By Andrea Anderson

NEW YORK (GenomeWeb News) A study appearing online last night in PLoS Genetics has found gene expression differences in brain samples from children with autism spectrum disorder compared to adults with the condition, hinting that different pathological processes may be at work in the autistic brain depending on age.

A California research team used arrays to assess almost three-dozen post mortem brain samples from individuals with or without autism, gauging both gene expression and copy number alterations in a region called the prefrontal cortex. Along with comparisons between unaffected and affected individuals, the investigators looked at how expression patterns in samples from toddlers and children with ASD compared with those in samples from adolescents and adults with ASD.

Though some gene expression patterns in the prefrontal cortex turned up regardless of age in the ASD group, researchers also found age-dependent gene expression alterations in autism. For example, samples from children with ASD tended to show atypical expression of genes contributing to neuron number consistent with some of the unusual early brain growth patterns previously described in ASD whereas adult autism cases were marked by unusual expression profiles involving genes from signaling, immune, and repair pathways.

"We're showing that the adult condition where you have neuron loss and you have immunological activation isn't the way it began. It's an outcome," co-corresponding author Eric Courchesne, director of the National Institutes of Health-University of California at San Diego's Autism Center of Excellence, told GenomeWeb Daily News.

For more than a decade, studies have been finding distinct early brain development patterns in autism, including excess neurons in certain parts of the brain. This overgrowth seems to stop sometime during childhood, Courchesne noted. And by adolescence or adulthood, the enlarged brain regions seen in childhood generally seem to disappear through processes such as neuron loss and/or thinning in some cortical areas.

That has made it tricky to figure out the molecular roots of the early brain overgrowth seen by neuroimaging experiments or postmortem analyses, authors of the new study explained, though previous genetic studies have garnered clues about some of the age-independent processes contributing to autism.

"Up until now, there has been no information on the developmental, molecular pathology of autism that is, what's going wrong early in the brain that's responsible for excess and abnormal brain growth," Courchesne explained.

He and his colleagues used Illumina microarrays to assess expression profiles across the genome in post-mortem prefrontal cortex samples, comparing the patterns in unaffected and affected individuals and in younger and older individuals with ASD.

Because they were dealing with RNA from post-mortem brain samples, which are often not collected immediately after death, the researchers sent samples to Illumina for processing with its DASL assay to help get as much signal as possible out of the microarray experiments.

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Age-Related Gene Expression Differences in Autism Detected in Post-Mortem Brain Samples

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