Cerebral Metabolic Effects of Intravenous Glycine in... : Journal of Clinical Psychopharmacology (original) (raw)

Original Contributions

Cerebral Metabolic Effects of Intravenous Glycine in Healthy Human Subjects

Neumeister, Alexander MD*; Carson, Richard PhD†; Henry, Shannan MS*; Planeta-Wilson, Beata MS†; Binneman, Brendon MD‡; Maguire, R. Paul PhD‡; Luckenbaugh, David A. MA§; D'Souza, Cyril MD*; Krystal, John H. MD*; Frost, J. James MD, PhD†

*Department of Psychiatry, Yale University School of Medicine, and †PET Center Yale School of Medicine, New Haven, CT; ‡Pfizer Incorporation; and §Oak Hill.

Received January 30, 2006; accepted after revision July 27, 2006.

This study was supported by grant Y-007-04 from the Yale-Pfizer Bioimaging Alliance.

Address correspondence and reprints requests to Alexander Neumeister, MD, Molecular Imaging Program, Clinical Neuroscience Division, Yale University School of Medicine, MSC 151E, Room 9-174, Building 1, 950 Campbell Ave, West Haven, CT 06516. E-mail: [email protected].

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.