ADHD: Genetics, Cognition and Neuroimaging

描述(由申请人提供)：注意力缺陷多动障碍(ADHD)是一种常见的儿童障碍，与学业失败、精神共病和心理社会残疾有关。由于家庭和双胞胎研究表明ADHD有很大的遗传成分，几个研究小组现在已经开始了对这种疾病的分子遗传学研究。这些研究已经产生了两个重复的发现：一个是ADHD和D4多巴胺受体基因之间的关联，另一个是ADHD和多巴胺转运蛋白基因之间的关联。ADHD的另一个被很好复制的特征是其认知功能障碍的模式，以及额叶-皮质下神经网络的结构和功能异常。值得注意的是，ADHD中的认知缺陷区域是适度可遗传的，其牵连的大脑结构的体积也是如此。因此，我们提出了一项网络拨款，旨在寻求在研究与注意力缺陷多动障碍(ADHD)相关的基本行为过程的科学家和那些研究ADHD遗传学的科学家之间建立合作伙伴关系。因此，目前的建议有三个主要事实：1)ADHD是可遗传的；2)它与一种认知功能障碍模式有关；3)它与大脑结构和功能异常有关。这些事实使我们相信，建立一个研究这些研究领域的研究人员网络将是卓有成效的。拟议网络的主要目标是：1)为基础和临床研究人员提供一个场所，以启动和探索专注于ADHD遗传学和认知的研究合作的潜力；2)确定适合ADHD分子遗传学研究的认知表型；3)确定适合ADHD分子遗传学研究的神经成像表型；4)设计研究项目，旨在发现与ADHD相关的神经心理和神经成像异常的基因；5)确定介导这些表型的候选基因；6)设计使用神经心理学和神经成像方法阐明ADHD病因中所涉及的基因变异的功能意义的方案；以及7)鼓励初级研究人员发展整合了遗传学、认知和神经成像领域的ADHD研究职业。

DESCRIPTION (provided by applicant): Attention Deficit Hyperactivity Disorder (ADHD) is a common disorder of childhood associated with school failure, psychiatric comorbidity and psychosocial disability. Because family and twin studies suggest that ADHD has a substantial genetic component, several research groups have now begun molecular genetic studies of the disorder. These studies have already produced two replicated findings: one showing an association between ADHD and the D4 dopamine receptor gene and the other between ADHD and the dopamine transporter gene. Another well replicated feature of ADHD is its pattern of cognitive dysfunction along with structural and functional abnormalities in frontal-subcortical neural networks. Notably, the areas of cognitive deficit seen in ADHD are moderately heritable, as are the volumes of implicated brain structures. We are thus proposing a networking grant which seeks to establish collaborative partnerships among scientists who study basic behavioral processes associated with attention deficit hyperactivity disorder (ADHD) and those who study the genetics of the disorder. Thus, there are three main facts that underlie the present proposal: 1) ADHD is heritable; 2) it is associated with a pattern of cognitive dysfunction; and 3) it is associated with structural and functional brain abnormalities. These facts lead us to believe that it will be fruitful to create a network of researchers studying these domains of inquiry. The main aims of the proposed network are: 1) to provide a venue for basic and clinical investigators to initiate and explore the potential of research collaborations that focus on genetics and cognition in ADHD; 2) to identify cognitive phenotypes suitable for molecular genetic studies of ADHD; 3) to identify neuroimaging phenotypes suitable for molecular genetic studies of ADHD; 4) to design research projects aimed at finding genes that mediate the neuropsychological and neuroimaging abnormalities associated with ADHD; 5) to identify candidate genes that mediate these phenotypes; 6) to design protocols that use neuropsychological and neuroimaging methods to clarify the functional significance of gene variants implicated in the etiology of ADHD; and 7) to encourage junior investigators to develop research careers that integrate the domains of genetics, cognition and neuroimaging in ADHD.