Fatigue

== Classification ==

===By type===

====Uni- or multi-dimensional====
Fatigue can be seen as a uni-dimensional phenomenon that influences different aspects of human life.<ref>{{cite journal |author1=Roald Omdal|author2=Svein Ivar Mellgren|author3= Katrine Brække Norheim|title=Pain and fatigue in primary Sjögren's syndrome |journal=Rheumatology |date=July 2021 |volume=6 |issue=7 |pages=3099–3106 |doi=10.1093/rheumatology/kez027|pmid=30815693 }}</ref><ref>{{Cite journal|title=Importance of fatigue and its measurement in chronic liver disease|first1=Lynn H|last1=Gerber|first2=Ali A|last2=Weinstein|first3=Rohini|last3=Mehta|first4=Zobair M|last4=Younossi|date=July 28, 2019|journal=World Journal of Gastroenterology|volume=25|issue=28|pages=3669–3683|doi=10.3748/wjg.v25.i28.3669|doi-access=free |pmid=31391765|pmc=6676553}}</ref> It can be multi-faceted and broadly defined, making understanding the causes of its manifestations especially difficult in conditions with diverse pathology including autoimmune diseases.<ref name="pmid31447842">{{cite journal | pmid=31447842 | year=2019 | last1=Zielinski | first1=M. R. | last2=Systrom | first2=D. M. | last3=Rose | first3=N. R. | title=Fatigue, Sleep, and Autoimmune and Related Disorders | journal=Frontiers in Immunology | volume=10 | page=1827 | doi=10.3389/fimmu.2019.01827 | pmc=6691096 | doi-access=free }}</ref>

A 2021 review considered that different "types/subsets" of fatigue may exist and that patients normally present with more than one such "type/subset". These different "types/subsets" of fatigue may be different dimensions of the same symptom, and the relative manifestations of each may depend on the relative contribution of different mechanisms. Inflammation may be the root causal mechanism in many cases.<ref name="pmid34599320" />

==== Physical ====
Physical fatigue, or [[muscle fatigue]], is the temporary physical inability of muscles to perform optimally. The onset of muscle fatigue during physical activity is gradual, and depends upon an individual's level of physical fitness – other factors include [[sleep deprivation]] and overall health.<ref name="WebMD">{{cite news|title=Weakness and fatigue|newspaper=Webmd|url=http://www.webmd.com/a-to-z-guides/weakness-and-fatigue-topic-overview|publisher=Healthwise Inc.|access-date=2 January 2013|archive-date=30 December 2012|archive-url=https://web.archive.org/web/20121230140117/http://www.webmd.com/a-to-z-guides/weakness-and-fatigue-topic-overview|url-status=live}}</ref> Physical fatigue can be caused by a lack of energy in the muscle, by a decrease of the efficiency of the [[neuromuscular junction]] or by a reduction of the drive originating from the [[central nervous system]], and can be reversed by rest.<ref>{{cite journal | vauthors = Gandevia SC | title = Spinal and supraspinal factors in human muscle fatigue | journal = Physiological Reviews | volume = 81 | issue = 4 | pages = 1725–1789 | date = October 2001 | pmid = 11581501 | doi = 10.1152/physrev.2001.81.4.1725 }}</ref> The central component of fatigue is triggered by an increase of the level of [[serotonin]] in the central nervous system.<ref name="pmid10919962">{{cite journal | vauthors = Davis JM, Alderson NL, Welsh RS | title = Serotonin and central nervous system fatigue: nutritional considerations | journal = The American Journal of Clinical Nutrition | volume = 72 | issue = 2 Suppl | pages = 573S–578S | date = August 2000 | pmid = 10919962 | doi = 10.1093/ajcn/72.2.573S | doi-access = free }}</ref> During motor activity, serotonin released in synapses that contact [[motor neuron]]s promotes [[muscle contraction]].<ref>{{cite journal | vauthors = Perrier JF, Delgado-Lezama R | title = Synaptic release of serotonin induced by stimulation of the raphe nucleus promotes plateau potentials in spinal motoneurons of the adult turtle | journal = The Journal of Neuroscience | volume = 25 | issue = 35 | pages = 7993–7999 | date = August 2005 | pmid = 16135756 | pmc = 6725458 | doi = 10.1523/JNEUROSCI.1957-05.2005 }}</ref> During high level of motor activity, the amount of serotonin released increases and a spillover occurs. Serotonin binds to extrasynaptic receptors located on the [[axonal initial segment]] of motor neurons with the result that [[Action potential|nerve impulse]] initiation and thereby muscle contraction are inhibited.<ref>{{cite journal | vauthors = Cotel F, Exley R, Cragg SJ, Perrier JF | title = Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 12 | pages = 4774–4779 | date = March 2013 | pmid = 23487756 | pmc = 3607056 | doi = 10.1073/pnas.1216150110 | doi-access = free | bibcode = 2013PNAS..110.4774C }}</ref>

