Browsing by Author "TRACK-TBI Investigators"

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    COMT Val 158 Met polymorphism is associated with post-traumatic stress disorder and functional outcome following mild traumatic brain injury
    (Elsevier, 2017-01) 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.; TRACK-TBI Investigators; Psychiatry, School of Medicine
    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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    DRD2 C957T polymorphism is associated with improved 6-month verbal learning following traumatic brain injury
    (Springer, 2017-01) Yue, John K.; Winkler, Ethan A.; Rick, Jonathan W.; Burke, John F.; McAllister, Thomas W.; Oh, Sam S.; Burchard, Esteban G.; Hu, Donglei; Rosand, Jonathan; Temkin, Nancy R.; Korley, Frederick K.; Sorani, Marco D.; Ferguson, Adam R.; Lingsma, Hester F.; Sharma, Sourabh; Robinson, Caitlin K.; Yuh, Esther L.; Tarapore, Phiroz E.; Wang, Kevin K.W.; Puccio, Ava M.; Mukherjee, Pratik; Diaz-Arrastia, Ramon; Gordon, Wayne A.; Valadka, Alex B.; Okonkwo, David O.; Manley, Geoffrey T.; TRACK-TBI Investigators; Psychiatry, School of Medicine
    Traumatic brain injury (TBI) often leads to heterogeneous clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism (SNP) in the dopamine D2 receptor (DRD2) may influence cognitive deficits following TBI. However, part of the association with DRD2 has been attributed to genetic variability within the adjacent ankyrin repeat and kinase domain containing 1 protein (ANKK1). Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether a novel DRD2 C957T polymorphism (rs6277) influences outcome on a cognitive battery at 6 months following TBI-California Verbal Learning Test (CVLT-II), Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), and Trail Making Test (TMT). Results in 128 Caucasian subjects show that the rs6277 T-allele associates with better verbal learning and recall on CVLT-II Trials 1-5 (T-allele carrier 52.8 ± 1.3 points, C/C 47.9 ± 1.7 points; mean increase 4.9 points, 95% confidence interval [0.9 to 8.8]; p = 0.018), Short-Delay Free Recall (T-carrier 10.9 ± 0.4 points, C/C 9.7 ± 0.5 points; mean increase 1.2 points [0.1 to 2.5]; p = 0.046), and Long-Delay Free Recall (T-carrier 11.5 ± 0.4 points, C/C 10.2 ± 0.5 points; mean increase 1.3 points [0.1 to 2.5]; p = 0.041) after adjusting for age, education years, Glasgow Coma Scale, presence of acute intracranial pathology on head computed tomography scan, and genotype of the ANKK1 SNP rs1800497 using multivariable regression. No association was found between DRD2 C947T and non-verbal processing speed (WAIS-PSI) or mental flexibility (TMT) at 6 months. Hence, DRD2 C947T (rs6277) may be associated with better performance on select cognitive domains independent of ANKK1 following TBI.
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    Functional Outcomes Over the First Year After Moderate to Severe Traumatic Brain Injury in the Prospective, Longitudinal TRACK-TBI Study
    (American Medical Association, 2021) McCrea, Michael A.; Giacino, Joseph T.; Barber, Jason; Temkin, Nancy R.; Nelson, Lindsay D.; Levin, Harvey S.; Dikmen, Sureyya; Stein, Murray; Bodien, Yelena G.; Boase, Kim; Taylor, Sabrina R.; Vassar, Mary; Mukherjee, Pratik; Robertson, Claudia; Diaz-Arrastia, Ramon; Okonkwo, David O.; Markowitz, Amy J.; Manley, Geoffrey T.; TRACK-TBI Investigators; Adeoye, Opeolu; Badjatia, Neeraj; Bullock, M. Ross; Chesnut, Randall; Corrigan, John D.; Crawford, Karen; Duhaime, Ann-Christine; Ellenbogen, Richard; Feeser, V. Ramana; Ferguson, Adam R.; Foreman, Brandon; Gardner, Raquel; Gaudette, Etienne; Goldman, Dana; Gonzalez, Luis; Gopinath, Shankar; Gullapalli, Rao; Hemphill, J. Claude; Hotz, Gillian; Jain, Sonia; Keene, C. Dirk; Korley, Frederick K.; Kramer, Joel; Kreitzer, Natalie; Lindsell, Chris; Machamer, Joan; Madden, Christopher; Martin, Alastair; McAllister, Thomas; Merchant, Randall; Ngwenya, Laura B.; Noel, Florence; Nolan, Amber; Palacios, Eva; Perl, Daniel; Puccio, Ava; Rabinowitz, Miri; Rosand, Jonathan; Sander, Angelle; Satris, Gabriella; Schnyer, David; Seabury, Seth; Sherer, Mark; Toga, Arthur; Valadka, Alex; Wang, Kevin; Yue, John K.; Yuh, Esther; Zafonte, Ross; Psychiatry, School of Medicine
