INTEGRATING BRAIN IMAGING AND GENETIC ANALYSIS OF ADHD

整合 ADHD 的脑成像和遗传分析

• 批准号: 7608291
• 负责人: Chandan J Vaidya
• 金额: $ 4.13万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7608291
• 关键词: 11 year old; Age; Brain; Brain imaging; Child; Computer Retrieval of Information on Scientific Projects Database; Corpus striatum structure; Diagnosis; Disease; Early Intervention; Functional Magnetic Resonance Imaging; Funding; Gender; Genotype; Grant; Hyperactive behavior; Image; Institution; Methylphenidate; Participant; Phenotype; Placebo Control; Relative (related person); Research; Research Personnel; Resolution; Resources; Sampling; Short-Term Memory; Source; Subgroup; Testing; United States National Institutes of Health; boys; clinical efficacy; disorder control; dopamine transporter; executive function; genetic analysis; girls; gray matter; indexing; neuropathology; novel; research study; response; treatment planning

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The proposal aims to examine functional and structural neuropathology underlying deficits of executive control (indexed by inhibitory control, working memory, and attentional set switching, in Attenton Deficit Hyperactivity Disorder (ADHD) using whole-brain structural and functional magnetic resonance imaging (fMRI). It is hypothesized that prefrontal-striatal-cerebellar circuitry underlying executive control is dysfunctional in ADHD due to abnormal dopaminergic function. We will test two predictions of this hypothesis - (1) fMRI will reveal that the functional activation in prefrontal-striatal-cerebellar regions during inhibitory control (Exp 2), working memory (Exp 3), and attentional set switching (Exp 4) will be abnormal in ADHD children (relative to control children) and will be normalized by the administration of methylphenidate in ADHD children. Sample for Experiments 2-4 will include 48 9-11 year old Combined-type ADHD children (24 girls and 24 boys) and 48 age, gender, and IQ-matched healthy children. (2) Functional response to methylphenidate in prefrontal-striatal regions underlying inhibitory control in ADHD will be influenced by dopamine transporter genotype (DAT1) (Exp 1). Sample for Experiment 1 will include 36 combined-type ADHD children (12 carriers of 480bp-10/10, 480bp-10/9, 440bp-9/9, each). These ADHD subjects were participants in an ongoing pharmocogenetic study at CNMC that found superior clinical efficacy of methylphenidate in carriers of 480bp than 440bp. We have the unique opportunity to examine the functional brain response to methylphenidate during inhibitory control in those same ADHD children. In al experiments, fMRI will be performed on ADHD children with administration of methylphenidate and placebo; control children (in Experiments 2-4) will be imaged without methylphenidate. Further, high resolution structural imaging will be used to examine whether regions activated during fMRI differ in gray matter volume between ADHD subgroups and controls. Novel features of our proposal include: I) examination of structural and functional brain differences in the same ADHD and control children and ii) examination of the functional brain response to methylphenidate in ADHD children in whom clinical efficacy of methylphenidate varied by DAT1 genotype. Examination of such genotype-phenotype relationships will elucidate potential etiological factors and neuropathophysiology of ADHD that will be useful in diagnosis, early intervention, and treatment planning.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该提案旨在使用全脑结构和功能磁共振成像（fMRI）检查注意缺陷多动障碍（ADHD）中执行控制缺陷（以抑制控制、工作记忆和注意力组转换为索引）的功能和结构神经病理学。假设执行控制的前额叶-纹状体-小脑回路在以下情况下功能失调： 由于多巴胺能功能异常而引起的多动症。 我们将检验这一假设的两个预测 - (1) fMRI 将揭示，ADHD 儿童（相对于对照儿童）在抑制控制（实验 2）、工作记忆（实验 3）和注意力组切换（实验 4）期间前额叶-纹状体-小脑区域的功能激活将异常，并且将通过哌醋甲酯的给药而正常化 在多动症儿童中。 实验2-4的样本将包括48名9-11岁混合型ADHD儿童（24名女孩和24名男孩）和48名年龄、性别和智商匹配的健康儿童。 (2) ADHD 抑制控制的前额叶-纹状体区域对哌醋甲酯的功能反应将受到多巴胺转运蛋白基因型 (DAT1) 的影响（实验 1）。 样品用于 实验1将包括36名组合型ADHD儿童（各12个480bp-10/10、480bp-10/9、440bp-9/9携带者）。 这些 ADHD 受试者参加了 CNMC 正在进行的一项药物遗传学研究，该研究发现哌醋甲酯在 480bp 携带者中的临床疗效优于 440bp 携带者。 我们有独特的机会来检查大脑的功能 这些 ADHD 儿童在抑制控制期间对哌醋甲酯的反应。 在所有实验中，将对多动症儿童进行功能磁共振成像，并给予哌醋甲酯和安慰剂；对照儿童（在实验 2-4 中）将在没有哌醋甲酯的情况下进行成像。 此外，高分辨率结构成像将用于检查功能磁共振成像期间激活的区域在 ADHD 亚组和对照组之间的灰质体积是否存在差异。 我们的新颖特点 建议包括：I) 检查同一 ADHD 儿童和对照儿童的大脑结构和功能差异；ii) 检查 ADHD 儿童对哌甲酯的功能性大脑反应，其中哌甲酯的临床疗效因 DAT1 基因型而异。 对这种基因型-表型关系的检查将阐明 ADHD 的潜在病因和神经病理生理学，这将有助于诊断、早期干预和治疗计划。