title: COMT Val 158 Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury.
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.
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
authors.forename: Ethan A
authors.initials: EA
authors.lastname: Winkler
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Yue
authors.affiliation: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: McAllister
authors.affiliation: Departments of Neurological Surgery and Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Temkin
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Sam S
authors.initials: SS
authors.lastname: Oh
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Ferguson
authors.affiliation: Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Hester F
authors.initials: HF
authors.lastname: Lingsma
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Burke
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
authors.forename: Marco D
authors.initials: MD
authors.lastname: Sorani
authors.affiliation: Department of Neurology, Harvard Medical School, Boston, MA, USA.|Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.affiliation: Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.|Department of Radiology, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Esther L
authors.initials: EL
authors.lastname: Yuh
authors.affiliation: Departments of Neurological Surgery and Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Barber
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
authors.forename: Phiroz E
authors.initials: PE
authors.lastname: Tarapore
authors.affiliation: Department of Neurology, Harvard Medical School, Boston, MA, USA.|Department of Neurology, San Francisco Veterans Administration Medical Center, San Francisco, CA, USA.
authors.forename: Raquel C
authors.initials: RC
authors.lastname: Gardner
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
authors.forename: Sourabh
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA, 94110, USA.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
authors.forename: Gabriela G
authors.initials: GG
authors.lastname: Satris
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.affiliation: Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Ava M
authors.initials: AM
authors.lastname: Puccio
authors.affiliation: Center for Neuroproteomics and Biomarkers Research, Departments of Psychiatry and Neuroscience, University of Florida, Gainesville, FL, USA.
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Wang
authors.affiliation: Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.|Department of Radiology, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Pratik
authors.initials: P
authors.lastname: Mukherjee
authors.affiliation: Seton Brain and Spine Institute, Austin, TX, USA.
authors.forename: Alex B
authors.initials: AB
authors.lastname: Valadka
authors.affiliation: Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: David O
authors.initials: DO
authors.lastname: Okonkwo
authors.affiliation: Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Center for Neuroscience and Regenerative Medicine, Bethesda, MD, USA.
authors.forename: Ramon
authors.initials: R
authors.lastname: Diaz-Arrastia
authors.affiliation: 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.|Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA. manleyg@neurosurg.ucsf.edu.
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Manley
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001930:Brain Injuries / Q000235:genetics* / Q000523:psychology*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003071:Cognition; D003072:Cognition Disorders / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense; D009483:Neuropsychological Tests; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D014633:Valine / Q000235:genetics
chemical_list: D008715:Methionine; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D014633:Valine
keywords: Cognitive function; Genetic factors; Human studies; Outcome measures; Traumatic brain injury