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

Jamie Horder, Max Andersson, Maria A. Mendez, Nisha Singh, Ämma Tangen, Johan Lundberg, Antony Gee, Christer Halldin, Mattia Veronese, Sven Bölte, Lars Farde, Teresa Sementa, Diana Cash, Karen Higgins, Debbie Spain, Federico Turkheimer, Inge Mick, Sudhakar Selvaraj, David J. Nutt, Anne Lingford-HughesOliver D. Howes, Declan G. Murphy, Jacqueline Borg

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Preliminary studies have suggested that -aminobutyric acid type A (GABAA) receptors, and potentially the GABAA 5 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 5 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 5 subunit availability in any brain region of adults with ASD compared to those without ASD. There were no differences in GABAA receptor or GABAA 5 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.

Original languageEnglish (US)
Article numbereaam8434
JournalScience translational medicine
Volume10
Issue number461
DOIs
StatePublished - Oct 3 2018

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'GABA<sub>A</sub> receptor availability is not altered in adults with autism spectrum disorder or in mouse models'. Together they form a unique fingerprint.

Cite this