Neurobiological studies of fatigue

Abstract

Fatigue is a symptom associated with many disorders, is especially common in women and in older adults, and can have a huge negative influence on quality of life. Although most past research on fatigue uses human subjects instead of animal models, the use of appropriate animal models has recently begun to advance our understanding of the neurobiology of fatigue. In this review, results from animal models using immunological, developmental, or physical approaches to study fatigue are described and compared. Common across these animal models is that fatigue arises when a stimulus induces activation of microglia and/or increased cytokines and chemokines in the brain. Neurobiological studies implicate structures in the ascending arousal system, sleep executive control areas, and areas important in reward. In addition, the suprachiasmatic nucleus clearly plays an important role in homeostatic regulation of the neural network mediating fatigue. This nucleus responds to cytokines, shows decreased amplitude firing rate output in models of fatigue, and responds to exercise, one of our few treatments for fatigue. This is a young field but very important as the symptom of fatigue is common across many disorders and we do not have effective treatments.

A Psychometric Study of the Multidimensional Fatigue Inventory to Assess Fatigue in Patients with Schizophrenia Spectrum Disorders

“…Interestingly, patients using antidepressants had a significantly higher level of mental fatigue, and people with schizophrenia (F 20.0-F 20.9) had significantly higher levels of reduced motivation and physical fatigue. People with depression are known to experience fatigue as one of the most prominent symptoms (Alsén et al 2010;Harrington, 2012;Visser & Smets, 1998), which might explain the higher level of mental fatigue shown in the present study. Furthermore, the reduced motivation among patients with schizophrenia might be an expression of negative symptoms like anhedonia connected to the disease, as well as the higher scores on physical fatigue might be connected to worse physical condition.…”

“…Fatigue can be a normal everyday experience or a symptom that indicates a disease including both somatic and psychiatric pathological conditions (Alsén, Brink, Brändström, Karlsson, & Persson, 2010;Harrington, 2012;Targum, Hassman, Pinho, & Fava, 2012). Depression and sleep disturbances have in particular been associated with fatigue (Palmese et al, 2011;Schneider, 1998;Stepnowsky, Palau, Zamora, Ancoli-Israel, & Loredo, 2011), which may also appear as a side effect of some medications (for example antipsychotic medication) (Targum et al, 2012).…”

“…Depression and sleep disturbances have in particular been associated with fatigue (Palmese et al, 2011;Schneider, 1998;Stepnowsky, Palau, Zamora, Ancoli-Israel, & Loredo, 2011), which may also appear as a side effect of some medications (for example antipsychotic medication) (Targum et al, 2012). There is no consensus concerning a definition of fatigue which is an individual experience that affects each person's daily activity differently, and that may have multiple aetiology with individual physical, emotional and mental signs (Harrington, 2012). Normal fatigue is described as an experience of tiredness after an exertion where energy is restored after rest, while pathological fatigue is seldom reduced after rest (Harrington, 2012).…”

“…There is no consensus concerning a definition of fatigue which is an individual experience that affects each person's daily activity differently, and that may have multiple aetiology with individual physical, emotional and mental signs (Harrington, 2012). Normal fatigue is described as an experience of tiredness after an exertion where energy is restored after rest, while pathological fatigue is seldom reduced after rest (Harrington, 2012). The opposite experience of fatigue can be termed as strength, vitality or alertness, which are positive emotions linked to health, motivation and engagement (Hunter, Marshall, Corcoran, Leeder, & Phelps, 2013;Nix, Ryan, Manly, & Deci, 1999).…”

Effects of Gc-Macrophage Activating Factor in Human Neurons; Implications for Treatment of Chronic Fatigue Syndrome

“…There exist several animal models to study the neurobiology of fatigue and many of them are centered on immunologically induced fatigue (Harrington, 2012). However, it is well assessed that, in addition to fatigue, persistent pain and systemic inflammation are the most debilitating symptoms of ME/CFS.…”