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Association of COMT Val158Met Genotype With Executive Functioning Following Traumatic Brain Injury

Received December 12, 2003; revised June 17, 2004; accepted June 24, 2004. From the Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, Maryland; the Defense and Veterans Brain Injury Center, Departments of Neurology and Neurosurgery, Walter Reed Army Medical Center, Washington, DC; the Uniformed Services University of Health Sciences, Bethesda, Maryland. Address correspondence to Dr. Warden, Defense and Veterans Brain Injury Center, Walter Reed Army Medical Center, P.O. Box 59181, Washington, DC 20012; deborah.warden{at}na.amedd.army.mil (E-mail).

Catechol-O-methyltransferase (COMT) is thought to functionally modulate dopamine neurons, thus likely influencing frontal-executive functioning. High enzyme activity (COMT Val) and low enzyme activity (COMT Met) are functional polymorphisms resulting from a G to A transition in exon 4 (codon 158) of the human COMT gene. Decreased cortical dopamine should result in poorer executive functioning. Therefore, the authors hypothesized that individuals with traumatic brain injury (TBI) and the low enzyme activity polymorphism would perform better on tests of executive functioning than individuals with the high enzyme activity polymorphism. One hundred thirteen individuals referred to the Defense and Veterans Brain Injury Center underwent a comprehensive TBI evaluation and were genotyped for the COMT polymorphism. Comparison of mean differences among the COMT genotype groups for several measures of aspects of executive functioning was conducted using analysis of variance (ANOVA) with adjustment for multiple comparisons. Homozygotes for the higher activity allele made more perseverative responses on the Wisconsin Card Sorting Test, while homozygotes for the lower activity allele had the least number of perseverative responses. While it cannot be determined whether TBI influenced the association of COMT Val158Met to executive functioning, these data extend the known relationship of genotype to executive performance seen in healthy comparison subjects and individuals with schizophrenia to individuals with TBI.

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