Endophenotypes of Persistent Post-Concussive Symptoms in Adolescents: CARE4Kids

PROJECT SUMMARY/ABSTRACT – Research Project Concussion or mild traumatic brain injury (mTBI) is the most common type of acquired brain injury in children and adolescents. While the majority of youth with concussion recover within 2-4 weeks, a substantial subset (15-30%) take longer to recover and develop persistent post-concussive symptoms (PPCS). This group experiences worse function, more pain and seeks a greater amount of medical assessments and treatments. Prolonged impairments in early and middle adolescents (EMA) can result in changes in developmental trajectory and long-term disability. There is no single agreed upon definition for PPCS and predictive algorithms are largely based on nonspecific subjective clinical symptoms. Furthermore, there are currently no good preventive strategies or targeted treatments. It is a major public health challenge to develop objective biological markers that better predict PPCS, which will provide the opportunity for improved prognostication, potential preventive interventions and new therapeutics based on underlying biological mechanisms. It is the central goal of this CARE4Kids Center Without Walls to discover objective autonomic, imaging and blood-based biomarkers that, when integrated with neuropsychological and neurological signs and symptoms, will optimally predict PPCS in EMA. Once identified, these biomarkers and clinical measures will then be validated in a more generalized group and developed into an improved predictive algorithm for PPCS. The linkage of objective biological measures to different clinical phenotypes (termed endophenotypes in this application) will provide a mechanistic understanding of different types of PPCS. It is hypothesized that endophenotypes may share pathobiology with migraine, dysautonomia, anxiety, depression or other symptoms commonly seen in those with PPCS. By understanding the underlying neurobiology of PPCS, it will become possible to develop mechanism- based prevention or treatment measures.