Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorder

Qiyun HUANG, Hester VELTHUIS, Andreia C. PEREIRA, Jumana AHMAD, Samuel F. COOKE, Claire L. ELLIS, Francesca M. PONTEDURO, Nicolaas A. J. PUTS, Mihail DIMITROV, Dafnis BATALLE, Man Lok Nichol WONG, Lukasz KOWALEWSKI, Glynis IVIN, Eileen DALY, Declan G. M. MURPHY, Gráinne M. MCALONAN

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3 Citations (Scopus)

Abstract

Altered reactivity and responses to auditory input are core to the diagnosis of autism spectrum disorder (ASD). Preclinical models implicate ϒ-aminobutyric acid (GABA) in this process. However, the link between GABA and auditory processing in humans (with or without ASD) is largely correlational. As part of a study of potential biosignatures of GABA function in ASD to inform future clinical trials, we evaluated the role of GABA in auditory repetition suppression in 66 adults (n = 28 with ASD). Neurophysiological responses (temporal and frequency domains) to repetitive standard tones and novel deviants presented in an oddball paradigm were compared after double-blind, randomized administration of placebo, 15 or 30 mg of arbaclofen (STX209), a GABA type B (GABAB) receptor agonist. We first established that temporal mismatch negativity was comparable between participants with ASD and those with typical development (TD). Next, we showed that temporal and spectral responses to repetitive standards were suppressed relative to responses to deviants in the two groups, but suppression was significantly weaker in individuals with ASD at baseline. Arbaclofen reversed weaker suppression of spectral responses in ASD but disrupted suppression in TD. A post hoc analysis showed that arbaclofen-elicited shift in suppression was correlated with autistic symptomatology measured using the Autism Quotient across the entire group, though not in the smaller sample of the ASD and TD group when examined separately. Thus, our results confirm: GABAergic dysfunction contributes to the neurophysiology of auditory sensory processing alterations in ASD, and can be modulated by targeting GABAB activity. These GABA-dependent sensory differences may be upstream of more complex autistic phenotypes. Copyright © 2023 The Author(s).

Original languageEnglish
Article number320
JournalTranslational Psychiatry
Volume13
Early online dateOct 2023
DOIs
Publication statusPublished - Dec 2023

Citation

Huang, Q., Velthuis, H., Pereira, A. C., Ahmad, J., Cooke, S. F., Ellis, C. L., Ponteduro, F. M., Puts, N. A. J., Dimitrov, M., Batalle, D., Wong, N. M. L., Kowalewski, L., Ivin, G, Daly, E., Murphy, D. G. M., & McAlonan, G. M. (2023). Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorder. Translational Psychiatry, 13, Article 320. https://doi.org/10.1038/s41398-023-02619-8

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