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The pathogenesis or the mechanisms and processes of Chronic fatigue syndrome (CFS) are gradually being revealed through research, including physiological and epidemiological studies. In a basic overview of CFS for health professionals, the CDC states that "After more than 3,000 research studies, there is now abundant scientific evidence that CFS is a real physiological illness."
Chronic fatigue syndrome (CFS) or (ME) has been described in a 2008 Toxicology journal article as, "a constellation of multi-system dysfunctions primarily involving the neurological (nervous system), endocrine (hormone system), and immune systems." The article states recent research suggests the potential that xenobiotic (chemicals), infectious agents, stress, and other insults in early-life may be a component of later-life CFS.
Pathophysiology (1) Immune system, InfectionEdit
A 2007 article in the journal Autoimmunity summarised; “The current concept is that CFS pathogenesis is a multi factorial condition in which an infective agent cause an aberrant immune response characterized by a shift to Th-2 (cytokine) dominant response. When the response fails to be switched-off, a chronic immune activation occurs and is clinically expressed in the symptomatology of CFS." 
When compared with CFS patients with normal natural killer cell activity, a 2006 study found those with lower levels reported less vigor, more daytime dysfunction, and more cognitive impairment; with the researchers suggesting this to be useful at subtyping. A systematic review on the immunology of CFS (published in 2003) found an inverse association between study quality and findings of low levels of natural killer cells (suggesting that the association may be related to study methodology), although no such association was found with studies finding abnormalities in T cells and cytokine levels. In 2006 an updated review on the phenomenology and pathophysiology of CFS found that, "immune system involvement in the pathogenesis of CFS seems certain but the findings on the specific mechanisms are still inconsistent." There is also evidence that people with CFS have improper gene expression including both over expression and under expression of genes involved in the immune system (see the gene expression section).
RNase L deregulationEdit
Several studies have detected an abnormal form and activity level of 2-5A synthetase/RNase L enzyme (antiviral immune response) in some CFS patients that appears to correlate with a reduction in exercise capacity. A review published in 2005 suggested that this impaired pathway is of clinical importance and that further studies addressing treatment of this deregulation are warranted. A study found that elevated RNase L did not correlate with alpha-delta sleep.
Autoimmune disorders, representing a hyperactive immune system, most likely through a cell-mediated process, have been suggested. In July 2005, researchers in the UK reported significant gene changes in the white blood cells in CFS patients consistent with the theory of immune system activation, possibly by an antigen triggering a constant immune fatigue state. The study, led by Dr Jonathan Kerr, discovered that 35 white blood cell genes, out of a total of 9,522 genes scanned were demonstrating differential function. There was also suggestion of neuronal and mitochondrial dysfunction as a result.
Immunodeficiency disorders (underactive immune system) have been reported. In 1989, an Australian study documented a loss of immunological integrity in one hundred CFS sufferers. The authors found disordered ratios of T-cell subsets and reduced levels of immunoglobulins specifically IgG 1 and IgG 3; there have since been other similar findings, and a review Most strikingly, using the French Multitest to measure the body's response to a variety of antigens, the Australian group found that 33% of the subjects were hypoallergic, meaning they had a reduced immune response to the tested antigens, while an additional 55% were completely anergic (no immune response to the antigens).
Cytokine pattern; several studies and a number of reviews indicate there is a cytokine pattern of type 2 response including Th2 T helper cell, bias in CFS. This promotes the humoral immune system which stimulates B cells and increases antibody production. It is suggested that this explains some immune dysfunctions in CFS. A reduction in Th1 response has also been found in some CFS studies. with implications for altered Th1/Th2 balance. Therapeutic interventions aimed at induction of a more favorable cytokine expression pattern and immune status are being investigated.
Often, there is evidence of enteroviruses, e.g. the Coxsackie virus. The type of enterovirus varies, which can affect symptoms. In the times of polio outbreaks, paresis was often found in ME patients; this is no longer the case. . Stomach biopsies of 80% of CFS patients showed the presence of enteroviruses in one study, as opposed to only 20% among controls, and nearly all biopsy specimens had microscopic evidence of mild chronic inflammation. Hyde and others suggest that these enteroviruses had been latent to be awakened by another, triggering infection, after which the immune system stays chronically active to combat the enterovirus. .
- Epstein-Barr virus
For many years the ubiquitous Epstein-Barr virus, present in 90% of the population, was the principal suspect based on abnormal immunologic responses observed in uncontrolled studies. Subsequent studies using various types of controls have had mixed conclusions.
Other implicated viruses include Ross river virus,  Borna disease,   Parvovirus B19   also herpes viruses Cytomegalovirus (HHV-5),    Human Herpesvirus Six (HHV-6) and HHV-7,    A review by Soto and Straus in 2000 states the evidence argues against an ongoing active herpes virus infection, more recent reviews suggest these viruses may play a role in triggering or perpetuating CFS in subtypes. 
Other immunological and infection findingsEdit
- A study published in 1995 found that 3 immunological tests (protein A binding, Raji cell, or C3/C4) best discriminated CFS patients from fatigued controls.
- A study found that while exercise worsened symptoms in CFS patients, it also increased allergen challenge response only in the CFS group, regardless of allergy status.
