NERUROCHEMISTRY & CHILDHOOD PSYCHOPATHOLOGY

该方案由行政和科学核心部分组成 服务于四个研究领域：(1)生化调节；(2) 神经递质受体生物化学；(3)神经化学 犬发作性睡病的研究及(4)临床神经化学和临床 儿童自闭症的遗传学研究。这次会议的中心主题是 项目是儿童普遍存在的发育障碍 用明确的生化指标反映中枢神经系统功能障碍 以及新陈代谢后果。该方案的调查范围 范围从基因调控、蛋白质结构和 神经药理学在诊断和治疗中的作用 婴儿自闭症。程序的每个组成部分都与 其他项目领域，同时保留一个单独的基础 科学探究。生化调节部分重点介绍 儿茶酚胺生物合成酶--多巴胺的调节 S羟基酶和苯乙醇胺N-甲基转移酶，来自 基因组通过翻译后事件。关于中国石油天然气集团公司 它们的结构、亚基组成和氨基酸序列 酶正在进行中，克隆编码它们的cdna探针的工作也在进行中 结构。这些探针和特异性抗体将被用来 研究酶调节的分子事件。这个 受体部分研究5HTIb和5HTIb的分子特性 5HTIc受体，是溶解和纯化这些蛋白质和 开发分子探针来研究它们的调控。 检测大脑5-羟色胺能的发育研究- 去甲肾上腺素能系统将是调控的协调努力 和感受器部分。发作性睡病科室研究 胆碱能、多巴胺能和神经化学缺陷 去甲肾上腺素能系统与犬发作性睡病有关，这是一种基因 紊乱也发生在儿童中。研究受体和 参与这些系统的酶正在进行中，组间也是如此。 努力研究它们的个体发育和基因调控。这个 临床科积累了一个庞大的儿童数据库 自闭症和相关的广泛性发育障碍，并有 开发了将它们分成四个更不同的， 同质临床分组。定义离散的工作正在进行中 与这些疾病相关的遗传、产前和生化标记 子类型。最后，一个新的项目区将研究基因 在具有自闭症先证者的多胎家庭中，使用A 鉴定限制性片段的一系列cDNAs探针 多态现象。

This program consists of an administrative and scientific core serving four investigative areas: (1) Biochemical Regulation; (2) Biochemistry of Neurotransmitter Receptors; (3) Neurochemical Studies in Canine Narcolepsy and (4) Clinical Neurochemical and Genetic Studies in infantile autism. The central theme of the program is that pervasive developmental disorders in children reflect central nervous system dysfunction with defined biochemical and metabolic consequences. The investigative scope of the program ranges from basic work in gene regulation, protein structure and neuropharmacology to diagnostic and therapeutic strategies in infantile autism. Each component of the program interdigitate with the other project areas while retaining a separate base of scientific inquiry. The biochemical Regulation section focuses on the regulation of the catecholamine biosynthetic enzymes, dopamine s-hydroxylase and phenylethanolamine N-methyltransferase, from genomic through posttranslational events. Studies on the structure, subunit composition and amino acid sequence of these enzymes are ongoing as is work cloning cDNA probes encoding their structure. These probes and specific antibodies will be used to investigate molecular events underlying enzyme regulation. The Receptor section studies the molecular characteristics of 5HTIb and 5HTIc receptors, is solubilizing and puriFying these proteins and developing molecular probes to study their regulation. Developmental studies examining the brain serotonergic- noradrenergic system will be a coordinated effort of the Regulation and Receptor sections. The Narcolepsy section studies neurochemical deficits in the cholinergic, dopaminergic and noradrenergic systems implicated in canine narcolepsy, a genetic disorder also occurring in children. Work on the receptors and enzymes involved in these systems is underway, as are intergroup efforts studying their ontogeny and genetic regulation. The Clinical section has accumulated a large database of children with autism and related pervasive developmental disorders, and has developed methods of subtyping them into four, more distinct, homogeneous clinical groups. Work is underway to define discrete genetic, prenatal and biochemical markers associated with these subtypes. Finally, a new project area will investigate genetic linkage in multiplex families with autistic probands, using a series of cDNA probes to identify restriction fragment polymorphisms.