A pilot in vivo proton magnetic resonance spectroscopy study of amino acid neurotransmitter response to ketamine treatment of major depressive disorder.
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.
Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, NY, USA.|Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, USA.
M S
MS
Milak
Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
C J
CJ
Proper
Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
S T
ST
Mulhern
Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
A L
AL
Parter
Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, NY, USA.|Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, USA.
L S
LS
Kegeles
Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, NY, USA.|Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, USA.|Department of Biostatistics, Columbia University, Mailman School of Public Health, New York, NY, USA.
R T
RT
Ogden
Department of Radiology, Weill Medical College of Cornell University, New York, NY, USA.
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X
Mao
Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, NY, USA.|Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, USA.
C I
CI
Rodriguez
Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, NY, USA.|Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, USA.
M A
MA
Oquendo
Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, USA.|Analytical Psychopharmacology Laboratory, the Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
R F
RF
Suckow
Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, USA.|Analytical Psychopharmacology Laboratory, the Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
T B
TB
Cooper
Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, NY, USA.|Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, USA.
J G
JG
Keilp
Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, USA.|Department of Radiology, Weill Medical College of Cornell University, New York, NY, USA.
D C
DC
Shungu
Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, NY, USA.|Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, USA.|Department of Radiology, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
J J
JJ
Mann
D000328:Adult; D000596:Amino Acids / Q000378:metabolism*; D000928:Antidepressive Agents / Q000097:blood / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007649:Ketamine / Q000097:blood / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010865:Pilot Projects; D066244:Proton Magnetic Resonance Spectroscopy; D011569:Psychiatric Status Rating Scales; D014316:Tritium / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D000928:Antidepressive Agents; D018377:Neurotransmitter Agents; D005973:Glutamine; D014316:Tritium; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D007649:Ketamine