, Volume 196, Issue 3, pp 451–460

Acute high-dose glycine attenuates mismatch negativity (MMN) in healthy human controls

  • Sumie Leung
  • Rodney J. Croft
  • Barry V. O’Neill
  • Pradeep J. Nathan
Original Investigation

DOI: 10.1007/s00213-007-0976-8

Cite this article as:
Leung, S., Croft, R.J., O’Neill, B.V. et al. Psychopharmacology (2008) 196: 451. doi:10.1007/s00213-007-0976-8



Schizophrenia is commonly associated with impairments in pre-attentive change detection as represented by reduced mismatch negativity (MMN). The neurochemical basis of MMN has been linked to N-methyl-d-aspartate (NMDA) receptor function. Glycine augments NMDA receptor function via stimulation of the glycine modulatory site of the NMDA receptor and has been shown to effectively reduce negative symptoms in schizophrenia. However, no study has investigated the possible effects of high-dose glycine on MMN. Further, the physiological consequences of administering high-dose glycine in subjects with normal NMDA receptor function are unknown.


The aim of the present project was to investigate the acute effects of a single large dose of glycine on the human MMN in healthy subjects.

Materials and methods

Sixteen healthy male subjects participated in a double blind, placebo-controlled, crossover design in which each subject was tested under two acute treatment conditions separated by a 1-week washout period; placebo and 0.8 g/kg glycine. The subjects were exposed to a duration-MMN paradigm with 50-ms standard tones (91%) and 100-ms deviant tones (9%).


The results showed that glycine significantly attenuated duration MMN amplitude at frontal electrodes. There was no effect of glycine on MMN latencies or on amplitudes or latencies of N1, N2 and P3a.


These findings suggest that an acute high dosage of glycine attenuates MMN in healthy controls, raising the possibility that optimal effects of glycine and other glycine agonists may depend on the integrity of the NMDA receptor system.


Mismatch negativity (MMN) Glycine Schizophrenia Glutamate NMDA receptors Cognition Electrophysiology 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Sumie Leung
    • 1
  • Rodney J. Croft
    • 1
    • 2
    • 5
  • Barry V. O’Neill
    • 1
  • Pradeep J. Nathan
    • 2
    • 3
    • 4
  1. 1.Biological Psychiatry Research Unit, Brain Sciences InstituteSwinburne University of TechnologyMelbourneAustralia
  2. 2.Behavioural Neuroscience Laboratory, School of Psychology, Psychiatry and Psychological MedicineMonash UniversityMelbourneAustralia
  3. 3.Brain Mapping Unit, Department of PsychiatryUniversity of CambridgeCambridgeUK
  4. 4.Clinical Pharmacology and Experimental MedicineGlaxoSmithKlineCambridgeUK
  5. 5.Brain Sciences InstituteSwinburne University of Technology, AustraliaMelbourneAustralia

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