byWolters Kluwer Health

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Levels of certain biomarkers in the blood are associated with symptom severity during recovery from concussion in adolescents—with some significant differences between male and female patients, reports astudyin theJournal of Head Trauma Rehabilitation.

"Our study builds on previous research suggesting that some brain-related markers may provide objective measures of brain injury in teens withconcussion," comments lead author Mia Pasini, MSN, PMHNP-BC, of Johns Hopkins University, Baltimore. "We also identifysex-specific differencesin biomarker levels, which may lend insights into the more severe symptoms and longer recovery after concussion in girls and young women."

The researchers analyzed data on 339 adolescents, aged 11 to 18 years, who had lasting symptoms one to five weeks after a concussion. Patients were drawn from the ongoing Concussion Assessment, Research, and Education for Kids (CARE4Kids) study, which seeks to better understand and develop targeted therapies for concussion in children and adolescents.

All participants underwent measurement of five biomarkers—proteins and lipids released from the brain after a concussion—previously linked totraumatic brain injuryin adults. In the new study of adolescents, biomarker levels and their association with the severity of post-concussion symptoms were evaluated.

The study included an assessment of sex-related differences in female compared to male patients. Previous studies have suggested that adolescent girls andyoung womenare disproportionately affected by persistent symptoms after concussion, with more severe symptoms and a longer recovery time.

Several biomarkers differed between female and male patients, after adjustment for age, body mass index, and time since concussion. For example,female patientshad higher levels of a protein called tau, which may reflect injury to thenerve fibers(axons) that transmit electrical impulses between brain cells (neurons).

The data also showed some subtle differences in the relationships between biomarker levels and post-concussion symptoms. In both sexes, higher levels of a marker called p-tau181 were associated with more severe cognitive symptoms. In female patients, higher levels of biomarkers related to neuronal damage (N-FL and UCH-L1) were associated with increased emotional symptoms. In contrast, amongmale patients, lower levels of N-FL, UCH-L1, and p-tau 181 were associated with increased physical and overall symptoms.

"These findings suggest that sex may moderate the relationship between biomarkers and symptom burden in adolescents following concussion," the researchers write. Some of the observed associations suggest a bidirectional relationship between hormone levels and brain injury due to concussion.

The study adds new evidence that brain-related biomarkers might play a useful role in monitoring recovery and guiding personalized care for young patients with concussion. Pasini and co-authors conclude, "Integratingbiomarker-guided strategies into a precision medicine framework is especially important for adolescent females, who are more likely to experience prolonged recovery and distinct symptom profiles compared to males, yet remain underrepresented in concussion research."

More information: Pasini, Mia et al, Sex Differences in Subacute Blood Biomarker Levels and Associations With Post-Concussion Symptom Severity in Adolescents With Concussion, Journal of Head Trauma Rehabilitation (2025). DOI: 10.1097/HTR.0000000000001110 journals.lww.com/headtraumareh … marker_levels.4.aspx Journal information: Journal of Head Trauma Rehabilitation

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