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Gene Associated With Autism May Alter How Brain Functions
Date:11/3/2010

By Jenifer Goodwin
HealthDay Reporter

WEDNESDAY, Nov. 3 (HealthDay News) -- People with a common genetic variant that's associated with autism have a "disconnect" between their frontal lobe and other areas of the brain important for language, brain scans show.

The disconnect may help explain some of the language and communication difficulties that are characteristic of autism, researchers report in the Nov. 3 issue of Science Translational Medicine.

About one-third of all people carry the variant of the CNTNAP2 gene that is associated with a heightened risk of autism, as well as attention-deficit/hyperactivity disorder, Tourette syndrome, schizophrenia and other language difficulties.

In the study, researchers performed functional MRI brain scans -- which measure blood flow in the brain -- on 32 children who had the gene variant. Half had an autism spectrum disorder, while half were developing normally.

Regardless of whether the kids had autism or not, children with the CNTNAP2 "risk" gene showed more activity in the frontal lobe of the brain (specifically, inside the prefrontal cortex) during a "language learning" task than those without the risk gene.

In those without the risk gene, activity in the prefrontal cortex decreased during the task. Instead, there was more connectivity between the frontal lobe and other areas of the brain, including the left side of the brain, which is involved with language.

In children with the risk gene variant, brain scans showed that the frontal lobe was "over-connected" to itself rather than connected in a normal fashion with the rest of the brain.

"In the kids who carry the risk version, instead of having nice clean connections between frontal lobe and the left side of the brain where you process language, you see more of a broad connection throughout the frontal lobe, almost as if it's talking to itself," said lead study author Ashley Scott-Van Zeeland, a postdoctoral research fellow at Scripps Translational Science Institute in San Diego.

"Instead of having a highly efficient connection to the left side of the brain, they are sampling all over the frontal lobe," the researcher said. "That could help explain some of the language difficulties in autism."

Scott-Van Zeeland did the research as a doctoral candidate at University of California, Los Angeles.

The CNTNAP2 gene helps "wire" the brain: It is known to be active in utero when the structure of the brain is forming, Scott-Van Zeeland said. Unlocking its role in brain function could help in the development of new early interventions or treatments for autism.

Experts point out, however, that the gene variant is part of the spectrum of normal gene variation, and those who have it will not necessarily develop any intellectual disorder.

With some one-third of the population possessing the gene variant, not everyone who has the variant has autism, of course. Conversely, there are plenty of people with autism who don't have the variant, said Dr. Gary Goldstein, president and CEO of the Kennedy Krieger Institute in Baltimore, which serves children and teens with autism and other developmental disorders. Goldstein was not involved with the study.

So it's important to keep in mind that while people who have the CNTNAP2 variant may be more susceptible to autism, there are other genetic or environmental triggers involved, he explained.

But this study does "break new ground," he said, in correlating a known risk gene for autism with alterations in brain activity, as seen in functional MRI imaging.

Previous studies have linked certain genes with autism, while others have shown an association between brain imaging and a child's behavior. But this is among the first to show how a gene associated with autism might alter how the brain functions, Goldstein said.

Think of the brain like an orchestra, he suggested. When the piano starts to play, the rest of the orchestra turns down the volume in order to hear the piano. In autism, perhaps the volume isn't being "turned down" inside the frontal lobe, making it difficult to shift attention to other things, he said.

"What they are really showing is when you have this risk gene, this part of the brain doesn't tune down in the same way it does in people who don't have it," Goldstein said. "That's consistent with what's seen in kids with autism. They have these very focused interests. They may very good at what they are doing, but they're not engaging others or the rest of their brain."

More information

The U.S. National Institutes of Health has more on autism.

SOURCES: Ashley Scott-Van Zeeland, Ph.D., postdoctoral research fellow, Scripps Translational Science Institute, San Diego, Calif.; Gary Goldstein, M.D., professor of pediatrics and neurology, Johns Hopkins University and president and CEO, Kennedy Krieger Institute, Baltimore; Nov. 3, 2010, Science Translational Medicine


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