Endophenotype presentation of athletes with concussion contingent on sex and time since injury.

Abstract

Introduction: Athletes with concussions experience heterogeneous symptoms and clinical trajectories. Subclassification provides diagnostic clarity that may improve prognostication and individualized treatments.

Methods: We hypothesized that endophenotypes of adolescent athletes with concussions differ based on sex and time since injury. Post-concussive testing was performed for athletes (n = 1385) in the North Texas Concussion Registry (ConTex) at four timepoints: acute [0-3 days post-injury (DPI)], subacute-early (4-7DPI), subacute-late (8-28DPI), and persistent (29+DPI). Six endophenotypes (cognitive, headache, ocular-motor, vestibular, affective, sleep) were constructed by allocating post-concussion testing data elements described by the Concussion Subtype Workgroup.

Results: Endophenotypes were defined using correlations between data elements and compared based on sex or time since injury. Correlograms revealed endophenotypes differed based on sex and time since injury. The affective endophenotype was dependent on the interaction between sex and time since injury and was more prevalent at the subacute-late and persistent timepoints. The sleep endophenotype became more prevalent at the persistent timepoint. Affective and sleep endophenotypes were interrelated with cognitive, vestibular, and headache endophenotypes at the persistent timepoint suggesting that dysregulated mood and sleep influence lingering symptoms.

Conclusions: Adolescent symptom-based concussion endophenotypes differ based on sex and time since injury. Clinical consideration may improve identification of separate trajectories following sport-related concussion and provide targeted care.