Molecular Genetic Study of Fear and Anxiety

恐惧和焦虑的分子遗传学研究

• 批准号: 6695269
• 负责人: Thomas Conrad GILLIAM
• 金额: $ 159.64万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6695269
• 关键词: anxiety; clinical research; fear; human subject; molecular genetics

DESCRIPTION (provided by applicant): In this program project we present a novel strategy for the identification of genes important for psychiatric disorders. The studies are aimed at normal and pathological expressions of anxiety in humans, and focus specifically on learned and innate fear in mice. Because fear is a universal affect conserved throughout phylogeny, it is possible to model fear in mice - an organism that is suitable for both physiological and genetic analysis. Fear conditioning is a measure of an organism's basic ability to learn about new dangerous or threatening stimuli or environments, and to respond appropriately. The study of fear conditioning offers two very significant advantages for molecular genetic analysis: the behavioral paradigms can be closely mimicked in human subjects, and the neurocircuitry, and associated information processing systems that underlie these behaviors, are relatively well understood, and highly conserved among vertebrates. Since, in their most general sense, anxiety disorders represent a malfunction in the neural mechanisms that detect danger and mobilize adaptive responses to that danger, we propose that a subset of genes that harbor genetic determinants for learned or innate forms of fear will also harbor susceptibility alleles for human anxiety disorders. Thus, we propose a translational study of fear and anxiety that combines direct molecular genetic study of learned and innate forms of fear in mice with genetic analysis of anxiety related behaviors, traits, and disorders in humans. The Program Project consists of five independent Projects and a Training Component. 1. Genetic and Behavioral Models of Fear States in Mice- 1A. Learned Fear (Kandel) 2A. Innate Fear (Hen). 2.Translation from Mouse to Human Fear and Anxiety: Genetic and Genomic Approaches (Gilliam). 3. Clinical Studies of Human Fear and Anxiety (Fyer). 4. Clinical Studies of Human Anxiety Disorders (Weissman).

描述（由申请人提供）：在此计划项目中，我们提出了一种鉴定对精神疾病重要的基因的新策略。这些研究针对人类焦虑的正常和病理表达，并专门针对小鼠学习和天生的恐惧。因为恐惧是整个系统发育中的普遍影响，因此可以模拟小鼠的恐惧 - 一种适合生理和遗传分析的生物体。恐惧条件是衡量生物体学习新危险或威胁刺激或环境并做出适当反应的基本能力的衡量。对恐惧调节的研究为分子遗传分析提供了两个非常重要的优势：在人类受试者中可以密切模仿行为范例，神经通行物以及这些行为基于这些行为的相关信息处理系统相对众所周知，并且在脊椎动物中得到了高度理解的理解。由于在最普遍的意义上，焦虑症代表了检测危险并动员对这种危险的适应性反应的神经机制中的故障，因此我们提出，具有对学习或先天恐惧的遗传决定因素的基因子集也将对人类焦虑症的敏感性具有易感性等位基因。因此，我们提出了一项对恐惧和焦虑的翻译研究，结合了小鼠的恐惧和先天恐惧的直接分子遗传研究，以及对人类焦虑相关行为，特征和疾病的遗传分析。 该计划项目由五个独立项目和一个培训组成。 1。小鼠1a中恐惧状态的遗传和行为模型。学会了恐惧（坎德尔）2a。先天恐惧（母鸡）。 2.从小鼠到人类恐惧和焦虑的翻译：遗传和基因组方法（Gilliam）。 3。人类恐惧与焦虑（FYER）的临床研究。 4。人类焦虑症的临床研究（Weissman）。