Autism_Epilepsy_Graphic_Q1People with autism show deficits in inhibitory activity of the neurotransmitter gamma-aminobutyric acid (GABA) that correlate with autistic behaviors demonstrated on key perceptual tests.

“Our findings provide evidence for an empirical link between a specific neurotransmitter measured in the brains of individuals with autism and an autistic behavioral symptom,” the authors, from Harvard University and the Massachusetts Institute of Technology (MIT), in Cambridge, conclude.

The new research was published online December 17 in Current Biology.

GABA receptor genes have been linked with autism in previous research, with some studies showing fewer GABA receptor subunits at autopsy in the brains of people with autism. In addition, compromised GABA signaling has been demonstrated in mouse models of autism.

To further understand the effect in humans, senior author Nancy Kanwisher, PhD, of the McGovern Institute for Brain Research at MIT, and colleagues recruited 21 people with autism and 20 persons without autism, who served as controls.

The participants were all given binocular rivalry tests, in which two conflicting images are presented simultaneously, one to each eye. The test challenges the brain to inhibit certain neural signals in order to achieve visual awareness and distinguish between the two images.

As expected, those with autism had a significantly slower binocular rivalry rate compared with the control participants (P = .001).

Magnetic resonance spectroscopy, which was used to evaluate GABA concentrations while individuals took the test, showed that in those with autism, the connection between the levels of GABA and performance on the binocular rivalry test was absent in comparison with the control individuals (P = .01).

Whereas GABA concentrations observed in the visual cortex corresponded with longer periods of perceptual suppression in the control participants (P = .002), the relationship was not observed in those with autism (P = .473).

“We show that the link between GABA and binocular rivalry dynamics is completely and specifically absent in autism,” the authors write.

They note that the differences were unique to GABA ― although glutamate levels are also believed to play a role in binocular rivalry, the changes observed in testing were similar among those with autism (P = .004) and those without autism (P = .03).

Although deficits in sensory perception have long been associated with autism, the study sheds important light on the neural mechanisms linked to the deficits, the authors note.

They suggest that the binocular rivalry test can be an indicator of disruptions of GABA signaling in autism.

“Although perceptual in nature, this [binocular rivalry] symptom strongly predicts higher-order clinical measures of autistic symptomatology and may be well poised to serve as a behavioral marker of a perturbation in GABAergic signaling in the autistic brain,” the authors write.

Neurologist Michael L. Goldstein, MD, University of Utah School of Medicine, in Salt Lake City, agreed that the study offers interesting insights, but its clinical implications remain to be seen.

“The idea that neural excitation/inhibition deficits could be one of the basic underlying mechanisms of autism is intriguing,” he told Medscape Medical News.

“How this will eventually be able to improve the difficulties faced by people diagnosed with autism remains unclear.”

Medications that adjust GABA levels have been shown to be effective in the treatment of epilepsy, but less is known of their effect in autism, he added.

“One could consider trying to see if GABA medications could improve autistic behavior,” Dr Goldstein said. “At this time, however, I don’t know of any studies where these medications have been used on autistic subjects in an attempt to improve their behavior.

“At this point, the study suggests a concept to describe the basis of autism. This concept may prove very useful for both understanding and helping patients with autism in the future,” he concluded.

The study received funding from 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. The authors and Dr Goldstein have disclosed no relevant financial relationships.

Curr Biol. Published online December 17, 2015

Source: MedScape