[Abstract Title]. - Society for Neuroscience

Topic: F.01.f. Working memory
Support: Alzheimers and Related Diseases Research Award Fund, Virginia Center on Aging
NIH grants (AG 19653 and others)
Title: The effect of COMT Val158Met on human working memory depends on age, task
difficulty and memory load
Authors: *M. LIN 1 , R. SUNDARARAJAN 2 , P. M. GREENWOOD 3 , R. PARASURAMAN 3 ,
K. J. FRYXELL 2 ;
1 Bioinformatics, 2 Mol. and Microbiol, George Mason Univ., Manassas, VA; 3 Psychology,
George Mason Univ., Fairfax, VA
Abstract: The age-related decline in working memory performance has been attributed to
decline in dopaminergic functioning (Braver & Barch, 2002). Normal variation in genes
controlling enzymes degrading dopamine in the synaptic cleft could affect enzyme efficiency,
thereby exerting greater effects in the older brain. The COMT Val158Met polymorphism shown
to influence rate of dopamine methylation in prefrontal cortex (Tunbridge et al., 2004) and has
been found to affect working memory and executive performance (Weinberger, 2005). We asked
whether normal aging would alter effects of the COMT SNP on spatial working memory
performance. The task required retention of up to 3 target dot locations for 3 sec. Memory was
assessed in the accuracy of a same/different decision indicating whether the probe dot and the
target dot were in the same location. There were 4 target-probe distances (differing in difficulty,
one match, and 3 non-match based on different target-probe distance) and 3 levels of memory
load (number of target locations). Factor analysis applied to working memory accuracy identified
three latent factors correlated with different experimental conditions: (1) match trials; (2) nonmatch
hard discrimination trials; (3) non-match easy discrimination trials. Mixed repeatedmeasures
ANOVAs assessed the influence of target-probe distance and memory load on
accuracy, as well as their interactions with COMT genotype and age. The influence of
discrimination difficulty on accuracy varied with COMT genotype (p < 0.001) and age group (p
< 0.001). The influence of memory load on accuracy varied with COMT genotype (p = 0.01) but
not with age group (p = 0.22).
Follow up mixed repeated-measures ANOVA on each factor assessed the influence of memory
load, COMT genotype, and age on accuracy. On match trials, the trend of decreasing accuracy
with increasing memory load was observed in young adults across COMT genotypes but not
observed in older adults with COMT Val/Val and Met/Met genotypes. On non-match hard
discrimination trials, COMT genotype and age did not change the effect of memory load on
accuracy. On non-match easy discrimination trials, COMT Val/Val performed better than the
Val/Met and Met/Met in both young and older adults across three memory loads. These results
confirm and extend our understanding of the role for genetic variation in dopamine availability
on working memory performance in humans.
References
Braver, T.S., Barch, D.M., 2002. Neurosci. Biobehav. Rev. 26, 809-817.
Tunbridge, E.M. et al. 2004. J Neurosci. 24, 5331-5335.
Weinberger, D.R. 2005. Clin Ther. 27 Suppl A, S8-S15.