MIT and Harvard University neuroscientists have found a link between a behavioral symptom of autism and reduced activity of a neurotransmitter whose job is to dampen neuron excitation. The findings suggest that drugs that boost the action of this neurotransmitter, known as GABA, may improve some of the symptoms of autism, the researchers say.

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.

“This is the first connection in humans between a neurotransmitter in the brain and an autistic behavioral symptom,” says Caroline Robertson, a postdoc at MIT’s McGovern Institute for Brain Research and a junior fellow of the Harvard Society of Fellows. “It’s possible that increasing GABA would help to ameliorate some of the symptoms of autism, but more work needs to be done.”

Robertson is the lead author of the study, which appears in the Dec. 17 online edition of Current Biology. The paper’s senior author is Nancy Kanwisher, the Walter A. Rosenblith Professor of Brain and Cognitive Sciences and a member of the McGovern Institute. Eva-Maria Ratai, an assistant professor of radiology at Massachusetts General Hospital, also contributed to the research.

Too little inhibition

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.

In this study, the researchers explored a visual task known as binocular rivalry, which requires brain inhibition and has been shown to be more difficult for people with autism. During the task, researchers show each participant two different images, one to each eye. To see the images, the brain must switch back and forth between input from the right and left eyes.

For the participant, it looks as though the two images are fading in and out, as input from each eye takes its turn inhibiting the input coming in from the other eye.

“Everybody has a different rate at which the brain naturally oscillates between these two images, and that rate is thought to map onto the strength of the inhibitory circuitry between these two populations of cells,” Robertson says.

She found that nonautistic adults switched back and forth between the images nine times per minute, on average, and one of the images fully suppressed the other about 70 percent of the time. However, autistic adults switched back and forth only half as often as nonautistic subjects, and one of the images fully suppressed the other only about 50 percent of the time.

Performance on this task was also linked to patients’ scores on a clinical evaluation of communication and social interaction used to diagnose autism: Worse symptoms correlated with weaker inhibition during the visual task.

The researchers then measured GABA activity using a technique known as magnetic resonance spectroscopy, as autistic and typical subjects performed the binocular rivalry task. In nonautistic participants, higher levels of GABA correlated with a better ability to suppress the nondominant image. But in autistic subjects, there was no relationship between performance and GABA levels. This suggests that GABA is present in the brain but is not performing its usual function in autistic individuals, Robertson says.

“GABA is not reduced in the autistic brain, but the action of this inhibitory pathway is reduced,” she says. “The next step is figuring out which part of the pathway is disrupted.”

“This is a really great piece of work,” says Richard Edden, an associate professor of radiology at the Johns Hopkins University School of Medicine. “The role of inhibitory dysfunction in autism is strongly debated, with different camps arguing for elevated and reduced inhibition. This kind of study, which seeks to relate measures of inhibition directly to quantitative measures of function, is what we really to need to tease things out.”

Early diagnosis

In addition to offering a possible new drug target, the new finding may also help researchers develop better diagnostic tools for autism, which is now diagnosed by evaluating children’s social interactions. To that end, Robertson is investigating the possibility of using EEG scans to measure brain responses during the binocular rivalry task.

“If autism does trace back on some level to circuitry differences that affect the visual cortex, you can measure those things in a kid who’s even nonverbal, as long as he can see,” she says. “We’d like it to move toward being useful for early diagnostic screenings.”

Thank you so much for your work. It gives hope.

This isn't at all surprising or news if you understand the glutamate-mediated Intense World theory of autism. Glutamate levels are extremely high in individuals with certain MTHFR mutations, which are correlated over 90 percent with autism. GABA balances glutamate; glutamate is the primary excitatory neurotransmitter, GABA turns off the nerve signaling. I really wish the researchers working on this stuff would make even a phone-it-in effort to look at the other research being done in their very area. I see 20 "amazing but totally redundant and partial discovery(Ies)!" every week.

I will thank you to quit it with the separationist language, thank you very much.

Apart from the fact that curebies depend on people thinking of what makes me me as if it is a separate thing to me (hence, separationist), real police officers have done a double-take at my response to it. It sets off PTSD symptoms.

Needless to say, stories about "diagnostic tools" coming from a source that uses separationist language is going to contribute to my getting less sleep at night, too.

Autism is not singularily a disease in my opinion. It is evolution. Don´t cure evolution.

Please explain how you can say "This is the first connection in humans between a neurotransmitter in the brain and an autistic behavioral symptom,”. See "The Molecular Basis of Autism" for a review covering Glutamate, GABA, Serotonin etc http://www.amazon.com/Molecula....

For GABA in particular there is this recent article http://www.jneuroinflammation.....

And there have been recent attempts at using NMDA antagonists (e.g. memantine, amantadine) to try to treat specific Autism behaviors going back to 2001 e.g. http://www.ncbi.nlm.nih.gov/pu...

Since autism is an inherently behavioral diagnosis there is a lot of prior art that should have been cited and I feel the claim of a "first connection" is overstated and that there is a LOT of missing prior art in the article.

Let's hope for a way to relieve the people with autism from some of their symptoms, thanks for good news

What if we can do it (Treatment) another way ??We need to go to the core of our being. We "ARE" energy beings. Lets use energy for treatment. No more drugs to treat symptoms. We "CAN" correct and re-pattern our energy, with ENERGY. NoviChi. Look it up.

I suppose that Autism could be just one of several conditions that are the result of an altered environment. The chronic pain condition I live with certainly seems to fit the hypersensitivity model. I would add that simply taking Gabapentin has not helped to reduce my pain severity or duration [and even low doses of Gabapentin greatly increased my "chronic fatigue" symptoms].

And beware the studies that suggest a role for a PharmaGiant product.

Reprinted with permission of MIT News