- A study found that fatigue persists in a significant minority of patients for six months or more after infections, suggesting post-infective fatigue syndrome is a valid illness model for investigating CFS.
- In a study on people who had glandular fever (which is caused by the Epstein-Barr virus), no difference was found between the levels of virus in the blood from patients who recovered quickly when compared with those whose fatigue lasted more than six months, although the latter had an altered immune response. The scientists involved believed this suggests CFS can be caused by neurological damage done (during the acute infection phase) to parts of the brain which control perception of fatigue and pain.
Pathophysiology (2) Nervous systemEdit
Chronic fatigue is a typical symptom of neurological diseases, including chronic fatigue syndrome, is also seen in diseases that affect the central, peripheral, and autonomic nervous systems (central fatigue). Enhanced perception of effort and limited endurance of sustained physical and mental activities are the main characteristics of central fatigue. Metabolic and structural lesions can cause muscle fatigability (peripheral fatigue) also disrupt the usual process of activation in pathways interconnecting the basal ganglia (peripheral nerves), thalamus, limbic system, and higher cortical centre are implicated in the pathophysiological process of central fatigue. A state of low cortisol might sensitise the HPA axis to development of persistent central fatigue after stress. 
Researchers have found evidence that CFS may involve distinct neurological abnormalities. MRI and SPECT scans show abnormalities within the brain. Studies have shown that CFS patients have abnormalities in blood flow to the brain possibly indicative of viral cause and similar but not identical compared to patients with clinical depression. A number of studies have shown that CFS patients have abnormal levels of neurotransmitters including increased serotonin (the opposite of what is found in primary depression). Reduced brain serotonin receptor sensitivity or number, and high auto antibodies to serotonin have also been found. Recent studies found altered gene expression in the brain’s serotonin and sympathetic nervous system pathways, with altered responses of the HPA axis to serotonin. Other reported neurotransmitter irregularities include glutamate, acetylcholine sensitivity associated increased cutaneous microcirculation, and autoantibodies to cholinergic receptors associated with central pain. Beta-endorphin, a natural pain killer, has been found to be low in CFS patients, the opposite of what is found in primary depression.
Dysautonomia is the disruption of the function of the autonomic nervous system (ANS). The ANS controls many aspects of homeostasis. The dysautonomia that evidences itself in CFS shows up mostly in problems of orthostatic intolerance - the inability to stand up without feeling dizzy, faint, nauseated, etc. Research into the orthostatic intolerance found in CFS indicates it is very similar to that found in postural orthostatic tachycardia syndrome (POTS) and hypocapnia. POTS and CFS patients exhibit reduced blood flows to the heart upon standing that result in reduced blood flow to the brain. The reduced blood flows to the heart are believed to originate in blood pooling in the lower body upon standing. Many CFS patients report symptoms of orthostatic intolerance and low or lowered blood pressure.  
- Inner-ear disorders
- Main article: balance disorder
Problems such as Meniere's, also tumor in the inner ear, or Benign Paroxysmal Positional Vertigo (BPPV) can cause dizziness, vertigo, and fatigue. Tinnitus is also quite common. Antibodies associated with hearing loss have been found in CFS and FMS patients with inner ear disorders
- Orthostatic hypotension
Syndromes of orthostatic intolerance, in particular neurally mediated hypotension (NMH) and postural orthostatic tachycardia syndrome (POTS), have been shown to be associated with chronic fatigue syndrome. These conditions, which reduce blood flow to the brain after periods of standing, can be diagnosed with a tilt table test. A clinical trial of fludrocortisone, a drug sometimes used to treat low blood pressure, showed little or no benefit for people with CFS.
There is some overlap in symptoms between depression and CFS, and sometimes cases of CFS are mistakenly attributed to clinical depression. There are, however, many clinical differences between the two. 
Clinical depression often responds well to physical exercise, whereas CFS is characterised by exercise intolerance but with a willingness to be active. (See section on post-exertion symptom exacerbation.) Comorbid depression occurs in 10-15% of CFS patients and should be treated as usual, except that the patient’s energy level, cognitive dysfunction and drug sensitivity must be taken into account.  Comorbid depression may be a pre-existing condition, or the result of living with CFS.
Stress and traumaEdit
The majority of people who experience stress/trauma do not develop CFS, but these factors (including infection) increase the likelihood of acquiring CFS within one year and a genetic disposition to CFS has been demonstrated. Two studies suggest that self-reported childhood stress/trauma significantly increases the likelihood of acquiring CFS as an adult: A preliminary study found a 3 to 8 fold increase (depending on the trauma type). A study involving participants from the Swedish Twin Registry found that in matched case-control analyses, higher emotional instability and self-reported stress were significant risk factors (odds ratios, 1.72 and 1.64, respectively), while in co-twin control analyses the risk of emotional instability decreased to 1.02 whereas that of stress increased to 5.81 (suggesting genetic influences); there was also no association between extraversion and fatigue. Anxiety disorders have been associated with CFS in 5-15 year olds.
