哌甲酯治疗注意缺陷多动障碍儿童缓解机制的多模态磁共振研究

项目名称： 哌甲酯治疗注意缺陷多动障碍儿童缓解机制的多模态磁共振研究

项目编号： No.81471382

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： 曹庆久

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）患病率高，结局不良，是重大的公共卫生问题。多国指南均推荐哌甲酯为治疗ADHD的一线药物。但该药个体反应差异大，疗效缓解者，症状基本消失，功能恢复，但部分患者未达缓解。影响哌甲酯治疗缓解的脑机制尚不清楚。本研究采用前瞻性设计，使用多模态磁共振成像（MRI）技术，收集未治疗的100例ADHD和50例对照儿童的MRI数据，经8周哌甲酯缓释片治疗后，根据疗效，将ADHD分为缓解和未缓解组，寻找缓解组特征性的脑结构及功能异常，探讨预测缓解的脑影像学标记；对缓解、未缓解和对照组各25例儿童再次收集MRI数据，通过治疗前后自身对照及组间比较，发现与症状缓解相关的脑结构及功能变化，揭示哌甲酯治疗缓解的脑神经机制，并重点探讨前扣带回-额-顶认知注意网络结构和功能异常及变化在缓解机制中的作用。本研究对深入理解ADHD的神经病理机制，进一步开展靶向治疗，提高疗效，改善预后具有重要意。

中文关键词： 儿童注意缺陷多动障碍；功能磁共振成像；哌甲酯；缓解；神经机制

英文摘要： Attention deficit/hyperactivity disorder (ADHD) is highly prevalent among children and adolescents and often associated with poor long-term outcomes in adulthood. It is thus a serious public health problem. Methylphenidate (MPH) is recommended as a first-line medication for ADHD in many countries, but the individual treatment response varies . Some patients present good response to MPH with minimal or no symptoms left and optimal functioning (remission) after treatment, while others are poor responders. However, little is known regarding the neural mechanisms underlining heterogeneous responsiveness to MPH. In this prospective, open-label and naturalistic observation study, we plan to use multimodal magnetic resonance imaging (MRI) technology to explore the neural mechanisms of remission in children with ADHD treated with MPH. The baseline multimodal MRI scans of 100 drug-native children with ADHD and 50 normal controls would be collected first. Patients with ADHD are then to be administered osmotic release oral system MPH (OROS-MPH) for 8 weeks. At the end of the 8th week , the response to OROS-MPH would be established and accordingly, the ADHD patients would be subdivided into remission and non-remission groups. The baseline structural and functional brain features of the remission group, which may act as good predictors of treatment response to MPH in ADHD, would be identified. The after-treatment MRI acquisition would be performed afterwards on a subsample of 25 remission ADHD, 25 non-remission ADHD and 25 normal control respectively. The brain structural and functional alterations related with remission in the remission group would be identified by both self-controlled (before and after MPH treatment) and group-wise comparison of MRI data, which would hence reveal the neural mechanisms of MPH treatment related remission in ADHD. We would also focus on the relationships between the structural and functional brain alterations in the cingulo-frontal-parietal cognitive-attention network and the improvement of symptoms in the remission group. The results of this study would contribute to our understanding of the pathophysiology of ADHD, add to the empirical evidences for targeted therapy of ADHD and have a great impact on the improvement of outcome of ADHD.

英文关键词： children with attention deficit/hyperactivity disorder;functional magnetic resonance imaging;methylphenidate;remission;neural mechanism