COMT ValMet polymorphism is associated with post-traumatic stress disorder and functional outcome following mild traumatic brain injury
Open accessAbstract
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 Val 158 Met 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 Met 158 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 Val 158 Met 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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Several studies indicate a role of the COMT gene in stress reactivity on a genetic and epigenetic level.
“as several studies indicate its role in stress reactivity on a genetic [46,47] and epigenetic level [48].”
From Dynamic DNA methylation changes in the COMT gene promoter region in response to mental stress and its modulation by transcranial direct current stimulation (2021) · cites this paper as [46]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,841 · see citing works
National Center for Injury Prevention and Control (U.S.). Division of Injury Response., Faul, M., Wald, M. M., Wu, L., & Coronado, V. G. (2010) · doi:10.15620/cdc.5571 · Cited by 3,494 · see citing works
Diagnostic and Statistical Manual of Mental Disorders
Raber, G., & Spokas, M. (2024) · doi:10.4135/9781071886229.n145 · Cited by 2,806 · see citing works
WILSON, J. T. L., PETTIGREW, L. E. L., & TEASDALE, G. M. (1998) · Journal of Neurotrauma · doi:10.1089/neu.1998.15.573 · Cited by 2,386 · see citing works
Effect of COMT Val 108/158 Met genotype on frontal lobe function and risk for schizophrenia
Egan, M. F., Goldberg, T. E., Kolachana, B. S., Callicott, J. H., Mazzanti, C. M., Straub, R. E., Goldman, D. A., & Weinberger, D. R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111134598 · Cited by 2,374 · see citing works
Chen, J., Lipska, B. K., Halim, N., Ma, Q. D., Matsumoto, M., Melhem, S., Kolachana, B. S., Hyde, T. M., Herman, M. M., Apud, J., et al. (2004) · The American Journal of Human Genetics · doi:10.1086/425589 · Cited by 1,675 · see citing works
Carroll, L., Cassidy, J. D., Peloso, P., Borg, J., von Holst, H., Holm, L., Paniak, C., & Pépin, M. (2004) · Journal of Rehabilitation Medicine · doi:10.1080/16501960410023859 · Cited by 1,326 · see citing works
Lotta, T. I., Vidgren, J., Tilgmann, C., Ulmanen, I., Melén, K., Julkunen, I., & Taskinen, J. (1995) · Biochemistry · doi:10.1021/bi00013a008 · Cited by 1,167 · see citing works
(2000) · PubMed · Cited by 858 · see citing works
Catechol-o-Methyltransferase, Cognition, and Psychosis: Val158Met and Beyond
Tunbridge, E. M., Harrison, P. J., & Weinberger, D. R. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.024 · Cited by 685 · see citing works
Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis
Mier, D., Kirsch, P., & Meyer-Lindenberg, A. (2010) · Molecular Psychiatry · doi:10.1038/mp.2009.36 · Cited by 464 · see citing works
McCrea, M., Iverson, G. L., McAllister, T. W., Hammeke, T. A., Powell, M. R., Barr, W., & Kelly, J. P. (2009) · The Clinical Neuropsychologist · doi:10.1080/13854040903074652 · Cited by 417 · see citing works
Self-citationExploring the convergence of posttraumatic stress disorder and mild traumatic brain injury
Stein, M. B., & McAllister, T. W. (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.08101604 · Cited by 391 · see citing works
Self-citationPonsford, J. L., Draper, K., & Schönberger, M. (2008) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617708080272 · Cited by 386 · see citing works
Yue, J. K., Vassar, M. J., Lingsma, H. F., Cooper, S. R., Okonkwo, D. O., Valadka, A. B., Gordon, W. A., Maas, A. I. R., Mukherjee, P., Yuh, E. L., et al. (2013) · Journal of Neurotrauma · doi:10.1089/neu.2013.2970 · Cited by 371 · see citing works
Self-citationBryant, R. A., & Harvey, A. G. (1998) · American Journal of Psychiatry · doi:10.1176/ajp.155.5.625 · Cited by 320 · see citing works
Polusny, M. A., Kehle, S. M., Nelson, N. W., Erbes, C. R., Arbisi, P. A., & THURAS, P. D. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.172 · Cited by 296 · see citing works
