RESPIRATORY & AUTONOMIC PATHOPHYSIOLOGY--PANIC DISORDER

呼吸系统

• 批准号: 6392173
• 负责人: WALTON Thompson ROTH
• 金额: $ 29.25万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-15 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6392173
• 关键词: anxiety disorders; autonomic nervous system; behavior test; behavioral /social science research tag; biomarker; carbon dioxide tension; chemoreceptors; clinical research; human subject; hyperpnea; noise; panic disorder; psychophysiology; pulmonary respiration; respiratory hypoxia; startle reaction

As is now more widely recognized, Panic Disorder often results in considerable emotional suffering and a reduction in quality of life. Although progress has been made in identifying its biological substrates, much about its pathophysiology and etiology remains obscure. Latest research findings in our laboratory and laboratories of other research groups point towards a central role for respiratory mechanisms. Experiments are proposed to investigate markers and mechanisms of Panic Disorder in and outside the laboratory. Respiratory, sympathetic, and parasympathetic measures in Panic Disorder patients of two types, those with and without prominent respiratory symptoms, will be examined and compared to measures in two groups without panic attacks, Generalized Anxiety Disorder patients and controls. In the laboratory the relative importance of several possible respiratory mechanisms will be determined by examining probe-specific and group-specific effects of several kinds of probes: increased inspired CO2, increased inspiratory resistance load, and decreased inspired O2. Each is known to produce feelings of suffocation at moderate intensities, and sometimes panic in Panic Disorder patients at high intensities. Respiratory responses to a noise stressor not directly linked to suffocation fears will serve as a comparison. To resolve contradictions in the literature about slower recovery from voluntary hyperventilation in Panic Disorder, which was a specific marker for Panic Disorder in one of our recent experiments, the effects of different durations of hyperventilation will be examined. In another experiment, central and peripheral chemoreceptor thresholds and sensitivities will be distinguished in Panic Disorder for the first time. Outside the laboratory two ways of recording pCO2 (transcutaneous vs. nasal prongs) will be compared methodologically, and it will be determined whether valid indices of respiratory sinus arrhythmia that take into account variations in breathing will distinguish patients with panic attack-related driving phobia from controls. The significance of this proposal lies in the possibility of its establishing specific and sensitive physiological markers of Panic Disorder, which could lead to better diagnosis and more appropriate treatment, facilitate research in the molecular genetics of Panic Disorder, and lead to a better understanding of dysfunctional biological control mechanisms.

正如现在更广泛认识到的那样，恐慌症常常导致相当大的情感痛苦和生活质量下降。 尽管在鉴定其生物底物方面已取得进展，但其病理生理学和病因学的许多内容仍不清楚。 我们实验室和其他研究小组实验室的最新研究结果表明呼吸机制发挥着核心作用。 建议进行实验来研究实验室内外恐慌症的标志物和机制。 将检查两种类型的惊恐障碍患者（有和没有明显呼吸道症状的患者）的呼吸、交感和副交感神经测量值，并与两组没有惊恐发作的广泛性焦虑症患者和对照组的测量值进行比较。 在实验室中，将通过检查几种探针的探针特异性和组特异性效应来确定几种可能的呼吸机制的相对重要性：吸入CO2增加、吸气阻力负荷增加和吸入O2减少。 众所周知，每一种在中等强度下都会产生窒息感，在高强度下有时会让恐慌症患者产生恐慌感。对与窒息恐惧没有直接关系的噪音应激源的呼吸反应将作为比较。 为了解决文献中关于恐慌症自愿过度换气恢复较慢的矛盾，这是我们最近的一项实验中恐慌症的一个特定标志，将检查不同持续时间的过度换气的影响。 在另一项实验中，首次区分恐慌症中的中枢和外周化学感受器阈值和敏感性。在实验室外，我们将对两种记录 pCO2 的方法（经皮与鼻尖）进行方法学比较，并将确定考虑呼吸变化的呼吸性窦性心律失常的有效指标是否能够将惊恐发作相关的驾驶恐惧症患者与对照组区分开来。 该提案的意义在于它有可能建立恐慌症的特异性和敏感的生理标志物，这可以带来更好的诊断和更合适的治疗，促进恐慌症的分子遗传学研究，并导致更好地理解功能失调的生物控制机制。