The CDC stated in 2006, their studies found gene mutation and abnormal gene activity levels in CFS patients that relate to the function of the hypothalamus-pituitary-adrenal (HPA) axis, which helps regulate the body's stress response. Earlier CFS research also found evidence that suggested abnormal stress response was associated with subtle dysfunction of the HPA axis. Questions remain about the pathophysiology of these findings. The controversy surrounding CFS has caused some social issues for patients and may contribute to their stress (see the Social issues section).
- Further information: psychoneuroimmunology
A 2006 review published in Current neurovascular research states that there is growing evidence of autoantibodies to neuronal or endothelial (interior surface of blood vessels) targets in psychiatric disorders and hypothesizes how autoantibodies can play a role in the psychiatric disorders present in CFS. Researchers involved in a review examining an immunological basis for CFS concluded that neuropsychiatric symptoms in CFS patients may be more closely related to disordered cytokine production by glial cells within the central nervous system rather than to circulating cytokines. In one study, autoantibodies for muscarinic cholinergic receptor had been found in over half of the CFS patients and seemed to correlate with the severity of the "feeling of muscle weakness". Elevated levels of nitric oxide (not to be confused with nitrous oxide) has been found in some CFS patients. One hypothesis is that elevated levels of nitric oxide may contribute to a "sensitization" of the nervous system that results in behavioral changes.
Pathophysiology (3) Endocrine system, OtherEdit
In a 2006 update in the journal Curr Opin Psychiatry it was said; “Recent advances in understanding the pathophysiology of chronic fatigue syndrome continue to demonstrate the involvement of the central nervous system. Hyperserotonergic state and hypoactivity of the hypothalamic-pituitary-adrenal (HPA} axis constitute other findings, but the question of whether these alterations are a cause or consequence of chronic fatigue syndrome still remains unanswered.”  Alterations in serotonin signaling can lead to physiologic and behavioral changes. A 2008 study of gene polymorphisms indicates genetic predisposition possibly resulting in enhanced activity of serotonin may be involved in the pathophysiology of CFS. 
The HPA axis controls levels of hormones such as cortisol in the body. It is activated in a circadian (daily) cycle and modulated by stress, digestion, illness and other factors, and is important in regulating energy metabolism, the immune system, stress responses and inflammation in the body.
The HPA axis has been much studied in CFS which has shown underactivation with low cortisol not caused by adrenal insufficiency. These results have not been replicated in all CFS patients, so it is not clear whether this is just a subset of patients. It is also not clear if the HPA axis abnormalities are a cause or a result of the illness. However, a review has concluded, that even if the HPA axis dysfunctions are secondary to other factors; they are a likely factor in symptom propagation in CFS.
Gene expression is the process by which the inheritable information in a gene, such as the DNA sequence, is made into a functional gene product, such as protein or RNA. Research into CFS has found abnormalities in gene expression, and the CDC has conducted over twenty related studies itself.  It has been found that patients with CFS have specific abnormalities in expression of multiple genes which are involved in the biological process of transport (both vesicle-mediated and protein transport) and this became accentuated when CFS patients exercise. Another study found that "the differentially expressed genes imply fundamental metabolic perturbations", such as those involved in purine and pyrimidine metabolism, glycolysis, oxidative phosphorylation, and glucose metabolism. Several other studies have also suggested a genetic component to CFS involving immune dysfunction; T cell activation, perturbation of neuronal and mitochondrial function, possible links to organophosphate exposure and virus infection; immune response, apoptosis, ion channel activity, signal transduction, cell-cell signaling, regulation of cell growth and neuronal activity; some of which may be treatable with drugs that are already available. Gene expression abnormalities have been found relating to the central nervous system, metabolism and immune system; and has been associated by the CDC with impaired response to physical and psychological stresses in people with CFS.  Linking genes to specific symptoms has been difficult, although is likely to be an important means to elucidate the pathogenesis of CFS.Seven subtypes of CFS/ME patients with distinct clinical differences have been identied in one gene expression study.
Polymorphism in biology occurs when two or more clearly different types exist in the same population of the same species. Preliminary studies have suggested that the risk of developing CFS may be influenced by polymorphisms in genes affecting the central nervous, endocrine, immune, and/or cardiovascular systems. A review published in 2007 stated that certain genetic polymorphisms might be regarded as predisposing factors.
Oxidative stress is an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily repair the resulting damage. Several studies and a review have implicated oxidative stress in CFS symptoms; especially relating to fatigue, pain and postexertional malaise/exercise intolerance. According to research, the findings on oxidative stress and nitrosative stress (nitric oxide-related toxicity); are associated with an inflammatory response, seem consistent with abnormal 2-5A synthetase/RNase L enzyme (antiviral) activity and involves an immune response, against disrupted lipid membrane components, (by-products of lipid peroxidation ) and to nitric-oxide modified amino acids that have have become immunogenic; related to symptoms and severity in CFS. Gene expression studies suggest a common link between oxidative stress, immune system dysfunction and potassium imbalance in CFS patients leading to impaired nerve balance strongly reflected in abnormal heart rate variability.
Metabolic disorders and mitochondrial disorders can cause symptoms that strongly resemble CFS. Mitochondrial disturbances have been discovered in patients diagnosed with postviral fatigue syndrome. and mitochondrial dysfunction is considered a factor in PVFS and CDC defined CFS patients.
