儿童早期酞酸酯类暴露与脑源性神经生长因子交互作用对注意缺陷多动障碍易感性的前瞻性研究

项目名称： 儿童早期酞酸酯类暴露与脑源性神经生长因子交互作用对注意缺陷多动障碍易感性的前瞻性研究

项目编号： No.81673180

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 沈敏

作者单位： 华中科技大学

项目金额： 25万元

中文摘要： ADHD是儿童期最常见的一种神经行为障碍，已成为一个重要的精神卫生和公共卫生问题。目前认为ADHD是遗传和环境因素共同作用的结果。研究显示PAEs暴露可引起神经生成减少，神经可塑性降低，海马与前额皮质容量减小；孕期暴露与儿童期暴露与多动冲动行为增加和执行功能障碍相关，但机制不清。BDNF调节DA能、胆碱酯能、5-羟色胺能神经元存活和神经递质释放，是神经可塑性的分子标记物，与ADHD发病相关。本研究以4岁以上儿童尿PAEs暴露水平及变化趋势，采用病例-对照研究，比较ADHD儿童与正常对照组暴露PAEs水平的差异，分析PAEs暴露对血清BDNF含量，以及PAEs暴露与BDNF基因多个位点多态性交互作用，建立儿童早期PAEs暴露与ADHD易感性的预测模型，阐明环境与基因交互作用对ADHD易感性的影响，为ADHD早期识别和干预提供科学依据。

中文关键词： 酞酸酯类；脑源性神经营养因子；注意缺陷多动障碍；易感性；儿童

英文摘要： Attention deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder. ADHD causes social, academic, and behavioral problems and persists into adulthood in 80% of cases. ADHD has become an important mental health and public health issue. However the etiology of ADHD is still unclear. The experts suggested that ADHD might be caused by gene-environment interactions, and related with plasticity of neurology.. Phthalate (PAEs) exposure on developmental appears that widespread disruptions in hippocampal functional and structural plasticity. Previous studies showed prenatal and neonatal exposure result in impaired neuronal growth and activity, prenatal urinary levels of phthalates were associated with increased odds of externalizing behaviors such as aggression, conduct problems, and attention problems in 4–9-year-old children. Child urinary concentrations of DEHP metabolites were found to be related to ADHD in children. .ADHD is a neurodevelopmental disorder. Brain-derived neurotrophic factors support neuronal survival, proliferation, and differentiation, as well as survival and synaptic plasticity in the central nervous system might be involved in ADHD susceptibility. Therefore, it is necessary to explore the novel risk factors into the predictive model and to improve the predictive ability of the model. This study aims to explore the influence on ADHD susceptibility of PAEs exposure during pregnancy and early childhood, and its interaction with BDNF gene polymorphism . A case-control study design will be used to follow the children aged 4 years and older in the cohort, and to collect urine and blood sample, to evaluate the syndromes of ADHD by CBCL and DSM-V, to analysis differences of PAEs exposure between case and control group, by controlling other co-variables and confounding factors. And to understand the impact on serum BDNF level due to critical role in ADHD. To establish predictive models to evaluate the risk of early PAEs exposure and its interaction with BDNF gene multiple polymorphisms on ADHD, to provide strong scientific evidences to prevent and identify ADHD in early childhood.

英文关键词： phthalates esters;PAEs;brain-derived neurotrophic factor;attention deficit and hyperactivity disorder;susceptibility;children