神经元发育通路为基础的哌甲酯药物遗传学研究

项目名称： 神经元发育通路为基础的哌甲酯药物遗传学研究

项目编号： No.81471381

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 杨莉

作者单位： 北京大学

项目金额： 70万元

中文摘要： 注意缺陷多动障碍（ADHD）是最常见的儿童行为障碍，患病率为学龄儿童的3%-6%。哌甲酯是最常用的治疗药物，药物反应存在个体差异。已知遗传因素是影响个体药物反应的最重要因素。国内外哌甲酯药物遗传学研究主要关注了药效学通路候选基因，关联基因的效应值较低。本项目在病因学研究最新发现的神经元发育通路基因基础上，在随机双盲安慰剂交叉对照哌甲酯治疗的ADHD患儿中，进行药物疗效的关联研究，整合基因和临床预测指标创建药物反应预测模型。申请人在ADHD的药物遗传领域已有十年以上工作积累，在国内外首先报告NET基因与哌甲酯疗效关联，ADRA2A基因与托莫西汀疗效关联，该领域的两篇论著被SCI收录，获国际神经精神药理学会青年研究者奖。去年在哈佛大学人类遗传学研究中心研修高级遗传学，完成了ADHD的疾病全基因组关联研究。本项目是申请人上一个国自然项目的深入。

中文关键词： 注意缺陷多动障碍；神经元发育；神经精神药理；临床治疗；神经心理学

英文摘要： Attention deficit hyperactivity disorder (ADHD) is the most common behavior disorder in childhood. The prevalence was estimated to be 3% - 6% among school age children. Methylphenidate is the most common used medication, though treatment response varied individually. It's recognized that genetic factors may be the most important factors affecting individual medication response. Pharmacogenetic research of ADHD medication focused much on candidate gene of pharmacodynamic pathway. The effict size of associated genes was relatively low. This study aims to perform an association study of common DNA variants of the neurodevelopmental network genes with therapeutic effect of methylphenidate in an randomized, double-blind, placebo-controlled trial, then integrate the genetic and clinical predicting variables to establish an predicting model for treatment response. The applicant has been working on pharmacogenetics of ADHD for more than ten years. We are the first to report the associations of NET with methylphenidate response, as well as ADRA2A with atomoxetine response. Two publications were cited by SCI. The applicant was awarded the Rafaelsen Young Investigator Award from CINP. The applicant studied advanced genetics in Human Genetics Research Centre of Harvard University last year. We have completed the GWAS of ADHD. This project is a progress of last funded NSFC program.

英文关键词： attention deficit hyperactivity disorder;neurodevelopment;psychoneuropharmacology;clinical treatment;neuropsychology