Kynurenine pathway metabolism and neurobiology of treatment-resistant depression: Comparison of multiple ketamine infusions and electroconvulsive therapy

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dc.contributor.authorAllen, Andrew P.
dc.contributor.authorNaughton, M.
dc.contributor.authorDowling, J.
dc.contributor.authorWalsh, A.
dc.contributor.authorO'Shea, R.
dc.contributor.authorShorten, George D.
dc.contributor.authorScott, Lucinda V.
dc.contributor.authorMcLoughlin, D. M.
dc.contributor.authorCryan, John F.
dc.contributor.authorClarke, Gerard
dc.contributor.authorDinan, Timothy G.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderHealth Research Boarden
dc.contributor.funderEuropean Commissionen
dc.contributor.funderSeventh Framework Programmeen
dc.contributor.funderBrain and Behavior Research Foundationen
dc.date.accessioned2018-02-13T11:59:13Z
dc.date.available2018-02-13T11:59:13Z
dc.date.issued2018-02-10
dc.date.updated2018-02-13T11:27:18Z
dc.description.abstractCurrent first-line antidepressants can take weeks or months to decrease depressive symptoms. Low dose ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, shows potential for a more rapid antidepressant effect, with efficacy also evident in previously treatment-resistant populations. However, a greater understanding of the physiological mechanisms underlying such effects is required. We assessed the potential impact of ketamine infusion on neurobiological drivers of kynurenine pathway metabolism in major depression (HPA axis hyperactivity, inflammation) in patients with treatment-resistant depression compared to gender-matched healthy controls. Furthermore, we assessed these biomarkers before and after electroconvulsive therapy (ECT), which is currently the gold standard for management of treatment-resistant depression. As previously demonstrated, treatment with ketamine and ECT was associated with improved depressive symptoms in patients. At baseline, waking cortisol output was greater in the ECT cohort, kynurenine was greater in the ketamine cohort, and kynurenic acid was less in patients compared to healthy controls, although inflammatory markers (IL-6, IL-8, IL-10 or IFN-γ) were similar in patients and controls. Furthermore, in patients who responded to ECT, the cortisol awakening response was decreased following treatment. Despite a trend towards lesser kynurenine concentrations in those who responded to ketamine, ketamine was not associated with significant alterations in any of the biomarkers assessed.en
dc.description.sponsorshipScience Foundation Ireland (SFI through the Irish Government's National Development Plan); Health Research Board (grants no HRA_POR/2011/23, HRA_POR/2012/32, HRA-POR-2-14-647); Brain and Behavior Research Foundation (NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (Grant Number 20771)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationAllen, A. P., Naughton, M., Dowling, J., Walsh, A., O'Shea, R., Shorten, G., Scott, L., McLoughlin, D. M., Cryan, J. F., Clarke, G. and Dinan, T. D. (2018) 'Kynurenine pathway metabolism and neurobiology of treatment-resistant depression: Comparison of multiple ketamine infusions and electroconvulsive therapy', Journal of Psychiatric Research, 100, pp.24-32. doi: 10.1016/j.jpsychires.2018.02.011en
dc.identifier.doi10.1016/j.jpsychires.2018.02.011
dc.identifier.endpage32en
dc.identifier.issn0022-3956
dc.identifier.journaltitleJournal of Psychiatric Researchen
dc.identifier.startpage24en
dc.identifier.urihttps://hdl.handle.net/10468/5449
dc.identifier.volume100
dc.language.isoenen
dc.publisherElsevieren
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/613979/EU/Microbiome Influence on Energy balance and Brain Development-Function Put into Action to Tackle Diet-related Diseases and Behavior./MYNEWGUTen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::HEALTH/201714/EU/Serotonin and GABA-B receptors in anxiety : from developmental risk factors to treatment./DEVANXen
dc.relation.urihttps://www.sciencedirect.com/science/article/pii/S0022395617310877
dc.rights© 2018, Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectDepressionen
dc.subjectKetamineen
dc.subjectCortisolen
dc.subjectImmuneen
dc.subjectCytokineen
dc.subjectKynurenineen
dc.titleKynurenine pathway metabolism and neurobiology of treatment-resistant depression: Comparison of multiple ketamine infusions and electroconvulsive therapyen
dc.typeArticle (peer-reviewed)en
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