Catechol-O-Methyltransferase (COMT) Genotypes and Working Memory: Associations with Differing Cognitive Operations
Gerard E. Bruder1,3, John G. Keilp1,4, Haiyan Xu2, Marina Shikhman3, Efrat Schori3, Jack M. Gorman5, T. Conrad Gilliam1,2,6
1Department of Psychiatry and 2Department of Genetics and Development, Columbia University, New York, USA; 3Department of Biopsychology and 4Department of Neuroscience, New York State Psychiatric Institute, New York, USA; 5Department of Psychiatry, Mount Sinai School of Medicine, NewYork, USA; 6Columbia Genome Center, New York, New York, USA
Received 18 January 2005; Revised 21 April 2005; accepted 4 May 2005.
Abstract
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.
Key Words: Catechol-O-methyltransferase, COMT genotypes, dopamine, executive function, working memory