Since one of the primary functions of GABA is to inhibit nerve cells from firing, it plays a key role in telling the body to "slow down.". The GABA system therefore acts as a sort of information filter, preventing the brain from becoming over-stimulated, the researchers explained.
"Impairing the GABA system could overwhelm the brain with sensory information, leading to both the behavior and the pattern of cell damage that emerges in autism," said John Hussman, Ph.D., a study co-author and president of The Hussman Foundation, one of the groups that funded the study.
The researchers examined 14 genes that encode portions of the GABA receptor in 470 Caucasian families. Of those families, 266 included more than one person with autism and 204 included one autistic individual. The team tested for associations between particular gene variants and the disease. They also applied sophisticated statistical methods designed to zero in on the effects of particular gene combinations.
The researchers found that one of the GABA receptor genes, GABRA4, is involved in the origin of autism. Moreover, they report, GABRA4 appears to increase autism risk through its interaction with a second GABA gene, GABRB1.
"This is a key finding for our understanding of the complexity of interactions that underlie autism," Pericak-Vance said. "We can now apply the analytical approach to other genes that may play a role in the disease." Such findings may ultimately yield a method to screen for individuals at high risk for the disease, she added.
"The new findings offer important new information for families affected by autism about the complexity of the disease," said clinical psychologist Michael Cuccaro, Ph.D., a study co-author also of the Duke Center for Human Genetics.
Furthermore, he added, existing medications already target the GABA system, including diazepam (Valium®) and some anti-epileptic drugs. "As we begin to understand the GABA system as it relates to the neurological underpinnings of autism, we may advance toward new therapies."
Collaborators on the study include D.Q. Ma, P.L. Whithead, M.M. Menold, E.R. Martin, A.E. Ashley-Koch, G.R. DeLong and J.R. Gilbert, all of Duke; H. Mei of North Carolina State University; M.D. Ritchie of Vanderbilt University; and H.H. Wright, Ruth Abramson of University of South Carolina.
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