Neurophysiological evidence that frontoparietal connectivity and GABA-A receptor changes underpin the antidepressant response to ketamine
dc.contributor.author | Sumner, RL | |
dc.contributor.author | McMillan, RL | |
dc.contributor.author | Forsyth, A | |
dc.contributor.author | Muthukumaraswamy, SD | |
dc.contributor.author | Shaw, AD | |
dc.date.accessioned | 2024-02-26T10:29:25Z | |
dc.date.issued | 2024-02-24 | |
dc.date.updated | 2024-02-24T20:38:32Z | |
dc.description.abstract | Revealing the acute cortical pharmacodynamics of an antidepressant dose of ketamine in humans with depression is key to determining the specific mechanism(s) of action for alleviating symptoms. While the downstream effects are characterised by increases in plasticity and reductions in depressive symptoms—it is the acute response in the brain that triggers this cascade of events. Computational modelling of cortical interlaminar and cortico-cortical connectivity and receptor dynamics provide the opportunity to interrogate this question using human electroencephalography (EEG) data recorded during a ketamine infusion. Here, resting-state EEG was recorded in a group of 30 patients with major depressive disorder (MDD) at baseline and during a 0.44 mg/kg ketamine dose comprising a bolus and infusion. Fronto-parietal connectivity was assessed using dynamic causal modelling to fit a thalamocortical model to hierarchically connected nodes in the medial prefrontal cortex and superior parietal lobule. We found a significant increase in parietal-to-frontal AMPA-mediated connectivity and a significant decrease in the frontal GABA time constant. Both parameter changes were correlated across participants with the antidepressant response to ketamine. Changes to the NMDA receptor time constant and inhibitory intraneuronal input into superficial pyramidal cells did not survive correction for multiple comparisons and were not correlated with the antidepressant response. These results provide evidence that the antidepressant effects of ketamine may be mediated by acute fronto-parietal connectivity and GABA receptor dynamics. Furthermore, it supports the large body of literature suggesting the acute mechanism underlying ketamine’s antidepressant properties is related to GABA-A and AMPA receptors rather than NMDA receptor antagonism. | en_GB |
dc.description.sponsorship | Health Research Council of New Zealand | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.identifier.citation | Vol. 14(1), article 116 | en_GB |
dc.identifier.doi | https://doi.org/10.1038/s41398-024-02738-w | |
dc.identifier.grantnumber | 18/193 | en_GB |
dc.identifier.grantnumber | 226709/Z/22/Z | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/135396 | |
dc.identifier | ORCID: 0000-0001-5741-7526 (Shaw, Alexander D) | |
dc.language.iso | en | en_GB |
dc.publisher | Springer Nature | en_GB |
dc.rights | © The Author(s) 2024. Open access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ | en_GB |
dc.title | Neurophysiological evidence that frontoparietal connectivity and GABA-A receptor changes underpin the antidepressant response to ketamine | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2024-02-26T10:29:25Z | |
exeter.article-number | 116 | |
dc.description | This is the final version. Available on open access from Springer nature via the DOI in this record | en_GB |
dc.description | Data availability: The data underlying this article cannot be shared publicly as it was not part of the original ethics application to do so. The data will be shared on reasonable request to the corresponding author. | en_GB |
dc.identifier.eissn | 2158-3188 | |
dc.identifier.journal | Translational Psychiatry | en_GB |
dc.relation.ispartof | Translational Psychiatry, 14(1) | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2024-01-05 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2024-02-24 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2024-02-26T10:27:01Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2024-02-26T10:29:37Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2024-02-24 |
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