Essential fatty acid deficienciesEdit
Essential fatty acid levels: Several studies published between 1990 a 2005 reported finding reduced levels of Omega-6 or Omega-3 essential fatty acids in cell membranes or serum in patients diagnosed with postviral fatigue syndrome or CDC defined CFS.One study conducted in 1999 on Oxford criteria defined CFS patients (Warren et al.) found no significant differences in fatty acid levels between treatment and placebo groups. There have also been two controlled systematic proton neurospectroscopy studies of CFS patients that found raised levels of choline in brain areas consistent with an abnormality of essential fatty acid and phospholipid metabolism in the brain in CFS patients. These changes have been considered due to essential fatty acid deficiencies resulting from delta 6 desaturase (D6D) enzyme inhibition in CFS. Some researchers have suggested D6D inhibition is linked to a possible viral cause. However, researchers at an Australian University of Newcastle who reported finding, in CDC criteria defined CFS patients; a dysregulation in D6D enzyme activity and fatty acid changes consistent with an inflammatory mediated event. Found that both gradual and sudden onset had the same fatty acid anomaly differentiaiting them from controls, the primary lipid changes were potentially non-viral induced. Whilst sudden onset CFS patients could be differentiated by a key post-viral modification to fatty acids. Other studies have shown that altered ratios of fatty acids and decreased availability of omega-3 EFAs plays a role in CFS symptoms and severity and is related to findings of lowered zinc and immune dysfunction, including the lowered mitogen-stimulated activation of some T cells. The decreased cell markers are also indicators of increased inflammation and low natural killer cell activation. The reduced EFA findings are considered indicative of; oxidative stress with reduced anti-oxidant status,   
Carnitine deficiency; is said to produce symptoms of fatigue and myalgia similar to PVFS, ME and CFS. Several studies have reported finding carnitine abnormalities in CFS patients. including lower serum total carnitine, free carnitine and acylcarnitine levels.The findings of reduced brain uptake of acetylcarnitine suggest that the levels of biosynthesis of neurotransmitters through acetylcarnitine might be reduced in some brain regions of CFS patients. There has been a contradictory study that included Oxford criteria defined patients. Others report of finding reduced levels of carnitine together with reduced essential fatty acids in patients with CDC defined CFS. Carnitine and its esters are considered to regulate the immune networks and inflammation, through carnitine-dependent; transfer of fatty acids into cells, and mitochondrial energy production from beta-oxidation of long-chain fatty acids. A gene expression study indicates altered; carnitine function, mitochondrial function, and fatty acid metabolism in PVFS. Also that profiles of plasma lipids in subgroups of CDC defined CFS patients suggest anomalies including beta-oxidation of fatty acids. As carnitine is considered an anti-oxidant, the lower plasma acetylcarnitine level may indicate, consumption by the increased oxidative stress in CFS.
A large study found that higher levels of exercise in childhood is associated with a lower risk of developing CFS later on. It also found that the development of CFS was not associated with other childhood or maternal factors such as psychological problems, academic ability, allergic tendencies, birth weight, birth order or obesity.
Abnormal lactic acid responses to exercise in some CFS patients, has been suggested to be a factor in CFS because it is commonly believed to be responsible for muscle fatigue. However, some scientists have found that lactic acid may actually help prevent muscle fatigue rather than cause it, by keeping muscles properly responding to nerve signals.
Other findings regarding CFS in general include:
- Researchers compared 48 CFS patients with 29 controls and found that 10 of the CFS patients tested positive for enterovirus RNA (most closely to that of the coxsackie B virus) in their muscles while all of the 29 controls tested negative. 28 of the 48 CFS patients had an abnormal lactate response to exercise, including 9 of the 10 who tested positive for enterovirus RNA.
- Researchers have found that children and teenagers with CFS are several times more likely to have some hyperflexible joints in an association with Ehlers-Danlos syndrome.
- ↑ CDC - CFS Basic Overview (PDF file, 31 KB)
- ↑ Dietert, RR, Dietert JM (2008 Feb 8). Possible role for early-life immune insult including developmental immunotoxicity in chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME). Toxicology.
- ↑ 3.0 3.1 Appel S, Chapman J, Shoenfeld Y (2007). Infection and vaccination in chronic fatigue syndrome: myth or reality?. Autoimmunity 40 (1): 48-53.
- ↑ Siegel SD, Antoni MH, Fletcher MA, Maher K, Segota MC, Klimas N (2006). Impaired natural immunity, cognitive dysfunction, and physical symptoms in patients with chronic fatigue syndrome: preliminary evidence for a subgroup?. J Psychosom Res 60 (6): 559-66. PMID 16731230.
- ↑ Lyall M, Peakman M, Wessely S (2003). A systematic review and critical evaluation of the immunology of chronic fatigue syndrome.. J Psychosom Res 55 (2): 79-90. PMID 12932505.
- ↑ Cho HJ, Skowera A, Cleare A, Wessely S (2006). Chronic fatigue syndrome: an update focusing on phenomenology and pathophysiology.. Curr Opin Psychiatry 19 (1): 67-73. PMID 16612182.
