title: 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.affiliation: Psychiatry and Research Department, Ezrath Nashim-Herzog Memorial Hospital, P.O. Box 3900, Givat Shaul 91351, Jerusalem, Israel. heresco@md.huji.ac.il
authors.forename: Uriel
authors.initials: U
authors.lastname: Heresco-Levy
authors.forename: Gali
authors.initials: G
authors.lastname: Bar
authors.forename: Raz
authors.initials: R
authors.lastname: Levin
authors.forename: Marina
authors.initials: M
authors.lastname: Ermilov
authors.forename: Richard P
authors.initials: RP
authors.lastname: Ebstein
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Javitt
mesh_terms: D000328:Adult; D001767:Blinking; D002908:Chronic Disease; D004576:Electromyography; D005260:Female; D018698:Glutamic Acid / Q000097:blood; D005998:Glycine / Q000097:blood*; D006801:Humans; D007266:Inhibition, Psychological; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013216:Reflex, Startle; D012559:Schizophrenia / Q000097:blood* / Q000503:physiopathology; D012720:Severity of Illness Index
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D007649:Ketamine; D005998:Glycine