Causes
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:
- Genetic factors
- Brain abnormalities
- A hyper-reactive immune system
- Viral or other infectious agents
- Psychiatric or emotional conditions
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.
Genetic Defects
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.
Central Nervous System and Hormone Abnormalities
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:
- Changes in Important Neurotransmitters. Some patients with CFS have abnormally high levels of serotonin -- a neurotransmitter (chemical messenger in the brain), deficiencies of dopamine -- an important neurotransmitter associated with feelings of reward, or imbalances between norepinephrine and dopamine. However, routine clinical testing for such chemical imbalances is cost-prohibitive.
- Stress Hormone Deficiencies. A number of studies on CFS patients have observed lower levels of cortisol, a stress hormone produced in the adrenal glands. Deficiencies of cortisol have been suggested as the reason why CFS patients have an impaired and weaker response to psychological or physical stresses, such as infection or exercise. However, administering replacement cortisol improves symptoms only in some patients.
- Disturbed Circadian Rhythms. Evidence suggests that, in certain patients, CFS is a disorder of the sleep-wake cycle, which is regulated by the so-called circadian clock, a nerve cluster in the HPA axis. Some mentally or physically stressful event, such as a viral infection, may disrupt natural circadian rhythms. An inability to reset these rhythms results in a perpetual cycle of sleep disturbances. Medications that improve sleep can be very helpful for certain patients with CFS.
