21] are not covered by the traditional or new methods of quantitative analysis of EEG spatiotemporal correlations.EEG nonstationarity implies that the EEG signal consists of quasi-stationary segments that reflect the changes in metastable states of the brain on different time scales [20,21], from microstates, with a duration of no more than several seconds [15,22], to macrostates, with a duration of tens or hundreds of minutes [23]. This concept of EEG nonstationarity provides a means for obtaining new insights into the cooperation of cortical structures. For this purpose, it is possible to estimate the EEG structural synchrony [15], i.e., the temporal synchronization of intersegmentary transitions between different EEG channels. Estimation of the spatiotemporal synchronization of local metastable states of neuronal networks appears to be a new measure of the integrative activity of the human brain.The functional importance of the EEG structural synchrony and segment characteristics has been described in a series of our works performed in several laboratories and with several cognitive and pharmacological paradigms [24][25][26][27]. In our previous work [28], changes in quasi-stationary segments of the EEG α activity were detected i...
Our findings confirm the hypothesis of disturbance of the 'translational homeostasis' in the pathogeneses of autism and schizophrenia, and would help explain why oxidative stress markers are discovered in most autism studies, whereas similar reports related to schizophrenia are far less consistent.
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