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

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