title: In vivo effects of ketamine on glutamate-glutamine and gamma-aminobutyric acid in obsessive-compulsive disorder: Proof of concept.
abstract: 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.
authors.affiliation: 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.
authors.forename: Carolyn I
authors.initials: CI
authors.lastname: Rodriguez
authors.affiliation: 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.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Kegeles
authors.affiliation: Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Levinson
authors.affiliation: 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.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Ogden
authors.affiliation: Department of Radiology, Weill Medical College of Cornell University, NY 10021, USA.
authors.forename: Xiangling
authors.initials: X
authors.lastname: Mao
authors.affiliation: 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.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Milak
authors.affiliation: 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.
authors.forename: Donna
authors.initials: D
authors.lastname: Vermes
authors.affiliation: Analytical Psychopharmacology Laboratory, the Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Xie
authors.affiliation: Department of Psychiatry, New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Liane
authors.initials: L
authors.lastname: Hunter
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford, Palo Alto, CA 94305, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Flood
authors.affiliation: 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.
authors.forename: Holly
authors.initials: H
authors.lastname: Moore
authors.affiliation: 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.
authors.forename: Dikoma C
authors.initials: DC
authors.lastname: Shungu
authors.affiliation: 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.
authors.forename: Helen B
authors.initials: HB
authors.lastname: Simpson
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism*; D005973:Glutamine / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D007649:Ketamine
keywords: Gamma-aminobutyric acid; Glutamate–glutamine; Ketamine; Magnetic resonance spectroscopy; Medial prefrontal cortex; Obsessive-compulsive disorder (OCD)