Carlson, K. F., Kehle, S. M., Meis, L. A., Greer, N. L., MacDonald, R. H., Rutks, I. R., Sayer, N. A., Dobscha, S. K., & Wilt, T. J. (2010) · Journal of Head Trauma Rehabilitation · doi:10.1097/htr.0b013e3181e50ef1 · Cited by 284 · see citing works
Gatt, J. M., Burton, K., Williams, L. M., & Schofield, P. R. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.09.014 · Cited by 281 · see citing works
McCauley, S. R., Boake, C., Levin, H. S., Contant, C. F., & Song, J. (2001) · Journal of Clinical and Experimental Neuropsychology · doi:10.1076/jcen.23.6.792.1016 · Cited by 265 · see citing works
Kennedy, J. E. (2007) · The Journal of Rehabilitation Research and Development · doi:10.1682/jrrd.2006.12.0166 · Cited by 261 · see citing works
Mild traumatic brain injury: a neuropsychiatric approach to diagnosis, evaluation, and treatment
Arciniegas, D. B., Anderson, C. A., Topkoff, J. L., & McAllister, T. W. (2005) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.a799 · Cited by 257 · see citing works
Self-citationGenes, cognition and brain through a COMT lens
Dickinson, D., & Elvevåg, B. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.05.014 · Cited by 253 · see citing works
Kolassa, I., Kolassa, S., Ertl, V., Papassotiropoulos, A., & de Quervain, D. J. ‐. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.10.009 · Cited by 245 · see citing works
Genetic Gating of Human Fear Learning and Extinction
Lonsdorf, T. B., Weike, A. I., Nikamo, P., Schalling, M., Hamm, A. O., & Öhman, A. (2009) · Psychological Science · doi:10.1111/j.1467-9280.2009.02280.x · Cited by 242 · see citing works
Jacobs, B., Beems, T., Stulemeijer, M., van Vugt, A. B., van der Vliet, T. M., Borm, G. F., & Vos, P. E. (2009) · Journal of Neurotrauma · doi:10.1089/neu.2009.1059 · Cited by 242 · see citing works
Harvey, A. G., & Bryant, R. A. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.4.626 · Cited by 207 · see citing works
Post-traumatic stress disorder: The role of trauma, pre-existing psychiatric disorders, and gender
Hapke, U., Schumann, A., Rumpf, H.-J., John, U., & Meyer, C. (2006) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-006-0654-6 · Cited by 201 · see citing works
Ho, B., Wassink, T. H., OʼLeary, D. S., Sheffield, V. C., & Andreasen, N. C. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001616 · Cited by 193 · see citing works
Warriors Versus Worriers: The Role of COMT Gene Variants
Stein, D. J., Newman, T. K., Savitz, J. B., & Ramesar, R. (2006) · CNS Spectrums · doi:10.1017/s1092852900014863 · Cited by 181 · see citing works
Luethcke, C. A., Bryan, C. J., Morrow, C. E., & Isler, W. C. (2010) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617710001207 · Cited by 177 · see citing works
Effects of COMT polymorphisms on brain function and behavior in health and disease
Witte, A. V., & Flöel, A. (2011) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2011.11.012 · Cited by 174 · see citing works
Manley, G. T., Diaz-Arrastia, R. R., Brophy, M. T., Engel, D. C., Goodman, C. J., Gwinn, K. A., Veenstra, T. D., Ling, G. S. F., Ottens, A. K., Tortella, F. C., et al. (2010) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2010.05.018 · Cited by 151 · see citing works
Self-citationOhnishi, T., Hashimoto, R., Mori, T., Nemoto, K., Moriguchi, Y., Iida, H., Noguchi, H., Nakabayashi, T., Hori, H., Ohmori, M., et al. (2005) · Brain · doi:10.1093/brain/awh702 · Cited by 151 · see citing works
Heinz, A., & Smolka, M. N. (2006) · Reviews in the Neurosciences · doi:10.1515/revneuro.2006.17.3.359 · Cited by 148 · see citing works
Preinjury Resilience and Mood as Predictors of Early Outcome following Mild Traumatic Brain Injury
McCauley, S. R., Wilde, E. A., Miller, E. R., Frisby, M. L., Garza, H. M., Varghese, R., Levin, H. S., Robertson, C. S., & McCarthy, J. J. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2012.2393 · Cited by 141 · see citing works
