Researchers reporting in the Cell Press journal Current Biology on December 17 have uncovered a direct link between the behavioral symptoms of people with autism and reduced action of an inhibitory neurotransmitter called GABA. GABA's primary responsibility is to dampen neural activity in the brain.
The findings suggest that drugs that increase brain concentrations of GABA might have potential for autism treatment, the researchers say.
"These findings mark the first empirical link between a specific neurotransmitter measured in the brains of individuals with autism and an autistic behavioral symptom," says Caroline Robertson of Harvard University and MIT's McGovern Institute for Brain Research.
Earlier evidence from genetic studies and animals had suggested an important role of GABA signaling in autism, but direct empirical evidence in humans had been lacking. Studies also showed that people with autism spectrum disorders are slower at a phenomenon called binocular rivalry, which is known to involve inhibition in the brain.
In binocular rivalry, two conflicting images are presented simultaneously, one to each eye. To make out one image or the other, the brain must inhibit neural signals to push one out of visual awareness. Typically, developing individuals suppress a visual image from awareness for many seconds at a time. People with autism, on the other hand, struggle to suppress the visual images.
Robertson, senior author Nancy Kanwisher of MIT, and their colleagues wanted to find out whether this difficulty could be traced to differences in GABA levels in the autistic brain. They asked 21 people with autism and 20 typical control individuals to complete a binocular rivalry task. As expected, adults with autism were slower to suppress the visual images.
The researchers then used magnetic resonance spectroscopy to measure GABA concentrations in the brain while individuals completed the task. Those measurements showed a strong link in typical control participants between binocular rivalry dynamics and levels of GABA. That connection between perception and GABA brain chemistry was completely absent in the brains of people with autism.
"Individuals with autism are known to have detail-oriented visual perception--exhibiting remarkable attention to small details in the sensory environment and difficulty filtering out or suppressing irrelevant sensory information," Robertson says. "It's long been thought this might have something to do with inhibition in the brain, and our findings lend support to this notion."
They note, however, that the GABA dysfunction that they've uncovered may vary substantially among people on the autism spectrum. There are also many other neurotransmitters that may play important roles in the behavioral manifestations of autism.
Further studies by the researchers will examine the genetic basis of the GABA imbalance. They are also examining binocular rivalry dynamics in children with autism and the potential of this phenomenon to serve as an early diagnostic marker.
This work was funded by a Harvard Milton Fund award, a NARSAD Young Investigator award, an MIT-MGH Strategic Partnership grant, and a grant from the Simons Center for the Social Brain.
Current Biology, Robertson et al.: "Reduced GABAergic Action in the Autistic Brain" http://dx.
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