Chronic Fatigue Syndrome

What Is Chronic Fatigue Syndrome?

Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is an illness characterized by profound disabling tiredness, a diminished capacity to perform routine tasks, and sleep disruption that lasts for more than 6 months.

1. Epidemiology of Chronic Fatigue Syndrome

Based on prevalence estimates from the Institute of Medicine, chronic fatigue syndrome affects around 0.2-2.6% of the global population. It mainly affects adults between 40 and 60 years, with a female predominance [1][2]. It also occurs in children and adolescents; however, it appears to be at a lower rate [3].

2. What Causes Chronic Fatigue Syndrome?

There are several causes of chronic fatigue syndrome including genetic, neurological, immunological, infectious, sleep-related, and psychiatric [2].

A. Is Chronic Fatigue Syndrome a Genetic Condition?

Several studies investigated the association between chronic fatigue syndrome and family genetic history. One of the studies compared the rate of chronic fatigue syndrome (CFS) between 25 individuals with CFS and 36 control subjects and found significantly higher rates of CFS in individuals with CFS relatives [4].

By analyzing data from a chronic fatigue twin registry, other studies found higher rates of chronic fatigue syndrome in monozygotic (identical) compared to dizygotic twins and that a genetic predisposition to chronic fatigue syndrome exists in female twins [5].

However, further investigations are required to confirm the involvement of family genetic history in the etiology of CFS [2].

B. Is Chronic Fatigue Syndrome a Neurological Condition?

Due to the presence of symptoms of fatigue, impaired concentration diminished attention and memory, and headache in cases of CFS, neuropsychological and neuroendocrine studies, were performed by several research groups.

Neuropsychological studies

Although studies tested the capacity of information processing, working memory, and poor learning in CFS individuals, the results showed that these individuals have normal cognitive and global intellectual abilities [6].

Neuroendocrine studies

Abnormalities in the hypothalamic-pituitary-adrenal axis and serotonin pathways were reported in patients with CFS. These individuals had an altered physiological response to stress associated with reduced levels of cortisol, a disorder of central neurotransmitters, and disturbance of the functional relationship between cortisol and central neurotransmitters [7].

C. Is Chronic Fatigue Syndrome an Immunological Condition?

Analysis of the immune system in CFS individuals demonstrated the presence of alterations affecting the function of natural killer (NK) cells and regulatory T and B cells, and higher frequencies of various autoantibodies [8] [9]. However, other studies showed the absence of changes in lymphocyte subsets in CFS individuals [10].

D. Is Chronic Fatigue Syndrome Due to Infections?

Although several studies reported potential associations between CSF and viral infections, such as Epstein–Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus (HHV) 6, HHV-7, HHV-8, human parvovirus B19 (B19V), enteroviruses, lentiviruses, the role of viral infections in CSF etiology have not been confirmed and remains inconclusive [11].

E. Is Chronic Fatigue Syndrome Due to Sleep Disruption?

Although many studies suggested an association between CSF and sleep disturbances using sleep parameters such as slow-wave sleep, apnea-hypopnea index, spectral activity, and multiple sleep latency testing, a recent study showed that the reported results are inconsistent due to subjects’ recruitment decisions, confounding factors, small sample sizes and unconfirmed findings [12].

F. Is Chronic Fatigue Syndrome a Psychiatric Condition?

Several studies suggested that CSF is a psychiatric disorder that originates in CSF individuals who have mood disorders, such as anxiety, and major depression, and somatization disorder which includes symptoms such as headaches, dizziness, generalized pain, bowel movement, and fatigue [13] [14].

H. Is Chronic Fatigue Syndrome Due to Lack of Exercise?

A study showed that CSF individuals have less physical activity than non-CSF individuals, suggesting that the lack of physical activity could aggravate fatigue in CSF patients [15]. Interestingly, another study showed that individuals with CSF who received a graded exercise program had improvements in physical activities and in some cognitive variables [16].

3. How Is Chronic Fatigue Syndrome Diagnosed?

Unfortunately, there is no specific test for CSF, and the diagnosis is based on the observation of symptoms including sleep disturbances, headaches, joint, and muscle pain, disabling tiredness, flu-like symptoms, dizziness, and heart palpitations.

4. How Is Chronic Fatigue Syndrome Treated?

The treatment of chronic fatigue syndrome is symptomatic and involves the use of a graded exercise program to improve physical activity, medications to control sleeping disruptions and pain, and cognitive behavioral therapy to improve cognitive disorders, and behaviors, and to develop coping strategies.

5. Frequently Asked Questions about What Is Chronic Fatigue Syndrome?

What is Chronic Fatigue Syndrome (CFS)?

Chronic Fatigue Syndrome, also known as myalgic encephalomyelitis (ME/CFS), is a complex disorder characterized by extreme fatigue that doesn’t improve with rest and may worsen with physical or mental activity.

What are the symptoms of CFS?

The main symptom of CFS is severe fatigue that lasts for at least six months and is not alleviated by rest. Other common symptoms include muscle pain, joint pain, headaches, unrefreshing sleep, memory problems, and difficulty concentrating.

What causes Chronic Fatigue Syndrome?

The exact cause of CFS is unknown, but it is believed to involve a combination of factors, including viral infections, immune system dysfunction, hormonal imbalances, and genetic predisposition. Psychological factors such as stress may also play a role.

How is Chronic Fatigue Syndrome diagnosed?

There is no specific test for CFS, so diagnosis is based on ruling out other possible causes of the symptoms. Doctors may perform a thorough medical history, physical examination, and various tests to rule out other conditions with similar symptoms.