Genetic association studies in patients with traumatic brain injury
Dardiotis, E., Fountas, K. N., Dardioti, M., Xiromerisiou, G., Kapsalaki, E. Z., Τάσιου, Α., & Hadjigeorgiou, G. M. (2009) · Neurosurgical FOCUS · doi:10.3171/2009.10.focus09215 · Cited by 130 · see citing works
Association of COMT Val158Met Genotype With Executive Functioning Following Traumatic Brain Injury
Lipsky, R. H., Sparling, M. B., Ryan, L. M., Xu, K., Salazar, A. M., Goldman, D. A., & Warden, D. L. (2005) · Journal of Neuropsychiatry · doi:10.1176/jnp.17.4.465 · Cited by 115 · see citing works
Empirical support for an involvement of the mesostriatal dopamine system in human fear extinction
Raczka, K. A., Mechias, M.-L., Gartmann, N., Reif, A., Deckert, J., Pessiglione, M., & Kalisch, R. (2011) · Translational Psychiatry · doi:10.1038/tp.2011.10 · Cited by 101 · see citing works
Posttraumatic Stress Disorder Symptoms During the First Six Months After Traumatic Brain Injury
Bombardier, C. H., Fann, J. R., Temkin, N. R., Esselman, P. C., Pelzer, E., Keough, M. E., & DIKMEN, S. S. (2006) · Journal of Neuropsychiatry · doi:10.1176/jnp.2006.18.4.501 · Cited by 82 · see citing works
Self-citationThurmond, V. A., Hicks, R. R., Gleason, T., Miller, A. C., Szuflita, N. S., Orman, J. A., & Schwab, K. A. (2010) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2010.06.034 · Cited by 78 · see citing works
Davidson, J. M., Cusimano, M. D., & Bendena, W. G. (2014) · The Neuroscientist · doi:10.1177/1073858414543150 · Cited by 77 · see citing works
Human fear reconsolidation and allelic differences in serotonergic and dopaminergic genes
Ågren, T., Furmark, T., Eriksson, E., & Fredrikson, M. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.5 · Cited by 72 · see citing works
Sandweiss, D. A. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.44 · Cited by 68 · see citing works
Harvey, A. G., Brewin, C. R., Jones, C., & Kopelman, M. D. (2003) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617703940069 · Cited by 67 · see citing works
Cytokine Gene Polymorphisms and Outcome after Traumatic Brain Injury
Waters, R. J., Murray, G. D., Teasdale, G. M., Stewart, J., Day, I. N. M., Lee, R. J., & Nicoll, J. A. R. (2013) · Journal of Neurotrauma · doi:10.1089/neu.2012.2792 · Cited by 65 · see citing works
Genetic Factors in Outcome After Traumatic Brain Injury
Diaz-Arrastia, R. R., & Baxter, V. K. (2006) · Journal of Head Trauma Rehabilitation · doi:10.1097/00001199-200607000-00007 · Cited by 57 · see citing works
Self-citationValente, N. L. M., Vallada, H., Cordeiro, Q., Bressan, R. A., Andreoli, S. B., Mari, J. D. J., & Mello, M. F. (2010) · Journal of Molecular Neuroscience · doi:10.1007/s12031-010-9474-2 · Cited by 55 · see citing works
Whyte, J., Vasterling, J. J., & Manley, G. T. (2010) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2010.06.031 · Cited by 49 · see citing works
Self-citationGraham, D. P., Helmer, D. A., Harding, M. J., Kosten, T. R., Petersen, N. J., & Nielsen, D. A. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.02.006 · Cited by 47 · see citing works
Ho, B., Wassink, T. H., OʼLeary, D. S., Sheffield, V. C., & Andreasen, N. C. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001652 · Cited by 45 · see citing works
COMT genotype affects brain white matter pathways in attention-deficit/hyperactivity disorder
Hong, S.-B., Zalesky, A., Park, S., Yang, Y.-H., Park, M.-H., Kim, B., Song, I. C., Sohn, C., Shin, M., Kim, B.-N., et al. (2014) · Human Brain Mapping · doi:10.1002/hbm.22634 · Cited by 44 · see citing works
Clark, R., DeYoung, C. G., Sponheim, S. R., Bender, T. L., Polusny, M. A., Erbes, C. R., & Arbisi, P. A. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.08.013 · Cited by 43 · see citing works
Wilker, S., Elbert, T. R., & Kolassa, I. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.08.015 · Cited by 42 · see citing works
Klucken, T., Kruse, O., Wehrum‐Osinsky, S., Hennig, J., Schweckendiek, J., & Stark, R. M. (2014) · Human Brain Mapping · doi:10.1002/hbm.22688 · Cited by 40 · see citing works
