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 K. Manji, Giulio Tononi, Carlos A. Zarate
The International Journal of Neuropsychopharmacology June 7, 2012 DOI: 10.1017/s1461145712000545 via OpenAlex
Summary
A single infusion of the NMDA receptor antagonist ketamine rapidly reduces depressive symptoms in patients with treatment-resistant major depressive disorder. In 30 patients, ketamine increased electroencephalogram slow wave activity during early non-REM sleep and raised plasma levels of brain-derived neurotrophic factor. The occurrence of high amplitude slow waves and their slope also increased, indicating enhanced synaptic strength. Changes in BDNF levels correlated with changes in EEG parameters, but only in patients who responded to ketamine. This suggests that enhanced synaptic plasticity, reflected by increased slow wave activity and BDNF, is part of the mechanism behind ketamine's rapid antidepressant effects.
Study at a glance
| 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 |
| Keywords | Antidepressant Brain-derived neurotrophic factor Psychology |
| Citations | 253 |
| Key finding | 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.