Publication Type Academic Article
Authors Milak M, Proper C, Mulhern S, Parter A, Kegeles L, Ogden R, Mao X, Rodriguez C, Oquendo M, Suckow R, Cooper T, Keilp J, Shungu D, Mann J
Journal Mol Psychiatry
Volume 21
Issue 3
Pagination 320-7
Date Published 08/18/2015
ISSN 1476-5578
Keywords Amino Acids, Antidepressive Agents, Brain, Depressive Disorder, Major, Ketamine, Neurotransmitter Agents
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.
DOI 10.1038/mp.2015.83
PubMed ID 26283639
PubMed Central ID PMC4758914
Back to Top