Investigating Correlates and Therapeutics of Fatigue

疲劳是一种跨医疗条件的全球性体验。它的定义是缺乏活力和压倒性的疲劳感，这与悲伤或虚弱是不同的。疲劳通常与抑郁等其他症状和行为聚集在一起，并与许多医疗条件有关，包括帕金森氏症等神经系统疾病，干燥综合征等自身免疫性疾病，并与治疗有关，如正在接受或完成癌症治疗的人。也有以疲劳为主要症状的不同症状，如慢性疲劳综合征、纤维肌痛或患有慢性冠状病毒病。人们对疲劳的主要原因仍知之甚少。其他人认为，疲劳是有生物学基础的，比如炎症反应的失调或应激反应的功能障碍，甚至神经细胞新陈代谢的紊乱，或者去甲肾上腺素和5-羟色胺等神经递质水平的下降。在试图理解疲劳时，需要考虑的其他因素还有疲劳与抑郁等其他症状的关系。一些研究表明，抑郁和疲劳的关系可能是双向的，这意味着这些情况可能有共同的机制。特定的免疫标记物与疲劳和抑郁相关的事实证明了这一共同机制的主张。其他人反对这一共同的机制假说，因为抑郁症状可能会通过药物治疗得到改善，而疲劳症状是抵抗力的。我们的调查使用标准化问卷对不同临床人群(癌症患者、纤维肌痛患者、慢性疲劳综合征患者、干燥综合征、类风湿性关节炎、系统性红斑狼疮和慢性COVID患者)的疲劳症状进行了表征，并确定了体力活动、疼痛、抑郁、疲劳灾难、压力和睡眠是否对他们的疲劳体验起到了作用。这项研究还将研究炎症和新陈代谢等生物过程在这些人疲劳中的潜在作用。我们还有兴趣了解健康的社会决定因素，如他们共同患有的慢性病、他们的社区环境、他们健康状况带来的经济压力、获得医疗保健的机会以及他们所在地区的气候变化如何影响他们的症状体验。从这项调查中收集的信息将有助于提高我们对疲劳的理解，并确定可能的目标，以开发治疗方法来缓解这种令人痛苦的症状。

Fatigue is a global experience across medical conditions. It is defined as a lack of energy and an overwhelming sense of tiredness that is distinguishable from sadness or weakness. Fatigue is often clustered with other symptoms and behaviors like depression, and has been associated with many medical conditions, including neurological diseases such as Parkinson's disease, autoimmune diseases such Sjogren's syndrome, and have been associated with treatments, such as those who are receiving or who completed cancer treatments. There are also different syndromes where fatigue presents as a main symptom, like chronic fatigue syndrome, fibromyalgia, or those suffering from long COVID. The main cause of fatigue remains poorly understood. Others argue that there is a biologic basis to explain fatigue such as dysregulation of inflammatory response or dysfunction in stress response or even disturbances in the metabolism of nerve cells, or perhaps decreased levels of neurotransmitters such as norepinephrine and serotonin. Other factors to consider when trying to understand fatigue is its relationship with other symptoms like depression. Some studies have shown that the relationship of depression and fatigue may be bidirectional, implying that these conditions may have shared mechanisms. This proposition for a shared mechanism is evidenced by the fact that specific immune markers are associated with both fatigue and depression. Others argue against this 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 (cancer patients, patients with fibromyalgia, chronic fatigue syndrome, Sjogren's syndrome, rheumatoid arthritis, Systemic Lupus Erythematosus, and those suffering from long COVID) using standardized questionnaires and determine if physical activity, pain, depression, fatigue catastrophizing, stress, and sleep play a role in their fatigue experience. This study will also examine the potential role of biologic processes such as inflammation and metabolism in fatigue for these individuals. We are also interested in looking at how social determinants of health like their comorbid chronic conditions, their community environment, financial stress from their health conditions, access to healthcare, and climate changes in their location affect their symptom experience. Information collected from this investigation will be useful to improve our understanding of fatigue and identify possible targets to develop therapeutics to alleviate this distressing symptom.