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Título: | Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorder | Autor: | Huang, Qiyun Velthuis, Hester Pereira, Andreia C. Ahmad, Jumana Cooke, Samuel F. Ellis, Claire L. Ponteduro, Francesca M. Puts, Nicolaas A. J. Dimitrov, Mihail Batalle, Dafnis Wong, Nichol M. L. Kowalewski, Lukasz Ivin, Glynis Daly, Eileen Murphy, Declan G. M. McAlonan, Gráinne M. |
Data: | 18-Out-2023 | Editora: | Springer Nature | Projeto: | This project was funded by an Independent Investigator Award (GMM) from the Brain and Behaviour Research Foundation and by Clinical Research Associates, L.L.C. (CRA), an affiliate of the Simons Foundation. Support is also acknowledged from Autistica (ACP) and the Institute for Translational Neurodevelopment at King’s College London and EU-AIMS (European Autism Interventions)/EU-AIMS-2-TRIALS, an Innovative Medicines Initiative Joint Undertaking under Grant Agreement no. 777394. In addition, this paper represents an independent research part funded by the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London. | Título da revista, periódico, livro ou evento: | Translational Psychiatry | Volume: | 13 | Número: | 1 | Resumo: | 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. | URI: | https://hdl.handle.net/10316/111192 | ISSN: | 2158-3188 | DOI: | 10.1038/s41398-023-02619-8 | Direitos: | openAccess |
Aparece nas coleções: | I&D CIBIT - Artigos em Revistas Internacionais I&D ICNAS - Artigos em Revistas Internacionais |
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Exploratory-evidence-for-differences-in-GABAergic-regulation-of-auditory-processing-in-autism-spectrum-disorderTranslational-Psychiatry.pdf | 4.09 MB | Adobe PDF | Ver/Abrir |
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