Catechol-O-Methyltransferase (COMT) Genotypes and Working Memory: Associations with Differing Cognitive Operations

Background Catechol-O-methyltransferase (COMT) is a strong candidate gene for schizophrenia and cognitive functions disrupted in this disorder. This report examines the relation of COMT genotypes to performance on a battery of working memory tests differing in the cognitive operations to be performed on the material. Methods A large sample of 402 healthy adults were tested on four working memory tests: Spatial Delayed Response (SDR), Word Serial Position Test (WSPT), N-back, and Letter–Number Sequencing. A subsample (n = 246) was tested on the Wisconsin Card Sorting Test (WCST). A saliva swab was used to obtain DNA from all participants. Results Letter–Number Sequencing, which requires both storage and manipulation of information, was the only working memory test that showed expected differences among COMT genotypes, with the met/met group showing the best performance and the val/val group the poorest performance. As in previous studies, the met/met group also performed better than the val/val group on the WCST. Conclusions COMT genotypes were not associated with performance on tests measuring simple storage, maintenance of temporal order or updating of information in working memory. Genotype differences in Letter–Number Sequencing and WCST suggest that higher-order components of processing (e.g., mental manipulation) are more closely related to this gene.