The Neuroendocrinology of Panic Disorder

惊恐障碍的神经内分泌学

• 批准号: 7198008
• 负责人: SMIT S SINHA
• 金额: $ 17.67万
• 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: 2003-03-15 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7198008
• 关键词: Acute; Address; Adrenal Glands; Antidepressive Agents; Anxiety; Area; Behavior; Biological Markers; Brain region; Breathing; Carbon Dioxide; Clinical; Clinical Research; Clinical Trials; Corticotropin; Corticotropin-Releasing Hormone; Data; Development; Disease; Disruption; Distress; Dose; Employee Strikes; Endocrine; Evaluation; Feedback; Functional disorder; Goals; Human; Hydrocortisone; Hypersensitivity; Hypothalamic structure; Individual; Instruction; Link; Maintenance; Major Depressive Disorder; Measures; Mediating; Mental Depression; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Methods; Metyrapone; Naloxone; Nature; Neuroendocrinology; Neurosecretory Systems; Neurotransmitters; Opioid; Opioid Receptor; Panic; Panic Disorder; Pathogenesis; Patients; Peripheral; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Physiological; Pituitary Gland; Post-Traumatic Stress Disorders; Principal Investigator; Production; Psychoneuroendocrinology; Psychophysiology; Reading; Regulation; Research; Research Design; Resources; Role; Salivary; Sodium Lactate; Specificity; Standards of Weights and Measures; Stress; System; Testing; Thinking; Traumatic Stress Disorders; Universities; Week; Work; biological adaptation to stress; career; endogenous opioids; hypothalamic-pituitary-adrenal axis; inhibitor/antagonist; nonhuman primate; programs; respiratory; response; skills; statistics; treatment duration; treatment effect

DESCRIPTION (provided by applicant): In this revised application for a Mentored Patient Oriented Research Career Development Award, the candidate, Smit S. Sinha, will develop expertise in the psychoneuroendocrinology of anxiety, with emphasis on the endogenous opioid system and its interactions with the hypothalamic-pituitary-adrenal axis in panic disorder. The endogenous opioid system is an integral aspect of the human stress response, and exerts widespread regulatory influence on specific neurotransmitter and neurohormonal systems located in key brain regions thought to regulate stress, anxiety and panic states. Of particular relevance to panic disorder is the evidence for opioid regulation of carbon dioxide sensitivity, which is abnormally heightened in panic and is a strong biological marker of the illness. Opioids also regulate attachment and separation behaviors, disruptions of which are strongly implicated in the development and maintenance of the illness. This proposal will also investigate HPA axis function in panic disorder. Disruptions of HPA function, particularly abnormal and increased central corticotropin releasing hormone (CRH) drive, have been implicated in the pathogenesis of major depressive disorder and PTSD. However, whether panic disorder involves central CRH dysregulation is not known. This is despite the prominent role of CRH in anxiogenesis and respiratory regulation. Preliminary data from the candidate and mentors suggest that panic disorder involves significant abnormalities in the opioid system and the CRH system. The candidate's research plan will 1. Assess the central functioning of both the endogenous opioid system and the CRH system with naloxone and metyrapone administration, respectively 2. Relate central opioid activity and CRH activity to CO2 sensitivity 3. Address functional interactions between these systems and 4. Assess the effects of medication treatment on these systems. The career development activities build on Dr. Sinha's background in clinical research and capitalizes on the resources of Columbia University. The overall goals are to acquire skills in the psychoneuroendocrinology of anxiety and stress with application to the pathophysiology of panic disorder. The comprehensive educational plan provides expert mentorship and didactic instruction in the key areas applied in the research plan: 1) neuroendocrinology 2) psychophysiology 3)research design and statistics and 4) clinical trials methodology.

描述（由申请人提供）：在这项修订的指导患者研究职业发展奖的修订申请中，候选人Smit S. Sinha将在焦虑的心理术中开发专业知识，重点是内源性阿片类药物系统及其与下丘脑垂体 - 雌性 - 肾上腺轴的相互作用。内源性阿片类药物系统是人类压力反应不可或缺的一部分，并且对位于被认为调节压力，焦虑和恐慌状态的关键大脑区域的特定神经递质和神经激素系统对特定神经递质和神经激素系统产生广泛的调节作用。与恐慌症特别相关的是二氧化碳敏感性的阿片类药物调节的证据，二氧化碳敏感性在恐慌中异常增强，并且是该疾病的强大生物学标志物。阿片类药物还调节依恋和分离行为，其破坏与疾病的发展和维持很大。该建议还将研究恐慌症中的HPA轴功能。 HPA功能的破坏，尤其是异常和中枢性皮质激素释放激素（CRH）驱动力的破坏，与主要抑郁症和PTSD的发病机理有关。但是，尚不清楚恐慌症是否涉及中央CRH失调。尽管CRH在焦虑生成和呼吸道调节中的重要作用仍然很重要。候选人和导师的初步数据表明，恐慌症涉及阿片类药物系统和CRH系统的明显异常。候选人的研究计划将1。评估内源性阿片类药物系统和CRH系统的中心功能与纳洛酮和甲酰胺剂的给药分别为2。将中央阿片类药物和CRH活性与CO2敏感性相关联3。解决这些系统与4之间的功能相互作用。评估对这些系统的药物治疗对这些系统的影响。职业发展活动基于Sinha博士的临床研究背景，并利用了哥伦比亚大学的资源。总体目标是通过在恐慌症的病理生理学中应用焦虑和压力的心理肌内分泌学的技能。全面的教育计划在研究计划中应用的关键领域提供了专家指导和教学指导：1）神经内分泌学2）心理生理学3）研究设计和统计学以及4）临床试验方法。