NEUROBIOLOGIC ORIGINS AND INNOVATIVE TREATMENT OF AUTISM

巴尔的摩-华盛顿STAART中心将研究自闭症患者运动规划和沟通障碍的神经生物学起源。其目标是确定构成自闭症核心表现的大脑发育的基本生物学变化，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、神经科学)，成员包括肯尼迪·克里格研究所(牵头机构)、国家儿童医学中心、约翰斯·霍普金斯大学、摩根州立大学和 乔治城大学。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(管理和临床)。我们还将获得两个智力低下和发育障碍研究中心在分子遗传学、细胞神经科学、功能神经成像和生物统计学方面的核心支持。第一个项目致力于5-羟色胺传入在5-羟色胺缺乏的自闭症新生动物模型出生后发育过程中皮质突触发生的启动和进展中的作用。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，以及在关键缺陷出现时对其进行治疗。第三个项目将把其他项目提供的对自闭症的了解扩展到生活的更晚阶段：学龄儿童。它将专注于运动执行及其与认知功能的关系。这个项目将使用结构和功能核磁共振程序来阐明高功能自闭症患者注意力、运动规划和执行功能的神经生物学基础。总体而言，这些项目应该会显著增加我们对自闭症个体发生学的了解，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.