GABA(A) receptor availability is not altered in adults with autism spectrum disorder or in mouse models
File(s)
Accepted version
Accepted version
Author(s)
Type
Journal Article
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.
Date Issued
2018-10-03
Date Acceptance
2017-12-15
Citation
Science Translational Medicine, 2018, 10 (461)
ISSN
1946-6234
Publisher
American Association for the Advancement of Science
Journal / Book Title
Science Translational Medicine
Volume
10
Issue
461
Copyright Statement
© 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works http://www.sciencemag.org/about/science-licenses-journal-article-reuse
Sponsor
Medical Research Council (MRC)
Commission of the European Communities
Grant Number
G1002226
607616
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
POSITRON-EMISSION-TOMOGRAPHY
HUMAN CEREBRAL-CORTEX
BENZODIAZEPINE-RECEPTOR
ASPERGER-SYNDROME
MOTION PERCEPTION
IN-VIVO
PET
BINDING
SYSTEM
BRAIN
Publication Status
Published
Article Number
ARTN eaam8434