PMID- 26104826
OWN - NLM
STAT- MEDLINE
DCOM- 20160329
LR  - 20231111
IS  - 1872-7123 (Electronic)
IS  - 0165-1781 (Print)
IS  - 0165-1781 (Linking)
VI  - 233
IP  - 2
DP  - 2015 Aug 30
TI  - In vivo effects of ketamine on glutamate-glutamine and gamma-aminobutyric acid in 
      obsessive-compulsive disorder: Proof of concept.
PG  - 141-7
LID - S0925-4927(15)30008-1 [pii]
LID - 10.1016/j.pscychresns.2015.06.001 [doi]
AB  - We previously reported the rapid and robust clinical effects of ketamine versus 
      saline infusions in a proof-of-concept crossover trial in unmedicated adults with 
      obsessive-compulsive disorder (OCD). This study examined the concurrent 
      neurochemical effects of ketamine versus saline infusions using proton magnetic 
      resonance spectroscopy ((1)H MRS) during the clinical proof-of-concept crossover 
      trial. Levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) 
      and the excitatory neurochemicals glutamate+glutamine (Glx) were acquired in the 
      medial prefrontal cortex (MPFC), a region implicated in OCD pathology. Seventeen 
      unmedicated OCD adults received two intravenous infusions at least 1 week apart, 
      one of saline and one of ketamine, while lying supine in a 3.0 T GE MR scanner. 
      The order of each infusion pair was randomized. Levels of GABA and Glx were 
      measured in the MPFC before, during, and after each infusion and normalized to 
      water (W). A mixed effects model found that MPFC GABA/W significantly increased 
      over time in the ketamine compared with the saline infusion. In contrast, there 
      were no significant differences in Glx/W between the ketamine and saline 
      infusions. Together with earlier evidence of low cortical GABA in OCD, our 
      findings suggest that models of OCD pathology should consider the role of 
      GABAergic abnormalities in OCD symptomatology.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Rodriguez, Carolyn I
AU  - Rodriguez CI
AD  - Department of Psychiatry, Columbia University, College of Physicians and 
      Surgeons, New York, NY 10032, USA; Department of Psychiatry, New York State 
      Psychiatric Institute, New York, NY 10032, USA. Electronic address: 
      cr2163@columbia.edu.
FAU - Kegeles, Lawrence S
AU  - Kegeles LS
AD  - Department of Psychiatry, Columbia University, College of Physicians and 
      Surgeons, New York, NY 10032, USA; Department of Psychiatry, New York State 
      Psychiatric Institute, New York, NY 10032, USA; Department of Radiology, Columbia 
      University, College of Physicians and Surgeons, New York, NY 10032, USA.
FAU - Levinson, Amanda
AU  - Levinson A
AD  - Department of Psychiatry, Columbia University, College of Physicians and 
      Surgeons, New York, NY 10032, USA.
FAU - Ogden, R Todd
AU  - Ogden RT
AD  - Department of Psychiatry, New York State Psychiatric Institute, New York, NY 
      10032, USA; Department of Biostatistics, Columbia University, Mailman School of 
      Public Health, New York, NY 10032, USA.
FAU - Mao, Xiangling
AU  - Mao X
AD  - Department of Radiology, Weill Medical College of Cornell University, NY 10021, 
      USA.
FAU - Milak, Matthew S
AU  - Milak MS
AD  - Department of Psychiatry, Columbia University, College of Physicians and 
      Surgeons, New York, NY 10032, USA; Department of Psychiatry, New York State 
      Psychiatric Institute, New York, NY 10032, USA.
FAU - Vermes, Donna
AU  - Vermes D
AD  - Department of Psychiatry, Columbia University, College of Physicians and 
      Surgeons, New York, NY 10032, USA; Department of Psychiatry, New York State 
      Psychiatric Institute, New York, NY 10032, USA.
FAU - Xie, Shan
AU  - Xie S
AD  - Analytical Psychopharmacology Laboratory, the Nathan S. Kline Institute for 
      Psychiatric Research, Orangeburg, NY 10962, USA.
FAU - Hunter, Liane
AU  - Hunter L
AD  - Department of Psychiatry, New York State Psychiatric Institute, New York, NY 
      10032, USA.
FAU - Flood, Pamela
AU  - Flood P
AD  - Department of Anesthesiology, Perioperative and Pain Medicine, Stanford, Palo 
      Alto, CA 94305, USA.
FAU - Moore, Holly
AU  - Moore H
AD  - Department of Psychiatry, Columbia University, College of Physicians and 
      Surgeons, New York, NY 10032, USA; Department of Psychiatry, New York State 
      Psychiatric Institute, New York, NY 10032, USA.
FAU - Shungu, Dikoma C
AU  - Shungu DC
AD  - Department of Psychiatry, New York State Psychiatric Institute, New York, NY 
      10032, USA; Department of Radiology, Weill Medical College of Cornell University, 
      NY 10021, USA.
FAU - Simpson, Helen B
AU  - Simpson HB
AD  - Department of Psychiatry, Columbia University, College of Physicians and 
      Surgeons, New York, NY 10032, USA; Department of Psychiatry, New York State 
      Psychiatric Institute, New York, NY 10032, USA.
LA  - eng
GR  - K24 MH091555/MH/NIMH NIH HHS/United States
GR  - K23MH092434/MH/NIMH NIH HHS/United States
GR  - K24MH09155/MH/NIMH NIH HHS/United States
GR  - UL1TR000040/TR/NCATS NIH HHS/United States
GR  - UL1 TR000040/TR/NCATS NIH HHS/United States
GR  - K23 MH092434/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150606
PL  - Ireland
TA  - Psychiatry Res
JT  - Psychiatry research
JID - 7911385
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0RH81L854J (Glutamine)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Adult
MH  - Cross-Over Studies
MH  - Excitatory Amino Acid Antagonists/administration & dosage/*pharmacology
MH  - Female
MH  - Glutamic Acid/drug effects/*metabolism
MH  - Glutamine/drug effects/*metabolism
MH  - Humans
MH  - Ketamine/administration & dosage/*pharmacology
MH  - Male
MH  - Obsessive-Compulsive Disorder/*drug therapy/*metabolism
MH  - Prefrontal Cortex/drug effects/*metabolism
MH  - Proton Magnetic Resonance Spectroscopy
MH  - Treatment Outcome
MH  - gamma-Aminobutyric Acid/drug effects/*metabolism
PMC - PMC4715460
MID - NIHMS705143
OTO - NOTNLM
OT  - Gamma-aminobutyric acid
OT  - Glutamate-glutamine
OT  - Ketamine
OT  - Magnetic resonance spectroscopy
OT  - Medial prefrontal cortex
OT  - Obsessive-compulsive disorder (OCD)
EDAT- 2015/06/25 06:00
MHDA- 2016/03/30 06:00
PMCR- 2016/08/30
CRDT- 2015/06/25 06:00
PHST- 2014/11/22 00:00 [received]
PHST- 2015/04/18 00:00 [revised]
PHST- 2015/06/01 00:00 [accepted]
PHST- 2015/06/25 06:00 [entrez]
PHST- 2015/06/25 06:00 [pubmed]
PHST- 2016/03/30 06:00 [medline]
PHST- 2016/08/30 00:00 [pmc-release]
AID - S0925-4927(15)30008-1 [pii]
AID - 10.1016/j.pscychresns.2015.06.001 [doi]
PST - ppublish
SO  - Psychiatry Res. 2015 Aug 30;233(2):141-7. doi: 10.1016/j.pscychresns.2015.06.001. 
      Epub 2015 Jun 6.