Genetic Influence of COMT and BDNF Gene Polymorphisms on Resilience in Healthy College Students
Kang, J. I., Kim, S. J., Song, Y. Y., Namkoong, K., & An, S. K. (2013) · Neuropsychobiology · doi:10.1159/000353257 · Cited by 39 · see citing works
COMT Val 158 Met and Cognitive and Functional Outcomes after Traumatic Brain Injury
Willmott, C., Withiel, T., Ponsford, J. L., & Burke, R. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2013.3308 · Cited by 33 · see citing works
Hill, S. Y., Lichenstein, S. D., Wang, S., Carter, H., & McDermott, M. (2013) · Advances in Molecular Imaging · doi:10.4236/ami.2013.34007 · Cited by 23 · see citing works
Willmott, C., Ponsford, J. L., McAllister, T. W., & Burke, R. (2013) · Brain Injury · doi:10.3109/02699052.2013.809553 · Cited by 21 · see citing works
Self-citationHumphreys, K. L., Scheeringa, M. S., & Drury, S. S. (2014) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2014.0077 · Cited by 14 · see citing works
The Influence ofBMXGene Polymorphisms on Clinical Symptoms after Mild Traumatic Brain Injury
Wang, Y.-J., Hsu, Y.-W., Chang, C., et al. (2014) · BioMed Research International · doi:10.1155/2014/293687 · Cited by 9 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [27]Willmott C Withiel T Ponsford J COMT Val158Met and cognitive and functional outcomes after traumatic brain injury J Neurotrauma 2014 31 1507 14 24786534
Cited by
Sorted by citations
Wiegand, A., Blickle, A., Brückmann, C., Weller, S., Nieratschker, V., & Plewnia, C. (2021) · Biomolecules · doi:10.3390/biom11111726 · Cited by 19 · see citing works
- Authors
- Winkler, E. A., Yue, J. K., Ferguson, A. R., Temkin, N. R., Stein, M. B., Barber, J., Yuh, E. L., Sharma, S., Satris, G. G., McAllister, T. W., Rosand, J., Sorani, M. D., Lingsma, H. F., Tarapore, P. E., Burchard, E. G., Hu, D., Eng, C., Wang, K. K. W., Mukherjee, P., Okonkwo, D. O., Diaz-Arrastia, R., & Manley, G. T.
- Affiliations
- San Francisco General Hospital (US)
- University of Washington (US)
- University of California San Diego (US)
- Indiana University School of Medicine (US)
- Broad Institute (US)
- Erasmus MC (NL)
- University of California, San Francisco (US)
- University of Florida (US)
- University of Pittsburgh Medical Center (US)
- Uniformed Services University of the Health Sciences (US)
- Corresponding author
- Manley, Geoffrey T.
- ORCID
- Winkler, Ethan A.
- Yue, John K.
- Ferguson, Adam R.
- Temkin, Nancy R.
- Stein, Murray B.
- Barber, Jason
- Yuh, Esther L.
- Sharma, Sourabh
- McAllister, Thomas W.
- Rosand, Jonathan
- Lingsma, Hester F.
- Tarapore, Phiroz E.
- Burchard, Esteban G.
- Hu, Donglei
- Eng, Celeste
- Wang, Kevin K.W.
- Mukherjee, Pratik
- Okonkwo, David O.
- Diaz-Arrastia, Ramon
- Manley, Geoffrey T.
- Venue
- Journal of Clinical Neuroscience
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 35
- Pages
- 109-116
- ISSN
- 0967-5868 (ISSN-L)
- PMC
- PMC5588892
- OpenAlex
- W2537707735
- Cited by
- 52
- References
- 61
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 9 · 2020: 4 · 2019: 8 · 2018: 11 · 2017: 4
- FWCI
- 7.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- NIH (RC2 NS069409, RC2 NS069409-02S1, U01 NS086090-01, DOD USAMRAA W81XWH-13-1-0441)
- Topics
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- COMT Val158Met polymorphism, catechol-O-methyltransferase, mild traumatic brain injury, post-traumatic stress disorder, functional outcome, Glasgow Outcome Scale-Extended, single nucleotide polymorphisms, genetic susceptibility, PTSD Checklist-Civilian Version
- MeSH terms
- Brain Injuries, Traumatic, Adult, Aged, Alleles, Catechol O-Methyltransferase, Ethnicity, Female, Humans, Male, Methionine, Middle Aged, Polymorphism, Genetic, Prospective Studies, Stress Disorders, Post-Traumatic, Valine, Glasgow Coma Scale, Substance-Related Disorders, Polymorphism, Single Nucleotide, Glasgow Outcome Scale
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
