Ketamine Enhances Visual Sensory Evoked Potential Long-term Potentiation in Patients With Major Depressive Disorder.

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dc.contributor.author Sumner, Rachael en
dc.contributor.author McMillan, Rebecca en
dc.contributor.author Spriggs, Meg J en
dc.contributor.author Campbell, Doug en
dc.contributor.author Malpas, Gemma en
dc.contributor.author Maxwell, Elizabeth en
dc.contributor.author Deng, Carolyn en
dc.contributor.author Hay, John en
dc.contributor.author Ponton, Rhys en
dc.contributor.author Kirk, Ian en
dc.contributor.author Sundram, Frederick en
dc.contributor.author Muthukumaraswamy, Suresh en
dc.date.accessioned 2019-11-04T19:38:44Z en
dc.date.issued 2020-01 en
dc.identifier.issn 2451-9022 en
dc.identifier.uri http://hdl.handle.net/2292/48823 en
dc.description.abstract BACKGROUND:The rapid-acting clinical effects of ketamine as a novel treatment for depression along with its complex pharmacology have made it a growing research area. One of the key mechanistic hypotheses for how ketamine works to alleviate depression is by enhancing long-term potentiation (LTP)-mediated neural plasticity. METHODS:The objective of this study was to investigate the plasticity hypothesis in 30 patients with depression noninvasively using visual LTP as an index of neural plasticity. In a double-blind, active placebo-controlled crossover trial, electroencephalography-based LTP was recorded approximately 3 to 4 hours following a single 0.44-mg/kg intravenous dose of ketamine or active placebo (1.7 ng/mL remifentanil) in 30 patients. Montgomery-Åsberg Depression Rating Scale scores were used to measure clinical symptoms. Visual LTP was measured as a change in the visually evoked potential following high-frequency visual stimulation. Dynamic causal modeling investigated the underlying neural architecture of visual LTP and the contribution of ketamine. RESULTS:Montgomery-Åsberg Depression Rating Scale scores revealed that 70% of participants experienced 50% or greater reduction in their depression symptoms within 1 day of receiving ketamine. LTP was demonstrated in the N1 (p = .00002) and P2 (p = 2.31 × 10-11) visually evoked components. Ketamine specifically enhanced P2 potentiation compared with placebo (p = .017). Dynamic causal modeling replicated the recruitment of forward and intrinsic connections for visual LTP and showed complementary effects of ketamine indicative of downstream and proplasticity modulation. CONCLUSIONS:This study provides evidence that LTP-based neural plasticity increases within the time frame of the antidepressant effects of ketamine in humans and supports the hypothesis that changes to neural plasticity may be key to the antidepressant properties of ketamine. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries Biological psychiatry. Cognitive neuroscience and neuroimaging en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Ketamine Enhances Visual Sensory Evoked Potential Long-term Potentiation in Patients With Major Depressive Disorder. en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.bpsc.2019.07.002 en
pubs.issue 1 en
pubs.begin-page 45 en
pubs.volume 5 en
dc.rights.holder Copyright: The author en
pubs.end-page 55 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Journal Article en
pubs.elements-id 782644 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Faculty Administration FMHS en
pubs.org-id Group Services en
pubs.org-id Pharmacy en
pubs.org-id School of Medicine en
pubs.org-id Psychological Medicine Dept en
pubs.org-id Science en
pubs.org-id Psychology en
dc.identifier.eissn 2451-9030 en
pubs.record-created-at-source-date 2019-09-10 en
pubs.dimensions-id 31495712 en


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