Metabotropic Glutamate Receptor 3 Genotype May Predict 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.