Evidence that brain-chemical imbalance drives autism symptoms

Study links autism symptoms to disregulated levels of neurotransmitter GABA; flags potential avenue for developing treatments

December 17, 2015

Imbalances in inhibitory GABA brain cell receptor activity (left) have been implicated in autism. A new study looks more closely at GABA brain activity and autism-related difficulties with screening out distracting images. The findings suggests a promising direction for future medicines. Illustration courtesy SAGE Therapeutics.

For the first time, researchers have documented a direct link between the severity of someone’s autism symptoms and brain levels of the neurotransmitter GABA, or gamma-aminobutyric acid. The findings advance hope for treatments that ease autism symptoms by enhancing the action of GABA – the brain’s primary “calming,” or inhibitory, neurotransmitter.

The study appears today in the journal Current Biology.

“Often, people with autism have trouble filtering irrelevant sensory information, and it’s long been thought this might have something to do with inhibition in the brain,” says study leader Caroline Robertson, a researcher with the Harvard Society of Fellows, in Cambridge, Mass.

Nearly a decade of basic research has suggested that reduced GABA activity in the brain plays a role in producing autism’s hallmark symptoms. But most of this research involved laboratory animals and genetic studies. The new study is the first to test the idea that GABA underlies autistic symptoms in people.

The researchers enrolled 41 participants – 21 of whom were mildly to severely affected by autism. The others were unaffected by the condition.

The participants performed a task that involves inhibition in the brain. They looked through binocular lenses that showed a different image to each eye. Typically, the brain switches between focusing on one or the other of the two images. This requires the brain to “inhibit,” or suppress one image.

The 21 participants with autism were slower to discern the two images than were the participants unaffected by the condition. This reflected their ability to suppress the competing image. It’s also consistent with previous research showing that many people with autism struggle with tasks that require blocking out distracting sights, sounds or other sensory input.

What’s more, their performance scores directly reflected the severity of their autism symptoms.

Next, the researchers used magnetic resonance spectroscopy to measure GABA levels in each participant’s brain. Among the participants unaffected by autism, the ability to suppress the competing image during the perception test increased in direct proportion to GABA levels in their brains. By contrast, GABA levels showed no relationship to test performance among the participants affected by autism.

“This shows that the link between GABA and the ability to suppress competing images is completely absent in autism,” Dr. Robertson says. “It also suggest a disruption in inhibitory signaling in the autistic brain.”

Dr. Robertson and her team call for further research advancing the idea that increasing GABA signaling in the brain – perhaps through medication – could ease symptoms in people disabled by the condition.

“We want to see more research bridging the gap between animal and human research on autistic neurobiology, with the aim of developing new medications to ease symptoms in people disabled by the condition,” she said.

The study was supported by a Milton Fund grant from Harvard University, a Seed Grant from the Simons Center for the Social Brain at the Massachusetts Institute of Technology and an MIT-Mass General Hospital Grand Challenge Award.

Autism Speaks has funded and continues to fund a broad range of pioneering research on GABA's role in autism. Read about these and all of Autism Speaks funded research projects using this website's Grant Search Engine. This work is made possible by the passion and generosity of the Autism Speaks community.

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