Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder
Wallace C. Duncan, Simone Sarasso, Fabio Ferrarelli, Jessica Selter, Brady A. Riedner, Nadia S. Hejazi, Peixiong Yuan, Nancy E. Brutsché, Husseini Manji, Giulio Tononi, Carlos A. Zarate
The International Journal of Neuropsychopharmacology June 7, 2012 DOI: 10.1017/s1461145712000545 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Patients with treatment-resistant major depressive disorder |
| Intervention | Ketamine infusion |
| Dose | single infusion |
| Topics | Depression Ketamine Neuroplasticity Esketamine |
| Keywords | Antidepressant Brain-derived neurotrophic factor Nmda receptor Neurotrophic factors Hippocampus Cognition |
| Citations | 253 |
| Key findings | Ketamine rapidly reduces depressive symptoms in treatment-resistant MDD and increases EEG slow wave activity and plasma BDNF, with changes in these measures linked only in responders. |
Abstract
The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant major depressive disorder (MDD). In rats, ketamine selectively increased electroencephalogram (EEG) slow wave activity (SWA) during non-rapid eye movement (REM) sleep and altered central brain-derived neurotrophic factor (BDNF) expression. Taken together, these findings suggest that higher SWA and BDNF levels may respectively represent electrophysiological and molecular correlates of mood improvement following ketamine treatment. This study investigated the acute effects of a single ketamine infusion on depressive symptoms, EEG SWA, individual slow wave parameters (surrogate markers of central synaptic plasticity) and plasma BDNF (a peripheral marker of plasticity) in 30 patients with treatment-resistant MDD. Montgomery-Åsberg Depression Rating Scale scores rapidly decreased following ketamine. Compared to baseline, BDNF levels and early sleep SWA (during the first non-REM episode) increased after ketamine. The occurrence of high amplitude waves increased during early sleep, accompanied by an increase in slow wave slope, consistent with increased synaptic strength. Changes in BDNF levels were proportional to changes in EEG parameters. Intriguingly, this link was present only in patients who responded to ketamine treatment, suggesting that enhanced synaptic plasticity - as reflected by increased SWA, individual slow wave parameters and plasma BDNF - is part of the physiological mechanism underlying the rapid antidepressant effects of NMDA antagonists. Further studies are required to confirm the link found here between behavioural and synaptic changes, as well as to test the reliability of these central and peripheral biomarkers of rapid antidepressant response.
Comparable studies
Other observational and cohort studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... | 2017 | Observational cohort | n = 59 |
| Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... | 2014 | Post hoc analysis of pooled data from four studies | n = 108 |
| An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder | 2011 | Observational cohort | n = 14 |
| Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... | 2019 | Observational cohort | n = 25 |
| Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression Patients with unipolar and bipolar treatment-resistant depression | 2018 | Observational cohort | n = 84 |
Citations in the library
Cited by 79
- Better Biomarkers, Faster Drugs, Stronger Models: Progress Towards Precision Psychiatry. Missouri medicine 2023
- Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics Annual Review of Medicine October 23, 2014
- Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression The International Journal of Neuropsychopharmacology October 8, 2013
- Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers Therapeutic Advances in Psychopharmacology 2020
- KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS Depression and Anxiety April 6, 2016
and 74 more in the library
Cites 11
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Brain-Derived Neurotrophic Factor and Initial Antidepressant Response to anN-Methyl-D-Aspartate Antagonist The Journal of Clinical Psychiatry September 8, 2009
- Rapid-acting antidepressant strategies: mechanisms of action The International Journal of Neuropsychopharmacology July 7, 2011
and 6 more in the library