Effects of metabotropic glutamate receptor 3 genotype on phonetic mismatch negativity.
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.
Department of Child Neuropsychiatry, University of Tokyo, Tokyo, Japan. yukik-tky@umin.ac.jp
Yuki
Y
Kawakubo
Motomu
M
Suga
Mamoru
M
Tochigi
Masato
M
Yumoto
Kenji
K
Itoh
Tsukasa
T
Sasaki
Yukiko
Y
Kano
Kiyoto
K
Kasai
D000328:Adult; D005838:Genotype; D006801:Humans; D060328:Magnetic Phenomena; D015225:Magnetoencephalography; D008297:Male; D010700:Phonetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*
D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3