Autistic Brain Structure Dramatically Different From Normal Brain

A post-mortem analysis of autistic and normal brain tissue found common gene expression changes that differentiated autistic brain from healthy brain. The study is the first to reveal how the disorder makes its mark at a molecular level.

"These results suggest that common molecular changes may underlie autism pathogenesis, despite the genetic heterogeneity of the disorder. This in turn may allow for the development of biomarkers and targeted therapeutic approaches," Irina Voineagu, MD, PhD, a postdoctoral fellow in neurology at University of California, Los Angeles (UCLA), told Medscape Medical News.

The results were published online May 25 in Nature.

The research team studied gene expression patterns in brain tissue samples from 19 autism cases and 17 controls.

"Several studies have evaluated gene expression in autism patients using blood and lymphocytes but gene expression has not been evaluated in brain from autistic individuals in a large number of individuals and in multiple brain regions," said Dr Voineagu.

No Distinction Between Regions After profiling 3 brain areas previously linked to autism — the superior temporal gyrus, prefrontal cortex, and cerebellar vermis — the researchers zeroed in on the cerebral cortex after finding that gene expression changes associated with autism were more pronounced in this region.

"Remarkably," they note, regional patterns of gene expression that typically distinguish frontal and temporal cortex were significantly attenuated in the autistic brain.

The cerebral cortex's frontal lobe plays a role in judgment, creativity, emotions, and speech; and the temporal lobes regulate hearing, language, and sound processing.

"In a healthy brain, hundreds of genes behave differently from region to region, and the frontal and temporal lobes are easy to tell apart," principal investigator Daniel Geschwind, MD, PhD, of UCLA noted in a statement.

"We didn't see this in the autistic brain. Instead, the frontal lobe closely resembles the temporal lobe. Most of the features that normally distinguish the 2 regions had disappeared," he added.

Environmental Component Simon G. Gregory, PhD, of the Duke Center for Human Genetics in Durham, North Carolina, who was not involved in the study, told Medscape Medical News, "What's intriguing is that they've identified a distinct lack of difference in the frontal and temporal cortex, which is present in the normal individuals."

Dr Voineagu and colleagues say their observations support "abnormal developmental patterning as a potential pathophysiological driver in autism spectrum disorder."

The researchers also found evidence that genes responsible for synaptic function and communication were down regulated in the autistic brains, whereas genes involved in immune function and inflammatory response were upregulated.

"The increased expression of genes associated with immune response hasn't been identified by previous genetic studies," Dr Gregory commented. "This would imply, as the study authors suggest, that there is some environmental component that is causing the elevated gene expression of the immune response genes or potentially there is an epigenetic component."

Dr Voineagu believes these observations, together with those of other research groups, "provide both molecular and structural evidence suggesting a relative diminution of cortical regional identity in autism."

Overall, "it's really a very interesting convergent paper and explains neuropathologically the different causes of autism. It needs to be replicated in an independent data set," said Dr Gregory.

The study was funded by the National Institute of Mental Health, the Canadian Institutes of Health Research, and Genome Canada. Tissue samples were provided by the Autism Tissue Project, the Harvard Brain Bank, and the Medical Research Council's London Brain Bank for Neurodegenerative Disease. The study authors and Dr Gregory have disclosed no relevant financial relationships.

Nature Published online May 25, 2011. View Article