DRD2 C957T polymorphism interacts with the COMT Val158Met polymorphism in human working memory ability

Haiyan Xu^a, Christoph B. Kellendonk^b, Eleanor H. Simpson^b, John G. Keilp^c,d, Gerard E. Bruder^c,e, H. Jonathan Polan^b,c, Eric R. Kandel^b,c, T. Conrad Gilliam^a,c,f

^aDepartment of Genetics and Development, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; ^bCenter for Neurobiology and Behavior, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; ^cDepartment of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; ^dDivision of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA; ^eDivision of Biopsychology, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA; ^fDepartment of Human Genetics, The University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA

Received 21 July 2006; revised 29 September 2006; accepted 3 October 2006. 

Abstract

The C957T polymorphism in the dopamine D2 receptor (DRD2) gene and the Val158Met polymorphism in the Catechol-O-Methyl-Transferase (COMT) gene affect dopamine transmission and have been found to be associated with schizophrenia. Since DRD2 in mice and the COMT gene in humans modulate working memory, we examined the relationship and possible interaction of both polymorphisms to working memory performance in 188 healthy adults. Subjects having the DRD2 C/C allele showed the poorest performance in a word serial position test. Moreover, the effect of the C957T genotype was strengthened when interaction with the COMT Val158Met polymorphism was included in the analysis. We propose that an interaction of the DRD2 C957T and COMT Val158Met may be involved in the generation of some working memory deficits in schizophrenia.

Key Words: Working memory; Dopamine D2 receptor; C957T polymorphism; Catechol-O-Methyl-Transferase; Val158Met polymorphism; Schizophrenia