[Recent progress of epidemiological research in search of the aetiology of autism].

Nihon Shinkei Seishin Yakurigaku Zasshi. 2011 Feb;31(1):29-34.

[Recent progress of epidemiological research in search of the aetiology of autism].
[Article in Japanese]

Tsuchiya KJ, Matsumoto K, Takei N.

Research Center for Child Mental Development, Hamamatsu University School of Medicine, Handayama 1-20-1 Higashiku, Hamamatsu, 431-3192 Japan. tsuchiya@hama-med.ac.jp

Abstract
Autism and autism spectrum disorders (ASDs) are neurodevelopmental disorders characterised by the behavioral traits of impaired social cognition and communication, and repetitive and/or obsessive behaviour and interests. Studies point towards increased prevalence of autism/ASD. However, no treatment or prevention for the disorder has been established, since the aetiological pathway of this disorder remains largely unknown. Considering this lack of knowledge, epidemiological studies are expected to give clues for a better understanding of the disorder. As such, advanced paternal age at birth and low birthweight (or intrauterine growth retardation) have been reported to be candidate risk factors. These findings allow us to propose novel research strategies in search of the aetiology of autism/ASD. Following this trend, the authors initiated a research project, "the Hamamatsu Birth Cohort for Mothers and Children (HBC)", seeking risk factors for autism/ASD extensively. The HBC is expected to enroll 1,200 dyads of mother and child and to follow them until the child becomes 4 years of age.

PLoS One. 2011 Feb 17;6(2):e16715.

PLoS One. 2011 Feb 17;6(2):e16715.

Autism and increased paternal age related changes in global levels of gene expression regulation.
Alter MD, Kharkar R, Ramsey KE, Craig DW, Melmed RD, Grebe TA, Bay RC, Ober-Reynolds S, Kirwan J, Jones JJ, Turner JB, Hen R, Stephan DA.

Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

Abstract
A causal role of mutations in multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations in global levels of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for changes in the overall distribution of gene expression levels. For instance, in mice, variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in variance might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on RNA from peripheral blood lymphocytes (PBL) of children with autism (n = 82) and controls (n = 64). Variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance. A decrease in the variance in the distribution of gene expression levels in PBL was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Global regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other neurodevelopmental disorders.

PMID: 21379579 [PubMed - in process]