• Ethan A Winkler, John K Yue, Adam R Ferguson, Nancy R Temkin, Murray B Stein, Jason Barber, Esther L Yuh, Sourabh Sharma, Gabriela G Satris, Thomas W McAllister, Jonathan Rosand, Marco D Sorani, Hester F Lingsma, Phiroz E Tarapore, Esteban G Burchard, Donglei Hu, Celeste Eng, Kevin K W Wang, Pratik Mukherjee, David O Okonkwo, Ramon Diaz-Arrastia, Geoffrey T Manley, and TRACK-TBI Investigators.
• Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Brain and Spinal Injury Center, San Francisco General Hospital, San Francisco, CA, USA.
• J Clin Neurosci. 2017 Jan 1; 35: 109-116.

AbstractMild traumatic brain injury (mTBI) results in variable clinical trajectories and outcomes. The source of variability remains unclear, but may involve genetic variations, such as single nucleotide polymorphisms (SNPs). A SNP in catechol-o-methyltransferase (COMT) is suggested to influence development of post-traumatic stress disorder (PTSD), but its role in TBI remains unclear. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val158Met polymorphism is associated with PTSD and global functional outcome as measured by the PTSD Checklist - Civilian Version and Glasgow Outcome Scale Extended (GOSE), respectively. Results in 93 predominately Caucasian subjects with mTBI show that the COMT Met158 allele is associated with lower incidence of PTSD (univariate odds ratio (OR) of 0.25, 95% CI [0.09-0.69]) and higher GOSE scores (univariate OR 2.87, 95% CI [1.20-6.86]) 6-months following injury. The COMT Val158Met genotype and PTSD association persists after controlling for race (multivariable OR of 0.29, 95% CI [0.10-0.83]) and pre-existing psychiatric disorders/substance abuse (multivariable OR of 0.32, 95% CI [0.11-0.97]). PTSD emerged as a strong predictor of poorer outcome on GOSE (multivariable OR 0.09, 95% CI [0.03-0.26]), which persists after controlling for age, GCS, and race. When accounting for PTSD in multivariable analysis, the association of COMT genotype and GOSE did not remain significant (multivariable OR 1.73, 95% CI [0.69-4.35]). Whether COMT genotype indirectly influences global functional outcome through PTSD remains to be determined and larger studies in more diverse populations are needed to confirm these findings.Copyright © 2016 Elsevier Ltd. All rights reserved.

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