    Importance: Moderate to severe traumatic brain injury (msTBI) is a major cause of death and disability in the US and worldwide. Few studies have enabled prospective, longitudinal outcome data collection from the acute to chronic phases of recovery after msTBI. Objective: To prospectively assess outcomes in major areas of life function at 2 weeks and 3, 6, and 12 months after msTBI. Design, setting, and participants: This cohort study, as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, was conducted at 18 level 1 trauma centers in the US from February 2014 to August 2018 and prospectively assessed longitudinal outcomes, with follow-up to 12 months postinjury. Participants were patients with msTBI (Glasgow Coma Scale scores 3-12) extracted from a larger group of patients with mild, moderate, or severe TBI who were enrolled in TRACK-TBI. Data analysis took place from October 2019 to April 2021. Exposures: Moderate or severe TBI. Main outcomes and measures: The Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS) were used to assess global functional status 2 weeks and 3, 6, and 12 months postinjury. Scores on the GOSE were dichotomized to determine favorable (scores 4-8) vs unfavorable (scores 1-3) outcomes. Neurocognitive testing and patient reported outcomes at 12 months postinjury were analyzed. Results: A total of 484 eligible patients were included from the 2679 individuals in the TRACK-TBI study. Participants with severe TBI (n = 362; 283 men [78.2%]; median [interquartile range] age, 35.5 [25-53] years) and moderate TBI (n = 122; 98 men [80.3%]; median [interquartile range] age, 38 [25-53] years) were comparable on demographic and premorbid variables. At 2 weeks postinjury, 36 of 290 participants with severe TBI (12.4%) and 38 of 93 participants with moderate TBI (41%) had favorable outcomes (GOSE scores 4-8); 301 of 322 in the severe TBI group (93.5%) and 81 of 103 in the moderate TBI group (78.6%) had moderate disability or worse on the DRS (total score ≥4). By 12 months postinjury, 142 of 271 with severe TBI (52.4%) and 54 of 72 with moderate TBI (75%) achieved favorable outcomes. Nearly 1 in 5 participants with severe TBI (52 of 270 [19.3%]) and 1 in 3 with moderate TBI (23 of 71 [32%]) reported no disability (DRS score 0) at 12 months. Among participants in a vegetative state at 2 weeks, 62 of 79 (78%) regained consciousness and 14 of 56 with available data (25%) regained orientation by 12 months. Conclusions and relevance: In this study, patients with msTBI frequently demonstrated major functional gains, including recovery of independence, between 2 weeks and 12 months postinjury. Severe impairment in the short term did not portend poor outcomes in a substantial minority of patients with msTBI. When discussing prognosis during the first 2 weeks after injury, clinicians should be particularly cautious about making early, definitive prognostic statements suggesting poor outcomes and withdrawal of life-sustaining treatment in patients with msTBI.
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    Invariance of the Bifactor Structure of Mild Traumatic Brain Injury (mTBI) Symptoms on the Rivermead Post-Concussion Symptoms Questionnaire across Time, Demographic Characteristics, and Clinical Groups: A TRACK-TBI Study
    (Sage, 2021) Agtarap, Stephanie; Kramer, Mark D.; Campbell-Sills, Laura; Yuh, Esther; Mukherjee, Pratik; Manley, Geoffrey T.; McCrea, Michael A.; Dikmen, Sureyya; Giacino, Joseph T.; Stein, Murray B.; Nelson, Lindsay D.; TRACK-TBI Investigators; Psychiatry, School of Medicine
    This study aimed to elucidate the structure of the Rivermead Postconcussion Symptoms Questionnaire (RPQ) and evaluate its longitudinal and group variance. Factor structures were developed and compared in 1,011 patients with mild traumatic brain injury (mTBI; i.e., Glasgow Coma Scale score 13-15) from the Transforming Research and Clinical Knowledge in TBI study, using RPQ data collected at 2 weeks, and 3, 6, and 12 months postinjury. A bifactor model specifying a general factor and emotional, cognitive, and visual symptom factors best represented the latent structure of the RPQ. The model evinced strict measurement invariance over time and across sex, age, race, psychiatric history, and mTBI severity groups, indicating that differences in symptom endorsement were completely accounted for by these latent dimensions. While highly unidimensional, the RPQ has multidimensional features observable through a bifactor model, which may help differentiate symptom expression patterns in the future.
