COMT Val 158 Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury

Ethan A Winkler; John K Yue; Thomas W McAllister; Nancy R Temkin; Sam S Oh; Esteban G Burchard; Donglei Hu; Adam R Ferguson; Hester F Lingsma; John F Burke; Marco D Sorani; Jonathan Rosand; Esther L Yuh; Jason Barber; Phiroz E Tarapore; Raquel C Gardner; Sourabh Sharma; Gabriela G Satris; Celeste Eng; Ava M Puccio; Kevin K W Wang; Pratik Mukherjee; Alex B Valadka; David O Okonkwo; Ramon Diaz-Arrastia; Geoffrey T Manley; TRACK-TBI Investigators

doi:10.1007/s10048-015-0467-8

COMT Val 158 Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury

Neurogenetics. 2016 Jan;17(1):31-41. doi: 10.1007/s10048-015-0467-8. Epub 2015 Nov 17.

Authors

Ethan A Winkler^{1

2}, John K Yue^{1

2}, Thomas W McAllister³, Nancy R Temkin⁴, Sam S Oh⁵, Esteban G Burchard⁵, Donglei Hu⁵, Adam R Ferguson^{1

2}, Hester F Lingsma⁶, John F Burke^{1

2}, Marco D Sorani^{1

2}, Jonathan Rosand^{7

8}, Esther L Yuh^{2

9}, Jason Barber⁴, Phiroz E Tarapore^{1

2}, Raquel C Gardner^{7

10}, Sourabh Sharma^{1

2}, Gabriela G Satris^{1

2}, Celeste Eng⁵, Ava M Puccio¹¹, Kevin K W Wang¹², Pratik Mukherjee^{2

9}, Alex B Valadka¹³, David O Okonkwo¹¹, Ramon Diaz-Arrastia^{14

15}, Geoffrey T Manley^{16

17}; TRACK-TBI Investigators

Collaborators

TRACK-TBI Investigators:
Shelly R Cooper, Kristen Dams-O'Connor, Wayne A Gordon, Allison J Hricik, Andrew I R Maas, David K Menon, David M Schnyer, Mary J Vassar

Affiliations

¹ Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.
² Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
³ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
⁴ Departments of Neurological Surgery and Biostatistics, University of Washington, Seattle, WA, USA.
⁵ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
⁶ Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands.
⁷ Department of Neurology, Harvard Medical School, Boston, MA, USA.
⁸ Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁹ Department of Radiology, University of California, San Francisco, San Francisco, CA, USA.
¹⁰ Department of Neurology, San Francisco Veterans Administration Medical Center, San Francisco, CA, USA.
¹¹ Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
¹² Center for Neuroproteomics and Biomarkers Research, Departments of Psychiatry and Neuroscience, University of Florida, Gainesville, FL, USA.
¹³ Seton Brain and Spine Institute, Austin, TX, USA.
¹⁴ Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
¹⁵ Center for Neuroscience and Regenerative Medicine, Bethesda, MD, USA.
¹⁶ Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA. manleyg@neurosurg.ucsf.edu.
¹⁷ Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA. manleyg@neurosurg.ucsf.edu.

Abstract

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.

Keywords: Cognitive function; Genetic factors; Human studies; Outcome measures; Traumatic brain injury.

Publication types

Clinical Trial
Multicenter Study
Observational Study
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Amino Acid Substitution*
Brain Injuries / genetics*
Brain Injuries / psychology*
Catechol O-Methyltransferase / genetics*
Cognition Disorders / genetics*
Cognition*
Female
Genetic Association Studies
Humans
Male
Methionine / genetics
Middle Aged
Mutation, Missense
Neuropsychological Tests
Pilot Projects
Polymorphism, Single Nucleotide*
Valine / genetics

COMT Val 158 Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury

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