COMT Val158Met polymorphism is associated with post-traumatic stress disorder and functional outcome following mild traumatic brain injury - PubMed (original) (raw)

Observational Study

doi: 10.1016/j.jocn.2016.09.017. Epub 2016 Oct 18.

John K Yue 1, Adam R Ferguson 1, Nancy R Temkin 2, Murray B Stein 3, Jason Barber 2, Esther L Yuh 4, Sourabh Sharma 1, Gabriela G Satris 1, Thomas W McAllister 5, Jonathan Rosand 6, Marco D Sorani 1, Hester F Lingsma 7, Phiroz E Tarapore 1, Esteban G Burchard 8, Donglei Hu 8, Celeste Eng 8, Kevin K W Wang 9, Pratik Mukherjee 4, David O Okonkwo 10, Ramon Diaz-Arrastia 11, Geoffrey T Manley 12; TRACK-TBI Investigators

Affiliations

Observational Study

COMT Val158Met polymorphism is associated with post-traumatic stress disorder and functional outcome following mild traumatic brain injury

Ethan A Winkler et al. J Clin Neurosci. 2017 Jan.

Abstract

Mild 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.

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

Copyright © 2016 Elsevier Ltd. All rights reserved.

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Conflict of interest statement

Conflict of interest

No competing financial interests exist.

Disclosure statement

The authors have no competing interests to disclose.

Figures

Fig. 1

Fig. 1

The COMT Val158Met polymorphism is associated with lower prevalence of qualifying for screening criteria for post-traumatic stress disorder (PTSD) at 6-months following mild traumatic brain injury. White, did not meet PTSD qualification on screening criteria; red, met PTSD qualification on screening criteria. COMT = Catechol-O-Methyltransferase. red, met PTSD qualification on screening criteria.

Fig. 2

Fig. 2

The COMT Val158Met polymorphism is associated with greater global functional outcome as measured by the Glasgow Outcome Scale Extended (GOSE) at 6-months following mild traumatic brain injury. White, GOSE score of 8; light gray, GOSE score of 7; dark gray, GOSE score of 5; red, GOSE score of 5. COMT = Catechol-O-Methyltransferase.

Fig. 3

Fig. 3

Global functional outcome is negatively associated with the presence of concomitant post-traumatic stress disorder at 6-months post-injury. (A–C) Graphs depicting proportion of individuals not meeting (white) or meeting (red) post-traumatic stress disorder (PTSD) screening criteria in all subjects (A), subjects with the COMT Met158 allele (B), and subjects with COMT Val158/Val158 homozygosity (C). COMT = Catechol-O-Methyltransferase.

References

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