A pilot in vivo proton magnetic resonance spectroscopy study of amino acid neurotransmitter response to ketamine treatment of major depressive disorder

Mol Psychiatry. 2016 Mar;21(3):320-7. doi: 10.1038/mp.2015.83. Epub 2015 Aug 18.

Abstract

The N-methyl-D-aspartate receptor antagonist ketamine can improve major depressive disorder (MDD) within hours. To evaluate the putative role of glutamatergic and GABAergic systems in ketamine's antidepressant action, medial prefrontal cortical (mPFC) levels of glutamate+glutamine (Glx) and γ-aminobutyric acid (GABA) were measured before, during, and after ketamine administration using proton magnetic resonance spectroscopy. Ketamine (0.5 mg kg(-1) intravenously) was administered to 11 depressed patients with MDD. Glx and GABA mPFC responses were measured as ratios relative to unsuppressed voxel tissue water (W) successfully in 8/11 patients. Ten of 11 patients remitted (50% reduction in 24-item Hamilton Depression Rating Scale and total score ⩽10) within 230 min of commencing ketamine. mPFC Glx/W and GABA/W peaked at 37.8%±7.5% and 38.0%±9.1% above baseline in ~26 min. Mean areas under the curve for Glx/W (P=0.025) and GABA/W (P=0.005) increased and correlated (r=0.796; P=0.018). Clinical improvement correlated with 90-min norketamine concentration (df=6, r=-0.78, P=0.023), but no other measures.

Publication types

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

MeSH terms

  • Adult
  • Amino Acids / metabolism*
  • Antidepressive Agents / blood
  • Antidepressive Agents / therapeutic use*
  • Brain / drug effects
  • Brain / metabolism*
  • Depressive Disorder, Major / drug therapy*
  • Female
  • Glutamic Acid / metabolism
  • Glutamine / metabolism
  • Humans
  • Ketamine / blood
  • Ketamine / therapeutic use*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neurotransmitter Agents / metabolism*
  • Pilot Projects
  • Proton Magnetic Resonance Spectroscopy
  • Psychiatric Status Rating Scales
  • Tritium / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Amino Acids
  • Antidepressive Agents
  • Neurotransmitter Agents
  • Glutamine
  • Tritium
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Ketamine