Chronic Fatigue Syndrome Pathophysiology

By Dr. Ananya Mandal, MDReviewed by Sally Robertson, B.Sc.

The underlying pathology of Chronic Fatigue Syndrome (CFS) is not clearly understood. There are several theories regarding the cause of this condition, ranging from viral infection such as glandular fever to abnormalities of the immune system and hormone imbalance.

CFS is classified as a chronic neurological condition by the World Health Organization. This classification has been accepted by the Department of Health but remains a controversial issue, with many members of the National Institute of Health and Care Excellence (NICE) and the Association of British Neurologists disagreeing with the classification.

Some of the suggested pathologies related to CFS include:

Viral infection

Many of the symptoms of CFS resemble those seen in viral infections and many researchers have therefore focused on viral causes. However, some CFS patients do not show symptoms of viral infection and experts remain divided in their opinion over whether a virus or another type of infection causes the condition. Many of those who support the theory that a virus causes CFS base their judgement on evidence such as the following:

1. Some CFS sufferers have been reported to have increased levels of antibodies to viruses such as herpesvirus 6, Epstein-Barr virus, parvovirus and measles. However, there is no solid research proving an increased incidence of any such infections in individuals with CFS.
2. The majority of cases of CFS illness start suddenly, with symptoms that resemble those seen with viral infection.

Hormone imbalance

Hormones involved in a system called the hypothalamus-pituitary-adrenal (HPA) axis in the brain are thought by some to play a role in CFS. This system regulates functions such as sleep and the stress response. Serotonin is of particular interest, as some CFS patients have been shown to have increased levels of this neurotransmitter. In some cases, CFS sufferers have also been shown to have dopamine deficiencies or imbalances in their norepinephrine and dopamine levels. Individuals with CFS also appear to have lower levels of the stress hormone cortisol, which may explain their impaired response to physical stresses such as infection and exercise. However, only some patients have responded positively to cortisol therapy.

Immune system abnormality

Some studies have shown various examples of immune system dysfunction in CFS. However, some research supports an overactive immune response, while other research supports an underactive system. Some studies have also shown that many individuals with CFS have allergies to certain foods, metals and other substances. On the other hand, most people with allergies do not have CFS.

Psychological aspects

Some experts believe that there is a psychological element to CFS. However, although psychosocial factors have been associated with CFS in many studies, this relationship is still not understood and no solid link between CFS and emotional problems or personality disorders has yet been established. It is possible that CFS leads to psychological problems rather than these problems causing CFS.

Further Reading

• All Chronic Fatigue Syndrome Content
• What is Chronic Fatigue Syndrome?
• Chronic Fatigue Syndrome Symptoms
• Chronic Fatigue Syndrome Classification
• Chronic Fatigue Syndrome Treatment