Does Anxiety Cause Vascular Dysfunction Through Inflammation and Sns Activation?

焦虑是最常见的精神疾病。焦虑与心血管疾病风险增加有关 事件，独立于传统的风险因素。然而，这种联系背后的机制是 这是未知的，也从未被证明治疗焦虑可以降低心血管风险。该项目将 解决这些重要问题。我们已经收集到了令人信服的数据，表明即使是适度的焦虑， 症状与交感神经激活、炎症和严重损害有关。 人体血管阻力功能。通过多学科方法，我们将解决三个具体问题： 目的：1）焦虑是否通过增加炎症反应或氧化应激而导致血管功能障碍？我们 将测量反映受试者炎症和氧化应激的离体内皮细胞蛋白， 焦虑症状得分在最高和最低四分位数。然后我们将测试抗炎药 （双水杨酸）和抗氧化剂（抗坏血酸）干预逆转高血压患者的血管功能障碍， 低焦虑受试者该目的还将检查外周阻力血管功能障碍是否是 也存在于大脑中，使用功能性MRI测量脑血流量，以及这是否得到改善 通过salsalate。2)焦虑症是否通过交感神经激活引起血管功能障碍？我们将测试 可乐定抑制交感神经4周是否能改善炎症、氧化应激和血管 高焦虑受试者的功能障碍程度高于低焦虑受试者。3)焦虑症的治疗是否会改善 交感神经激活、炎症、氧化应激和血管功能障碍？我们将随机分配 高度焦虑的受试者接受新的基于正念的接受和承诺疗法（ACT）或时间 控制这种疗法已被证明在我们的手中和其他人有实质性和持久的影响， 焦虑症状我们将测试ACT是否会在以下方面产生更大的改善： 交感神经活动、反映炎症和氧化的内皮细胞蛋白 应力和前臂阻力血管功能。该项目应：A）提供令人信服的证据， 焦虑会导致血管损伤B）阐明焦虑对大脑皮层的影响机制。 脉管系统C）帮助开发新的表型，用于未来对焦虑分类、严重程度和 治疗D）提出心血管风险分层和预防的新策略。我们将实现 这些目标是通过调查专家之间独特的多学科合作实现的， 心血管生物学、精神病学、行为心理学和神经影像学。

Anxiety is the most common psychiatric disorder. Anxiety is associated with increased risk of cardiovascular events, independent of conventional risk factors. However, the mechanisms underiying this link are unknown, and it has never been proved that treating anxiety reduces cardiovascular risk. This project will address these important issues. We have gathered compelling data demonstrating that even modest anxiety symptoms are associated with sympathetic nerve activation, inflammation, and profound impairment of resistance vessel function in humans. Using a multidisciplinary approach, we will address three speciflc aims: 1) Does anxietv produce vascular dvsfunction through increased inflammation or oxidant stress? We will measure ex vivo endothelial cell proteins reflecting inflammation and oxidant stress in subjects with anxiety symptom scores in the highest and lowest quartiles. We will then test whether anti-inflammatory (salsalate) and anti-oxidant (ascorbic acid) interventions reverse vascular dysfunction in high compared to low anxiety subjects. This aim will additionally examine whether peripheral resistance vessel dysfunction is also present in the brain using functional MRI to measure cerebral blood flow, and whether this is improved by salsalate. 2) Does anxietv produce vascular dysfunction through svmpathetic activation? We will test whether sympathetic inhibition with clonidine for 4 weeks improves inflammation, oxidant stress and vascular dysfunction to a greater degree in high than low anxiety subjects. 3) Does treatment of anxietv improve svmpathetic activation, inflammation, oxidant stress and Vascular dvsfunction? We will randomly assign subjects with high anxiety to a novel mindfulness-based acceptance and commitment therapy (ACT) or time control. This therapy has been shown in our hands and others to have substantial and durable effects on anxiety symptoms. We will test whether ACT produces signiflcantly greater improvements in microneurographic sympathetic nerve activity, endothelial cell proteins reflecting inflammation and oxidant stress, and forearm resistance vessel function. This project should: A) Provide compelling evidence that anxiety causes vascular damage. B) Elucidate mechanisms involved in the effects of anxiety on the vasculature. C) Help develop novel phenotypes for future research on anxiety classiflcation, severity and treatment. D) Suggest new strategies for cardiovascular risk stratiflcation and prevention. We will achieve these goals through a distinctive multidisciplinary collaboration between investigators expert in cardiovascular biology, psychiatry, behavioral psychology and neuroimaging.