title: Cerebral metabolic effects of intravenous glycine in healthy human subjects.
abstract: Enhancing N-methyl-D-aspartate (NMDA) receptor function via increasing synaptic concentrations of glycine is currently investigated as a novel approach to treat schizophrenia. The neural correlates of enhanced NMDA receptor function in humans, however, are unclear to date. The present study determines the effects of intravenous administration of the glycine on regional cerebral metabolic rate of glucose (rCMRGlu) in healthy control subjects by using [18F]fluorodeoxyglucose and positron emission tomography and on neuropsychological behavioral measures. Thirteen healthy volunteers were recruited, and 12 subjects completed the protocol. These individuals participated in 1 magnetic resonance imaging study and 2 [18F]fluorodeoxyglucose positron emission tomography studies. In a double-blind, randomized, controlled, crossover design, participants received on one test day an intravenous glycine infusion and on the other test day a placebo infusion. There were no significant behavioral and neuropsychological effects of glycine compared with placebo. However, there was a significant reduction of whole-brain CMRGlu during administration of glycine compared with placebo (t = 2.60, df = 11, P = 0.023). In the a priori-selected regions of interest, there was a significant reduction in the cerebellum (t = -3.18, df = 11, P = 0.009) and the dorsolateral prefrontal cortex (t = -2.31, df = 11, P = 0.041). When corrected for whole-brain CMRGlu, rCMRGlu differences were not significant. This study suggests that studies of whole-brain cerebral metabolism may be useful for studying glycine-related mechanisms in healthy humans because there is not a clear cognitive or behavioral signal related to glycine administration at doses thought to be important clinically in patient populations.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06516, USA. alexander.neumeister@yale.edu
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
authors.forename: Richard
authors.initials: R
authors.lastname: Carson
authors.forename: Shannan
authors.initials: S
authors.lastname: Henry
authors.forename: Beata
authors.initials: B
authors.lastname: Planeta-Wilson
authors.forename: Brendon
authors.initials: B
authors.lastname: Binneman
authors.forename: R Paul
authors.initials: RP
authors.lastname: Maguire
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.forename: Cyril
authors.initials: C
authors.lastname: D'Souza
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.forename: J James
authors.initials: JJ
authors.lastname: Frost
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D001519:Behavior / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D016000:Cluster Analysis; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage; D005998:Glycine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D012016:Reference Values; D012694:Serine / Q000097:blood
chemical_list: D014150:Antipsychotic Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D012694:Serine; D005998:Glycine