Observations that disparate treatments work for select patients appear to support the idea that subtypes of CFS require distinct approaches. The existence of subgroups may also explain why CFS researchers are frequently unable to replicate their results in subsequent studies; patient selection in studies to date has not reflected such careful discrimination. Researchers are now, however, working to define the subgroups of CFS and identify which treatments are most effective for each.
It should be noted that while the subgroup theory is interesting, in some cases the differences among patient populations may also reflect stages of disease. For instance, in initial stages of the disease, many patients are extremely symptomatic and fit a particular psychological profile including alarm, denial, and anger. In contrast, patients in later phases of the disease typically have learned to cope better with their symptoms and have a degree of acceptance. Patients' mental and emotional status may have biological consequences that bear on their physical symptoms. Such a relationship is not yet documented in CFS patients, however, and remains subject to research.
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, the majority of patients report some preceding moderate to serious physical illness (such as a chronic viral infection) or emotional event (like an episode of depression). Some experts theorize that such events, alone or in combination, may interact with certain neurologic and genetic abnormalities to trigger the event. 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 abnormality that experts can point to with assurance. Research published in 2001 indicates that CFS is more common among identical twins (who share the same genes) than fraternal twins (who share only some genes). Inheritance, then, may play a role in roughly 30 - 50% of cases, similar to the influence thought to occur in depression or alcoholism, although specific genes have not yet been identified.
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