Is there a cure for Chronic Fatigue Syndrome?

Currently, there is no cure for CFS. Treatment focuses on managing symptoms and improving quality of life. This may include medications to relieve pain and improve sleep, as well as lifestyle changes such as pacing activities and managing stress.

Can exercise help with Chronic Fatigue Syndrome?

While exercise is important for overall health, it can be challenging for people with CFS due to their extreme fatigue and other symptoms.

A carefully tailored exercise program, such as graded exercise therapy, may be beneficial for some individuals, but it should be approached cautiously and under the guidance of a healthcare professional.

Is Chronic Fatigue Syndrome a mental illness?

No, CFS is not a mental illness, although psychological factors such as stress may contribute to its development or exacerbation. CFS is recognized as a physical illness by major medical organizations, including the World Health Organization and the Centers for Disease Control and Prevention.

Can children get Chronic Fatigue Syndrome?

Yes, children and adolescents can develop Chronic Fatigue Syndrome. It may manifest differently in younger individuals compared to adults, with symptoms such as difficulty concentrating, school absences, and reduced participation in activities.

How common is Chronic Fatigue Syndrome?

CFS is estimated to affect between 0.1% and 0.4% of the population, though rates may vary depending on the criteria used for diagnosis and other factors. It can occur in people of all ages, genders, and ethnicities.

What should I do if I think I have Chronic Fatigue Syndrome?

If you are experiencing persistent, unexplained fatigue along with other symptoms of CFS, it’s important to consult with a healthcare professional. They can perform a thorough evaluation to determine the cause of your symptoms and develop an appropriate treatment plan.


Although chronic fatigue syndrome appears to be associated with psychiatric and neurological disorders, other factors such as viral infections, immunity, and hereditary, may also be involved. A better understanding of the etiology of this syndrome using studies that comprise larger cohorts of CSF patients would certainly lead to the development of more efficient therapies that are specific to chronic fatigue syndrome.


[1] course/epidemiology.html

[2] Afari, N. and Buchwald, D., 2003. Chronic fatigue syndrome: a review. American Journal of Psychiatry160(2), pp.221-236.

[3] Lim, E.J., Ahn, Y.C., Jang, E.S., Lee, S.W., Lee, S.H. and Son, C.G., 2020. Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Journal of translational medicine18(1), pp.1-15.

[4] Walsh, C.M., Zainal, N.Z., Middleton, S.J. and Paykel, E.S., 2001. A family history study of chronic fatigue syndrome. Psychiatric genetics11(3), pp.123-128.

[5] Buchwald, D., Herrell, R., Ashton, S., Belcourt, M., Schmaling, K., Sullivan, P., Neale, M. and Goldberg, J., 2001. A twin study of chronic fatigue. Psychosomatic medicine63(6), pp.936-943.

[6] Tiersky, L.A., Johnson, S.K., Lange, G., Natelson, B.H. and Deluca, J., 1997. Neuropsychology of chronic fatigue syndrome: a critical review. Journal of Clinical and Experimental Neuropsychology19(4), pp.560-586.

[7] Parker, A.J.R., Wessely, S. and Cleare, A.J., 2001. The neuroendocrinology of chronic fatigue syndrome and fibromyalgia. Psychological medicine31(8), pp.1331-1345.

[8] Barker, E., Fujimura, S.F., Fadem, M.B., Landay, A.L. and Levy, J.A., 1994. Immunologic abnormalities associated with chronic fatigue syndrome. Clinical Infectious Diseases18(Supplement_1), pp.S136-S141.

[9] Brenu, E.W., Huth, T.K., Hardcastle, S.L., Fuller, K., Kaur, M., Johnston, S., Ramos, S.B., Staines, D.R. and Marshall-Gradisnik, S.M., 2014. Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis. International immunology26(4), pp.233-242.

[10] Mikecz, A.V., Konstantinov, K., Buchwald, D.S., Gerace, L. and Tan, E.M., 1997. High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology40(2), pp.295-305.

[11] Rasa, S., Nora-Krukle, Z., Henning, N., Eliassen, E., Shikova, E., Harrer, T., Scheibenbogen, C., Murovska, M. and Prusty, B.K., 2018. Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Journal of translational medicine16(1), pp.1-25.

[12] Maksoud, R., Eaton-Fitch, N., Matula, M., Cabanas, H., Staines, D. and Marshall-Gradisnik, S., 2021, May. Systematic Review of Sleep Characteristics in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. In Healthcare (Vol. 9, No. 5, p. 568). Multidisciplinary Digital Publishing Institute.

[13] Stewart, D.E., 1990. Emotional disorders misdiagnosed as physical illness: Environmental hypersensitivity, candidiasis hypersensitivity, and chronic fatigue syndrome. International Journal of Mental Health19(3), pp.56-68.

[14] Shorter, E., 2008. From paralysis to fatigue: a history of psychosomatic illness in the modern era. Simon and Schuster.

[15] van der Werf, S.P., Prins, J.B., Vercoulen, J.H., van der Meer, J.W. and Bleijenberg, G., 2000. Identifying physical activity patterns in chronic fatigue syndrome using actigraphic assessment. Journal of psychosomatic research49(5), pp.373-379.

[16] Wallman, K.E., Morton, A.R., Goodman, C., Grove, R. and Guilfoyle, A.M., 2004. Randomised controlled trial of graded exercise in chronic fatigue syndrome. Medical Journal of Australia180(9), pp.444-448.

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