Grant: Team Grant: Health Challenges in Chronic Inflammation Initiative - (Full Appl)

Chronic inflammatory diseases, such as rheumatoid arthritis, hepatitis and inflammatory bowel disease share many common features. Among the most significant of these are changes in the brain that lead to behavioral symptoms of fatigue, depression, cognitive dysfunction and social withdrawal. Such debilitating symptoms markedly diminish the quality of life of hundreds of thousands of Canadians living with these conditions. One might think, of course a patient with inflammatory bowel disease, liver disease, or rheumatoid arthritis will be depressed, anxious and distracted; who wouldn't be? We contend that these behavioral changes are not a response to disease. Rather, a fundamental alteration occurs in the way in which the brain functions in the face of a chronic inflammatory disease. Despite the impact of these symptoms, the mechanisms of brain dysfunction in chronic inflammation are not well understood. Furthermore, there is an increasing appreciation that altered central nervous system function has considerable consequences for disease progression; this too has not been explored. We wish to address these shortcomings by understanding how persistent inflammation may cause disturbances in the brain and how chronic immune-mediated inflammatory diseases reprogram the brain to alter neuronal function, precipitating co-morbid behavioral dysfunction, which influences the disease processes. To effectively examine these important problems we have assembled a trans-disciplinary team of experts in the management of chronic inflammatory disease: neuroscientists, psychiatrists and imaging experts who are fluent in understanding brain-body communication and plasticity of brain function. Our unique basic-clinical-translational research team is poised to facilitate the discovery of common central mechanisms underlying the neurological and psychological conditions associated with chronic inflammation. Translating our discoveries to improve patient outcomes is our ultimate goal.