- ↑ Tiev KP, Demettre E, Ercolano P, Bastide L, Lebleu B, Cabane J (2003). RNase L levels in peripheral blood mononuclear cells: 37-kilodalton/83-kilodalton isoform ratio is a potential test for chronic fatigue syndrome.. Clin Diagn Lab Immunol 10 (2): 315-6. PMID 12626460.
- ↑ Demettre E, Bastide L, D'Haese A, De Smet K, De Meirleir K, Tiev KP, Englebienne P, Lebleu B (2002). Ribonuclease L proteolysis in peripheral blood mononuclear cells of chronic fatigue syndrome patients.. J Biol Chem 277 (38): 35746-51. PMID 12118002.
- ↑ Shetzline SE, Martinand-Mari C, Reichenbach NL, Buletic Z, Lebleu B, Pfleiderer W, Charubala R, De Meirleir K, De Becker P, Peterson DL, Herst CV, Englebienne P, Suhadolnik RJ (2002). Structural and functional features of the 37-kDa 2-5A-dependent RNase L in chronic fatigue syndrome.. J Interferon Cytokine Res 22 (4): 443-56. PMID 12034027.
- ↑ Suhadolnik RJ, Peterson DL, O'Brien K, Cheney PR, Herst CV, Reichenbach NL, Kon N, Horvath SE, Iacono KT, Adelson ME, De Meirleir K, De Becker P, Charubala R, Pfleiderer W (1997). Biochemical evidence for a novel low molecular weight 2-5A-dependent RNase L in chronic fatigue syndrome.. J Interferon Cytokine Res 17 (7): 377-85. PMID 9243369.
- ↑ Fremont M, El Bakkouri K, Vaeyens F, Herst CV, De Meirleir K, Englebienne P (2005). 2',5'-Oligoadenylate size is critical to protect RNase L against proteolytic cleavage in chronic fatigue syndrome.. Exp Mol Pathol 78 (3): 239-46. PMID 15924878.
- ↑ Suhadolnik RJ, Reichenbach NL, Hitzges P, Sobol RW, Peterson DL, Henry B, Ablashi DV, Muller WE, Schroder HC, Carter WA, et al (1994). Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome.. Clin Infect Dis 18 (Suppl 1): S96-104. PMID 8148461.
- ↑ 13.0 13.1 Nijs J, De Meirleir K, Meeus M, McGregor NR, Englebienne P (2004). Chronic fatigue syndrome: intracellular immune deregulations as a possible etiology for abnormal exercise response.. Med Hypotheses 62 (5): 759-65. PMID 15082102.
- ↑ Snell CR, Vanness JM, Strayer DR, Stevens SR (2002). Physical performance and prediction of 2-5A synthetase/RNase L antiviral pathway activity in patients with chronic fatigue syndrome.. In Vivo 16 (2): 107-9. PMID 12073768.
- ↑ Nijs J, Meeus M, McGregor NR, Meeusen R, de Schutter G, van Hoof E, de Meirleir K (2005). Chronic fatigue syndrome: exercise performance related to immune dysfunction.. Med Sci Sports Exerc 37 (10): 1647-54. PMID 16260962.
- ↑ 16.0 16.1 Snell CR, Vanness JM, Strayer DR, Stevens SR (2005). Exercise capacity and immune function in male and female patients with chronic fatigue syndrome (CFS).. In Vivo 19 (2): 387-90. PMID 15796202.
- ↑ Nijs J, De Meirleir K (2005). Impairments of the 2-5A synthetase/RNase L pathway in chronic fatigue syndrome.. In Vivo 19 (6): 1013-21. PMID 16277015.
- ↑ Van Hoof E, De Becker P, Lapp C, Cluydts R, De Meirleir K (2007). Defining the occurrence and influence of alpha-delta sleep in chronic fatigue syndrome.. Am J Med Sci 333 (2): 78-84. PMID 17301585.
- ↑ Kennedy G, Spence V, Underwood C, Belch JJ. Increased neutrophil apoptosis in chronic fatigue syndrome. J Clin Pathol. 2004 Aug;57(8):891-3.
- ↑ Patarca R, Klimas NG, Lugtendorf S, Antoni M, Fletcher MA. Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression. Clin Infect Dis. 1994 Jan;18 Suppl 1:S147-53.
- ↑ Original Research Paper, from the Journal of Clinical Pathology http://www.cfids.org/cfidslink/2005/cfs-gene.pdf
- ↑ (Jan. 2001) "Food Intolerance in Chronic Fatigue Syndrome". ': Conference Paper 15, Seattle WA: American Association for Chronic Fatigue Syndrome.
- ↑ Logan AC, Wong C (2001). Chronic fatigue syndrome: oxidative stress and dietary modifications. Alternative medicine review : a journal of clinical therapeutic 6 (5): 450-9.
- ↑ 24.0 24.1 24.2 24.3 24.4 24.5 Nightingale Research Foundation; Goldstein, Jay E.; Byron M. Hyde (1992). The Clinical and scientific basis of myalgic encephalomyelitis/chronic fatigue syndrome, 521-538, chapter57, The Role of Food Intolerance in Chronic Fatigue Syndrome, Ogdensburg, N.Y: Nightingale Research Foundation.
