Document Detail

Effects of metabotropic glutamate receptor 3 genotype on phonetic mismatch negativity.
MedLine Citation:
PMID:  22022368     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The genetic and molecular basis of glutamatergic dysfunction is one key to understand schizophrenia, with the identification of an intermediate phenotype being an essential step. Mismatch negativity (MMN) or its magnetic counterpart, magnetic mismatch field (MMF) is an index of preattentive change detection processes in the auditory cortex and is generated through glutamatergic neurotransmission. We have previously shown that MMN/MMF in response to phoneme change is markedly reduced in schizophrenia. Variations in metabotropic glutamate receptor (GRM3) may be associated with schizophrenia, and has been shown to affect cortical function. Here we investigated the effect of GRM3 genotypes on phonetic MMF in healthy men.
METHODS: MMF in response to phoneme change was recorded using magnetoencephalography in 41 right-handed healthy Japanese men. Based on previous genetic association studies in schizophrenia, 4 candidate SNPs (rs6465084, rs2299225, rs1468412, rs274622) were genotyped.
RESULTS: GRM3 rs274622 genotype variations significantly predicted MMF strengths (p = 0.009), with C carriers exhibiting significantly larger MMF strengths in both hemispheres compared to the TT subjects.
CONCLUSIONS: These results suggest that variations in GRM3 genotype modulate the auditory cortical response to phoneme change in humans. MMN/MMF, particularly those in response to speech sounds, may be a promising and sensitive intermediate phenotype for clarifying glutamatergic dysfunction in schizophrenia.
Yuki Kawakubo; Motomu Suga; Mamoru Tochigi; Masato Yumoto; Kenji Itoh; Tsukasa Sasaki; Yukiko Kano; Kiyoto Kasai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-10-11
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-10-24     Completed Date:  2012-02-17     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e24929     Citation Subset:  IM    
Department of Child Neuropsychiatry, University of Tokyo, Tokyo, Japan.
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MeSH Terms
Magnetic Phenomena*
Polymorphism, Single Nucleotide / genetics
Receptors, Metabotropic Glutamate / genetics*
Reg. No./Substance:
0/Receptors, Metabotropic Glutamate; 0/metabotropic glutamate receptor 3

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