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Chronic Fatigue Syndrome: Pathophysiology and Treatment


Senior Member
North West, England, UK
Apologies if already posted:


Purpose. This Funding Opportunity Announcement (FOA) issued by the Office of Research on Women's Health (ORWH) and co-sponsoring Institutes and Centers (ICs) of the National Institutes of Health (NIH) encourages investigator(s)-initiated applications that propose to examine the etiology, diagnosis, pathophysiology, and treatment of chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME/CFS) in diverse groups and across the lifespan. Innovative applications that address gaps in the understanding of the environmental and biological risk factors, the determinants of heterogeneity among patient populations, and the common mechanisms influencing the multiple body systems that are affected in CFS are encouraged. The NIH is particularly interested in funding interdisciplinary research that will enhance our knowledge of the disease process and provide evidence based solutions to improve the diagnosis, treatment, and quality of life of all persons with CFS.

Areas of interest where scientific opportunities exist to meet the objectives of this funding opportunity cut across many disciplines. Applications within, but not limited to the following, may propose to:

Explore whether pathogenesis and pathophysiology differ relative to age, sex, developmental period, racial/ethnic background, and co-morbid conditions
Compare the diagnostic criteria and symptomatology of CFS in children and adolescents with those of adults
Describe the epidemiology of CFS in older adults and explore the relationship of CFS to general complaints of fatigue and exhaustion in the elderly.
Conduct case-control comparisons of CFS with syndromes such as fibromyalgia, interstitial cystitis, chronic pelvic pain syndrome, irritable bowel syndrome and other multisystemic illnesses that have similar or overlapping symptomatology
Conduct genetic epidemiologic and cellular biologic studies investigating whether polymorphisms in clock-related genes alters cellular function in peripheral cardiovascular tissue or mediates abnormalities in peripheral endocrine function that are characteristic of the autonomic nervous system dysfunction associated with CFS.

Develop novel and objective biological markers for the diagnosis of CFS
Develop and validate techniques for linking biomarkers to behavioral responses associated with CFS
Develop/refine objective measures for fatigue or sleepiness and severity of associated sleep disturbances
Develop/refine technologies to improve the identification and measurement of precipitating factors
Conduct longitudinal studies and studies with multiple sampling points to capture the progression of CFS symptomatology
Explore the role of neuroimaging modalities in the diagnosis, treatment and progression of CFS

Risk Factors
Identify environmental, including dietary, and other precipitants and geographic correlates of CFS
Conduct animal studies to elucidate the effects of environmental exposures, including endocrine disrupters, on the stress response contributing to CFS.
Identify the biological antecedent or triggering events that precipitate CFS
Explore multi-systemic factors as precipitants to CFS symptoms
Conduct population studies to elucidate potential genetic risk factors
Examine the role of genetic polymorphisms in the pathogenesis and diagnosis of CFS
Explore the relationship of co-morbid conditions and CFS
Explore the potential relationship of CFS with other chronic pain syndromes

Neurological and Behavioral Factors
Study the nature of psychiatric comorbidity in CFS patients
Elucidate the factors/mechanisms mediating common symptomatology in CFS: cognitive deficits, chronic pain, and/or inability to sustain physical exertion
Elucidate the factors/mechanisms involved in altered sleep states, disrupted circadian regulation, or other causes of impaired or ineffective sleep
Study the relationships between cognitive deficits and sleep disturbances or sleep disorders
Investigate long-term cognitive, psychosocial, and physical health outcomes in children and adolescents with CFS
Investigate the relationships of fatigue and CFS to other comorbid medical conditions or disabilities common in older patients, and/or to the drug effects and interactions of medications used to treat these conditions

Physiologic Interactions
Study the role of neuroendocrine and neuroimmune functions in CFS pathogenesis and pathophysiology
Study the role of neuro-cardiovascular regulation in the loss of the normal control of blood pressure, heart rate and contractility in CFS patients
Study the action of mediators (i.e., cytokines, chemokines) on the multiple, interacting, feedback-controlled systems that are dysregulated in CFS (pathogenesis and pathophysiology)
Study the mechanisms and consequences of dysregulation in the major physiologic control systems to better understand the multi-system symptoms among CFS patients
Study the role of oxidative stress in the pathogenesis of and marginal nutritional deficiencies in the etiology of CFS.
Explore the relationships of fatigue and CFS to biochemical mediators associated with frailty in the elderly, such as pro-inflammatory cytokines.

Treatment and Quality of Life
Conduct clinical trials in CFS patients to determine the efficacy of reliable and valid strategies that are used to improve quality of life in other chronic diseases
Conduct definitive trials to determine the effectiveness of currently prescribed pharmacologic, behavioral and other treatments used in CFS
Develop and test new pharmacologic and nonpharmacologic strategies for ameliorating symptoms that impair quality of life in patients with CFS
Study perceptions, attitudes, and behaviors that influence both the course of CFS and the quality of care provided to CFS patients
Examine the role of self-medication with alcohol, illicit drugs, and/or prescription drugs in CFS patients.
Examine the use and establish the efficacy and safety of dietary supplements in the treatment of CFS
Develop and test the efficacy of interventions to ameliorate fatigue and CFS that are targeted at the specific needs of the elderly

Methodological Considerations
Multidisciplinary studies and collaboration among investigators with expertise in appropriate disciplines are encouraged. When investigators are at different institutions, individual R01 applications may include consortium arrangements.
Collaborative arrangements with ongoing studies that provide patient populations, specimens, and data are encouraged. Such arrangements should be clearly delineated in the application.
Investigators are encouraged to use the CFS case definition as presented in Fukuda, et al. Annals of Internal Medicine 1994; 121: 953-9. If other case definitions are proposed, they should be clearly defined and the rationale for the alternative choice clearly delineated. Similar care should be given to definition of sub-groupings for CFS patients, if you choose to consider them.
Methods and procedures used in selecting patients or their specimens should be precisely defined and described in detail. Care should be given to the criteria used for case definition and the manner in which the criteria are applied. Similar care should be given to descriptions of procedures and methods for enrolling subjects in comparison groups.

Sorry if this has already been discussed, but from the UK, it looks a pretty big deal.