Melissa G Papini, Jacinta Thorne, Aleksandra K Gozt, Andre N C Avila, Caerwen S Ellery, Ruby Gilroy, Geena Gill, Francesca Buhagiar, Elizabeth Thomas, Amanda Armstrong, Steve Pedrini, Kevin Taddei, Ralph N Martins, Alexander Ring, Glenn Arendts, Antonio Celenza, John Charles Iliff, Dan Xu, Stephen Honeybul, Gill Cowen, Ben Smedley, Daniel Fatovich, Michael Bynevelt, Carmela Pestell, Melinda Fitzgerald, Sarah C Hellewell
Divergent acute profiles of blood biomarkers, white matter diffusivity, and coping style distinguish mTBI recovery trajectories, providing hypothesis-generating support for biologically informed molecular, microstructural, and psychological mTBI phenotypes.
OBJECTIVES: Blood-based and diffusion MRI (dMRI) biomarkers of white matter injury after acute mild traumatic brain injury (mTBI) were examined to: (1) distinguish mTBI from healthy controls (HC); (2) quantify inter-modality relationships; (3) identify associations between acute biomarker changes and recovery; (4) evaluate moderating influences of resilience and coping style.
METHODS: 36 adults with mTBI (37.6±13.7 years; 37.1% female) and 35 HC participants (34.2 ± 11.9; 47.1% female) underwent baseline testing (≤ 9 days post-mTBI) including: blood-sampling (neurofilament light-chain [NfL], brain-derived tau, glial fibrillary acidic protein, ubiquitin carboxyl terminal hydroxylase-L1, four-repeat tau [4R-tau]), dMRI analysis of 48 white matter tracts, symptom (Post-Concussion Symptom Scale [PCSS]) and psychological questionnaires (Brief Resilience Scale, Utrecht Coping List). Recovery was determined at 3-, 6- and 12-month follow-ups using PCSS scores. Associations were evaluated using correlations, logistic regression, and exploratory moderation analyses.
TRIAL REGISTRATION NUMBER: ACTRN12619001226190.
RESULTS: 37.1% of participants reported persistent symptoms at 3 months, 42.9% and 28.6% at 6 and 12 months, respectively. NfL and 4R-tau were acutely elevated post-mTBI, alongside widespread increases in radial, mean, and axial diffusivity. Divergent recovery trajectories were defined by distinct baseline biomarker profiles: elevated NfL and mean diffusivity characterized recovered participants, while elevated 4R-tau and radial diffusivity characterized those who remained symptomatic. NfL was associated with recovery at 3 months and 4R-tau with symptomatic status at 12 months. Coping style, not resilience, moderated blood biomarker-outcome relationships.
CONCLUSION: Divergent acute profiles of blood biomarkers, white matter diffusivity, and coping style distinguish mTBI recovery trajectories, providing hypothesis-generating support for biologically informed molecular, microstructural, and psychological mTBI phenotypes.
TRIAL REGISTRATION NUMBER: ACTRN12619001226190 approved March 2023.