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

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Abstract

Rationale

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.

Objectives

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%).

Results

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.

Conclusions

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.

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Acknowledgements

This study was funded by a research grant from Blackmore’s Ltd. Fellowship funding for PJN was provided by the National Health and Medical Research Council (NHMRC) of Australia (Grant 345709).

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Authors and Affiliations

  1. Biological Psychiatry Research Unit, Brain Sciences Institute, Swinburne University of Technology, Melbourne, Australia

    Sumie Leung, Rodney J. Croft & Barry V. O’Neill

  2. Behavioural Neuroscience Laboratory, School of Psychology, Psychiatry and Psychological Medicine, Monash University, Melbourne, Australia

    Rodney J. Croft & Pradeep J. Nathan

  3. Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, UK

    Pradeep J. Nathan

  4. Clinical Pharmacology and Experimental Medicine, GlaxoSmithKline, Cambridge, UK

    Pradeep J. Nathan

  5. Brain Sciences Institute, Swinburne University of Technology, Australia, P.O. Box 218, John Street Hawthorn, Melbourne, 3122, Australia

    Rodney J. Croft

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  1. Sumie Leung
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Correspondence to Rodney J. Croft.

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Leung, S., Croft, R.J., O’Neill, B.V. et al. Acute high-dose glycine attenuates mismatch negativity (MMN) in healthy human controls. Psychopharmacology 196, 451–460 (2008). https://doi.org/10.1007/s00213-007-0976-8

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  • DOI: https://doi.org/10.1007/s00213-007-0976-8

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