Treble-Barna and Colleagues Across Pitt Publish Outcomes Following Severe TBI Study in Neurorehabilitation and Neural Repair

December 9, 2021

Amery Treble-Barna, PhD, assistant professor in the Department of Physical Medicine & Rehabilitation, along with colleagues from the University of Pittsburgh, published a study in Neurorehabilitation and Neural Repair titled “Acute Brain-Derived Neurotrophic Factor DNA Methylation Trajectories in Cerebrospinal Fluid and Associations with Outcomes Following Severe Traumatic Brain Injury in Adults.”

Epigenetic biomarkers have the potential to explain outcome heterogeneity following traumatic brain injury (TBI) but are largely unexplored. This exploratory pilot study characterized brain-derived neurotrophic factor (BDNF) DNA methylation trajectories following severe TBI. Brain-derived neurotrophic factor DNA methylation trajectories in cerebrospinal fluid (CSF) over the first 5 days following severe TBI in 112 adults were examined in association with 3- and 12-month outcomes. 

Group-based trajectory analysis revealed low and high DNA methylation groups at two BDNF cytosine-phosphate-guanine (CpG) targets that showed suggestive associations (P < .05) with outcomes. Membership in the high DNA methylation groups was associated with better outcomes after controlling for age, sex, and injury severity. Associations of age × trajectory group interactions with outcomes at a third CpG site revealed a pattern of the same or better outcomes with higher ages in the high DNA methylation group and worse outcomes with higher ages in the low DNA methylation group.

Although no observed associations met the empirical significance threshold after correcting for multiple comparisons, suggestive associations of the main effect models were consistent in their direction of effect and were observed across two CpG sites and two outcome time points. The team’s results suggest that higher acute CSF BDNF DNA methylation may promote recovery following severe TBI in adults, and this effect may be more robust with higher age. While the results require replication in larger and racially diverse independent samples, BDNF DNA methylation may serve as an early postinjury biomarker helping to explain outcome heterogeneity following TBI.

View the full study.

Other Contributors

Lacey W. Heinsberg
Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA

Ava M. Puccio
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

John R. Shaffer
Department of Oral Biology, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA, USA

David O. Okonkwo
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Sue R. Beers
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Daniel E. Weeks
Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA

Yvette P. Conley
Department of Health Promotion and Development, University of Pittsburgh School of Nursing, Pittsburgh, PA, USA