Abstract
Traumatic brain injury (TBI) affects millions of Americans each year and has been shown to disproportionately impact those subject to greater disparities in health. Female sex is one factor that has been associated with disparities in health outcomes, including in TBI, but sex differences in biomarker levels and behavioral outcomes after TBI are underexplored. This study included participants with both blunt and blast TBI with majority rating their TBI as mild. Time since injury was 5.4 (2.0, 15.5) years for females and 6.8 (2.4, 11.3) years for males. The aim of this cross sectional study is to investigate the relationship between postconcussive, depression, and post-traumatic stress disorder (PTSD) symptoms, as well as health related quality of life (HRQOL), and the levels of glial fibrillary acidic protein (GFAP), total tau (t-tau), neurofilament light chain (NfL), and ubiquitin C-terminal hydrolase-L1 (UCH-L1). Behavioral outcomes were evaluated with the Neurobehavioral Symptom Inventory (NSI), Patient Health Questionnaire-9 (PHQ-9), PTSD Checklist- Civilian Version (PCL-C), short form (SF)-36, and plasma levels of total tau, GFAP, NfL, and UCHL-1 measured with the Simoa-HDX. We observed that females had significantly higher levels of GFAP and tau (ps < 0.05), and higher PHQ-9 scores, NSI total scores, NSI- vestibular, NSI-somatosensory, NSI-affective sub-scale scores (ps < 0.05)), than males. In addition, females had lower scores in HRQOL outcomes of role limitations due to emotional problems, vitality, emotional well-being, social functioning, and pain compared to males (ps < 0.05). Correlation analysis showed positive associations between levels of tau and the NSI-total and NSI-cognitive sub-scale scores (ps < 0.05) in females. No significant associations were found for NfL or GFAP with NSI scores. For female participants, negative correlations were observed between tau and NfL concentrations and the SF-36 physical function subscale (ps < 0.05), as well as tau and the social function subscale (p < 0.001), while GFAP levels positively correlated with role limitations due to emotional problems (p = 0.004). No significant associations were observed in males. Our findings suggest that sex differences exist in TBI-related behavioral outcomes, as well as levels of biomarkers associated with brain injury, and that the relationship between biomarker levels and behavioral outcomes is more evident in females than males. Future studies are warranted to corroborate these results, and to determine the implications for prognosis and treatment. The identification of candidate TBI biomarkers may lead to development of individualized treatment guidelines.
Highlights
Traumatic brain injury (TBI) affects over one million Americans each year and may lead to long-term debilitating behavioral symptoms in groups with greater health disparities (Center for Disease Control and Prevention, National Center for Injury Prevention and Control CDC, 2021)
This study is the first to examine levels of circulating biomarkers and symptom scores in the context of sex differences in chronic TBI. In this cross-sectional convenience sample analysis, we found that levels of circulating plasma glial fibrillary acidic protein (GFAP) and tau were significantly higher in the female group compared to the male group
Behavioral symptoms of depression, Neurobehavioral Symptom Inventory (NSI) total, NSIvestibular, NSI-somatosensory, and NSI- affective scores were higher in the female group as well
Summary
Traumatic brain injury (TBI) affects over one million Americans each year and may lead to long-term debilitating behavioral symptoms in groups with greater health disparities (Center for Disease Control and Prevention, National Center for Injury Prevention and Control CDC, 2021). Sex differences in TBI behavioral outcomes have been suggested, but possible molecular underpinnings are unclear. Exploring TBI outcomes and potential candidate TBI biomarkers based on sex differences might lead to development of precision medicine therapies. In a review of sex differences in mild TBI, researchers found that females have a proportionally higher incidence of concussions in sports; comparisons of symptom prevalence between the sexes have had mixed results (Merritt et al, 2019). Other reviews highlight the paucity of studies evaluating sex differences in blood-based biomarkers in TBI (Strathmann et al, 2014; Gupte et al, 2019)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
