Perceived Fatigue and Energy are Independent Unipolar States: Supporting Evidence

Bryan D. Loy, Michelle H. Cameron, Patrick J. O'Connor, Medical Hypotheses, Available online 19 February 2018, ISSN 0306-9877, doi:10.1016/j.mehy.2018.02.014.

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.
When mental and physical aspects of energy and fatigue were measured in individuals with Friedreich’s ataxia, low physical energy was found while no differences were observed for mental energy or mental or physical fatigue. This type of information appears logical and is potentially useful because Friedreich’s ataxia is a disease that targets pyramidal nerves, causing muscle incoordination and reduced physical activity that worsens over time yet largely preserves mental functioning.

Progress in the treatment of Friedreich ataxia

Geneieve Tai, Louise A. Corben, Eppie M. Yiu, Sarah C. Milne, Martin B. Delatycki, Neurologia i Neurochirurgia Polska, Available online 19 February 2018, ISSN 0028-3843, doi:10.1016/j.pjnns.2018.02.003.

Friedreich ataxia (FRDA) is a progressive neurological disorder affecting approximately 1 in 29,000 individuals of European descent. At present, there is no approved pharmacological treatment for this condition however research into treatment of FRDA has advanced considerably over the last two decades since the genetic cause was identified. Current proposed treatment strategies include decreasing oxidative stress, increasing cellular frataxin, improving mitochondrial function as well as modulating frataxin controlled metabolic pathways. Genetic and cell based therapies also hold great promise. Finally, physical therapies are being explored as a means of maximising function in those affected by FRDA.