Electrophysiological biomarkers of antidepressant response to ketamine in treatment-resistant depression: Gamma power and long-term potentiation

Pharmacol Biochem Behav. 2020 Feb;189:172856. doi: 10.1016/j.pbb.2020.172856. Epub 2020 Jan 17.


Over the last two decades, the discovery of ketamine's antidepressant properties has galvanized research into the neurobiology of treatment-resistant depression. Nevertheless, the mechanism of action underlying antidepressant response to ketamine remains unclear. This study reviews electrophysiological studies of ketamine's effects in individuals with depression as well as healthy controls, with a focus on two putative markers of synaptic potentiation: gamma oscillations and long-term potentiation. The review focuses on: 1) measures of gamma oscillations and power and their relationship to both acute, psychotomimetic drug effects as well as delayed antidepressant response in mood disorders; 2) changes in long-term potentiation as a promising measure of synaptic potentiation following ketamine administration; and 3) recent efforts to model antidepressant response to ketamine using novel computational modeling techniques, in particular the application of dynamic causal modeling to electrophysiological data. The latter promises to better characterize the mechanisms underlying ketamine's antidepressant effects.

Keywords: Dynamic causal modeling; Electrophysiology; Gamma; Ketamine; Long-term potentiation.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use*
  • Biomarkers
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Gamma Rhythm / drug effects*
  • Humans
  • Ketamine / pharmacology*
  • Ketamine / therapeutic use*
  • Long-Term Potentiation / drug effects*
  • Synaptic Potentials / drug effects


  • Antidepressive Agents
  • Biomarkers
  • Ketamine