Investigating Correlates and Therapeutics of Fatigue

疲劳被定义为缺乏能量和强烈的疲倦感，与悲伤或虚弱不同。在没有抑郁症等心理合并症的情况下，疲劳与许多神经系统疾病有关，包括多发性硬化症、帕金森病、运动神经元病、中风和脊髓灰质炎后综合征。对疲劳的病理生理学仍然知之甚少。促炎细胞因子（TNF α, IL-1 β, IL-6）的失调，HPA轴功能障碍，星形胶质细胞代谢紊乱以及神经递质（去甲肾上腺素，血清素）水平降低都被认为是其机制。抑郁症状和疲劳之间的关系可能是双向的，这意味着这些情况有共同的机制。与神经植物症状（包括疲劳）相关的细胞因子也与高抑郁率相关，这一事实证明了这种关联。另一些人则反对共享机制假说，因为抑郁症状可能会随着药物治疗而改善，而疲劳症状则具有抵抗性。本研究采用标准化问卷调查的方法，对不同临床人群（健康志愿者、纤维肌痛患者、慢性疲劳综合征患者和情绪障碍患者）的疲劳症状进行了表征，并确定体力活动、疼痛、抑郁、疲劳灾难化、压力和白天嗜睡是否在他们的疲劳体验中发挥了作用。本研究还将探讨血浆细胞因子、基因表达和下丘脑-垂体-肾上腺轴（HPA）功能在这些个体疲劳症状中的潜在作用。从这项调查中收集的信息将有助于提高我们对疲劳可能的病因机制的理解。

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 mood disorders) 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.