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  • COMT Val158Met Polymorphism is Associated with Post-traumatic Stress Disorder and Functional Outcome Following Mild Traumatic Brain Injury

    Final Number:

    Ethan Winkler MD PhD; John Yue BA; Adam Ferguson PhD; Nancy Temkin Phd; Murray Stein; Esther Yuh; Thomas McAllister MD; Phiroz Tarapore MD; Kevin Wang PhD; David Okonkwo MD, PhD; Ramon Diaz-Arrastia MD, PHD; Geoffrey Manley MD, PhD

    Study Design:

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2015 Annual Meeting

    Introduction: 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.

    Methods: A retrospective analysis was conducted of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to determine 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, we demonstrate 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]).

    Conclusions: The COMT Val158Met polymorphism (rs4680) is associated with incidence of PTSD and functional outcome following isolated, uncomplicated mTBI, and may exert a protective effect. Larger studies in more diverse populations are needed to confirm the role of COMT Val158Met in psychological health following mTBI. Whether COMT Val158/Val158 homozygotes would benefit from heightened clinical surveillance and/or pharmacologic and behavioral therapy targeted towards symptomatic manifestations of PTSD remain to be determined.

    Patient Care: It will lead to better identification of a subgroup of patients at highest risk for the development of PTSD following TBI who may benefit from close post-traumatic clinical surveillance.

    Learning Objectives: By the conclusion of the session, participants should be able to: 1. Understand the incidence and relevance of PTSD following mild TBI 2. Describe the known risk factors with an emphasis on the COMT single nucleotide polymorphism that are associated with development of PTSD following mild TBI 3. Describe the importance of a potential underlying relationship between PTSD and functional outcome following TBI


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