Elsevier

Psychiatry Research

Volume 218, Issue 3, 30 August 2014, Pages 356-358
Psychiatry Research

Brief report
A recently-discovered NMDA receptor gene, GRIN3B, is associated with duration mismatch negativity

https://doi.org/10.1016/j.psychres.2014.04.032Get rights and content

Abstract

The study explored associations between mismatch negativity and N-methyl-d-aspartic acid receptor subunit genes, GRIN1, GRIN2B and GRIN3B in healthy subjects and schizophrenia. Nineteen single-nucleotide polymorphisms were genotyped in 138 schizophrenia patients and 103 healthy subjects. Rs2240158 of GRIN3B was significantly associated with mismatch negativity in healthy subjects.

Introduction

Glutamatergic neurotransmission mediated by N-methyl-d-aspartate (NMDA) receptors plays an important role in the pathogenesis of schizophrenia. Auditory mismatch negativity (MMN) may be a surrogate index of NMDA receptor function. Auditory MMN is an event-related potential (ERP) elicited by a discernible change in a train of standard sounds. MMN reflects the auditory echoic memory and is elicited even when the individual is not attending to the stimuli (Naatanen and Winkler, 1999). Administering NMDA receptor antagonists ketamine or MK-801 reduced the MMN amplitude in healthy human subjects (Umbricht et al., 2000). In addition, MMN has been suggested as an schizophrenia endophenotype (Turetsky et al., 2007).

Inconclusive associations between schizophrenia and NMDA receptor subunit genes have been reported (Sodhi et al., 2008). The main hypothesis of this study was that NMDA receptor subunit genes GRIN1, GRIN2B and GRIN3B are associated with duration MMN. In addition, the association pattern can be different between healthy subjects and schizophrenia patients. It is noteworthy that GRIN3B, the most recently discovered subunit of the NMDA receptor, has not been examined in previous studies.

Section snippets

Subjects

Patients with schizophrenia (n=138; mean age±S.D. 38.21±10.09 years; 45.7% male; education 13.26±2.74 years) and healthy subjects who had no current or lifetime mental disorders (n=78; mean age±S.D. 32.78±11.53 years; 38.8% male; education 15.50±3.36) were enrolled. The control group included 25 subjects under 18 years from an early-schizophrenia study. The diagnosis of schizophrenia was made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision.

Results

Ninety-seven healthy subjects and 119 schizophrenia patients completed the MMN procedure. The MMN mean amplitude was significantly less negative in patients than in healthy subjects (−0.42±0.68 μV and −1.06±0.92 μV, p<0.001). Age was the only variable that was significantly correlated with MMN after controlling for the effect of affected status (Pearson partial correlation coefficient=0.39; P<0.0001). For patients, MMN was not correlated with PANSS scores, typical or atypical antipsychotic agents

Discussion

This study found a significant association between GRIN3B and duration MMN in healthy subjects, which supported the involvement of the glutamatergic system in MMN. GRIN3B encodes for NR3B, most recently identified member of the NMDA receptor family. The classical NMDA receptor is a heterotetramer comprised of two essential glycine-binding NR1 subunits and two glutamate-binding NR2 subunits. NR3-containing NMDA receptors formed by NR1 and NR3 subunits can be activated by glycine alone and have

Acknowledgments

We thank the National Center for Genome Medicine at Academia Sinica, Taiwan, for genotyping support. This Center was supported by Grants from the National Core Facility Program for Biotechnology of National Science Council Taiwan. We also thank the Department of Medical Research, National Taiwan University Hospital for the support of laboratory experiments. This work was supported by the National Science Council Taiwan (NSC-98-2314-B-002-047-MY3, NSC-96-3112-B-002-039) and National Taiwan

References (12)

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Institution where the work was performed: National Taiwan University Hospital.

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