Effects of Metabotropic Glutamate Receptor 3 Genotype on Phonetic Mismatch Negativity 英文参考文献.docVIP

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Effects of Metabotropic Glutamate Receptor 3 Genotype on Phonetic Mismatch Negativity 英文参考文献.doc

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Effects of Metabotropic Glutamate Receptor 3 Genotype on Phonetic Mismatch Negativity 英文参考文献

EffectsofMetabotropicGlutamateReceptor3Genotype onPhoneticMismatchNegativity YukiKawakubo1*,MotomuSuga2,MamoruTochigi2,MasatoYumoto3,KenjiItoh4,TsukasaSasaki5, YukikoKano1,KiyotoKasai2 1Department of Child Neuropsychiatry, University of Tokyo, Tokyo, Japan, 2Department of Neuropsychiatry, University of Tokyo, Tokyo, Japan, 3Department of Laboratory Medicine, University of Tokyo, Tokyo, Japan, 4Department of Cognitive and Speech Sciences, University of Tokyo, Tokyo, Japan, 5Health Service Center, UniversityofTokyo,Tokyo,Japan Abstract Background:Thegeneticandmolecularbasisofglutamatergicdysfunctionisonekeytounderstandschizophrenia,with the identification of an intermediate phenotype being an essential step. Mismatch negativity (MMN) or its magnetic counterpart,magneticmismatchfield(MMF)isanindexofpreattentivechangedetectionprocessesintheauditorycortex 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 genotypesonphoneticMMFinhealthymen. Methods:MMFinresponsetophonemechangewasrecordedusingmagnetoencephalographyin41right-handedhealthy Japanese men. Based on previous genetic association studies in schizophrenia, 4 candidate SNPs (rs6465084, rs2299225, rs1468412,rs274622)weregenotyped. Results: GRM3 rs274622 genotype variations significantly predicted MMF strengths (p=0.009), with C carriers exhibiting significantlylargerMMFstrengthsinbothhemispherescomparedtotheTTsubjects. Conclusions:TheseresultssuggestthatvariationsinGRM3genotypemodulatetheauditorycorticalresponsetophoneme change in humans. MMN/MMF, particularly those in response to speech sounds, may be a promising and sensitive intermediatephenotypeforclarifyingglutamatergicdysfunctioninschizophrenia. Citation: Kawakubo Y, Sug