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Autism Researchers Discover ‘Epigenetic’ Changes

Findings suggest how genes and environmental stresses may interact to cause autism
November 07, 2011


  In recent years, scientists have identified rare genetic mutations that in and of themselves can produce autism. They have likewise found a large number of genetic changes that increase the risk that a child will develop this disorder. However, fewer than 20 percent of those with an autism spectrum disorder (ASD) harbor identifiable gene defects directly related to the disease.

A new study provides strong evidence that, in some cases, the development of autism stems—not from mutations in the genes themselves—but from problems with proteins that help control gene expression inside a cell. The study was co-funded by Autism Speaks and was made possible by donations to its Autism Tissue Program. It appears today in the Archives of General Psychiatry.

Epigenetics is the study of gene regulation and organization that occurs independent of changes in a gene’s “code,” or DNA sequence. Indeed, the vast majority of genes in a given cell remain off, or inactive, at a given time. As in other parts of the body, normal brain development and function depend on the right genetic “switches” being flipped on or off at the right time. Histone methylation is one such epigenetic switch.

Autism scientists have speculated that increased risk of autism might result from problems in the control of gene expression in brain cells. Like DNA mutations, these epigenetic changes can be inherited and run in families. But they can also be caused by exposure to chemicals, lack of crucial nutrients and other many possible stresses, explain study co-authors neurobiologist Schahram Akbarian, M.D., Ph.D., and bioinformatics expert Zhiping Weng, Ph.D., both at the University of Massachusetts Medical School in Worcester.

In terms of autism risk, such stresses might have their strongest effect in the womb or in the first months after birth, both crucial periods of brain development, Akbarian and Weng say. Just as important, Akbarian adds, “In order to develop new therapies for autism, we must first understand these biological changes on a molecular level.”

In performing their work, Akbarian, Weng and their colleagues compared donated, postmortem brain tissue from persons who were diagnosed with autism with that donated from same-age persons who died without an autism diagnosis. Instead of looking for changes in the actual genes, or DNA molecules, within brain cells, they examined the histone molecules that package and organize the DNA.

In doing so, they noted marked differences and abnormalities that might account for the disruption of normal gene activity, brain development and brain cell function. Although no single epigenetic change was found in all of the brain tissues affected by autism, the researchers saw an overall pattern of hundreds of abnormal changes scattered throughout this material, which in essence “wraps” a cell’s genes. These changes were most frequently seen on genes associated with increased risk for autism and other neurodevelopmental disorders.

For now, the cause of these abnormalities remains unclear, Akbarian says. So these findings open up a new and exciting field for exploring possible causes—and treatment—of disabling forms of autism.

“We know that autism is caused by a combination of both genetic and environmental factors," says Autism Speaks Chief Science Officer Geri Dawson, Ph.D. “This study shows that environmental factors may be acting on the genes themselves, disrupting their normal function. This, in turn, helps us better understand how environmental factors may be contributing to autism risk.” 

A parent-supported program of Autism Speaks, the Autism Tissue Program is dedicated to furthering scientific understanding of autism, autism related disorders and the human brain. It makes brain tissue available to as many qualified scientists as possible to advance autism research and unravel the mysteries of this and related neurological conditions. For more information on the ATP and opportunities for family registration, please visit the ATP website.

--Reported by Autism Speaks science writer Madeleine Johnson