Muscle strength testing can be used to determine the presence of a [[neuromuscular disease]], but cannot determine its cause. Additional testing, such as [[electromyography]], can provide diagnostic information, but information gained from muscle strength testing alone is not enough to diagnose most neuromuscular disorders.<ref>{{cite journal | vauthors = Enoka RM, Duchateau J | title = Muscle fatigue: what, why and how it influences muscle function | journal = The Journal of Physiology | volume = 586 | issue = 1 | pages = 11–23 | date = January 2008 | pmid = 17702815 | pmc = 2375565 | doi = 10.1113/jphysiol.2007.139477 | author-link = Roger M. Enoka }}</ref>

==== Mental ====  <!--Linked from [[Template:Mental processes]]-->

Mental fatigue is a temporary inability to maintain optimal cognitive performance. The onset of mental fatigue during any cognitive activity is gradual, and depends upon an individual's cognitive ability, and also upon other factors, such as sleep deprivation and overall health.

Mental fatigue has also been shown to decrease physical performance.<ref name="Marcora 2009 857–864" /> It can manifest as [[somnolence]], [[lethargy]], [[directed attention fatigue]], or disengagement. Research also suggests that mental fatigue is closely linked to the concept of [[ego depletion]], though the validity of the concept is disputed. For example, one pre-registered study of 686 participants found that after exerting mental effort, people are likely to disengage and become less interested in exerting further effort.<ref>{{cite journal | vauthors = Lin H, Saunders B, Friese M, Evans NJ, Inzlicht M | title = Strong Effort Manipulations Reduce Response Caution: A Preregistered Reinvention of the Ego-Depletion Paradigm | journal = Psychological Science | volume = 31 | issue = 5 | pages = 531–547 | date = May 2020 | pmid = 32315259 | pmc = 7238509 | doi = 10.1177/0956797620904990 }}</ref>

Decreased attention can also be described as a more or less decreased [[level of consciousness]].<ref>{{cite book|title=Difficult Diagnosis 2| vauthors  = Giannini AJ |publisher=W.B. Saunders Co.|year=1991|isbn=978-0-7216-3481-4| veditors = Taylor RB |location= Philadelphia|page=156|chapter=Fatigue, Chronic|oclc=954530793}}</ref> In any case, this can be dangerous when performing tasks that require constant concentration, such as operating large vehicles. For instance, a person who is sufficiently somnolent may experience [[microsleep]]. However, objective cognitive testing can be used to differentiate the neurocognitive deficits of brain disease from those attributable to tiredness.<ref name="pmid29355911">{{cite journal |vauthors=Possin KL, Moskowitz T, Erlhoff SJ, Rogers KM, Johnson ET, Steele NZ, Higgins JJ, Stiver J, Alioto AG, Farias ST, Miller BL, Rankin KP |title=The Brain Health Assessment for Detecting and Diagnosing Neurocognitive Disorders |journal=J Am Geriatr Soc |volume=66 |issue=1 |pages=150–156 |date=January 2018 |pmid=29355911 |pmc=5889617 |doi=10.1111/jgs.15208 |url=}}</ref><ref name="pmid30884965">{{cite journal |vauthors=Menzies V, Kelly DL, Yang GS, Starkweather A, Lyon DE |title=A systematic review of the association between fatigue and cognition in chronic noncommunicable diseases |journal=Chronic Illn |volume=17 |issue=2 |pages=129–150 |date=June 2021 |pmid=30884965 |pmc=6832772 |doi=10.1177/1742395319836472 |url=}}</ref><ref name="pmid38079429">{{cite journal |vauthors=Elliott TR, Hsiao YY, Randolph K, Urban RJ, Sheffield-Moore M, Pyles RB, Masel BE, Wexler T, Wright TJ |title=Efficient assessment of brain fog and fatigue: Development of the Fatigue and Altered Cognition Scale (FACs) |journal=PLOS ONE |volume=18 |issue=12 |pages=e0295593 |date=2023 |pmid=38079429 |pmc=10712873 |doi=10.1371/journal.pone.0295593 |doi-access=free |bibcode=2023PLoSO..1895593E |url=}}</ref><!--It would also be interesting to read more about the ways in which the [[neurocognitive]] deficits of caused by fatigue differ from those caused by tiredness-->

