Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorder
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 correlat...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-10-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02619-8 |
| _version_ | 1797451381347450880 |
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| author | 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 Nichol M. L. Wong Lukasz Kowalewski Glynis Ivin Eileen Daly Declan G. M. Murphy Gráinne M. McAlonan |
| author_facet | 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 Nichol M. L. Wong Lukasz Kowalewski Glynis Ivin Eileen Daly Declan G. M. Murphy Gráinne M. McAlonan |
| author_sort | Qiyun Huang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T14:52:52Z |
| format | Article |
| id | doaj.art-080c60be586548ea8e74626428104029 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-09T14:52:52Z |
| publishDate | 2023-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-080c60be586548ea8e746264281040292023-11-26T14:19:09ZengNature Publishing GroupTranslational Psychiatry2158-31882023-10-0113111310.1038/s41398-023-02619-8Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorderQiyun Huang0Hester Velthuis1Andreia C. Pereira2Jumana Ahmad3Samuel F. Cooke4Claire L. Ellis5Francesca M. Ponteduro6Nicolaas A. J. Puts7Mihail Dimitrov8Dafnis Batalle9Nichol M. L. Wong10Lukasz Kowalewski11Glynis Ivin12Eileen Daly13Declan G. M. Murphy14Gráinne M. McAlonan15Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonSchool of Human Sciences, University of GreenwichDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonSouth London and Maudsley NHS Foundation Trust PharmacyDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonAbstract 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.https://doi.org/10.1038/s41398-023-02619-8 |
| spellingShingle | 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 Nichol M. L. Wong Lukasz Kowalewski Glynis Ivin Eileen Daly Declan G. M. Murphy Gráinne M. McAlonan Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorder Translational Psychiatry |
| title | Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorder |
| title_full | Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorder |
| title_fullStr | Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorder |
| title_full_unstemmed | Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorder |
| title_short | Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorder |
| title_sort | exploratory evidence for differences in gabaergic regulation of auditory processing in autism spectrum disorder |
| url | https://doi.org/10.1038/s41398-023-02619-8 |
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