Department of Neurology, Oregon Health & Science University, Portland, OR, United States.
Department of Neurology, Oregon Health & Science University, Portland, OR, United States; Multiple Sclerosis Center of Excellence-West, VA Portland Health Care System, Portland, OR, United States.
Med Hypotheses. 2018 Apr;113:46-51. doi: 10.1016/j.mehy.2018.02.014. Epub 2018 Feb 19.
Persistent fatigue is a common problem (∼20-45% of U.S. population), with higher prevalence and severity in people with medical conditions such as cancer, depression, fibromyalgia, heart failure, sleep apnea and multiple sclerosis. There are few FDA-approved treatments for fatigue and great disagreement on how to measure fatigue, with over 250 instruments used in research. Many instruments define fatigue as "a lack of energy", thus viewing energy and fatigue states as opposites on a single bipolar continuum. In this paper, we hypothesize that energy and fatigue are distinct perceptual states, should be measured using separate unipolar scales, have different mechanisms, and deficits should be treated using tailored therapies. Energy and fatigue independence has been found in both exploratory and confirmatory factor analysis studies. Experiments in various fields, including behavioral pharmacology and exercise science, often find changes in energy and not fatigue, or vice versa. If the hypothesis that energy and fatigue are independent is correct, there are likely different mechanisms that drive energy and fatigue changes. Energy could be increased by elevated dopamine and norepinephrine transmission and binding. Fatigue could be increased by elevated brain serotonin and inflammatory cytokines and reduced histamine binding. The hypothesis could be tested by an experiment that attempts to produce simultaneously high ratings of energy and fatigue (such as with two drugs using a randomized, double-blind, placebo-controlled design), which would offer strong evidence against the common viewpoint of a bipolar continuum. If the hypothesis is correct, prior literature using bipolar instruments will be limited, and research on the prevalence, mechanisms, and treatment of low energy and elevated fatigue as separate conditions will be needed. In the immediate future, measuring both energy and fatigue using unipolar measurement tools may improve our understanding of these states and improve therapeutic outcomes.
持续疲劳是一个常见的问题（∼20-45%的美国人口），在患有癌症、抑郁症、纤维肌痛、心力衰竭、睡眠呼吸暂停和多发性硬化症等疾病的人群中，疲劳的患病率和严重程度更高。目前针对疲劳症，仅有少数获得美国食品药品监督管理局（FDA）批准的治疗方法，而且对于如何衡量疲劳症也存在很大争议，在研究中使用了超过 250 种仪器。许多仪器将疲劳定义为“缺乏能量”，因此将能量和疲劳状态视为单一双极连续体上的对立面。在本文中，我们假设能量和疲劳是不同的感知状态，应使用单独的非双极量表进行测量，具有不同的机制，并且应该使用量身定制的疗法来治疗缺陷。在探索性和验证性因子分析研究中都发现了能量和疲劳的独立性。包括行为药理学和运动科学在内的各个领域的实验通常发现能量发生变化而不是疲劳，或者反之亦然。如果能量和疲劳独立的假设是正确的，那么可能存在不同的机制来驱动能量和疲劳的变化。能量可以通过增加多巴胺和去甲肾上腺素的传递和结合来增加。疲劳可以通过增加脑内血清素和炎性细胞因子以及减少组胺结合来增加。该假设可以通过实验来检验，该实验试图同时产生高能量和疲劳评分（例如使用两种药物，采用随机、双盲、安慰剂对照设计），这将有力地证明了与常见的双极连续体观点相反。如果该假设是正确的，那么使用双极仪器的先前文献将受到限制，并且需要研究低能量和高疲劳作为独立病症的患病率、机制和治疗方法。在不久的将来，使用非双极测量工具同时测量能量和疲劳可能会提高我们对这些状态的理解，并改善治疗效果。
