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

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; O Howes; D G Murphy; J Borg

doi:10.1126/scitranslmed.aam8434

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

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-HughesO Howes, D G Murphy, J Borg

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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.

Original language	English
Article number	eaam8434
Number of pages	12
Journal	Science Translational Medicine
Volume	10
Issue number	461
Early online date	3 Oct 2018
DOIs	https://doi.org/10.1126/scitranslmed.aam8434
Publication status	Published - 3 Oct 2018

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GABAA Receptor Availability Is_HORDER_Accepted10November2017_GREEN AAMAccepted author manuscript, 702 KB
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Horder, J., Andersson, M., Mendez Hernandez, M. A., Singh, N., Tangen, A., Lundberg, J., Gee, A., Halldin, C., Veronese, M., Bolte, S., Farde, L., Sementa, T., Cash, D., K, H., Spain, D., Turkheimer, F., Mick, I., Selvaraj, S., Nutt, DJ., ... Borg, J. (2018). GABA_A receptor availability is not altered In adults with autism spectrum disorder or in mouse models. Science Translational Medicine, 10(461), Article eaam8434. https://doi.org/10.1126/scitranslmed.aam8434

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

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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doi = "10.1126/scitranslmed.aam8434",

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Horder, J, Andersson, M, Mendez Hernandez, MA , Singh, N, Tangen, A, Lundberg, J, Gee, A, Halldin, C, Veronese, M, Bolte, S, Farde, L, Sementa, T , Cash, D, K, H, Spain, D , Turkheimer, F, Mick, I, Selvaraj, S, Nutt, DJ, Lingford-Hughes, A, Howes, O , Murphy, DG & Borg, J 2018, 'GABA_A receptor availability is not altered In adults with autism spectrum disorder or in mouse models', Science Translational Medicine, vol. 10, no. 461, eaam8434. https://doi.org/10.1126/scitranslmed.aam8434

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T1 - GABAA receptor availability is not altered In adults with autism spectrum disorder or in mouse models

AU - Horder, J

AU - Andersson, M

AU - Mendez Hernandez, M A

AU - Singh, N

AU - Tangen, Amma

AU - Lundberg, J

AU - Gee, A

AU - Halldin, C

AU - Veronese, M

AU - Bolte, S

AU - Farde, L

AU - Sementa, T

AU - Cash, D

AU - K, Higgins

AU - Spain, D

AU - Turkheimer, F

AU - Mick, I

AU - Selvaraj, S

AU - Nutt, DJ

AU - Lingford-Hughes, A

AU - Howes, O

AU - Murphy, D G

AU - Borg, J

PY - 2018/10/3

Y1 - 2018/10/3

N2 - 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.

AB - 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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U2 - 10.1126/scitranslmed.aam8434

DO - 10.1126/scitranslmed.aam8434

M3 - Article

SN - 1946-6234

VL - 10

JO - Science Translational Medicine

JF - Science Translational Medicine

IS - 461

M1 - eaam8434

ER -

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

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