Research ArticleAutism Spectrum Disorder

GABAA receptor availability is not altered in adults with autism spectrum disorder or in mouse models

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Science Translational Medicine  03 Oct 2018:
Vol. 10, Issue 461, eaam8434
DOI: 10.1126/scitranslmed.aam8434

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A window into the ASD brain

A leading hypothesis for autism spectrum disorder (ASD) is that this condition is associated with an imbalance between excitatory glutamate and inhibitory GABA neurotransmission in the brain. To investigate one aspect of GABA signaling, Horder et al. measured the availability of the GABAA receptor in adults with ASD using positron emission tomography. No differences were found compared to control subjects without ASD in two studies performed at different clinical centers. GABAA receptor availability was also normal in three different mouse models of ASD. However, adults with ASD did display altered performance on a GABA-sensitive perceptual task, suggesting that although GABAA receptor density seemed to be normal, GABA signaling pathways could be impaired.

Abstract

Preliminary studies have suggested that γ-aminobutyric acid type A (GABAA) receptors, and potentially the GABAA α5 subtype, are deficient in autism spectrum disorder (ASD). However, prior studies have been confounded by the effects of medications, and these studies did not compare findings across different species. We measured both total GABAA and GABAA α5 receptor availability in two positron emission tomography imaging studies. We used the tracer [11C]flumazenil in 15 adults with ASD and in 15 control individuals without ASD and the tracer [11C]Ro15-4513 in 12 adults with ASD and in 16 control individuals without ASD. All participants were free of medications. We also performed autoradiography, using the same tracers, in three mouse models of ASD: the Cntnap2 knockout mouse, the Shank3 knockout mouse, and mice carrying a 16p11.2 deletion. We found no differences in GABAA receptor or GABAA α5 subunit availability in any brain region of adults with ASD compared to those without ASD. There were no differences in GABAA receptor or GABAA α5 subunit availability in any of the three mouse models. However, adults with ASD did display altered performance on a GABA-sensitive perceptual task. Our data suggest that GABAA receptor availability may be normal in adults with ASD, although GABA signaling may be functionally impaired.

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