Influence of Dopamine-Related Genes on Neurobehavioral Recovery after Traumatic Brain Injury during Early Childhood.
The present study examined the association of dopamine-related genes with short- and long-term neurobehavioral recovery, as well as neurobehavioral recovery trajectories over time, in children who had sustained early childhood traumatic brain injuries (TBI) relative to children who had sustained orthopedic injuries (OI). Participants were recruited from a prospective, longitudinal study evaluating outcomes of children who sustained a TBI (n = 68) or OI (n = 72) between the ages of 3 and 7 years. Parents completed ratings of child executive function and behavior at the immediate post-acute period (0-3 months after injury); 6, 12, and 18 months after injury; and an average of 3.5 and 7 years after injury. Thirty-two single nucleotide polymorphisms (SNPs) in dopamine-related genes (dopamine receptor D2 [DRD2], solute carrier family 6 member 3 [SLC6A3], solute carrier family 18 member A2 [SLC18A2], catechol-o-methyltransferase [COMT], and ankyrin repeat and kinase domain containing 1 [ANKK1]) were examined in association with short- and long-term executive function and behavioral adjustment, as well as their trajectories over time. After controlling for premorbid child functioning, genetic variation within the SLC6A3 (rs464049 and rs460000) gene was differentially associated with neurobehavioral recovery trajectories over time following TBI relative to OI, with rs464049 surviving multiple testing corrections. In addition, genetic variation within the ANKK1 (rs1800497 and rs2734849) and SLC6A3 (rs464049, rs460000, and rs1042098) genes was differentially associated with short- and long-term neurobehavioral recovery following TBI, with rs460000 and rs464049 surviving multiple testing corrections. The findings provide preliminary evidence that genetic variation in genes involved in DRD2 expression and density (ANKK1) and dopamine transport (SLC6A3) plays a role in neurobehavioral recovery following pediatric TBI.
1 Division of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
Amery
A
Treble-Barna
2 Division of Physical Medicine and Rehabilitation, Department of Pediatrics, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
Shari L
SL
Wade
3 Division of Human Genetics, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
Lisa J
LJ
Martin
3 Division of Human Genetics, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
Valentina
V
Pilipenko
4 Department of Psychology, Alberta Children's Hospital Research Institute, Hotchkiss Brain Institute, University of Calgary , Calgary, Alberta, Canada .
Keith Owen
KO
Yeates
5 Division of Developmental and Behavioral Pediatrics and Psychology, Department of Pediatrics, Case Western Reserve University and Rainbow Babies and Children's Hospital , Cleveland, Ohio.
H Gerry
HG
Taylor
2 Division of Physical Medicine and Rehabilitation, Department of Pediatrics, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
Brad G
BG
Kurowski
D000070642:Brain Injuries, Traumatic / Q000235:genetics* / Q000503:physiopathology*; D002394:Catechol O-Methyltransferase / Q000235:genetics; D002648:Child; D002652:Child Behavior / Q000502:physiology*; D002675:Child, Preschool; D004298:Dopamine / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D017448:Receptors, Dopamine D2 / Q000235:genetics; D020127:Recovery of Function / Q000502:physiology*; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics
C581293:DRD2 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; C493452:SLC18A2 protein, human; C493214:SLC6A3 protein, human; D050493:Vesicular Monoamine Transport Proteins; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D004298:Dopamine
TBI; behavior; genetic factors; neurotransmitters; pediatric brain injury