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Landmark Study Identifies Altered Brain Chemistry in People With Autism

This is the first time, in humans, that a neurotransmitter in the brain has been linked to autistic behavior — full stop.  (Image: SeRVe Photography via Compfight cc)
This is the first time, in humans, that a neurotransmitter in the brain has been linked to autistic behavior — full stop. (Image: SeRVe Photography via Compfight cc)

Neuroscientists from Harvard University and Massachusetts Institute of Technology (MIT) have made a discovery that could give new insights into diagnosing and understanding the treatment of autism. They have identified a link between the activity of a specific neurotransmitter known as GABA (gamma-aminobutyric acid), and the symptoms of autism.

Brain activity is controlled by a constant interplay of inhibition and excitation, which is mediated by different neurotransmitters. GABA is one of the most important inhibitory neurotransmitters, and studies of animals with autism-like symptoms have found reduced GABA activity in the brain. However, until now, there has been no direct evidence for such a link in humans, according to MIT News.

“This is the first time in humans that a neurotransmitter in the brain has been linked to autistic behavior — full stop,” said Caroline Robertson, who led the research, and is a postdoc at MIT’s McGovern Institute for Brain Research. “This theory that the GABA signaling pathway plays a role in autism has been shown in animal models, but, until now, we never had evidence for it actually causing autistic differences in humans.”

The GABA neurotransmitter’s role is to inhibit brain cells from firing in response to signals received from the external environment. Robertson told The Huffington Post it was “to curb ‘runaway excitation’ in the brain. GABA is responsible for signaling that neurons should turn off, or stop firing,” she said. “It tends to come into play… when information is being transmitted and it needs to be shut down or filtered out.”

By using a visual test that prompted different reactions in autistic and normal brains, the neuroscientists were able to confirm the different reactions were accompanied with a “breakdown in the signaling pathway used by GABA,” which is one of the “brain’s chief inhibitory neurotransmitters.”

“It’s necessary to filter out signals in the external world that aren’t relevant to the task at hand,” Robertson said. “GABA helps us in this kind of inhibition.”

Although the discovery may not lead autism treatments directly, Robertson said the findings do offer an invaluable insight into the role that neurotransmitters, such as GABA, may play in the disorder. The study also suggests that the screening of younger children for autism using similar visual tests could help clinicians to intervene sooner.

“Autism is often described as a disorder in which all the sensory input comes flooding in at once. So the idea that an inhibitory neurotransmitter was important fit with the clinical observations,” Robertson said. “In addition, people with autism often have seizures — there is a 20 to 25 percent comorbidity between autism and epilepsy — and we think seizures are runaway excitation in the brain.”

Watch this video by The National Autistic Society about what autism is:

Researchers have long speculated that the lack of GABA inhibition to overexcited neurons is the primary cause of the hypersensitivity to sensory input seen in individuals with autism.

Many symptoms of autism arise from hypersensitivity to sensory input. For example, children with autism are often very sensitive to things that wouldn’t bother other children as much, such as someone talking elsewhere in the room or a scratchy sweater. Scientists have speculated that reduced brain inhibition might underlie this hypersensitivity by making it harder to tune out distracting sensations, writes MIT News.

Using a magnetic resonance spectroscopy, which is a brain-imaging technique that can measure the levels of certain neurotransmitters in the brain, researchers found that while those with autism did show normal levels of excitatory neurotransmitters, GABA was far lower than expected.

“What we think we’re seeing is evidence of a deficit in the GABA-ergic signaling pathway,” Robertson said. “It’s not that there’s no GABA in the brain… it’s that there’s some step along that pathway that’s broken.”

However, fixing that pathway is easier said than done.

“It’s very diverse,” Robertson said. “There are two forms of GABA receptors, A and B, and the GABA A receptor can take multiple forms. We may be able to use this test to look at the effectiveness of drugs to give us a better idea about which of those receptors isn’t working properly. But it’s very complex.

“If these findings hold true in children as well as adults… right now, we cannot diagnose autism in children who cannot speak, but that’s when early intervention would be most effective,” she continued. “But before children can talk, they can see, so we may be able to use this type of visual task to screen children, and see if there’s something imbalanced in their brains.”

Robertson has warned that understanding the signaling pathway for GABA is not a cure-all for autism.

“I’m excited about this study, but there are many other molecules in the brain, and many of them may be associated with autism in some form,” she said. “We were looking at the GABA story, but we’re not done screening the autistic brain for other possible pathways that may play a role. But this is one, and we feel good about this one.”

The findings were published in the online edition of Current Biology.

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