Mechanisms of Sympathetic Overactivity in Post-traumatic Stress Disorder

创伤后应激障碍中交感神经过度活跃的机制

• 批准号: 8921491
• 负责人: Jeanie Park
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8921491
• 关键词: Address; Afghanistan; Anxiety Disorders; Arithmetic; Baroreflex; Biofeedback; Biological Markers; Blood Pressure; Blood Vessels; Breathing; Cardiovascular Diseases; Cardiovascular system; Chronic; Clinical; Data; Devices; Disease; Electrocardiogram; Exhibits; Functional disorder; Future; General Population; Goals; Heart Rate; Human; Hyperactive behavior; Hypertension; Inflammation; Inflammatory; Intervention; Investigation; Iraq; Literature; Long-Term Effects; Major Depressive Disorder; Measurable; Measures; Mediating; Meditation; Muscle; Nerve; Nerve Endings; Patients; Physiology; Population; Post-Traumatic Stress Disorders; Pressoreceptors; Psyche structure; Reaction; Regulation; Relaxation; Research; Rest; Risk; Role; Staging; Stimulus; Stress; Sympathetic Nervous System; System; Techniques; Testing; Therapeutic; Translating; Trauma; Veterans; base; blood pressure reduction; cardiovascular disorder risk; cardiovascular risk factor; combat; disorder control; heart disease risk; heart rate variability; hemodynamics; high risk; improved; insight; novel; pilot trial; prevent; programs; public health relevance; relating to nervous system; research study; respiratory; response; virtual reality; young man; young woman

 DESCRIPTION (provided by applicant): Post-traumatic stress disorder (PTSD) is a highly prevalent anxiety disorder that is associated with an increased risk of cardiovascular (CV) disease and hypertension. Given the large numbers of Veterans returning from Iraq and Afghanistan afflicted with PTSD, addressing this under-recognized but highly significant consequence of PTSD is of paramount importance. The mechanisms underlying increased CV risk in PTSD remains unknown. One potential mechanism is overactivation of the sympathetic nervous system (SNS), both at rest and during stress. Previous studies have shown that PTSD patients have higher resting heart rates and blood pressure (BP), greater cardiovascular reactivity during stress, and reduced heart rate variability, suggesting a state of heightened sympathetic activity. Although SNS hyperactivity is implicated in PTSD based on these observed indirect derangements, SNS regulation has never before been rigorously investigated in this population, and the underlying mechanisms and potential interventions targeting SNS activity and CV risk remain unexplored. The goals of this study are to determine if: 1) PTSD patients have higher resting SNS activity, and greater SNS reactivity during mental stress; 2) PTSD patients have abnormal arterial baroreflex sensitivity (BRS) that underlies SNS overactivity at baseline and during mental stress; 3) device-guided slow breathing (DGB) acutely improves SNS activity and BRS in PTSD patients; and 4) 8 weeks of daily DGB therapy improves SNS activity and hemodynamic profiles at rest and during mental stress. Furthermore, given that around half of PTSD patients have comorbid major depression (MD), and MD is independently associated with CV risk and SNS dysregulation, we hypothesize that comorbid MD augments SNS reactivity at rest and during mental stress in PTSD patients. To achieve these goals, we will measure sympathetic nerve activity directly using microneurography in young, prehypertensive veterans with PTSD (with and without MD) compared to non-PTSD controls (with and without MD) at rest and during mental stress, perform arterial baroreflex testing using the modified Oxford technique, and perform an 8-week pilot trial on the benefits of DGB on SNS reactivity and regulation. We hypothesize that PTSD patients have greater SNS activity at baseline and greater SNS reactivity during sympathoexcitation with mental stress, both related to combat recall and other forms of mental stress. We expect that these derangements are independent of MD, but that comorbid MD augments SNS reactivity in PTSD. We further propose that SNS overactivity is mediated by arterial baroreflex dysfunction at rest and during mental stress. Finally, previous studies have shown that device guided slow breathing (DGB), in which breathing is slowed to subphysiologic rates (of 5-6 breaths/minute) via an interactive biofeedback device, reduces BP, SNS activity, and improves BRS in patients with hypertension. DGB has never previously been tested in PTSD and may be a novel nonpharmacologic approach to reducing SNS activity and restoring BRS in these patients. We hypothesize that DGB acutely improves SNS overactivity, BP, and BRS, and chronically leads to sustained reductions in SNS and BRS at rest and during stress, in prehypertensive patients with PTSD. Improving SNS overactivity and BRS may have long term benefits on reducing CV risk in PTSD patients.

 描述（由申请人提供）： 创伤后应激障碍（PTSD）是一种高度流行的焦虑症，与心血管（CV）疾病和高血压的风险增加有关。鉴于大量从伊拉克和阿富汗返回的退伍军人患有创伤后应激障碍，解决创伤后应激障碍的这种未被充分认识但非常重要的后果至关重要。PTSD患者心血管风险增加的机制尚不清楚。一个潜在的机制是交感神经系统（SNS）的过度激活，无论是在休息和压力。先前的研究表明，PTSD患者具有较高的静息心率和血压（BP），在压力期间具有更大的心血管反应性，并且心率变异性降低，这表明交感神经活动增强的状态。虽然SNS活动过度与PTSD有关，但SNS调节在此人群中从未进行过严格的研究，并且针对SNS活动和CV风险的潜在机制和潜在干预措施尚未探索。本研究的目的是确定：1）PTSD患者是否具有较高的静息SNS活性，以及在精神应激期间较高的SNS反应性; 2）PTSD患者是否具有异常的动脉压力反射敏感性（BRS），这是基线时和精神应激期间SNS过度活性的基础; 3）设备引导的缓慢呼吸（DGB）是否能显著改善PTSD患者的SNS活性和BRS;和4）8周的每日DGB治疗改善了休息时和精神应激期间的SNS活动和血液动力学特征。此外，鉴于约一半的PTSD患者患有共病的抑郁症（MD），MD与CV风险和SNS失调独立相关，我们假设共病的MD增强了PTSD患者在休息时和精神压力期间的SNS反应。为了实现这些目标，我们将直接测量交感神经活动，在年轻的，高血压前期退伍军人与PTSD（有和没有MD）相比，非PTSD对照（有和没有MD）在休息和精神压力，进行动脉压力感受器反射测试使用改良牛津技术，并进行为期8周的试点试验的好处，DGB的SNS反应性和调节。我们假设PTSD患者在基线时有更大的SNS活动，在精神压力下交感神经兴奋时有更大的SNS反应性，两者都与战斗回忆和其他形式的精神压力有关。我们预计这些紊乱是独立的MD，但共病MD增强SNS反应性PTSD。我们进一步提出，SNS过度活跃介导的动脉压力感受性反射功能障碍在休息和精神压力。最后，之前的研究表明，通过交互式生物反馈装置将呼吸减慢至亚生理速率（5-6次呼吸/分钟）的装置引导的缓慢呼吸（DGB）可降低血压、SNS活动并改善高血压患者的BRS。DGB以前从未在PTSD中进行过测试，可能是一种新的非药物方法，可以减少SNS活动并恢复这些患者的BRS。我们假设，DGB急性改善SNS过度活动，BP和BRS，并长期导致持续减少SNS和BRS在休息和压力，在高血压前期PTSD患者。改善SNS过度活动和BRS可能对降低PTSD患者的CV风险具有长期益处。