ChainWhiteWWhile the cause or causes of chronic fatigue syndrome (ME/CFS) are still unclear researchers have documented numerous abnormalities that have sparked considerable speculation regarding its cause. Overall, research findings suggest chronic fatigue syndrome (ME/CFS) is a multi-systemic disorder involving the immune, neuroendocrine and cardiovascular systems.

Triggering Chronic Fatigue Syndrome (ME/CFS): A wide variety of events including infection, injury, physical or psychological stress and toxin exposure have been reported to trigger chronic fatigue syndrome (ME/CFS). Not all patients can identify a triggering event. How such a process occurs is still unclear but researchers are increasingly focused on the central nervous system and the ways that stressful events such as injury and infection can affect the functioning of the brain.

Central Nervous System Dysfunction: Several models of chronic fatigue syndrome (ME/CFS) begin with an external event (infection, toxin, physical or psychological stressor) that ultimately translates into central nervous system damage. Abnormal patterns of brain activity, reduced brain blood flows, reduced gray matter volume, altered metabolic findings, and others suggest areas of the brain involved in the stress response, energy production, concentration, motivation, fatigue and pain are damaged in chronic fatigue syndrome (ME/CFS).

Immune Defects: The flu-like symptoms chronic fatigue syndrome (ME/CFS) patients often experience at the diseases onset has made the immune system an important research emphasis. Several immune abnormalities could contribute to the problems patients face.

  • Impaired Cellular Immune Response – Two abnormalities in the responses cells have to infection in the ‘interferon pathway’ have been documented. An antiviral enzyme in this pathway called the RNase L has been shown to be fragmented in many patients. A subset of chronic fatigue syndrome (ME/CFS) patients also display increased activity of another enzyme called protein-kinase R (PKR) that is involved in killing cells infected with pathogens. These problems suggest the immune systems of chronic fatigue syndrome (ME/CFS) patients could have troubles finding pathogens and killing the cells they’ve infected.

  • Natural Killer (NK) and T-cell Dysfunction – NK and T-cells are two other components of the immune response to pathogens. A set of chronic fatigue syndrome (ME/CFS) patients have been shown to have reduced NK cell numbers and poor NK and T-cell functioning. These problems also could interfere with the ability of the immune system to find infected cells and kill them. Intriguingly some researchers believe that chronic immune activation due to an underlying chronic infection has caused these cells to ‘burn out’.

  • Th1/Th2 Imbalance – There are two general branches (Th1/Th2) of the immune system. Some patients appear to have an over activation of the anti-inflammatory (Th2) branch and an under activation of the pro-inflammatory (Th1) branch of the immune system. This could cause increased rates of allergy and sensitivity on the one hand and difficulty fighting off pathogens on the other.

An Undiagnosed Chronic Infection: Chronic fatigue syndrome (ME/CFS) patients were recently reported to be 18’s more likely to harbor a pathogen than healthy controls. The NK cell ‘burn-out’, increased T-cell activation and increased rates of cell suicide (apoptosis) in CFS could be caused by a chronic infection. Some study results suggest that antiviral drug therapy may be able to cure some CFS patients but much more study is needed.  Herpesviruses and enteroviruses are the main candidates.  

Impaired Stress Response: A significant number of patients have reduced hypothalamic-pituitary-adrenal (HPA) axis functioning and lowered cortisol levels. Since the stress response is important in mobilizing the bodies energy stores for activity an impaired stress response could contribute to the fatigue patients experience. Because the HPA axis also plays an important role in down regulating the immune response low HPA axis activity could also contribute to the chronic immune activation believed present.

Increased Sympathetic and Decreased Parasympathetic Nervous System (SNS/PNS) Activation: Increased SNS activity could result in narrowed blood vessels and the low blood volume, reduced brain and muscle blood flows, heart abnormalities under stress and other problems seen in chronic fatigue syndrome (ME/CFS). Reduced PNS activity could also contribute to unrefreshing sleep.

Genetics: Recent studies suggest there is a strong genetic component to chronic fatigue syndrome (ME/CFS). While chronic fatigue syndrome (ME/CFS) is not strictly hereditary some evidence suggests that it runs in family. Several gene mutation studies have found increased rates of neuro-endocrine and immune mutations in the disease.


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