Theories abound about the causes of chronic fatigue syndrome. No primary cause has been found that explains all cases of CFS, and no blood tests or brain scans can definitively diagnose the condition.
Convergence of Factors. A number of experts believe that CFS develops from a convergence of conditions that may include the following:
For example, most patients report some moderate-to-serious physical illness (such as a chronic viral infection) or emotional event (like an episode of depression) before CFS. Some experts theorize that such events, alone or in combination, may interact with certain neurologic and genetic abnormalities to trigger CFS.
Still, it is not clear what sequence of events actually leads to the fatigue and other prominent symptoms of this disorder. Nor is there any specific brain or nervous system problem that experts can point to with assurance.
CFS has been linked with genes involved in the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. These genes control response to trauma, injury, and other stressful events. Nevertheless, researchers have been unable to determine how the genetic variations influence symptoms.
A number of studies have found alterations in genes involved with immune function, communication between cells, and transfer of energy to cells.
Researchers have identified many different genes in patients with CFS related to blood disease, immune system function, and infection. However, no clear pattern has been found.
Abnormal levels of certain chemicals regulated in the brain system known as the hypothalamus-pituitary-adrenal (HPA) axis have been proposed as a cause of CFS. This system controls important functions, including sleep, stress response, and depression. Of particular interest to researchers are the following chemicals and other factors controlled by the HPA axis:
It is still not clear whether any of these changes are causes of chronic fatigue syndrome, or merely findings in some patients.
Because most of the features of CFS resemble those of a lingering viral illness, many researchers have focused on the possibility that a virus or some other infectious agent causes the syndrome in some cases.
Still, not all CFS patients show signs of infection. Although experts have long been divided on whether infections play any role in this disorder, subtypes of viral-related and non-viral CFS may both exist.
Viruses. The theory that CFS has a viral cause is not based on hard evidence, but on various observations that suggest an association, such as the following:
CFS has sometimes been referred to as the "chronic fatigue immune dysfunction syndrome." A number of studies have found many irregularities of the immune system. Some components appear to be over-reactive, while others appear to be under-reactive, but no consistent picture has emerged to explain CFS as a disease of the immune system.
Allergies. Some studies have reported that a majority of CFS patients have allergies to foods, pollen, metals (such as nickel or mercury), or other substances. One theory is that allergens, like viral infections, may trigger a cascade of immune abnormalities leading to CFS. However, most allergic people do not have CFS.
Autoimmune Abnormalities. The risk profile for chronic fatigue syndrome is similar to the risk profiles for a number of autoimmune diseases. Studies are inconsistent, however, in reporting the presence of autoantibodies (antibodies that attack the body's own tissues) in CFS, and the disease is unlikely to be due to autoimmunity.
Studies have observed that some patients who fit the strict criteria for chronic fatigue syndrome also have symptoms of a condition known as neurally mediated hypotension (NMH). NMH causes a dramatic drop in blood pressure when a person stands up, even for as little as 10 minutes. Its immediate effects can be lightheadedness, nausea, and fainting.
However, studies have reported no higher incidence of NMH in chronic fatigue patients.
Psychological, personality, and social factors are strongly associated with chronic fatigue in most patients. The complex relationship between physical and emotional factors has yet to be fully understood, however. Studies have not found any consistent association between emotional or personality disorders and CFS to explain a causal role. Psychological factors, then, are unlikely to be a primary cause of CFS. However, they may play a role in increasing susceptibility to the disorder. In many cases, CFS promotes psychological and social dysfunction.
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