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

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

Author information

1
Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
2
Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, USA.
3
Department of Biostatistics, Columbia University, Mailman School of Public Health, New York, NY, USA.
4
Department of Radiology, Weill Medical College of Cornell University, New York, NY, USA.
5
Analytical Psychopharmacology Laboratory, the Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
6
Department of Radiology, Columbia University, College of Physicians and Surgeons, New York, NY, USA.

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.

PMID:
26283639
PMCID:
PMC4758914
DOI:
10.1038/mp.2015.83
[Indexed for MEDLINE]
Free PMC Article

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