Fatigue is defined as a lack of energy and an overwhelming sense of tiredness that is distinguishable from sadness or weakness. Fatigue in the absence of psychological co-morbidities such as depression, has been associated with many neurological conditions, including multiple sclerosis, Parkinsons disease, motor neuron disease, stroke and post-polio syndromes. The pathophysiology of fatigue remains poorly understood. Dysregulation of pro-inflammatory cytokines (TNF alpha, IL-1 beta, IL-6), HPA axis dysfunction, disturbances of astroglia metabolism, and decreased levels of neurotransmitters (norepinephrine, serotonin) have all been proposed as mechanisms. The relationship between symptoms of depression and fatigue may be bidirectional, implying that these conditions have shared mechanisms. This association is evidenced by the fact that the cytokines associated with neurovegetative symptoms including fatigue are also associated with high rates of depression. Others argue against the shared mechanism hypothesis, as depressive symptoms may improve with pharmacotherapy, while symptoms of fatigue are resistive. Our investigation characterizes the symptoms of fatigue from different clinical populations (healthy volunteers, patients with fibromyalgia, chronic fatigue syndrome, and depression) using standardized questionnaires and determine if physical activity, pain, depression, fatigue catastrophizing, stress, and daytime sleepiness play a role in their fatigue experience. This study will also examine the potential role of plasma cytokines, gene expression, and hypothalamic-pituitary-adrenal axis (HPA) functioning in symptoms of fatigue in these individuals. Information collected from this investigation will be useful to improve our understanding of the possible etiologic mechanisms of fatigue.

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National Institute of Nursing Research
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Saligan, Leorey N (2014) The relationship between physical activity, functional performance and fatigue in sarcoidosis. J Clin Nurs 23:2376-8
Lukkahatai, Nada; Majors, Benjamin; Reddy, Swarnalatha et al. (2013) Gene expression profiles of fatigued fibromyalgia patients with different categories of pain and catastrophizing: a preliminary report. Nurs Outlook 61:216-224.e2
Lukkahatai, Nada; Saligan, Leorey N (2013) Association of catastrophizing and fatigue: a systematic review. J Psychosom Res 74:100-9