- ↑ Lloyd A, Wakefield D, Boughton C, Dwyer J (1989). Immunological abnormalities in the chronic fatigue syndrome.. Med J Aust 151 (3): 122-4. PMID 2787888.
- ↑ Peterson PK, Shepard J, Macres M, et al (1990). A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome. Am. J. Med. 89 (5): 554–60.
- ↑ Lloyd A, Hickie I, Wakefield D, Boughton C, Dwyer J (1990). A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome. Am. J. Med. 89 (5): 561–8.
- ↑ Hilgers A, Frank J (1994). [Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes]. Wien Med Wochenschr 144 (16): 399–406.
- ↑ Natelson BH, LaManca JJ, Denny TN, et al (1998). Immunologic parameters in chronic fatigue syndrome, major depression, and multiple sclerosis. Am. J. Med. 105 (3A): 43S–49S.
- ↑ 30.0 30.1 30.2 Patarca R (2001). Cytokines and chronic fatigue syndrome. Ann. N. Y. Acad. Sci. 933: 185–200.
- ↑ Skowera A, Cleare A, Blair D, Bevis L, Wessely SC, Peakman M (2004). High levels of type 2 cytokine-producing cells in chronic fatigue syndrome. Clin. Exp. Immunol. 135 (2): 294–302.
- ↑ Hanson SJ, Gause W, Natelson B (2001). Detection of immunologically significant factors for chronic fatigue syndrome using neural-network classifiers. Clin. Diagn. Lab. Immunol. 8 (3): 658–62.
- ↑ Visser J, Graffelman W, Blauw B, et al (2001). LPS-induced IL-10 production in whole blood cultures from chronic fatigue syndrome patients is increased but supersensitive to inhibition by dexamethasone. J. Neuroimmunol. 119 (2): 343–9.
- ↑ Bennett AL, Chao CC, Hu S, Buchwald D, Fagioli LR, Schur PH, Peterson PK, Komaroff AL (1997). Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome.. J Clin Immunol 17 (2): 160-6. PMID 9083892.
- ↑ Visser JT, De Kloet ER, Nagelkerken L (2000). Altered glucocorticoid regulation of the immune response in the chronic fatigue syndrome. Ann. N. Y. Acad. Sci. 917: 868–75.
- ↑ Patarca-Montero R, Antoni M, Fletcher MA, Klimas NG (2001). Cytokine and other immunologic markers in chronic fatigue syndrome and their relation to neuropsychological factors. Appl Neuropsychol 8 (1): 51–64.
- ↑ Gaab J, Rohleder N, Heitz V, et al (2005). Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome. Psychoneuroendocrinology 30 (2): 188–98.
- ↑ Visser J, Blauw B, Hinloopen B, et al (1998). CD4 T lymphocytes from patients with chronic fatigue syndrome have decreased interferon-gamma production and increased sensitivity to dexamethasone. J. Infect. Dis. 177 (2): 451–4.
- ↑ Klimas NG, Salvato FR, Morgan R, Fletcher MA (1990). Immunologic abnormalities in chronic fatigue syndrome. J. Clin. Microbiol. 28 (6): 1403–10.
- ↑ Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES (2000). The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. Pharmacol. Rev. 52 (4): 595–638.
- ↑ Ramsay MA (1986), "Postviral Fatigue Syndrome. The saga of Royal Free disease", Londen, ISBN 0-906923-96-4
- ↑ Chia JK, Chia AY (2007). Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. J Clin Pathol Online preprint.
- ↑ Jones J, Ray C, Minnich L, Hicks M, Kibler R, Lucas D (1985). Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies.. Ann Intern Med 102 (1): 1-7. PMID 2578266.
- ↑ Straus S, Tosato G, Armstrong G, Lawley T, Preble O, Henle W, Davey R, Pearson G, Epstein J, Brus I (1985). Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection.. Ann Intern Med 102 (1): 7-16. PMID 2578268.
- ↑ Holmes GP, Kaplan JE, Stewart JA, Hunt B, Pinsky PF, Schonberger LB (1987). A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause?. JAMA 257 (17): 2297-302.
- ↑ Kawai K, Kawai A (1992). Studies on the relationship between chronic fatigue syndrome and Epstein-Barr virus in Japan.. Intern Med 31 (3): 313-8. PMID 1319246.
- ↑ Lerner A, Beqaj S, Deeter R, Fitzgerald J (2004). IgM serum antibodies to Epstein-Barr virus are uniquely present in a subset of patients with the chronic fatigue syndrome.. In Vivo 18 (2): 101-6. PMID 15113035.
- ↑ Selden SM, Cameron AS (1996). Changing epidemiology of Ross River virus disease in South Australia. Med. J. Aust. 165 (6): 313–7.
- ↑ Hickie I, Davenport T, Wakefield D, et al (2006). Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ 333 (7568): 575.
- ↑ Li YJ, Wang DX, Zhang FM, Liu ZD, Yang AY, Ykuta K (2003). [Detection of antibody against Borna disease virus-p24 in the plasma of Chinese patients with chronic fatigue syndrome by Western-blot analysis]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 17 (4): 330–3.
- ↑ Kitani T, Kuratsune H, Fuke I, et al (1996). Possible correlation between Borna disease virus infection and Japanese patients with chronic fatigue syndrome. Microbiol. Immunol. 40 (6): 459–62.
