Pediatric Mild Traumatic Brain Injury and the ABCD Study: A Prospective Behavioral, Psychiatric, Neurocognitive, Imaging, and Genetic Investigation

Mild traumatic brain injury (mTBI) is a major public health problem in the United States. Data from the Adolescent Brain Cognitive Development (ABCD) study afford our team an opportunity to significantly advance the study of mTBI-associated behavioral, psychiatric, and neurocognitive problems which are very controversial. We shall analyze biopsychosocial data generated since 2016 from this ten-year prospective longitudinal 21-site national study of an enrolled cohort of over 11,000 nine/ten-year old children who have been subsequently evaluated annually. The study design permits a rare analysis of predictive factors and mechanisms of post-injury behavioral, psychiatric, and neurocognitive outcomes by examining child and family variables collected pre-injury and post-injury in the 237 children who have so far suffered a mTBI in the years subsequent to enrollment. The mTBI group will be compared with two groups of children 1) with a post-enrollment accidental bone fracture (orthopedic injury; OI); and 2) a lifetime “no injury” (NI) group. Additional children who have had a mTBI will be identified and will be compared with OI and NI controls in the first month of the study, and at the end of year 2 and middle of year 4 of the five-year study. There are three unique aspects of the proposed study. 1) Pre-injury and post-injury sequential structural and functional neuroimaging data facilitate predictive and mediation analyses of behavioral, psychiatric, and neurocognitive outcomes using individual pre- versus post-injury changes and group differences in brain maturation trajectories. 2) Genetic data permit predictive and moderation analyses of outcomes using a novel systems biology approach not based on candidate genes. 3) The proposed study evaluates multiple neurocognitive domains before and after mTBI. The study will examine 3 major hypotheses: (1) Change in behavioral measures and changes in neurocognitive function will be of greater magnitude, and new-onset psychiatric disorders will occur at a significantly higher rate, in children with mTBI compared with children with OI and NI. (2) Behavioral changes, new-onset psychiatric disorders, and neurocognitive function changes in children will be predicted by pre-injury child variables (sex, adaptive function, academic and cognitive function, lifetime psychiatric disorders, behavioral ratings, brain structure and functional MRI measures, and genetic factors), and pre-injury family variables (socioeconomic status, family function, family psychiatric history) in children with mTBI, OI, and NI. (3) The occurrence and pattern of behavioral changes, new-onset psychiatric disorders, and neurocognitive function changes will be mediated by child brain variables (trajectory of brain maturation), post-injury family variables (functioning and stressors), and injury variables (age at injury, time-since-injury, severity, presence of a brain lesion, and extent of diffuse axonal injury) and moderated by child gene structure (genetic factors), in children with mTBI, OI, and NI.