NEUROBIOLOGIC ORIGINS AND INNOVATIVE TREATMENT OF AUTISM

巴尔的摩-华盛顿STAART中心将研究自闭症运动规划和沟通障碍的神经生物学起源。其目标是确定大脑发育的基本生物学改变，这些改变是自闭症核心表现的基础，并通过早期识别和干预将这些见解转化为有效的治疗方法。为了实现这一目标，我们召集了一个由22名研究人员组成的小组，他们代表7个学科（精神病学、神经心理学、心理学、言语语言病理学、发育儿科学、神经科学），组成一个联盟，涉及肯尼迪克里格研究所（牵头机构）、儿童国家医学中心、约翰霍普金斯大学、摩根州立大学和 乔治敦大学。我们提出了3个研究项目（1个基础科学和2个临床）和两个核心（行政和临床）。我们还将在分子遗传学，细胞神经科学，功能性神经影像学和生物统计学方面获得两个精神发育迟滞和发育障碍研究中心的核心支持。第一个项目解决了5-HT传入的启动和突触在皮质发育过程中的作用，在新生儿5-HT耗尽自闭症动物模型的出生后的发展。第二个项目将通过对自闭症高危幼儿的研究，解决症状的起源、早期神经生物学机制以及在出现关键缺陷时的治疗。第三个项目将把其他项目提供的对自闭症的理解扩展到以后的生活中：学龄儿童。它将专注于运动执行及其与认知功能的关系。 本计画将使用结构与功能性磁振造影程序来阐明高功能自闭症个体注意力、运动规划与执行功能的神经生物学基础。总的来说，这些项目应该大大增加我们对自闭症个体发生的认识，从而导致新的治疗方法的发展。

This Baltimore-Washington STAART Center will study the neurobiological origins of motor planning and communication impairments in autism. The goal is to identify fundamental biologic alterations of brain development that underlie the core manifestations of autism and to translate these insights into effective therapies through early identification and intervention. In order to accomplish this goal, we have assembled a group of 22 investigators representing 7 disciplines (psychiatry, neuropsychology, psychology, speech-language pathology, developmental pediatrics, neuroscience) in a consortium involving the Kennedy Krieger Institute (lead agency), Children's National Medical Center, Johns Hopkins University, Morgan State University, and Georgetown University. We propose 3 research projects (1 basic science and 2 clinical) and two cores (administration and clinical). We will also have the core support of two Mental Retardation and Developmental Disabilities Research Centers in molecular genetics, cellular neuroscience, functional neuroimaging, and biostatistics. The first project addresses the role of 5-HT afferents in the initiation and progression of synaptogenesis in the cortex during postnatal development in a neonatal 5-HT depleted animal model of autism. The second project will address origins of symptoms, early neurobiological mechanisms, and treatment of key deficits near the time of their emergence through studies of toddlers at high risk for autism. The third project will extend understanding of autism provided by the other projects to a point later in life: in school-aged children. It will focus on motor execution and its relationship to cognitive functioning. This project will use structural and functional MRI procedures to elucidate the neurobiological basis of attention, motor planning, and executive function in individuals with high functioning autism. Taken as a whole, the projects should add significantly to our knowledge of the ontogeny of autism and thereby lead to the development of novel treatment approaches.