Cited by 144Treatment of Major DepressionElectroconvulsive Therapy StudiesTryptophan and brain disorders

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

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Milak, M S, Proper, C J, Mulhern, S T, Parter, A L, Kegeles, L S, Ogden, R T, Mao, X, Rodriguez, C I +6 more·2016·Molecular Psychiatry

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.

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  1. [29]Sanacora G Gueorguieva R Epperson CN Wu YT Appel M Rothman DL Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression Archives of general psychiatry 2004 61 7 705 713 15237082
  2. [32]Biersack HJ Letter to the Editor Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2012
  3. [33]Graham MM Menda Y Letter to the Editor Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2012

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Authors
Milak, M. S., Proper, C. J., Mulhern, S. T., Parter, A. L., Kegeles, L. S., Ogden, R. T., Mao, X., Rodriguez, C. I., Oquendo, M. A., Suckow, R. F., Cooper, T. B., Keilp, J. G., Shungu, D. C., & Mann, J. J.
Affiliations
  • New York State Psychiatric Institute (US)
  • Columbia University (US)
  • Cornell University (US)
  • Nathan Kline Institute for Psychiatric Research (US)
Venue
Molecular Psychiatry
Published
2015-08-18
Volume
21
Issue
3
Pages
320-327
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
OpenAlex
W1846441878
Cited by
144
References
106
Citations by year
2026: 7 · 2025: 10 · 2024: 7 · 2023: 10 · 2022: 20 · 2021: 14 · 2020: 10 · 2019: 14 · 2018: 17 · 2017: 15 · 2016: 18 · 2015: 2
FWCI
12.49
Type
journal article
Language
en
Open access
Locations
  • Molecular Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5r01mh093637-04)
  • National Institute of Mental Health (R01 MH-093637, R01MH075895, K23MH092434)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
ketamine, major depressive disorder, NMDA receptor antagonists, antidepressant mechanism, glutamate, glutamine, GABA, medial prefrontal cortex, glutamatergic system, GABAergic system, norketamine, rapid-acting antidepressants, 1H NMR
MeSH terms
Adult, Amino Acids, Antidepressive Agents, Brain, Major Depressive Disorder, Female, gamma-Aminobutyric Acid, Glutamine, Humans, Ketamine, Magnetic Resonance Imaging, Male, Middle Aged, Pilot Projects, Psychiatric Status Rating Scales, Tritium, Neurotransmitter Agents, Glutamic Acid, Proton Magnetic Resonance Spectroscopy

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