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

Research output: Contribution to journalArticle

J Horder, M Andersson, M A Mendez Hernandez, N Singh, Amma Tangen, J Lundberg, A Gee, C Halldin, M Veronese, S Bolte, L Farde, T Sementa, D Cash, Higgins K, D Spain, F Turkheimer, I Mick, S Selvaraj, DJ Nutt, A Lingford-Hughes & 3 more O Howes, D G Murphy, J Borg

Original languageEnglish
JournalScience Translational Medicine
Volume10
Issue number461
Early online date3 Oct 2018
DOIs
Accepted/In press10 Nov 2017
E-pub ahead of print3 Oct 2018
Published3 Oct 2018

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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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