We propose to continue the work of our CFS CRC. The central theme and goal of the Center is to stratify CFS patients based on differences in cardiovascular and neuropsychological function. The purpose of our Center will be to continue to use the syndromic approach to identify subgroups of patients with different putative organic causes for their fatiguing illness. In the past grant cycle, we have identified two such -- one implicating the brain and another implicating abnormalities in peripheral cardiovascular function. We plan to bring in CFS patients and categorize them based on the variables that track these putative organic causes -- namely cognitive dysfunction and cardiac stroke volume. By using a median split approach, we will have data from 4 groups of patients and can make a priori hypotheses about which group will show the biggest differences from our sedentary healthy controls during experimental testing. The work we propose begins at the molecular level of serotonin receptor function and spinal fluid constitution, moves on to the physiological level in experiments on brain blood flow, on the structure and function of the heart, and on orthostatic intolerance and continues to the system level in a longitudinal study that follows the illness patterns of different subsets of CFS patients over time. Thanks to prior NIAID support, we have put together a broad team of experts -- all with major interests in understanding CFS. The group is headed by a neurologist-scientist and is comprised of psychologists, physiologists expert in behavioral medicine, exercise and activity assessments, and a superb statistician. New collaborations were initiated - one with a physician in Germany who is expert in autoantibodies and another with an NIMH researcher expert in central factors in fatiguing illness. We propose a three tiered strategy for the next 5 years of our Center's activities. First, we will use ideas synthesized from data generated from our original Center to fuel new studies aimed at understanding the abnormalities and/or causes of CFS. The second tier uses probes known to uncover subtle abnormalities in brain and cardiovascular function. The third tier is a longitudinal study of CFS to determine the pattern of illness over time and how illness and psychosocial factors interact over time.
Showing the most recent 10 out of 72 publications
