Divisions of Pediatric Rehabilitation Medicine (Ms Smith-Paine and Fisher and Drs Wade and Kurowski), Biostatistics and Epidemiology (Dr Zhang and Mr Zang), and Human Genetics (Dr Martin), Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio; Department of Psychology, Alberta Children's Hospital Research Institute, and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada (Dr Yeates); Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio (Dr Taylor); and Department of Pediatrics, The Ohio State University, Columbus (Dr Taylor).
J Head Trauma Rehabil. 2020 Jul/Aug;35(4):262-269. doi: 10.1097/HTR.0000000000000564.
This study examined whether carrying dopamine-related "risk" genes-either the dopamine transporter (DAT1) 10-repeat allele or dopamine receptor-4 (DRD4) 7-repeat allele-moderated the association of family environment and executive function (EF) following traumatic brain injury (TBI) in early childhood.
Caregivers of children with TBI or orthopedic injury (OI) completed the Behavior Rating Inventory of Executive Function (BRIEF) at postinjury visits. General linear models examined gene by environment interactions as moderators of the effects of TBI on EF at 12 months and 7 years postinjury.
At 12 months, we did not find any significant gene by environment interactions. At 7 years, we found a significant 3-way interaction among combined carrier status, level of permissive parenting, and injury type. For children exposed to more optimal parenting, carriers of DAT1 and/or DRD4 risk alleles with TBI showed significantly worse parent-reported EF than carriers with OI. In those with less optimal parenting, carriers and noncarriers with TBI, as well as carriers with OI, showed significantly worse parent-reported EF than noncarriers with OI, with medium to large effect sizes.
The findings highlight the importance of considering polygenetic and environmental factors in future studies of recovery following TBI and other injuries in childhood.
本研究旨在探讨多巴胺相关“风险”基因(多巴胺转运体[DAT1] 10 重复等位基因或多巴胺受体-4[DRD4] 7 重复等位基因)是否调节了儿童期创伤性脑损伤(TBI)后家庭环境与执行功能(EF)之间的关联。
TBI 或骨科损伤(OI)患儿的照料者在损伤后就诊时完成行为评定量表的执行功能(BRIEF)。一般线性模型检验了基因-环境相互作用作为 TBI 对损伤后 12 个月和 7 年 EF 影响的调节因素。
在 12 个月时,我们没有发现任何显著的基因-环境相互作用。在 7 岁时,我们发现了一个联合携带状态、宽容养育水平和损伤类型之间的显著 3 路相互作用。对于暴露于更优养育环境的儿童,携带 DAT1 和/或 DRD4 风险等位基因的 TBI 患儿的父母报告的 EF 明显差于携带 OI 的患儿。在养育环境较差的情况下,TBI 患儿的携带和非携带者,以及 OI 患儿的携带者,其父母报告的 EF 明显差于非 OI 患儿,具有中到大的效应量。
这些发现强调了在未来研究 TBI 和儿童其他损伤后的恢复时,考虑多基因和环境因素的重要性。