The Neuroendocrinology of Panic Disorder

惊恐障碍的神经内分泌学

• 批准号: 6866683
• 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 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6866683
• 关键词: anxiety; carbon dioxide; clinical research; corticotropin releasing factor; endogenous opioid; human subject; hypothalamic pituitary adrenal axis; mental disorder chemotherapy; metyrapone; naloxone; neuroendocrine system; neurohormones; neurotransmitters; panic disorder; pathologic process; patient oriented research; posttraumatic stress disorder; psychopharmacology; psychophysiology; stress

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)：在这份修订后的以患者为导向的研究职业发展奖的申请中，候选人Smit S.Sinha将发展焦虑的心理神经内分泌学方面的专业知识，重点是内源性阿片系统及其与恐慌症中的下丘脑-垂体-肾上腺轴的相互作用。内源性阿片系统是人类应激反应的一个组成部分，对位于关键大脑区域的特定神经递质和神经激素系统产生广泛的调节影响，这些区域被认为是调节应激、焦虑和恐慌状态的关键区域。与恐慌症特别相关的是阿片类药物调节二氧化碳敏感性的证据，这种敏感性在恐慌中异常升高，是疾病的强烈生物标志。阿片类药物还调节依恋和分离行为，这种行为的中断与疾病的发展和维持密切相关。这项建议还将研究惊恐障碍中HPA轴的功能。HPA功能的紊乱，特别是中枢促肾上腺皮质激素释放激素(CRH)驱动的异常和增加，与严重抑郁障碍和创伤后应激障碍的发病机制有关。然而，恐慌症是否与中枢CRH失调有关尚不清楚。这是尽管CRH在焦虑产生和呼吸调节方面的突出作用。来自候选人和导师的初步数据表明，惊恐障碍涉及阿片类药物系统和CRH系统的显著异常。候选人的研究计划将1.评估内源性阿片系统和CRH系统的中枢功能，分别使用纳洛酮和美曲酮2.将中枢阿片活性和CRH活性与二氧化碳敏感性联系起来3.解决这些系统之间的功能相互作用和4.评估药物治疗对这些系统的影响。职业发展活动以辛哈博士在临床研究方面的背景为基础，并利用哥伦比亚大学的资源。总体目标是获得焦虑和压力的心理神经内分泌学方面的技能，并将其应用于恐慌症的病理生理学。综合教育计划在研究计划中应用的关键领域提供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，4)临床试验方法学。