Depression following traumatic brain injury (TBI) affects approximately 1 in 5 patients in the first year after injury—even in cases initially classified as “mild”. Identifying individuals at highest risk remains a major clinical and medicolegal challenge, particularly when neuroimaging appears normal.

A recent study from the TRACK-TBI collaboration, published in Brain Communications (2025), investigated whether glial fibrillary acidic protein (GFAP)—a blood biomarker released after neurological trauma—might help predict who is most vulnerable.

The findings were striking: Lower day-of-injury GFAP concentrations were associated with a significantly higher risk of depression over the following year—but only in patients with a negative CT scan. This inverse association was not observed in those with CT-visible intracranial pathology.

Interestingly, the authors propose that low GFAP levels may reflect pre-existing glial dysfunction, which has been implicated in major depressive disorder. Prior studies of post-mortem brain tissue in individuals with depression have consistently found reduced GFAP expression and astrocyte density, particularly in limbic and prefrontal areas—suggesting that biological vulnerability may precede injury.

GFAP is already approved for use in identifying patients who may require neuroimaging following TBI. This study suggests it may also have prognostic value for identifying those at risk of psychiatric sequelae, even in the absence of proven structural brain injury.

For clinicians, this reinforces the importance of early psychological surveillance, even when acute imaging is normal.
For medicolegal professionals, it supports the need for a nuanced approach to claims where subjective psychological symptoms follow an apparently “mild” injury.

As GFAP testing becomes more accessible, this line of research opens the door to more targeted mental health interventions in TBI care.

Reference:
Eagle SR et al., Brain Communications, 2025. https://doi.org/10.1093/braincomms/fcaf123