NEUROBIOLOGY AND GENETICS OF AUTISM

尽管多年来的研究努力，人们对 自闭症(AD)和NO的病因或病理生理学 治疗。三个重大进展增加了这样一种可能性 在解开AD的奥秘方面可以取得进展：(1)形态计量学 使用MERI的分析表明，阿尔茨海默病儿童的大脑在 体积与白质有显著差异，(2)POMC通路 化合物B-内啡肽和ACTH的反应和相互作用在 阿尔茨海默病儿童的挑战和(3)人类基因组计划 提前提供了一份密集的人类基因组图谱，包括 大约一半的表达基因(EST)。 阿尔茨海默病儿童脑体积偏大的观察 控制措施已经被几个研究小组记录在案。这一扩张 定位于白质和大脑的相关区域。 这些发现可以在最近招募的新队列中重复吗 儿童阿尔茨海默病儿童？使用序列MRI扫描，是否可以达到 青春期对阿尔茨海默病患者大脑发育有何影响？这些发现是 在整个AD儿童样本中是一致的吗？项目2：磁共振成像是 解决这些问题。 观察到一些孩子失去了社交和/或语言技能 在AD的早期病程是一个轶事，但一致的发现。做这些事吧 孩子们有正常的发育和退化吗？完全的自闭症患者 回归与纯语言回归是分开存在的？这是不是 来自MRI研究的神经生物学训练区分了这些AD儿童 用倒退？项目3：回归将调查一组非常 并回答以下有关自闭症回归的问题。 前两项新进展来自研究人员在 UCI。核磁共振和阿片类药物的发现都可能代表遗传差异。 在阿尔茨海默病和正常儿童之间和/或在这组儿童中 诊断为阿尔茨海默病。利用人类基因组框架和遗传分析 在加州大学洛杉矶分校，我们可以特别询问神经生物学上的差异 代表导致阿尔茨海默病的基因的作用(几项研究估计 AD基因座的数目为3-6个)。是这六个基因座中的一些 以大脑大小的表型为代表？是这六个人中的一些人 自闭症回归的表型特征所代表的基因座 亚型？项目1：遗传学旨在回答这个问题。 对于AD来说，我们对潜在的生物学知识知之甚少，它是 重要的是我们以系统的方式寻找线索，使用 我们的基因知识作为一种工具。我们的研究提供了去哪里的线索 开始遗传学研究。这笔拨款是为了利用这些线索 全力以赴。所有的病例，甚至很大一部分都不太可能 在大多数病例中，阿尔茨海默病纯粹是遗传的。但有些AD肯定是遗传的，而且 找到这些基因是迈向以下目标的关键第一步 理解这种灾难性的紊乱。

Despite years of research efforts, there is little understanding of the etiology or pathophysiology of Autistic Disorder (AD) and no treatment. Three significant developments have raised the possibility that progress can be made in unraveling the mysteries of AD: (1) morphometric analyses using MERI have shown that the brains of AD children ar larger in volume with significant differences in white matter, (2) the POMC pathway compounds B-endorphin and ACTH respond and interact differently before and after challenge in some children with AD and (3) the Human Genome Project has provided ahead of schedule a dense map of the human genome including about half of the expressed genes (ESTs). The observation that the brains of AD children are larger than normal controls has been documented by several research teams. This enlargement is localized to white matter and to the association regions of the brain. Can these findings be replicated in a newly-recruited cohort of late childhood children with AD? Using sequential MRI scan, can the effects of puberty on brain development in AD be defined? Are these findings consistent across the entire sample of AD children? Project 2: MRI is addressing these points. The observation that some children lose skills, social and/or verbal in the early course of AD is an anecdotal but consistent finding. Do these children have normal development and regress? Does a Full Autistic Regression exist separate from a Language-Only Regression? Does the neurobiological train from the MRI study differentiate these AD children with regression? Project 3: Regression will investigate a group of very young AD children and answer these questions about Autistic Regression. The first two new developments are from studies by researchers at UCI. Both the MRI and opiate findings could represent genetics differences between AD and normal children and/or within this group of children diagnosed as AD. Using the Human Genome framework and the genetic analysis expertise at UCI we can ask specifically if neurobiological differences represent the action of genes contributing to AD (several studies estimate the number of AD loci is 3-6). Are some of these half-dozen loci represented by the phenotypes of brain size? Are some of these half-dozen loci represented by the phenotypic characteristic of Autistic Regression subtypes? Project 1: Genetics is designed to answer this question. For AD, where we known so little by the underlying biology, it is essential that we pursue clues in a systematic fashion, using the state of our genetic knowledge as a tool. Our research provides clues on where to begin the genetics search. This grant is designed to exploit those clues to the fullest. It is unlikely that all cases, or even a large proportion of cases, of AD are purely genetic. But some AD surely is genetic, and finding those genes constitutes a critical first step towards understanding this disastrous disorder.