Association of blood-based glial fibrillary acidic protein level with depression and suicidal ideation following traumatic brain injury with Glasgow Coma Scale score 13 to 15: a TRACK-TBI study

Shawn R Eagle; Raquel C Gardner; Sonia Jain; Xiaoying Sun; Ava Puccio; David Brent; Lindsay D Nelson; Michael A McCrea; Joseph T Giacino; David O Okonkwo; John K Yue; Geoffrey T Manley; Murray B Stein; TRACK-TBI Investigators

doi:10.1093/braincomms/fcaf123

Association of blood-based glial fibrillary acidic protein level with depression and suicidal ideation following traumatic brain injury with Glasgow Coma Scale score 13 to 15: a TRACK-TBI study

Brain Commun. 2025 Mar 25;7(2):fcaf123. doi: 10.1093/braincomms/fcaf123. eCollection 2025.

Authors

Collaborators

TRACK-TBI Investigators:
Ann-Christine Duhaime, Adam R Ferguson, Shankar Gopinath, Ramesh Grandhi, C Dirk Keene, Christine Mac Donald, Amy Markowitz, Randall Merchant, Pratik Mukherjee, Laura B Ngwenya, Claudia Robertson, Andrea Schneider, David Schnyer, Sabrina R Taylor, Kevin Wang, Ross Zafonte

Affiliations

¹ Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA.
² Department of Epidemiology, Sheba Medical Center, Ramat Gan 52621, Israel.
³ Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA 92093, USA.
⁴ Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
⁵ Department of Physical Medicine and Rehabilitation, Harvard University, Cambridge, MA 02129, USA.
⁶ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94143, USA.

Abstract

Blood-based glial fibrillary acidic protein (GFAP) level within 24 h of traumatic brain injury (TBI) has been inversely associated with post-traumatic stress disorder at 6 months in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study. We sought to assess the relationship between day-of-injury GFAP and cumulative prevalence (CI) of depression or suicidal ideation in the first year after injury among patients presenting with Glasgow Coma Scale 13-15 who participated in Transforming Research and Clinical Knowledge in Traumatic Brain Injury (n = 1511). Multivariable logistic regression models were used to assess the association of day-of-injury GFAP levels with year 1 CI of depression or suicidal ideation adjusting for age, sex, prior TBI, psychiatric history and acute intracranial trauma on head computed tomography (CT) scan. Subgroup analyses categorized into 'high' and 'low' risk for mental health problems based upon a history of psychiatric disorder or TBI. Overall, 20.4% reported depression and 11.3% reported suicidal ideation in the first year. Participants with depression had significantly lower GFAP compared with participants without depression overall (median = 149.9 pg/mL versus 306.9 pg/mL, P < 0.001) and CT-negative high risk and CT-negative low risk subgroups. Participants with suicidal ideation had lower GFAP in the overall sample (155.8 pg/mL versus 299.1 pg/mL, P = 0.001). We found an interaction between GFAP and CT status, reflecting an inverse association of GFAP with cumulative depression among CT- subjects (adjusted odds ratio = 0.84, 95% CI: 0.77-0.92), but not among CT+ subjects. Blood biomarkers may warrant future investigation as potential predictors of depression following TBI in patients without evidence of acute intracranial trauma on CT scan.

Keywords: GFAP; blood biomarker; suicidal ideation; traumatic brain injury.