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    Life After Mild Traumatic Brain Injury: Widespread Structural Brain Changes Associated With Psychological Distress Revealed With Multimodal Magnetic Resonance Imaging
    (Elsevier, 2022-03-16) Sibilia, Francesca; Custer, Rachel M.; Irimia, Andrei; Sepehrband, Farshid; Toga, Arthur W.; Cabeen, Ryan P.; TRACK-TBI Investigators; Psychiatry, School of Medicine
    Background: Traumatic brain injury (TBI) can alter brain structure and lead to onset of persistent neuropsychological symptoms. This study investigates the relationship between brain injury and psychological distress after mild TBI using multimodal magnetic resonance imaging. Methods: A total of 89 patients with mild TBI from the TRACK-TBI (Transforming Research and Clinical Knowledge in Traumatic Brain Injury) pilot study were included. Subscales of the Brief Symptoms Inventory 18 for depression, anxiety, and somatization were used as outcome measures of psychological distress approximately 6 months after the traumatic event. Glasgow Coma Scale scores were used to evaluate recovery. Magnetic resonance imaging data were acquired within 2 weeks after injury. Perivascular spaces (PVSs) were segmented using an enhanced PVS segmentation method, and the volume fraction was calculated for the whole brain and white matter regions. Cortical thickness and gray matter structures volumes were calculated in FreeSurfer; diffusion imaging indices and multifiber tracts were extracted using the Quantitative Imaging Toolkit. The analysis was performed considering age, sex, intracranial volume, educational attainment, and improvement level upon discharge as covariates. Results: PVS fractions in the posterior cingulate, fusiform, and postcentral areas were found to be associated with somatization symptoms. Depression, anxiety, and somatization symptoms were associated with the cortical thickness of the frontal-opercularis and occipital pole, putamen and amygdala volumes, and corticospinal tract and superior thalamic radiation. Analyses were also performed on the two hemispheres separately to explore lateralization. Conclusions: This study shows how PVS, cortical, and microstructural changes can predict the onset of depression, anxiety, and somatization symptoms in patients with mild TBI.
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    Recovery After Mild Traumatic Brain Injury in Patients Presenting to US Level I Trauma Centers: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study
    (American Medical Association, 2019-06-03) Nelson, Lindsay D.; Temkin, Nancy R.; Dikmen, Sureyya; Barber, Jason; Giacino, Joseph T.; Yuh, Esther; Levin, Harvey S.; McCrea, Michael A.; Stein, Murray B.; Mukherjee, Pratik; Okonkwo, David O.; Robertson, Claudia S.; Diaz-Arrastia, Ramon; Manley, Geoffrey T.; TRACK-TBI Investigators; McAllister, Thomas; Psychiatry, School of Medicine
    Question How common are persistent, injury-related functional limitations following mild traumatic brain injury vs orthopedic trauma? Findings In this cohort study of 1154 patients with mild traumatic brain injury and 299 patients with orthopedic trauma serving as controls, 53% of participants with mild traumatic brain injury reported impairment 12 months postinjury vs 38% of those with orthopedic trauma. Patients with intracranial abnormalities had the poorest outcomes; however, patients without abnormalities also reported problems at 12 months. Meaning Many patients who present to level I trauma centers with mild traumatic brain injury experience difficulties at 12 months postinjury, suggesting that this injury is not always benign; better follow-up and treatment appear to be needed.
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    Smaller Regional Brain Volumes Predict Posttraumatic Stress Disorder at 3 Months after Mild Traumatic Brain Injury
    (Elsevier, 2021) Stein, Murray B.; Yuh, Esther; Jain, Sonia; Okonkwo, David O.; Mac Donald, Christine L.; Levin, Harvey; Giacino, Joseph T.; Dikmen, Sureyya; Vassar, Mary J.; Diaz-Arrastia, Ramon; Robertson, Claudia S.; Nelson, Lindsay D.; McCrea, Michael; Sun, Xiaoying; Temkin, Nancy; Taylor, Sabrina R.; Markowitz, Amy J.; Manley, Geoffrey T.; Mukherjee, Pratik; TRACK-TBI Investigators; Psychiatry, School of Medicine
    Background: Brain volumes in regions such as the hippocampus and amygdala have been associated with risk for the development of posttraumatic stress disorder (PTSD). The objective of this study was to determine whether a set of regional brain volumes, measured by magnetic resonance imaging at 2 weeks following mild traumatic brain injury, were predictive of PTSD at 3 and 6 months after injury. Methods: Using data from TRACK-TBI (Transforming Research and Clinical Knowledge in TBI), we included patients (N = 421) with Glasgow Coma Scale scores 13-15 assessed after evaluation in the emergency department and at 2 weeks, 3 months, and 6 months after injury. Probable PTSD diagnosis (PTSD Checklist for DSM-5 score, ≥33) was the outcome. FreeSurfer 6.0 was used to perform volumetric analysis of three-dimensional T1-weighted magnetic resonance images at 3T obtained 2 weeks post injury. Brain regions selected a priori for volumetric analyses were insula, hippocampus, amygdala, superior frontal cortex, rostral and caudal anterior cingulate, and lateral and medial orbitofrontal cortices. Results: Overall, 77 (18.3%) and 70 (16.6%) patients had probable PTSD at 3 and 6 months. A composite volume derived as the first principal component incorporating 73.8% of the variance in insula, superior frontal cortex, and rostral and caudal cingulate contributed to the prediction of 3-month (but not 6-month) PTSD in multivariable models incorporating other established risk factors. Conclusions: Results, while needing replication, provide support for a brain reserve hypothesis of PTSD and proof of principle for how prediction of at-risk individuals might be accomplished to enhance prognostic accuracy and enrich clinical prevention trials for individuals at the highest risk of PTSD following mild traumatic brain injury.