- ↑ Kerr JR (2005). Pathogenesis of parvovirus B19 infection: host gene variability, and possible means and effects of virus persistence. J. Vet. Med. B Infect. Dis. Vet. Public Health 52 (7-8): 335–9.
- ↑ 53.0 53.1 Devanur LD, Kerr JR (2006). Chronic fatigue syndrome. J. Clin. Virol. 37 (3): 139–50.
- ↑ Beqaj SH, Lerner AM, Fitzgerald JT (2007). Immunoassay with cytomegalovirus early antigens from gene products p52 and CM2 (UL44 and UL57) detect active infection in patients with chronic fatigue syndrome. J Clin Pathol.
- ↑ Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT (2002). IgM serum antibodies to human cytomegalovirus nonstructural gene products p52 and CM2(UL44 and UL57) are uniquely present in a subset of patients with chronic fatigue syndrome. In Vivo 16 (3): 153–9.
- ↑ Lerner AM, Dworkin HJ, Sayyed T, et al (2004). Prevalence of abnormal cardiac wall motion in the cardiomyopathy associated with incomplete multiplication of Epstein-barr Virus and/or cytomegalovirus in patients with chronic fatigue syndrome. In Vivo 18 (4): 417–24.
- ↑ Chapenko S, Krumina A, Kozireva S, et al (2006). Activation of human herpesviruses 6 and 7 in patients with chronic fatigue syndrome. J. Clin. Virol. 37 Suppl 1: S47–51.
- ↑ Kondo K (2007). [Chronic fatigue syndrome and herpesvirus reactivation]. Nippon Rinsho 65 (6): 1043–8.
- ↑ De Bolle L, Naesens L, De Clercq E (2005). Update on human herpesvirus 6 biology, clinical features, and therapy. Clin. Microbiol. Rev. 18 (1): 217–45.
- ↑ (2000) Chronic Fatigue Syndrome and Herpesviruses: the Fading Evidence.. Herpes 7 (2): 46-50. PMID 11867001.
- ↑ Komaroff AL, Jacobson S, Ablashi DV, Yamanishi K (2006). Highlights from 5th International Conference on HHV-6 and -7. Herpes 13 (3): 81–2.
- ↑ Komaroff AL (2006). Is human herpesvirus-6 a trigger for chronic fatigue syndrome?. J. Clin. Virol. 37 Suppl 1: S39–46.
- ↑ Natelson BH, Ellis SP, Braonain PJ, DeLuca J, Tapp WN (1995). Frequency of deviant immunological test values in chronic fatigue syndrome patients.. Clin Diagn Lab Immunol 2 (2): 238-40. PMID 7697537.
- ↑ Sorensen B, Streib JE, Strand M, Make B, Giclas PC, Fleshner M, Jones JF (2003). Complement activation in a model of chronic fatigue syndrome.. J Allergy Clin Immunol 112 (2): 397-403. PMID 12897748.
- ↑ Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group (2006). Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study.. BMJ 333 (7568): 575. PMID 16950834.
- ↑ Cameron B, Bharadwaj M, Burrows J, Fazou C, Wakefield D, Hickie I, Ffrench R, Khanna R, Lloyd A (2006). Prolonged illness after infectious mononucleosis is associated with altered immunity but not with increased viral load.. J Infect Dis 193 (5): 664-71. PMID 16453261.
- ↑ Chaudhuri A, Behan PO (2004). Fatigue in neurological disorders. Lancet 363 (9413): 978-88.
- ↑ Schwartz RB, Garada BM, Komaroff AL, et al (1994). Detection of intracranial abnormalities in patients with chronic fatigue syndrome: comparison of MR imaging and SPECT. AJR. American journal of roentgenology 162 (4): 935–41.
- ↑ Abu-Judeh HH, Levine S, Kumar M, et al (1998). Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Nuclear medicine communications 19 (11): 1065–71.
- ↑ Schwartz RB, Komaroff AL, Garada BM, et al (1994). SPECT imaging of the brain: comparison of findings in patients with chronic fatigue syndrome, AIDS dementia complex, and major unipolar depression. AJR. American journal of roentgenology 162 (4): 943–51.
- ↑ MacHale SM, Lawŕie SM, Cavanagh JT, et al (2000). Cerebral perfusion in chronic fatigue syndrome and depression. The British Journal of Psychiatry : the journal of mental science 176: 550–6.
- ↑ Fischler B, D'Haenen H, Cluydts R, et al (1996). Comparison of 99m Tc HMPAO SPECT scan between chronic fatigue syndrome, major depression and healthy controls: an exploratory study of clinical correlates of regional cerebral blood flow. Neuropsychobiology 34 (4): 175–83.
- ↑ Demitrack MA, Gold PW, Dale JK, Krahn DD, Kling MA, Straus SE (1992). Plasma and cerebrospinal fluid monoamine metabolism in patients with chronic fatigue syndrome: preliminary findings. Biol. Psychiatry 32 (12): 1065–77.
- ↑ Badawy AA, Morgan CJ, Llewelyn MB, Albuquerque SR, Farmer A (2005). Heterogeneity of serum tryptophan concentration and availability to the brain in patients with the chronic fatigue syndrome. J. Psychopharmacol. (Oxford) 19 (4): 385–91.
