Different Types of Autism Disorders Share Abnormal Pattern of Brain Cells

UCLA researchers say changes in brain cells could be key to understanding, treating the disease

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UCLA scientists and their colleagues have found evidence that an abnormal pattern of brain cells is common in people with different types of autism disorders.

The abnormal pattern discovered in the study, reported today in the online edition of the journal Cell, concerns a certain type of “epigenetic mark,” a chemical modification that occurs frequently on chromosomes and helps regulate the activity of nearby genes.

The findings suggest that although autism disorders have multiple causes, they mostly involve problems in a common set of biological pathways, which are actions among certain molecules within a cell that lead to specific changes such as turning genes on or off, or assembling new molecules. The findings may lead to a better understanding of how autism disorders arise, and perhaps one day to the development of drugs that target some of these aberrant pathways.

“The uniformity of this abnormal pattern in the autism samples was surprising, given that these samples were from people whose autism was known to have different causes,” said Dr. Daniel Geschwind, study co-senior author and the Gordon and Virginia MacDonald Distinguished Chair in Human Genetics at the David Geffen School of Medicine at UCLA. “It suggests the possibility that different factors can cause autism disorders through a set of common pathways.”

Geschwind and colleagues Shyam Prabhakar, of the Genome Institute of Singapore, and Jonathan Mill, of the University of Exeter Medical School in England, evaluated brain tissue of 45 people who had autism spectrum disorders and 49 who did not. The team mapped one specific type of epigenetic mark called “histone acetylation.”

Epigenetic abnormalities are certainly plausible suspects in autism disorders, said Geschwind, who is also professor of neurology and psychiatry at UCLA. They are not only extremely common — occurring in about one of every 68 American children — but also have no known cause in the vast majority of cases.

In the study, mapping of histone acetylation marks revealed the same broad pattern or “signature” of abnormality in more than 80 percent of the samples from the cerebral cortexes of the autism cases, compared to the non-autism cases. The cortex, the most advanced brain region, is the one that appears to be most affected in autism disorders. The abnormal pattern, which did not appear in samples from other parts of the brain, involved changes at more than 5,000 locations on the human genome.

Scientists have only recently begun to conduct systematic investigations of epigenetic abnormalities in people, but they have already found that these abnormal chemical modifications contribute to cancers and other important diseases. This study was the first to map this type of epigenetic mark across the genome in a human disease.

“Thus, in addition to its value to autism research, this work paves the way for similar studies aimed at understanding other diseases,” Geschwind said.

The team now hopes to determine which of the many epigenetic abnormalities uncovered in the study are true causes of autism behaviors — and could thus be potential targets for future autism drugs. Drugs that affect histone acetylation have already been developed as potential cancer treatments, and some older psychiatric drugs also influence histone acetylation.