The [[perception]] of mental fatigue is believed to be modulated by the brain's [[reticular activating system]] (RAS).<ref name="pmid24926625">{{cite journal |vauthors=Ishii A, Tanaka M, Watanabe Y |title=Neural mechanisms of mental fatigue |journal=Rev Neurosci |volume=25 |issue=4 |pages=469–79 |date=2014 |pmid=24926625 |doi=10.1515/revneuro-2014-0028 |url=}}</ref><ref name="pmid28690375">{{cite journal |vauthors=Garcia-Rill E, Virmani T, Hyde JR, D'Onofrio S, Mahaffey S |title=Arousal and the control of perception and movement |journal=Curr Trends Neurol |volume=10 |issue= |pages=53–64 |date=2016 |pmid=28690375 |pmc=5501251 |doi= |url=}}</ref><ref name="pmid31216564">{{cite journal |vauthors=Jones BE |title=Arousal and sleep circuits |journal=Neuropsychopharmacology |volume=45 |issue=1 |pages=6–20 |date=January 2020 |pmid=31216564 |pmc=6879642 |doi=10.1038/s41386-019-0444-2 |url=}}</ref><ref name="pmid37155119">{{cite journal |vauthors=Taran S, Gros P, Gofton T, Boyd G, Briard JN, Chassé M, Singh JM |title=The reticular activating system: a narrative review of discovery, evolving understanding, and relevance to current formulations of brain death |journal=Can J Anaesth |volume=70 |issue=4 |pages=788–795 |date=April 2023 |pmid=37155119 |pmc=10203024 |doi=10.1007/s12630-023-02421-6 |url=}}</ref><ref name="pmid31751025">{{cite book|pmid=31751025|title=Neuroanatomy, Reticular Activating System|date=2024 | vauthors = Arguinchona JH, Tadi P }}</ref>

Fatigue impacts a driver's reaction time, awareness of hazards around them and their attention. Drowsy drivers are three times more likely to be involved in a car crash, and being awake over 20 hours is the equivalent of driving with a blood-alcohol concentration level of 0.08%.<ref>{{cite web |title=Drowsy Driving is Impaired Driving |url=https://www.nsc.org/road-safety/safety-topics/fatigued-driving |website=National Safety Council |access-date=31 January 2019 |archive-date=1 February 2019 |archive-url=https://web.archive.org/web/20190201014026/https://www.nsc.org/road-safety/safety-topics/fatigued-driving |url-status=live }}</ref>

====Neurological fatigue====

People with [[multiple sclerosis]] experience a form of overwhelming tiredness that can occur at any time of the day, for any duration, and that does not necessarily recur in a recognizable pattern for any given patient, referred to as "neurological fatigue", and often as "multiple sclerosis fatigue" or "lassitude".<ref name="pmid32672087">{{cite journal | vauthors = Hubbard AL, Golla H, Lausberg H | title = What's in a name? That which we call ''Multiple Sclerosis Fatigue'' | journal = Multiple Sclerosis | volume = 27 | issue = 7 | pages = 983–988 | date = June 2021 | pmid = 32672087 | pmc = 8142120 | doi = 10.1177/1352458520941481 }}</ref><ref>{{cite journal | vauthors = Mills RJ, Young CA, Pallant JF, Tennant A | title = Development of a patient reported outcome scale for fatigue in multiple sclerosis: The Neurological Fatigue Index (NFI-MS) | journal = Health and Quality of Life Outcomes | volume = 8 | page = 22 | date = February 2010 | pmid = 20152031 | pmc = 2834659 | doi = 10.1186/1477-7525-8-22 | doi-access = free }}</ref><ref>{{Cite web|url=https://www.tiktok.com/@msfighter101/video/7242002519809854763|title=TikTok - Make Your Day|website=www.tiktok.com|access-date=2024-03-26|archive-date=2024-03-26|archive-url=https://web.archive.org/web/20240326105609/https://www.tiktok.com/@msfighter101/video/7242002519809854763|url-status=live}}</ref>

People with [[autoimmune diseases]] including inflammatory rheumatic diseases such as [[rheumatoid arthritis]], [[psoriatic arthritis]] and primary [[Sjögren's syndrome]], experience similar fatigue.<ref name="pmid34599320"/><ref name="pmid31447842"/>
Attempts have been made to isolate causes of [[central nervous system fatigue]].

