Cerebral metabolic effects of intravenous glycine in healthy human subjects.
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.
Neumeister
Alexander
A
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06516, USA. alexander.neumeister@yale.edu
Carson
Richard
R
Henry
Shannan
S
Planeta-Wilson
Beata
B
Binneman
Brendon
B
Maguire
R Paul
RP
Luckenbaugh
David A
DA
D'Souza
Cyril
C
Krystal
John H
JH
Frost
J James
JJ
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
D014150:Antipsychotic Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D012694:Serine; D005998:Glycine