Neuroimaging Measures of Psychological Distress as Predictors of Articular and Arterial Inflammation and Treatment Response in Rheumatoid Arthritis

项目摘要/摘要 类风湿关节炎(RA)是一种慢性、自身免疫性、全身性炎症性疾病，其特征是 动脉粥样硬化的负担更重，心血管疾病(CVD)事件的风险更高 通过慢性全身性炎症对易发生动脉粥样硬化的动脉的影响。类风湿关节炎患者 也倾向于有更高水平的负面心理特征，如慢性压力、抑郁和 焦虑，已被证明与类风湿性关节炎患者的心血管疾病的相关性比普通人群更强。 心理痛苦程度越高，关节肿胀和其他症状也越多。 关节疾病活动性的衡量标准，以及他们对免疫调节剂的反应比人低30%-50% 没有痛苦。综上所述，这些发现表明可能存在一种迄今未被研究的炎症性疾病 将大脑与动脉壁、关节和脂肪组织中的类风湿关节炎相关的炎症联系起来的轴，可能 RA免疫表型的中介特征。不过，与此相关的问题 到目前为止，仍未对炎性轴进行研究。具体地说，1)类风湿性关节炎患者的心理困扰是否会使 免疫调节药物治疗减轻关节和动脉部位炎症负担的能力，2) 这些联系是否通过增加的造血组织活性来调节，以及3)功能如何 杏仁核与其他脑区的连通性影响关节和血管炎症。 关节和动脉炎症可通过摄取放射性标记葡萄糖进行非侵入性成像 正电子发射断层扫描(PET)检测动脉壁[18F-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、血管相关 炎症和心血管事件在先前对非RA人群的研究中。FDG-PET与脑功能的结合 磁共振成像(MRI)可以评估大脑各区域的激活和连接 与压力和对威胁的反应性有关的是动脉和关节炎症的增加 以及造血激活的程度。 目的1：探讨应激相关神经生物学活动与 类风湿关节炎的关节和动脉治疗反应。 目的2：探讨神经连通性与造血活性和 类风湿关节炎中的血管和关节炎症。 该项目的首要目标是确定1)类风湿性关节炎的心理困扰是否会削弱 免疫调节药物治疗以减轻关节和动脉部位的炎症负担，2)是否 这些联系是通过增加造血组织的活性来调节的，以及3)功能如何 杏仁核与其他大脑区域的连接会加剧组织炎症。

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.