=== By timescale ===

==== Acute ====
Acute fatigue is that which is temporary and self-limited. Acute fatigue is most often caused by an [[infection]] such as the [[common cold]] and can be cognized as one part of the [[sickness behavior]] response occurring when the [[immune system]] fights an [[infection]].<ref name="Brain, Behavior, and Immunity 2012 pp. 552–558">{{cite journal |last1=Piraino |first1=B. |last2=Vollmer-Conna |first2=U. |last3=Lloyd |first3=A.R. |title=Genetic associations of fatigue and other symptom domains of the acute sickness response to infection |journal=Brain, Behavior, and Immunity |date=May 2012 |volume=26 |issue=4 |pages=552–558 |doi=10.1016/j.bbi.2011.12.009 |pmid=22227623 |pmc=7127134 }}</ref>

Other common causes of acute fatigue include [[Major depressive disorder|depression]] and chemical causes, such as [[dehydration]], [[poison]]ing, [[low blood sugar]], or [[Mineral (nutrient)|mineral]] or [[vitamin]] deficiencies.

==== Prolonged ====
Prolonged fatigue is a self-reported, persistent (constant) fatigue lasting at least one month.<ref name="pmid34589772">{{cite journal |vauthors=Billones R, Liwang JK, Butler K, Graves L, Saligan LN |title=Dissecting the fatigue experience: A scoping review of fatigue definitions, dimensions, and measures in non-oncologic medical conditions |journal=Brain Behav Immun Health |volume=15 |issue= |pages=100266 |date=August 2021 |pmid=34589772 |pmc=8474156 |doi=10.1016/j.bbih.2021.100266 |url=}}</ref><ref name="pmid18458765">{{cite journal |vauthors=Griffith JP, Zarrouf FA |title=A systematic review of chronic fatigue syndrome: don't assume it's depression |journal=Prim Care Companion J Clin Psychiatry |volume=10 |issue=2 |pages=120–8 |date=2008 |pmid=18458765 |pmc=2292451 |doi=10.4088/pcc.v10n0206 }}</ref>

==== Chronic ====
Chronic fatigue is a self-reported fatigue lasting at least 6 consecutive months. Chronic fatigue may be either persistent or relapsing.<ref name="CDC1994">{{cite journal | vauthors = Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A | title = The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group | journal = Annals of Internal Medicine | volume = 121 | issue = 12 | pages = 953–959 | date = December 1994 | pmid = 7978722 | doi = 10.7326/0003-4819-121-12-199412150-00009 | author-link2 = Stephen Straus | s2cid = 510735 | author-link = Keiji Fukuda | author-link6 = Anthony L. Komaroff }}</ref> Chronic fatigue is a symptom of many chronic illnesses and of [[idiopathic chronic fatigue]].{{medical citation needed|date=July 2023}}

===By effect===

Fatigue can have significant negative impacts on quality of life.<ref>{{cite journal |last1=Hemmett |first1=L. |last2=Holmes |first2=J. |last3=Barnes |first3=M. |last4=Russell |first4=N. |title=What drives quality of life in multiple sclerosis? |journal=QJM |date=October 2004 |volume=97 |issue=10 |pages=671–676 |doi=10.1093/qjmed/hch105 |pmid=15367738 |doi-access=free }}</ref><ref>{{cite journal | pmc=8267792 | year=2021 | last1=Mæland | first1=E. | last2=Miyamoto | first2=S. T. | last3=Hammenfors | first3=D. | last4=Valim | first4=V. | last5=Jonsson | first5=M. V. | title=Understanding Fatigue in Sjögren's Syndrome: Outcome Measures, Biomarkers and Possible Interventions | journal=Frontiers in Immunology | volume=12 | page=703079 | doi=10.3389/fimmu.2021.703079 | pmid=34249008 | doi-access=free }}</ref> Profound and debilitating fatigue is the most common complaint reported among individuals with autoimmune disease, such as systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, celiac disease, [[Myalgic encephalomyelitis/chronic fatigue syndrome|Myalgic Encephalomyelitis/chronic fatigue syndrome]], and rheumatoid arthritis.<ref name="pmid34599320" />

