Neuroimaging Measures of Psychosocial Stress as Predictors of Articular and Arterial Inflammation, Cardiometabolic Disease, and Treatment Response in Rheumatoid Arthritis

项目概要/摘要 类风湿性关节炎（RA）是一种慢性、自身免疫性、全身性炎症性疾病，其特征在于显著的 动脉粥样硬化的负担更大，心血管疾病（CVD）事件的风险增加， 通过慢性全身性炎症对动脉粥样硬化倾向动脉的影响介导。RA患者 也往往有更高水平的负面心理特征，如慢性压力，抑郁， 焦虑，这已被证明是更强的相关性，心血管疾病的RA比一般人群。 更高水平的心理痛苦也与更多的关节肿胀和其他疾病有关。 关节疾病活动的措施，他们对免疫调节剂的反应比人低30-50%， 没有痛苦。总之，这些发现表明，可能有一个迄今未研究的炎症 连接大脑与动脉壁、关节和脂肪组织中RA相关炎症的轴， 介导RA免疫表型的特征。然而，有关这方面的问题 迄今尚未研究的炎性轴仍然存在。具体而言，1）RA中的心理困扰是否会削弱 免疫调节药物治疗降低关节和动脉部位炎症负荷的能力，2） 这些关联是否通过增加造血组织活性介导，以及3）功能如何 杏仁核与其他脑区的连接影响关节和血管炎症。 关节和动脉炎症可以通过摄取放射性标记的葡萄糖进行非侵入性成像 使用正电子发射断层扫描（PET）检测动脉壁中的[18氟脱氧葡萄糖（FDG）]。激活 杏仁核也可以以同样的方式成像，并与感知的压力，血管 炎症和CVD事件。FDG-PET与脑功能成像的结合 磁共振成像（MRI）允许评估大脑区域的激活和连接 与压力和对威胁的反应有关的是动脉和关节炎症的增加 和造血激活的程度。 目的1：研究应激相关神经生物学活动与 关节和动脉治疗反应。 目的2：探讨神经连接与造血活动的关系， 血管和关节炎。 该项目的总体目标是确定1）RA中的心理困扰是否会削弱 免疫调节药物治疗，以减少关节和动脉部位的炎症负荷，2）是否 这些关联是通过增加造血组织活性来介导的，以及3）功能如何 杏仁核与其他脑区的连接增强了组织炎症。

Project Summary/Abstract Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic inflammatory disease characterized by a markedly greater burden of atherosclerosis and a heightened risk for cardiovascular disease (CVD) events, presumably mediated through the effects of chronic systemic inflammation on atherosclerosis prone arteries. RA patients also tend to have higher levels of negative psychological characteristics, such as chronic stress, depression, and anxiety, which have been shown to be more strongly associated with CVD in RA than in the general population. Higher levels of psychological distress were also associated with a greater number of swollen joints and other measures of articular disease activity, and their responses to immunomodulators is 30-50% lower than people without distress. Taken together, these findings suggest that there may be a heretofore unstudied inflammatory axis linking the brain with RA-associated inflammation in the arterial wall, joints, and adipose tissue that may mediate characteristic features of the RA immunophenotype. However, relevant questions regarding this heretofore unstudied inflammatory axis remain. Specifically, 1) whether psychological distress in RA blunts the ability of immunomodulating pharmacotherapies to reduce inflammatory burden in articular and arterial sites, 2) whether these associations are mediated through increased hematopoietic tissue activity, and 3) how functional connectivity of the amygdala with other brain regions influences articular and vascular inflammation. Articular and arterial inflammation can be imaged non-invasively via uptake of radiolabeled glucose [18fluorodeoxy-glucose (FDG)] in the arterial wall detected using positron emission tomography (PET). Activation of the amygdala can also be imaged in the same way, and has been correlated with perceived stress, vascular inflammation, and CVD events in prior studies of non-RA populations. Combining FDG-PET with brain functional magnetic resonance imaging (MRI) allows assessment of how activation and connectivity of regions of the brain associated with stress and responsiveness to threat is related to increased arterial and articular inflammation and the degree of hematopoietic activation. Aim 1: To investigate the associations between stress-associated neurobiological activity and articular and arterial treatment response in RA. Aim 2: To investigate the associations of neuroconnectivity with hematopoietic activity and vascular and articular inflammation in RA. The overarching goal of the project is to identify 1) whether psychological distress in RA blunts the ability of immunomodulating pharmacotherapies to reduce inflammatory burden in articular and arterial sites, 2) whether these associations are mediated through increased hematopoietic tissue activity, and 3) how functional connectivity of the amygdala with other brain regions potentiates tissue inflammation.