Kynurenine pathway metabolism and the neurobiology of treatment-resistant depression: Comparison of multiple ketamine infusions and electroconvulsive therapy.
Andrew P. Allen, Maura Naughton, J. Dowling, Aaron M. Walsh, R. O’shea, G. D. Shorten, L. Scott, Declan M. Mcloughlin, J. Cryan, G. Clarke, T. Dinan
Journal of Psychiatric Research February 10, 2018 DOI: 10.1016/j.jpsychires.2018.02.011 via Semantic Scholar
Summary
Current first-line antidepressants often take weeks to improve symptoms, but low-dose ketamine may work faster, even in treatment-resistant depression. This study compared the effects of ketamine infusion and electroconvulsive therapy (ECT) on biological markers related to stress and inflammation in patients with treatment-resistant depression versus healthy controls. Both treatments improved depressive symptoms. At baseline, patients showed differences in cortisol and kynurenine pathway metabolites compared to controls, though inflammatory markers were similar. After ECT, the cortisol awakening response decreased in responders. Ketamine showed a trend toward reduced kynurenine in responders but did not significantly alter any measured biomarkers.
Study at a glance
| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Patients with treatment-resistant depression and gender-matched healthy controls |
| Keywords | Medicine |
| Citations | 53 |
| Key finding | Ketamine and ECT improved depressive symptoms, but only ECT was associated with significant changes in the cortisol awakening response, while ketamine did not significantly alter measured biomarkers. |
Abstract
Current 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 lower 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 reduced kynurenine concentrations in those who responded to ketamine, ketamine was not associated with significant alterations in any of the biomarkers assessed.