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)是一种高度普遍的焦虑症，与心血管疾病和高血压的风险增加有关。鉴于从伊拉克和阿富汗返回的大批退伍军人患有创伤后应激障碍，解决这一未得到充分认识但意义重大的创伤后应激障碍后果至关重要。创伤后应激障碍患者心血管风险增加的机制尚不清楚。一种可能的机制是交感神经系统(SNS)在休息和应激时过度激活。先前的研究表明，PTSD患者的静息心率和血压(BP)更高，应激期间心血管反应性更强，心率变异性降低，这表明交感神经活动增强。尽管根据这些观察到的间接错乱，SNS过度活动与创伤后应激障碍有关，但在这一人群中，SNS调节以前从未被严格研究过，针对SNS活动和心血管风险的潜在机制和潜在干预仍未被探索。本研究的目标是确定：1)PTSD患者是否有更高的静息SNS活动，以及在精神应激期间更大的SNS反应；2)PTSD患者有异常的动脉压力反射敏感性(BRS)，这是基线和精神应激期间SNS过度活动的基础；3)设备引导的慢呼吸(DGB)显著改善PTSD患者的SNS活动和BRS；以及4)每天8周的DGB疗法改善静息和精神应激期间的SNS活动和血流动力学特征。此外，考虑到大约一半的PTSD患者患有严重抑郁(MD)，并且MD与心血管风险和SNS调节失调独立相关，我们假设，在PTSD患者的休息和精神应激期间，MD并存会增加SNS的反应性。为了实现这些目标，我们将使用显微神经图术直接测量患有PTSD的年轻高血压前期退伍军人(有和没有MD)与非PTSD对照组(有和没有MD)在静息和精神应激期间的交感神经活动，使用改进的牛津技术进行动脉压力感受性反射测试，并进行为期8周的DGB对SNS反应性和调节的益处的先导性试验。我们假设PTSD患者在基线时有更高的SNS活性，在交感兴奋与精神应激时有更高的SNS反应，这两者都与战斗回忆和其他形式的精神应激有关。我们认为这些错位与MD无关，但MD并存会增加PTSD的SNS反应性。我们进一步提出，SNS过度活动是由静息和精神应激时动脉压力反射功能障碍所介导的。最后，先前的研究表明，设备引导的慢呼吸(DGB)，即通过交互式生物反馈设备将呼吸减慢到亚生理频率(5-6次/分钟)，可以降低高血压患者的BP、SNS活动，并改善BRS。DGB以前从未在创伤后应激障碍中进行过测试，可能是一种减少SNS活性和恢复这些患者BRS的新的非药物方法。我们假设DGB能显著改善患有创伤后应激障碍的高血压前期患者的SNS过度活动、BP和BRS，并长期导致静息和应激时SNS和BRS的持续减少。改善SNS过度活动和BRS可能对降低创伤后应激障碍患者的心血管风险有长期益处。