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Pediatric traumatic brain injury (TBI) can lead to adverse emotional, social, and behavioral consequences. However, outcome is difficult to predict due to significant individual variability, likely reflecting a complex interaction between injury- and child-related variables. Among these variables are genetically determined individual differences, which can modulate TBI outcome through their influence on neuroplasticity mechanisms. In this study, we examined the effect of Val66Met, a common polymorphism of the brain-derived neurotrophic factor gene known to be involved in neuroplasticity mechanisms, on behavioral symptoms of mild TBI (mTBI) sustained in early childhood. This work is part of a prospective, longitudinal cohort study of early TBI. The current sample consisted of 145 children between ages 18 and 60 months assigned to one of three participant groups: mild TBI, orthopedic injury, or typically developing children. Participants provided a saliva sample to detect the presence of the Val66Met polymorphism, and the Child Behavior Checklist was used to document the presence of behavioral symptoms at 6- and 18-months post-injury. Contrary to our initial hypothesis, at 6 months post-injury, non-carriers of the Val66Met polymorphism in the mTBI group presented significantly more internalizing symptoms (e.g., anxiety/depression and somatic complaints) than Val66Met carriers, who were similar to orthopedically injured and typically developing children. However, at 18 months post-injury, all children with mTBI presented more internalizing symptoms, independent of genotype. The results of the study provide evidence for a protective effect of the Val66Met polymorphism on internalizing behavior symptoms 6 months after early childhood mTBI.

• Testing a comprehensive and longitudinal prediction model of quality of life after early mild TBI. • BDNF Val66Met polymorphism predicts better quality of life 6 months after early mild TBI. • Higher parental distress determines poorer quality of life 18 months after early mild TBI. • Genetic factors linked to neuroplasticity may be important to recovery in the early phase post-TBI. Mild traumatic brain injury (mTBI) in early childhood is prevalent, and some children may be at risk for short- and long-term difficulties that could affect quality of life (QoL). Despite growing efforts to understand associations between potential risk factors and outcomes after injury, prognosis is elusive and lacks the inclusion of genetic variables which may convey additional predictive power. This study assessed which factors contribute to pediatric QoL 6 and 18 months post-recruitment in 159 participants (mTBI = 52; orthopedic injury [OI] = 43; typically developing controls [TDC] = 64) aged 18 to 60 months at the time of injury (M = 37.50, SD = 11.69). Family environment, injury characteristics, and child cognitive-behavioral functioning were assessed at 6 months via parent questionnaires and socio-cognitive assessment. QoL was determined using the Pediatric Quality of Life Inventory at both time points. Genetic information (Brain-derived neurotrophic factor [BDNF] genotype) was collected using saliva samples. Hierarchical regression analyses testing biological, family-environmental, injury and cognitive-behavioral factors revealed that the BDNF Val66Met polymorphism was a significant independent predictor of better QoL 6 months post-injury in the mTBI group. Lower parental distress significantly and independently predicted higher QoL 18 months after mTBI, and 6 months post-recruitment in the TDC group. At 18 months, models were non-significant for both control groups. Genetic factors involved in neuroplasticity may play an important role in recovery 6 months after mTBI and contribute to outcome via their interplay with environmental factors. Over time, family factors appear to become the primary determinants of post-mTBI outcome. [ABSTRACT FROM AUTHOR]