Mild Traumatic Brain Injury Biomarkers: Current Status and Future Directions

Mild traumatic brain injury (mTBI) contributes substantially to years lived with disability (YLD), decreases health-related quality of life, and imposes significant costs on healthcare systems and society. Millions of people experience mTBI each year, and healthcare costs for mTBI in just the first year after injury exceed 44 billion USD. Despite the common occurrence of mTBI, estimates of incidence, prevalence, related disability, and costs vary widely. This variance is attributed to the underreporting of head impacts, inconsistent definitions of mTBI, and a lack of objective biomarkers. Currently available clinical blood biomarkers primarily assist in ruling out CT-detectable intracranial injury rather than definitively diagnosing mTBI itself, underscoring the continued need for objective, portable, and clinically specific biomarkers. Numerous imaging findings, blood proteins, and physiological measures are under investigation for these purposes, and some may have multiple uses. Specific biomarkers for acute diagnosis are needed urgently. Although many systematic reviews have been published, most focus on a single biomarker or class of biomarkers. Given the breadth of potential biomarker categories, conducting a comprehensive, systematic review across modalities is challenging. Here, we provide a narrative review summarizing the extant literature across major biomarker domains studied in adolescents and adults. We emphasize candidates supported by the most robust evidence to guide continued research and clinical translation.