title: High-dose glycine impairs the prepulse inhibition measure of sensorimotor gating in humans.
abstract: An impaired capacity to filter or 'gate' sensory information is a core deficit in cognitive function associated with schizophrenia. These deficits have been linked in part to N-methyl-d-aspartate (NMDA) receptor dysfunction. An association between high levels of glycine, a positive allosteric modulator of the NMDA receptor, and sensorimotor gating impairments (i.e. prepulse inhibition (PPI) deficit) have been reported in animal models of schizophrenia as well as patients with schizophrenia. This study examined the acute effects of modulating the glycine site of the NMDA receptor (with high-dose glycine) on sensory gating as measured by PPI. Sixteen healthy male subjects (final sample size of 12) participated in a double-blind, placebo-controlled, crossover design in which each subject was tested under two acute treatment conditions separated by at least a 5-day washout period; placebo and 0.8 g/kg glycine. PPI was recorded 45 min post treatment using electromyography of the eye-blink response. Relative to placebo, high-dose glycine significantly impaired sensorimotor gating as demonstrated by a decrease in PPI (t(11) = -2.983, p < 0.05). Administration of a high dose of glycine is associated with impairments in PPI supporting earlier observations in animals and patients with schizophrenia. This result, when taken together with findings in patients, suggests that high synaptic levels of glycine may have some clinically relevant detrimental effects and suggests a potential dissociation of clinical symptomatology and sensory information processing as a function of NMDA receptor modulation in schizophrenia.
authors.affiliation: Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, UK. bo236@cam.ac.uk
authors.forename: B V
authors.initials: BV
authors.lastname: O'Neill
authors.forename: R J
authors.initials: RJ
authors.lastname: Croft
authors.forename: C
authors.initials: C
authors.lastname: Mann
authors.forename: O
authors.initials: O
authors.lastname: Dang
authors.forename: S
authors.initials: S
authors.lastname: Leung
authors.forename: M P
authors.initials: MP
authors.lastname: Galloway
authors.forename: K L
authors.initials: KL
authors.lastname: Phan
authors.forename: P J
authors.initials: PJ
authors.lastname: Nathan
mesh_terms: D000293:Adolescent; D000328:Adult; D001288:Attention / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005998:Glycine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects*; D055139:Sensory Gating / Q000187:drug effects*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine