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COMT Val158Met polymorphism is associated with post-traumatic stress disorder and functional outcome following mild traumatic brain injury.
Winkler, Ethan A; Yue, John K; Ferguson, Adam R; Temkin, Nancy R; Stein, Murray B; Barber, Jason; Yuh, Esther L; Sharma, Sourabh; Satris, Gabriela G; McAllister, Thomas W; Rosand, Jonathan; Sorani, Marco D; 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.
Afiliación
  • Winkler EA; 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.
  • Yue JK; 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.
  • Ferguson AR; 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.
  • Temkin NR; Department of Neurological Surgery and Biostatistics, University of Washington, Seattle, WA, USA.
  • Stein MB; Department of Psychiatry, University of California, San Diego, San Diego, CA, USA; Department of Family and Preventative Medicine, University of California, San Diego, San Diego, CA, USA.
  • Barber J; Department of Neurological Surgery and Biostatistics, University of Washington, Seattle, WA, USA.
  • Yuh EL; 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.
  • Sharma S; 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.
  • Satris GG; 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.
  • McAllister TW; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Rosand J; 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.
  • Sorani MD; 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.
  • Lingsma HF; Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Tarapore PE; 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.
  • Burchard EG; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
  • Hu D; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
  • Eng C; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
  • Wang KK; Center for Neuroproteomics and Biomarkers Research, Departments of Psychiatry and Neuroscience, University of Florida, Gainesville, FL, USA.
  • Mukherjee P; 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.
  • Okonkwo DO; Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  • Diaz-Arrastia R; Department of Neurology, Uniformed Services University of the Health Sciences, and Center for Neuroscience and Regenerative Medicine, Bethesda, MD, USA.
  • Manley GT; 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. Electronic address: manleyg@neurosurg.ucsf.edu.
J Clin Neurosci ; 35: 109-116, 2017 Jan.
Article en En | MEDLINE | ID: mdl-27769642
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo Genético / Trastornos por Estrés Postraumático / Catecol O-Metiltransferasa / Lesiones Traumáticas del Encéfalo Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Neurosci Asunto de la revista: NEUROLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo Genético / Trastornos por Estrés Postraumático / Catecol O-Metiltransferasa / Lesiones Traumáticas del Encéfalo Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Neurosci Asunto de la revista: NEUROLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos