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Reduced GABAergic Action in the Autistic Brain: Current Biology


•Behavioral marker of inhibitory/excitatory neurotransmission is perturbed in autism
•Marker predicts higher-order autistic symptom severity
•Inhibitory and excitatory neurotransmitters measured in the brain predict behavior
•Action of the inhibitory neurotransmitter, GABA, is reduced the autistic brain
An imbalance between excitatory/inhibitory neurotransmission has been posited as a central characteristic of the neurobiology of autism [ 1 ], inspired in part by the striking prevalence of seizures among individuals with the disorder [ 2 ]. Evidence supporting this hypothesis has specifically implicated the signaling pathway of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), in this putative imbalance: GABA receptor genes have been associated with autism in linkage and copy number variation studies [ 3–7 ], fewer GABA receptor subunits have been observed in the post-mortem tissue of autistic individuals [ 8, 9 ], and GABAergic signaling is disrupted across heterogeneous mouse models of autism [ 10 ]. Yet, empirical evidence supporting this hypothesis in humans is lacking, leaving a gulf between animal and human studies of the condition. Here, we present a direct link between GABA signaling and autistic perceptual symptomatology. We first demonstrate a robust, replicated autistic deficit in binocular rivalry [ 11 ], a basic visual function that is thought to rely on the balance of excitation/inhibition in visual cortex [ 12–15 ]. Then, using magnetic resonance spectroscopy, we demonstrate a tight linkage between binocular rivalry dynamics in typical participants and both GABA and glutamate levels in the visual cortex. Finally, we show that the link between GABA and binocular rivalry dynamics is completely and specifically absent in autism. These results suggest a disruption in inhibitory signaling in the autistic brain and forge a translational path between animal and human models of the condition.

via Reduced GABAergic Action in the Autistic Brain: Current Biology.

This finding has revolutionary implications for the biology of autism.  For example, it is possible that exposure to certain drugs (such as antidepressants) during pregnancy may predispose to autism.  This study will prompt many more studies of the effect of GABA in autism.  There are already a number of drugs available that mimic or transmute the effects of GABA in the brain.  There is, of course, gabapentin, which is an analog of GABA but is thought to act at an entirely different neurotransmitter site.  There is also baclofen, which resembles GABA as well.   Finally, there is the are newer drugs that may be used either in research or therapeutically.

The study itself is an eloquent demonstration of the ability of the MR scanner to detect individual chemical compounds in the brain.  It discovered that there is no change in the total amount of GABA (an inhibitory neurotransmitter) in the brain, but that autistic people seem to have difficulty controlling their binocular vision because of a deficiency in signalling due to a defect in the GABA pathway.

The study also offers the possibility of non-invasively detecting and evaluating the severity of autism, a potentially life-saving breakthrough.  Only time will tell, after replication and extension of these findings, what new diagnostic and therapeutic techniques can accomplish.

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