Transcutaneous Vagal Nerve Stimulation in Veterans with Posttraumatic Stress Disorder

创伤后应激障碍（PTSD）是退伍军人管理局的一个重要关注点， 与相当大的发病率，增加精神卫生保健费用和经济损失有关。 生产力国防部最近召开的一次科学状况会议， 发现创伤后应激障碍的药物靶点得出结论，十年的研究花费了数百万美元， 对于创伤后应激障碍，几乎没有产生新的有效药物治疗方法。除了功效上的限制外， 药物治疗可能受到副作用或依从性差的限制， 由于创伤记忆的重新激活，心理治疗干预可能无法容忍。 电治疗代表了治疗创伤后应激障碍和精神疾病的新视野， 将军前几代的电治疗受到复杂的治疗需求的限制。 手术和麻醉程序，费用高，缺乏保险报销， 程序或常规精神病学随访。这阻碍了这些措施的广泛实施。 精神病学的治疗。新的非侵入性经皮颈（颈）迷走神经 刺激（tcVNS）器械经济且不需要手术植入 克服电治疗的这些限制，以及避免副作用或其他 PTSD药物治疗的局限性。迷走神经刺激可使前壁和后壁增强， 扣带和减少对创伤应激脚本的反应，以及外周 心血管/交感神经和免疫功能，所有这些都表明它们可以作用于 神经生物学和生理系统维持创伤后应激障碍的症状。我们的初步数据 显示tcVNS（但不是假刺激）与脚本暴露联合应用时 特定的创伤记忆阻断了压力对外周血管收缩增加的影响 和用直接心血管测量（射血前期，或 PEP），并减少炎症标志物（白细胞介素-6）和炎症反应，同时增强 前扣带回功能的影响本项目将探讨tcVNS或假手术的影响 治疗退伍军人的大脑，心血管/交感神经和免疫反应 创伤后应激障碍退伍军人将经历接触创伤性脚本压力与高 分辨率正电子发射断层扫描（HRPET）测量脑功能和外周 血液中的心血管/交感神经功能和免疫生物标志物。退伍军人将接受 用tcVNS或假刺激每日两次治疗三个月，然后重复这些治疗。 措施我们假设tcVNS而不是假刺激将导致脑/ 心血管/交感神经和免疫反应的压力退伍军人与创伤后应激障碍，以及 PTSD的症状，长期治疗。该项目将提供有关 tcVNS对PTSD的神经生物学和生理学的机制，以及它可能 减轻创伤后应激障碍的症状

Posttraumatic stress disorder (PTSD) is an important concern of the Veterans Administration, associated with considerable morbidity, increased mental healthcare costs and loss of economic productivity. A recent State of the Science conference convened by the Department of Defense on Discovering Drug Targets for PTSD concluded that a decade of research costing millions of dollars had yielded few new effective drug treatments for PTSD. In addition to limitations in efficacy, pharmacological treatments can be limited by side effects or poor compliance, while psychotherapeutic interventions may not be tolerated due to re-activation of traumatic memories. Electrical treatments represent a new horizon in the treatment of PTSD and psychiatric disorders in general. Earlier generations of electrical treatments were limited by the need for complicated surgical and anesthetic procedures, high cost, and lack of reimbursement by insurance for procedures or routine psychiatric follow-up. This prevented wide-spread implementation of these treatments in psychiatry. New non-invasive transcutaneous cervical (neck) Vagal Nerve Stimulation (tcVNS) devices that are economical and do not require surgical implantation overcome these limitations of electrical treatments, as well as avoiding side effects or other limitations to medication treatments for PTSD. VNS results in both enhancement of anterior cingulate and reduction in insula responses to traumatic stress scripts as well as peripheral cardiovascular / sympathetic and immune function, all of which indicate that they could act on neurobiological and physiological systems that maintain symptoms of PTSD. Our preliminary data shows that tcVNS (but not sham stimulation) when applied in conjunction with exposure to scripts of specific traumatic memories blocks the effects of stress on increased peripheral vasoconstriction and sympathetic tone as measured with direct cardiovascular measures (pre-ejection period, or PEP) and reduces inflammatory markers (Interleukin-6) and insula response while enhancing anterior cingulate function in PTSD. This project will explore the effects of tcVNS or sham treatment on brain, cardiovascular / sympathetic and immune response to stress in veterans with PTSD. Veterans will undergo exposure to traumatic script stress in conjunction with High Resolution Positron Emission Tomography (HRPET) measurement of brain function and peripheral cardiovascular /sympathetic function and immune biomarkers in blood. Veterans will then undergo three months of twice daily treatment with tcVNS or sham stimulation followed by a repeat of these measures. We hypothesize that tcVNS but not sham stimulation will result in a reduction in brain / cardiovascular / sympathetic and immune response to stress in veterans with PTSD, as well as symptoms of PTSD with long term treatment. This project will provide information about mechanisms of tcVNS on the neurobiology and physiology of PTSD and ways in which it may ameliorate symptoms of PTSD.