The ability to adapt behaviour in a flexible way is a crucial cognitive function. Set-shifting and maintenance are complex cognitive processes, which are often impaired in several neuropsychiatric and neurodegenerative diseases. The genetic basis of these processes is poorly understood. We aimed to investigate the association between genetic variants of the metabotropic glutamate receptor 3 (GRM3) and cognitive set-shifting in healthy individuals. The relationship between 14 selected single nucleotide polymorphisms (SNPs) of the GRM3 gene and cognitive set-shifting as measured by perseverative errors using the modified card sorting test (MCST). Results show that SNP rs17676277 is related to the performance on the MCST. Subjects with the TT genotype showed significantly less perseverative errors as compared with the AA (P = 0.025) and AT (P = 0.0005) and combined AA/AT genotypes (P = 0.0005). Haplotype analyses suggest the involvement of various SNPs of the GRM3 gene in perseverative error processing in a dominant model of inheritance. The findings strongly suggest that the genetic variation (rs17676277 and three haplotypes) in the metabotropic GRM3 is related to cognitive setshifting in healthy individuals independent of working memory.

Baune, B.T., Suslow, T., Beste, C., Birosova, E., Domschke, K., Sehlmeyer, C., and Konrad, C. (2010), Association between genetic variants of the metabotropic glutamate receptor 3 (GRM3) and cognitive set shifting in healthy individuals, Genes, Brain and Behavior, 9: 459-466.