Autism Changes Molecular Structure of the Brain

has the potential to revolutionize the way physicians think about and treat autism.

The study, performed by principal investigator Dr. Daniel Geschwind, is the first to reveal how autism affects the brain at the molecular level, and how the structure of an autistic human mind differs vastly from that of a healthy human mind.

Dr. Geschwind, the Gordon and Virginia MacDonald Distinguished Chair in Human Genetics and a professor of neurology and psychiatry at the David Geffen School of Medicine at UCLA, stated "If you randomly pick twenty people with autism, the cause of each person's disease will be unique. Yet when we examined how genes and proteins interact in autistic people's brains, we saw well-defined shared patterns. This common thread could hold the key to pinpointing the disorder's origins."

Geschwind and his research team evaluated and compared brain tissue samples (acquired after death) from nineteen autistic patients and seventeen healthy participants; they studied the cerebral cortex, as well as the frontal and temporal lobes of the brain.

The researchers honed in on the development of a gene's DNA sequence and how this sequence is copied into RNA, which controls the mixture of cellular molecules called proteins. Proteins possess the job of a specific task, assigned by the gene, to perform in the cell.

First author Irina Voineagu, a UCLA postdoctoral fellow in neurology, was reportedly surprised "to see similar gene expression patterns in most of the autistic brains we studied. From a molecular perspective, half of these brains shared a common genetic signature. Given autism's numerous causes, this was an unexpected and exciting finding," she said.

Several common patterns were identified in the minds of the autistic patients when the researchers examined the cerebral cortex's frontal lobe (which handles creativity, judgment, emotions and speech) and the temporal lobes (which control hearing, language, and the processing and interpreting of sounds).

When the scientists compared the brains of the healthy to each other, and then did the same with the autistic brain samples, they were stunned at what they discovered: While the healthy brains all showed different levels of the genes from each other, there was virtually no difference between the brains of the autistic patients.

"In a healthy brain, hundreds of genes behave differently from region to region, and the frontal and temporal lobes are easy to tell apart," Geschwind said. "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 two regions had disappeared."

Other patterns became clear as research continued; the autistic brain showed a decrease of genes responsible for neuron function and communication, but an increase of genes involved in immune function and inflammatory response.

"Several of the genes that cropped up in these shared patterns were previously linked to autism," said Geschwind. "By demonstrating that this pathology is passed from the genes to the RNA to the cellular proteins, we provide evidence that the common molecular changes in neuron function and communication are a cause, not an effect, of the disease."

The research team plans to expand their search into the rest of the brain for causes and effects of autism.

Over the last decade, diagnoses have expanded tenfold, as was shown recently in a study performed by the CDC. In light of the rise of the disorder, these findings offer a much needed fresh understanding and perspective of the disorder, as well as how autism develops in the mind by modifying genes and proteins that are essential for a healthy mind to function.

This study was published May 25, 2011 in the online edition of Nature.