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Published on: January 30, 2018
Brain-Derived Neurotrophic Factor Val66Met and Behavioral Adjustment after Early Childhood Traumatic Brain Injury
Amery Treble-Barna1, Shari L Wade2, Valentina Pilipenko3
1Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Insights
The brain-derived neurotrophic factor (BDNF) Val66Met gene variant impacts behavioral adjustment differently in children with traumatic brain injury (TBI) versus orthopedic injury (OI). The Met allele may increase risk for long-term behavioral issues in TBI survivors.
Area of Science:
- Neuroscience
- Genetics
- Developmental Psychology
Background:
- Childhood traumatic brain injury (TBI) and orthopedic injury (OI) can affect behavioral adjustment.
- The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is linked to neurodevelopment and behavior.
Purpose of the Study:
- To investigate the differential impact of the BDNF Val66Met polymorphism on behavioral adjustment in children with TBI compared to those with OI.
- To explore the long-term effects of this genetic variation on behavior following early childhood injury.
Main Methods:
- A prospective, longitudinal study followed children aged 3-7 years with TBI (n=69) or OI (n=72).
- Parent-reported behavioral data (Child Behavior Checklist) were collected at multiple time points post-injury.
- Longitudinal mixed models analyzed the interaction between BDNF Val66Met allele status and injury group.
Main Results:
- A significant interaction was found between BDNF Val66Met allele status and injury group for Internalizing, Externalizing, and Total Behavior problems.
- Children with TBI carrying the Met allele showed a trend towards poorer behavioral adjustment compared to Val/Val homozygotes.
- Children with OI showed an opposite trend, with Met carriers exhibiting better adjustment.
Conclusions:
- The BDNF Val66Met polymorphism differentially affects behavioral adjustment in children with early TBI versus OI.
- The Met allele, associated with reduced BDNF secretion, may confer a risk for poorer long-term behavioral adjustment in children with TBI.
Abstract:
The present study examined the differential effect of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on behavioral adjustment in children with traumatic brain injury (TBI) relative to children with orthopedic injury (OI). Participants were drawn from a prospective, longitudinal study of children who sustained a TBI (n = 69) or OI (n = 72) between 3 and 7 years of age. Parents completed the Child Behavior Checklist (CBCL) at the immediate post-acute period, 6, 12, and 18 months after injury, and an average of 3.5 and 7 years after injury. Longitudinal mixed models examined the BDNF Val66Met allele status (Met carriers vs. Val/Val homozygotes) × injury group (TBI vs. OI) interaction in association with behavioral adjustment. After adjusting for continental ancestry, socioeconomic status, time post-injury, and pre-injury functioning, the allele status × injury group interaction was statistically significant for Internalizing, Externalizing, and Total Behavior problems. Post hoc within-group analysis suggested a consistent trend of poorer behavioral adjustment in Met carriers relative to Val/Val homozygotes in the TBI group; in contrast, the opposite trend was observed in the OI group. These within-group differences, however, did not reach statistical significance. The results support a differential effect of the BDNF Val66Met polymorphism on behavioral adjustment in children with early TBI relative to OI, and suggest that the Met allele associated with reduced activity-dependent secretion of BDNF may impart risk for poorer long-term behavioral adjustment in children with TBI.
