Bick Johanna, Zhu Tong, Stamoulis Catherine, Fox Nathan A, Zeanah Charles, Nelson Charles A
Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Radiation Oncology, University of Michigan, Ann Arbor.
JAMA Pediatr. 2015 Mar;169(3):211-9. doi: 10.1001/jamapediatrics.2014.3212.
Severe neglect in early life is associated with compromises in brain development and associated behavioral functioning. Although early intervention has been shown to support more normative trajectories of brain development, specific improvements in the white matter pathways that underlie emotional and cognitive development are unknown.
To examine associations among neglect in early life, early intervention, and the microstructural integrity of white matter pathways in middle childhood.
DESIGN, SETTING, AND PARTICIPANTS: The Bucharest Early Intervention Project is a randomized clinical trial of high-quality foster care as an intervention for institutionally reared children in Bucharest, Romania, from 2000 through the present. During infancy, children were randomly selected to remain in an institution or to be placed in foster care. Those who remained in institutions experienced neglect, including social, emotional, linguistic, and cognitive impoverishment. Developmental trajectories of these children were compared with a group of sociodemographically matched children reared in biological families at baseline and several points throughout development. At approximately 8 years of age, 69 of the original 136 children underwent structural magnetic resonance imaging scans.
Four estimates of white matter integrity (fractional anisotropy [FA] and mean [MD], radial [RD], and axial [AD] diffusivity) for 48 white matter tracts throughout the brain were obtained through diffusion tensor imaging.
Significant associations emerged between neglect in early life and microstructural integrity of the body of the corpus callosum (FA, β = 0.01 [P = .01]; RD, β = -0.02 [P = .005]; MD, β = -0.01 [P = .02]) and tracts involved in limbic circuitry (fornix crus [AD, β = 0.02 (P = .046)] and cingulum [RD, β = -0.01 (P = .02); MD, β = -0.01 (P = .049)]), frontostriatal circuitry (anterior [AD, β = -0.01 (P = .02)] and superior [AD, β = -0.02 (P = .02); MD, β = -0.01 (P = .03)] corona radiata and external capsule [right FA, β = 0.01 (P = .03); left FA, β = 0.01 (P = .03); RD, β = -0.01 (P = .01); MD, β = -0.01 (P = .03)]), and sensory processing (medial lemniscus [AD, β = -0.02 (P = .045); MD, β = -0.01 (P = .04)] and retrolenticular internal capsule [FA, β = -0.01 (P = .002); RD, β = 0.01 (P = .003); MD, β = 0.01 (P = .04)]). Follow-up analyses revealed that early intervention promoted more normative white matter development among previously neglected children who entered foster care.
Results suggest that removal from conditions of neglect in early life and entry into a high-quality family environment can support more normative trajectories of white matter growth. Our findings have implications for public health and policy efforts designed to promote normative brain development among vulnerable children.
clinicaltrials.gov Identifier: NCT00747396.
早年的严重忽视与大脑发育及相关行为功能的损害有关。尽管早期干预已被证明有助于支持大脑发育更符合规范的轨迹，但对情绪和认知发展至关重要的白质通路的具体改善情况尚不清楚。
研究早年忽视、早期干预与童年中期白质通路微观结构完整性之间的关联。
设计、背景和参与者：布加勒斯特早期干预项目是一项随机临床试验，从2000年至今，将高质量寄养作为罗马尼亚布加勒斯特机构养育儿童的一种干预措施。在婴儿期，儿童被随机选择留在机构或被安置在寄养家庭。留在机构中的儿童经历了忽视，包括社会、情感、语言和认知匮乏。将这些儿童的发育轨迹与一组在基线时以及整个发育过程中几个时间点在亲生家庭中养育的社会人口统计学匹配儿童进行比较。在大约8岁时，最初的136名儿童中有69名接受了结构磁共振成像扫描。
通过扩散张量成像获得了全脑48条白质束的白质完整性的四项估计值（分数各向异性[FA]以及平均[MD]、径向[RD]和轴向[AD]扩散率）。
早年忽视与胼胝体主体的微观结构完整性（FA，β = 0.01 [P = 0.01]；RD，β = -0.02 [P = 0.005]；MD，β = -0.01 [P = 0.02]）以及涉及边缘回路的束（穹窿脚[AD，β = 0.02（P = 0.046）]和扣带[RD，β = -0.01（P = 0.02）；MD，β = -0.01（P = 0.049）]）、额纹状体回路（前[AD，β = -0.01（P = 0.02）]和上[AD，β = -0.02（P = 0.02）；MD，β = -0.01（P = 0.03）]放射冠和外囊[右侧FA，β = 0.01（P = 0.03）；左侧FA，β = 0.01（P = 0.03）；RD，β = -0.01（P = 0.01）；MD，β = -0.01（P = 0.03）]）以及感觉处理（内侧丘系[AD，β = -0.02（P = 0.045）；MD，β = -0.01（P = 0.04）]和豆状核后内侧囊[FA，β = -0.01（P = 0.002）；RD，β = 0.01（P = 0.003）；MD，β = 0.01（P = 0.04）]）之间存在显著关联。后续分析表明，早期干预促进了进入寄养家庭的先前被忽视儿童的白质发育更符合规范。
结果表明，早年脱离忽视环境并进入高质量家庭环境可支持白质生长更符合规范的轨迹。我们的研究结果对旨在促进弱势儿童大脑规范发育的公共卫生和政策努力具有启示意义。
clinicaltrials.gov标识符：NCT00747396。
