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（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PTSD的退伍军人，解决了这种PTSD的认可但高度重大的后果至关重要。 PTSD中CV风险增加的机制仍然未知。一种潜在的机制是在静止和压力期间的交感神经系统（SNS）过度激活。先前的研究表明，PTSD患者的静息心率和血压（BP）较高，压力期间的心血管反应较高，心率变异性降低，表明交感神经活动的状态升高。尽管基于这些观察到的间接发展的PTSD，SNS多动症与PTSD有关，但SNS调节PTSD患者的伪影具有异常的伪影（BRS），这是基线和精神压力下SNS过度活动的基础。 2）PTSD患者在基线和精神压力时患有异常伪像；压力; 3）设备引导的缓慢呼吸（DGB）急性改善PTSD患者的SNS活性和BRS； 4）每天8周的DGB治疗可改善静止和精神压力下的SNS活性和血液动力学特征。此外，鉴于大约一半的PTSD患者患有合并症的重度抑郁症（MD），而MD与CV风险和SNS失调独立相关，因此我们假设合并症MD在PTSD患者的休息和精神压力下增加了SNS反应性。为了实现这些目标，与非PTSD（有或没有MD）的年轻，高血压前退伍军人中，与非PTSD对照（有或没有MD）在静止和精神压力下，使用修改后的牛津技术，对8周的PITER进行了对DG的效果进行了对DG的效果，我们将使用PTSD（有或没有MD）直接测量交感神经活动（有或没有MD）。我们假设PTSD患者在基线时具有较大的SNS活性，而在精神压力和精神压力的交感神经期间，SNS反应性较高，这既与战斗召回和其他形式的精神压力有关。我们期望这些演变与MD无关，但是合并的MD增强了PTSD中的SNS反应性。我们进一步提出，SNS过度活动是由静止和精神压力下的动脉压力反射功能障碍介导的。最后，先前的研究表明，设备引导了缓慢的呼吸（DGB），其中呼吸缓慢到亚物理率（5-6次呼吸/分钟）通过交互式生物反馈装置，减少BP，SNS活性，并改善高血压患者的BR。 DGB以前从未在PTSD中进行过测试，并且可能是一种新型的非药物方法来减少SNS活性并恢复这些患者的BR。我们假设DGB急性地改善了SNS过度活动，BP和BR，并且长期导致静止和压力期间SNS和BRS的持续减少，患有PTSD的型前期患者。改善SNS过度和BRS可能会在减少PTSD患者的CV风险方面具有长期的益处。