• Neurosurgery · Aug 2015

    178 COMT Val158Met is Associated With Domain-Specific Cognitive Impairment Following Mild Traumatic Brain Injury.

    • John K Yue, Ethan A Winkler, Thomas W McAllister, Nancy Temkin, Adam Ferguson, Hester F Lingsma, Esther Yuh, Phiroz E Tarapore, Sourabh Sharma, Ava Puccio, Kevin Wang, Pratik Mukherjee, Alex B Valadka, David O Okonkwo, Ramon Diaz-Arrastia, and Geoffrey T Manley.
    • Neurosurgery. 2015 Aug 1;62 Suppl 1:225.

    IntroductionMild traumatic brain injury (mTBI) results in variable clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism in catechol-o-methyltransferase (COMT), an enzyme that degrades catecholamine neurotransmitters, may influence cognitive deficits following moderate and/or severe head trauma. However, this has been disputed and its role in mTBI has yet to be studied.MethodsA retrospective analysis of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study was conducted to determine whether the COMT Val158Met polymorphism influences outcome on a cognitive battery 6 months following mTBI Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), Trail Making Test (TMT), and California Verbal Learning Test (CVLT).ResultsIn 93 predominately white subjects, we demonstrate that the COMT Met158 allele associates with improved processing speed (mean increase 10.3 points, 95% CI [3.5-17.1], P = .004) and mental flexibility (mean decrease 21.6 seconds [1.4-41.8], P = .037) on WAIS-PSI and TMT, respectively, compared with Val158/Val158 homozygotes. The association between the COMT Met158 allele and WAIS-PSI persists after controlling for effects of age and years of education (mean increase 8.0 points [1.4-14.7], P = .019). The association between the COMT Met158 allele and TMT completion times demonstrated a statistical trend after controlling for age and education (mean decrease 16.1 seconds [-34.0 to 1.8], P = .078). Older age and decreased education associate with impairment on WAIS-PSI and TMT independent of COMT. COMT Val158Met did not influence verbal learning on CVLT.ConclusionCOMT Val158Met may exert domain-specific cognitive protection following mTBI.

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