Sex Differences in Subacute Blood Biomarker Levels and Associations With Post-Concussion Symptom Severity in Adolescents With Concussion.

OBJECTIVE

This study examined sex differences in subacute plasma biomarkers in adolescents post-concussion and their associations with post-concussion symptom (PCS) burden. We hypothesized that biomarker levels would differ by sex and relate to PCS severity.

SETTING

Participants were recruited from outpatient settings as part of the Concussion Assessment, Research, and Education for Kids (CARE4Kids) multi-site observational study.

PARTICIPANTS

Adolescents 11 to 17.99 years with a concussion based on Concussion In Sport Group criteria were eligible. Participants were assessed 7 to 35 days post-injury and required to report at least one PCS exceeding pre-injury baseline. A total of 339 participants (174 females, 145 males) with both blood biomarkers and PCS data were analyzed.

DESIGN

Plasma levels of glial fibrillary acidic protein, neurofilament light chain (NFL), ubiquitin C-terminal hydrolase (UCH-L1), tau, and phosphorylated tau at threonine 181 (p-tau181) were measured and compared between sexes. PCS severity was assessed using the Post-Concussion Symptom Inventory, 2nd Ed (PCSI-2) Retrospective Adjusted Post-Injury Difference (RAPID) scoring system.

MAIN MEASURES: Primary outcomes were sex differences in biomarker levels and their associations with RAPID scores.

RESULTS

Females had significantly higher tau (females: M = 6.18, SD = 8.02; males: M = 4.55, SD = 5.53; P = .012) and lower p-tau181/tau ratios (females: M = 6.18, SD = 8.02; males: M = 4.55, SD = 5.53; P = .002) after adjusting for age, BMI, and days post-injury. In both sexes, cognitive symptoms were associated with higher p-tau181. In females, emotional symptoms were associated with elevated NFL and UCH-L1. In males, physical and overall symptoms were associated with lower NFL, UCH-L1, and p-tau181.

CONCLUSION

This study highlights sex-specific biomarker differences during adolescent concussion recovery and the importance of understanding how sex differences may influence symptom burden and recovery trajectories. Future research should examine hormonal influences on biomarker profiles and prolonged symptomatology.