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

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.