Brain enlargement in autism due to brain changes occurring before age 2

Mon, May 2, 2011 — A study by UNC researchers finds that children with autism who had enlarged brains at age 2 continued to have enlarged brains at ages 4 and 5. However, this increased brain growth did not continue beyond age 2.

Brain enlargement in autism due to brain changes occurring before age 2
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These images show brain maturation measured by cortical thickness for a representative subject with autism at age 2 (left) and age 4 (right). Thicker areas of cortex are shown in red, while thinner cortical areas are displayed in green. Source: C. Vachet.

CHAPEL HILL, NC — In 2005, researchers from the University of North Carolina at Chapel Hill found that 2-year-old children with autism have brains up to 10 percent larger than children of the same age without autism.

Now a follow-up study by UNC researchers has found that the children who had enlarged brains at age 2 continued to have enlarged brains at ages 4 and 5, but the amount of the enlargement was to the same degree found at age 2. This increased brain growth did not continue beyond 2 years of age and the changes detected at age 2 were due to overgrowth prior to that time point. In addition, the study found that the cortical enlargement was associated with increased folding on the surface of the brain (or increased surface area) and not an increase in the thickness of the outer layer of the brain (or gray matter).

“Brain enlargement resulting from increased folding on the surface of the brain is most likely genetic in origin and a result of an increase in the proliferation of neurons in the developing brain,” said Heather Cody Hazlett, PhD, assistant professor in the Department of Psychiatry, who is the lead author of the new study, which is published in the May 2011 issue of Archives of General Psychiatry.

In both the 2005 study and the new study, Hazlett and colleagues analyzed magnetic resonance imaging (MRI) scans of the children’s brains using computer software developed for that purpose by Martin Styner, PhD, an assistant professor of computer science and psychiatry at UNC, and Guido Gerig, PhD, formerly at UNC and now at the University of Utah.

“From earlier work by our group on head circumference or head size in children with autism, we think that brain overgrowth in many children with autism may actually be happening around the first birthday. Together these findings suggest that we should be searching for genes that may underlie the over-proliferation of neurons in this early post-natal period,” said Joseph Piven, MD, senior author of the new study and director of the Carolina Institute for Developmental Disabilities.

UNC is currently leading two separate studies aimed at that goal. Hazlett leads the Brain Development in School Age Children with Autism study, which is funded by Autism Speaks. “It was important to continue to follow these children to track their brain development to see if the brain and behavioral differences we observed were maintained as the children matured,” said Hazlett.

UNC is also leading the Infant Brain Imaging Study (IBIS), a National Institutes of Health-funded multi-center study which includes four sites around the U.S. “We are studying infant children at high genetic risk for autism, by virtue of their having an older brother or sister with autism – somewhere around 20 percent of those children will develop autism. We are doing brain scans and behavior assessments on those children at 6, 12 and 24 months of age to look at how the brain develops in the subgroup that develop autism before they have symptoms of autism at 6 months of age and over the interval that they develop autism - between 6 and 24 months of age, in most cases,” Piven said.  “We are also looking at whether specific gene alterations may be responsible.”

More information about IBIS is available at http://www.ibisnetwork.org/.

Authors of the May 2011 article in Archives of General Psychiatry, in addition to Hazlett, are Michele Poe, PhD, Guido Gerig, PhD, Martin Styner, PhD, Chad Chappell, Rachel Gimpel Smith, Clement Vachet, MS, and Piven.

The UNC authors are all affiliated with one or more of the following: The Department of Psychiatry in the School of Medicine, the Carolina Institute for Developmental Disabilities, the Frank Porter Graham Child Development Institute, and the Department of Computer Science in the College of Arts and Sciences.

Media contact: Tom Hughes, (919) 966-6047, tahughes@unch.unc.edu

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