The Utility of clinical and Blood-Based Biomarkers to Discriminate between Typical and Prolonged Pediatric mTBI Symptom Recovery
Date of Award
Doctor of Philosophy (PhD)
Hoelzle, James B.
Meier, Timothy B.
Prolonged recovery following mild traumatic brain injury (mTBI) is poorly understood, particularly in pediatric samples, despite significant work to understand prolonged postconcussive symptoms (PPS). Emerging evidence in adult mTBI literature suggests blood-based biomarkers have diagnostic and prognostic value, but there is limited research examining this in pediatric mTBI. Further, while adult research documents that combining physiological biomarkers, emotional distress and symptom reports more optimally differentiates between mTBI and healthy controls, it is unknown if this finding will replicate in pediatric samples. This project examined foundational relationships between clinical, cognitive, inflammatory markers, and kynurenine pathway (KP) metabolites following mTBI in adolescents (N=104). Across the entire sample, higher report of emotional distress was related to lower levels of kynurenic acid (KynA), a putatively neuroprotective metabolite of the KP. Further, adolescents with prolonged recovery (PPS+) had lower KynA than those with typical mTBI recovery (PPS-) and healthy controls (HC). The HC group had higher KynA/QuinA ratios (a neuroprotective index) compared to both mTBI groups. Females, regardless of group, had lower KynA and lower KynA/3HK and KynA/QuinA than males. Finally, combinations of key variables discriminated HC and mTBI, as well as adolescents with and without PPS. Taken together, this research suggests a differential balance of KP metabolites in adolescent females following mTBI is strongly associated with emotional distress at a post-acute timepoint.