High glycine levels are associated with prepulse inhibition deficits in chronic schizophrenia patients.

Abstract	Prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating, is decreased in schizophrenia. The validity of a glutamatergic, N-methyl-d-aspartate receptor (NMDAR)-mediated model of PPI disruption is presently equivocal. The NMDAR antagonist ketamine disrupts PPI in rodents, but may increase PPI in healthy volunteers. Glycine (GLY), which acts as an obligatory co-agonist at the NMDAR-GLY site, induces PPI deficits in rats although, consistent with the hypo-NMDAR hypothesis, improves negative and cognitive symptoms in schizophrenia patients. We assessed the hypothesis that GLY serum levels may affect PPI parameters in schizophrenia. Forty-five chronically ill medicated schizophrenia patients and 37 matched healthy comparison subjects were tested for PPI of the eyeblink component of the startle reflex measured by electromyogram recording. Patients' demographic variables, symptom severity scores and GLY, serine and glutamate serum levels were obtained. Patients showed deficient PPI in blocks two and three of the PPI session and differed from controls in terms of change of degree of PPI as a function of the prepulse to eliciting stimulus interval. GLY levels correlated negatively with PPI parameters, such that patients with the highest GLY levels showed decreased PPI (rs=-0.4, p=0.03). These preliminary findings indirectly support previous observations on ketamine effects upon PPI in humans and suggest a dissociation of symptomatology and PPI changes as function of NMDAR modulation in schizophrenia.
Authors	Uriel Heresco-Levy, Gali Bar, Raz Levin, Marina Ermilov, Richard P Ebstein, Daniel C Javitt
Journal	Schizophrenia research (Schizophr Res) Vol. 91 Issue 1-3 Pg. 14-21 (Mar 2007) ISSN: 0920-9964 [Print] Netherlands
PMID	17276036 (Publication Type: Journal Article)
Chemical References	Receptors, N-Methyl-D-Aspartate Glutamic Acid Ketamine Glycine
Topics	Adult Blinking Chronic Disease Electromyography Female Glutamic Acid (blood) Glycine (blood) Humans Inhibition, Psychological Ketamine (pharmacology) Male Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors) Reflex, Startle Schizophrenia (blood, physiopathology) Severity of Illness Index

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