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）：在这个项目中，我们提出了一种新的策略来鉴定对精神疾病重要的基因。这些研究针对人类焦虑的正常和病理性表达，并特别关注小鼠的习得性和先天性恐惧。由于恐惧是一种在整个系统发育过程中保守的普遍情感，因此可以在小鼠（一种适合生理和遗传分析的生物体）中模拟恐惧。恐惧调节是衡量生物体了解新的危险或威胁性刺激或环境并做出适当反应的基本能力的指标。恐惧条件反射的研究为分子遗传学分析提供了两个非常重要的优势：可以在人类受试者中密切模仿行为范式，并且这些行为背后的神经回路和相关信息处理系统相对较好地被理解，并且在脊椎动物中高度保守。因为，从最普遍的意义上来说，焦虑症代表了检测危险并调动对危险的适应性反应的神经机制的故障，因此我们提出，包含习得或先天恐惧形式的遗传决定因素的基因子集也将包含人类焦虑症的易感等位基因。因此，我们提出了一项恐惧和焦虑的转化研究，它将小鼠习得和先天恐惧形式的直接分子遗传学研究与人类焦虑相关行为、特征和疾病的遗传分析结合起来。 该计划项目由五个独立项目和一个培训部分组成。 1. 小鼠恐惧状态的遗传和行为模型- 1A。习得性恐惧（坎德尔）2A。与生俱来的恐惧（母鸡）。 2.从小鼠到人类的恐惧和焦虑的翻译：遗传和基因组方法（Gilliam）。 3.人类恐惧和焦虑的临床研究（Fyer）。 4.人类焦虑症的临床研究（Weissman）。