Fatigue has been described by sufferers as 'incomprehensible' due to its unpredictable occurrence, lack of relationship to physical effort and different character as compared to tiredness.<ref>{{Cite journal|title=I've lost the person I used to be— Experiences of the consequences of fatigue following myocardial infarction|first1=Ulla|last1=Fredriksson-Larsson|first2=Pia|last2=Alsen|first3=Eva|last3=Brink|date=January 21, 2013|journal=International Journal of Qualitative Studies on Health and Well-being|volume=8|issue=1|pages=20836|doi=10.3402/qhw.v8i0.20836|pmid=23769653|pmc=3683631}}</ref> 

Fatigue that dissociates by quantum with disease activity represents a large health economic burden and unmet need to patients and to society.<ref name="pmid34599320" />

===Formal classification===
The [[World Health Organization]]'s [[ICD-11]] classification<ref name="ICD-11">{{Cite web|title=ICD-11 - Mortality and Morbidity Statistics {{!}} MG22 Fatigue|url=https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/1109546957|date=2019|website=World Health Organization|access-date=2023-04-25|archive-date=2018-08-01|archive-url=https://archive.today/20180801205234/https://icd.who.int/browse11/l-m/en%23/http://id.who.int/icd/entity/294762853#/http://id.who.int/icd/entity/1109546957|url-status=live}}</ref>
includes a category MG22 Fatigue (typically fatigue following exertion but sometimes may occur in the absence of such exertion as a symptom of health conditions), and many other categories where fatigue is mentioned as a secondary result of other factors.<ref>
* 8E49 Postviral fatigue syndrome
* QE84 Acute stress reaction, Combat fatigue
* 6A70-6A7Z Depressive disorders
* 07 Sleep-wake disorders
* FB32.5 Muscle strain or sprain, causing muscular fatigue
* NF01.3 Heat fatigue, transient
* MA82.Y Voice disturbances, causing voice fatigue
* BD1Z Heart failure, unspecified, causing myocardial fatigue
* JA65.Y Conditions predominantly related to pregnancy, causing fatigue which complicates pregnancy
* SD91 Fatigue consumption disorder, causing coughing, fever, diarrhea, chest pain etc.
* MG2A Ageing associated decline in intrinsic capacity, causing senile fatigue
* NF07.2 Exhaustion due to exposure
* NF01 Heat exhaustion
* 6C20 Bodily distress disorder.
[[ICD-11]]</ref> It does not include any fatigue-based psychiatric illness (unless it is accompanied by related psychiatric symptoms).<ref name="Desai2018">{{cite journal |last1=Desai |first1=Geetha |last2=Sagar |first2=Rajesh |last3=Chaturvedi |first3=Santosh K |title=Nosological journey of somatoform disorders: From briquet's syndrome to bodily distress disorder |journal=Indian Journal of Social Psychiatry |date=2018 |volume=34 |issue=5 |pages=29 |doi=10.4103/ijsp.ijsp_37_18 |doi-access=free }}</ref><ref name="pmid32701520">{{cite journal |last1=Basavarajappa |first1=Chethan |last2=Dahale |first2=Ajit Bhalchandra |last3=Desai |first3=Geetha |title=Evolution of bodily distress disorders |journal=Current Opinion in Psychiatry |date=September 2020 |volume=33 |issue=5 |pages=447–450 |doi=10.1097/YCO.0000000000000630 |pmid=32701520 |s2cid=220731306 }}</ref> 

[[DSM-5]] lists 'fatigue or loss of energy nearly every day' as one factor in diagnosing depression.<ref>{{Cite web|url=https://www.psycom.net/depression/major-depressive-disorder/dsm-5-depression-criteria|title=Depression Definition and DSM-5 Diagnostic Criteria|date=August 26, 2022|website=www.psycom.net|access-date=March 21, 2024|archive-date=February 13, 2024|archive-url=https://web.archive.org/web/20240213040922/https://www.psycom.net/depression/major-depressive-disorder/dsm-5-depression-criteria|url-status=live}}</ref>