Ketamine Has Distinct Electrophysiological and Behavioral Effects in Depressed and Healthy Subjects
Allison C. Nugent, Elizabeth D. Ballard, T. Gould, Lawrence T. Park, Ruin Moaddel, Nancy E. Brutsché, Carlos A. Zarate
Molecular Psychiatry February 27, 2018 DOI: 10.1038/s41380-018-0028-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 60 |
| Population | Unmedicated subjects with major depressive disorder and healthy controls |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Topics | Esketamine Ketamine |
| Citations | 254 |
| Key findings | Baseline gamma power moderates the relationship between post-ketamine gamma power and antidepressant response, with opposite associations in MDD subjects depending on their baseline gamma level. |
Abstract
Ketamine’s mechanism of action was assessed using gamma power from magnetoencephalography (MEG) as a proxy measure for homeostatic balance in 35 unmedicated subjects with major depressive disorder (MDD) and 25 healthy controls enrolled in a double-blind, placebo-controlled, randomized cross-over trial of 0.5 mg/kg ketamine. MDD subjects showed significant improvements in depressive symptoms, and healthy control subjects exhibited modest but significant increases in depressive symptoms for up to 1 day after ketamine administration. Both groups showed increased resting gamma power following ketamine. In MDD subjects, gamma power was not associated with the magnitude of the antidepressant effect. However, baseline gamma power was found to moderate the relationship between post-ketamine gamma power and antidepressant response; specifically, higher post-ketamine gamma power was associated with better response in MDD subjects with lower baseline gamma, with an inverted relationship in MDD subjects with higher baseline gamma. This relationship was observed in multiple regions involved in networks hypothesized to be involved in the pathophysiology of MDD. This finding suggests biological subtypes based on the direction of homeostatic dysregulation and has important implications for inferring ketamine’s mechanism of action from studies of healthy controls alone.