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Effect of Metabotropic Glutamate Receptor 3 Genotype on N-Acetylaspartate Measures in the Dorsolateral Prefrontal Cortex

OBJECTIVE: This study was carried out to confirm prior evidence of an effect of a single nucleotide polymorphism (SNP) in the metabotropic glutamate receptor 3 (GRM3) gene (a putative risk factor for schizophrenia) on measures of N-acetylaspartate in healthy comparison subjects. METHOD: Fifty-four carefully screened healthy volunteers genotyped at SNP rs6465084 underwent magnetic resonance spectroscopic imaging (MRSI) at 3 T and selected neuropsychological testing. RESULTS: The A/A genotype group exhibited a significant reduction of N-acetylaspartate/creatine levels in the right dorsolateral prefrontal cortex compared to the G carriers. A tendency in the same direction was seen in the left dorsolateral prefrontal cortex and in the white matter adjacent to the prefrontal cortex. CONCLUSIONS: These findings provide further evidence that GRM3 affects prefrontal function and that variation in GRM3, monitored by SNP rs6465084, affects GRM3 function.

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				H.-Y. Tan, Q. Chen, S. Sust, J. W. Buckholtz, J. D. Meyers, M. F. Egan, V. S. Mattay, A. Meyer-Lindenberg, D. R. Weinberger, and J. H. Callicott Epistasis between catechol-O-methyltransferase and type II metabotropic glutamate receptor 3 genes on working memory brain function PNAS, July 24, 2007; 104(30): 12536 - 12541. [Abstract] [Full Text] [PDF]

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