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Schizophr Res. 2018 Jan;191:61-69. doi: 10.1016/j.schres.2017.05.031. Epub 2017 Jun 9.

The effects of glycine on auditory mismatch negativity in schizophrenia.

Author information

1
School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, Australia. Electronic address: lmg001@uowmail.edu.au.
2
Centre for Human Psychopharmacology, Swinburne University of Technology, Victoria, Australia.
3
School of Psychology and Priority Research Centre for Translational Neuroscience and Mental Health, University of Newcastle, Newcastle, Australia; Schizophrenia Research Institute, Sydney, Australia.
4
Monash Alfred Psychiatry Research Centre, Monash University, Melbourne, Australia.
5
Monash Alfred Psychiatry Research Centre, Monash University, Melbourne, Australia; Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; School of Psychology and Psychiatry, Monash University, Melbourne, Australia.
6
Department of Psychology and York Neuroimaging Centre, University of York, York, United Kingdom; School of Psychology and Counselling, Queensland University of Technology, Kelvin Grove, Australia.
7
School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, Australia; Schizophrenia Research Institute, Sydney, Australia.
8
School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, Australia.

Abstract

Glycine increases N-methyl-d-aspartate receptor (NMDAR) mediated glutamatergic function. Mismatch negativity (MMN) is a proposed biomarker of glutamate-induced improvements in clinical symptoms, however, the effect of glycine-mediated NMDAR activation on MMN in schizophrenia is not well understood. This study aimed to determine the effects of acute and 6-week chronic glycine administration on MMN in schizophrenia patients. MMN amplitude was compared at baseline between 22 patients (schizophrenia or schizoaffective disorder; receiving stable antipsychotic medication; multi-centre recruitment) and 21 age- and gender-matched controls. Patients underwent a randomised, double-blind, placebo-controlled clinical trial with glycine added to their regular antipsychotic medication (placebo, n=10; glycine, n=12). MMN was reassessed post-45-minutes of first dose (0.2g/kg) and post-6-weeks treatment (incremented to 0.6g/kg/day). Clinical symptoms were assessed at baseline and post-6-weeks treatment. At baseline, duration MMN was smaller in schizophrenia compared to controls. Acute glycine increased duration MMN (compared to placebo), whilst this difference was absent post-6-weeks treatment. Six weeks of chronic glycine administration improved PANSS-Total, PANSS-Negative and PANSS-General symptoms compared to placebo. Smaller baseline duration MMN was associated with greater PANSS-Negative symptoms and predicted (at trend level) PANSS-Negative symptom improvement post-6-weeks glycine treatment (not placebo). These findings support the benefits of chronic glycine administration and demonstrate, for the first time, that acute glycine improves duration MMN in schizophrenia. This result, together with smaller baseline duration MMN predicting greater clinical treatment response, suggests the potential for duration MMN as a biomarker of glycine-induced improvements in negative symptoms in schizophrenia.

KEYWORDS:

Glycine; Mismatch negativity; N-methyl-d-aspartate; Negative symptoms; Schizophrenia

PMID:
28602646
DOI:
10.1016/j.schres.2017.05.031
[Indexed for MEDLINE]

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