COMT Val 158 Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury
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Mild 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 which 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 not been studied. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val 158 Met 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) Trail B minus Trail A time, and California Verbal Learning Test, Second Edition Trial 1–5 Standard Score (CVLT-II). All patients had an emergency department Glasgow Coma Scale (GCS) of 13–15, no acute intracranial pathology on head CT, and no polytrauma as defined by an Abbreviated Injury Scale (AIS) score of ≥3 in any extracranial region. Results in 100 subjects aged 40.9 (SD 15.2) years (COMT Met 158 /Met 158 29 %, Met 158 /Val 158 47 %, Val 158 /Val 158 24 %) show that the COMT Met 158 allele (mean 101.6 ± SE 2.1) associates with higher nonverbal processing speed on the WAIS-PSI when compared to Val 158 /Val 158 homozygotes (93.8 ± SE 3.0) after controlling for demographics and injury severity (mean increase 7.9 points, 95 % CI [1.4 to 14.3], p = 0.017). The COMT Val 158 Met polymorphism did not associate with mental flexibility on the TMT or with verbal learning on the CVLT-II. Hence, COMT Val 158 Met may preferentially modulate nonverbal cognition following uncomplicated mTBI.
Registry: ClinicalTrials.gov Identifier NCT01565551
KeywordsTraumatic brain injury Genetic factors Cognitive function Outcome measures Human studies
The authors would like to thank the following contributors to the development of the TRACK-TBI database and repositories by organization and alphabetical order by last name:
QuesGen Systems, Inc.: Vibeke Brinck, MS, and Michael Jarrett, MBA
One Mind for Research: General Peter Chiarelli, US Army (Ret.), and Garen Staglin, MBA
Thomson Reuters: Sirimon O’Charoen, PhD
This work was supported by the following grants: NIH RC2 NS069409, NIH RC2 NS069409-02S1, NIH U01 NS086090-01, DOD USAMRAA W81XWH-13-1-0441, DOD W81XWH-14-2-0176
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflicts of interest.
Research involving human participants
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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