- ↑ Cleare AJ, Bearn J, Allain T, et al (1995). Contrasting neuroendocrine responses in depression and chronic fatigue syndrome. Journal of affective disorders 34 (4): 283–9.
- ↑ Cleare AJ, Messa C, Rabiner EA, Grasby PM (2005). Brain 5-HT1A receptor binding in chronic fatigue syndrome measured using positron emission tomography and [11C]WAY-100635. Biol. Psychiatry 57 (3): 239–46.
- ↑ Klein R, Berg PA (1995). High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders. Eur. J. Med. Res. 1 (1): 21–6.
- ↑ Goertzel BN, Pennachin C, de Souza Coelho L, Gurbaxani B, Maloney EM, Jones JF (2006). Combinations of single nucleotide polymorphisms in neuroendocrine effector and receptor genes predict chronic fatigue syndrome. Pharmacogenomics 7 (3): 475–83.
- ↑ Dinan TG, Majeed T, Lavelle E, Scott LV, Berti C, Behan P (1997). Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome. Psychoneuroendocrinology 22 (4): 261–7.
- ↑ 80.0 80.1 Kuratsune H, Yamaguti K, Lindh G, et al (2002). Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain. Neuroimage 17 (3): 1256–65.
- ↑ Spence VA, Khan F, Kennedy G, Abbot NC, Belch JJ (2004). Acetylcholine mediated vasodilatation in the microcirculation of patients with chronic fatigue syndrome. Prostaglandins Leukot. Essent. Fatty Acids 70 (4): 403–7.
- ↑ Tanaka S, Kuratsune H, Hidaka Y, et al (2003). Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome. Int. J. Mol. Med. 12 (2): 225–30.
- ↑ Conti F, Pittoni V, Sacerdote P, Priori R, Meroni PL, Valesini G (1998). Decreased immunoreactive beta-endorphin in mononuclear leucocytes from patients with chronic fatigue syndrome. Clin. Exp. Rheumatol. 16 (6): 729–32.
- ↑ Panerai AE, Vecchiet J, Panzeri P, et al (2002). Peripheral blood mononuclear cell beta-endorphin concentration is decreased in chronic fatigue syndrome and fibromyalgia but not in depression: preliminary report. The Clinical journal of pain 18 (4): 270–3.
- ↑ Goldstein DS, Robertson D, Esler M, Straus SE, Eisenhofer G (2002). Dysautonomias: clinical disorders of the autonomic nervous system. Ann. Intern. Med. 137 (9): 753–63.
- ↑ Galland BC, Jackson PM, Sayers RM, Taylor BJ (2008). A matched case control study of orthostatic intolerance in children/adolescents with chronic fatigue syndrome. Pediatr. Res. 63 (2): 196–202.
- ↑ Natelson BH, Intriligator R, Cherniack NS, Chandler HK, Stewart JM (2007). Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome. Dyn Med 6: 2.
- ↑ Newton JL, Okonkwo O, Sutcliffe K, Seth A, Shin J, Jones DE (2007). Symptoms of autonomic dysfunction in chronic fatigue syndrome. QJM 100 (8): 519-26.
- ↑ Tanaka H (2007). [Autonomic function and child chronic fatigue syndrome]. Nippon Rinsho 65 (6): 1105–12.
- ↑ Stewart JM, Gewitz MH, Weldon A, Arlievsky N, Li K, Munoz J (1999). Orthostatic intolerance in adolescent chronic fatigue syndrome. Pediatrics 103 (1): 116–21.
- ↑ Godefroy WP, Hastan D, van der Mey AG (2007). Translabyrinthine surgery for disabling vertigo in vestibular schwannoma patients. Clin Otolaryngol 32 (3): 167–72.
- ↑ Heller U, Becker EW, Zenner HP, Berg PA (1998). [Incidence and clinical relevance of antibodies to phospholipids, serotonin and ganglioside in patients with sudden deafness and progressive inner ear hearing loss]. HNO 46 (6): 583-6.
- ↑ Tolan R, Stewart J. "Chronic Fatigue Syndrome", eMedicine, August 17 2006, retrieved November 9 2006.
- ↑ Rowe, PC. "General Information Brochure on Orthostatic Intolerance and its Treatment", Chronic Fatigue Clinic, Johns Hopkins Children's Center, February 2003, retrieved November 9 2006.
- ↑ Rowe P, Calkins H, DeBusk K, McKenzie R, Anand R, Sharma G, Cuccherini B, Soto N, Hohman P, Snader S, Lucas K, Wolff M, Straus S (2001). Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial. JAMA 285 (1): 52-9.
- ↑ 96.0 96.1 Stein E (2001), "How to differentiate CFS from Psychiatric Disorder", Presented at The Alison Hunter Memorial Foundation Third International Clinical and Scientific Conference, Sydney, Australia
- ↑ Salit IE (1997). Precipitating factors for the chronic fatigue syndrome.. J Psychiatr Res 31 (1): 59-65. PMID 9201648.
- ↑ Theorell T, Blomkvist V, Lindh G, Evengard B. Critical life events, infections, and symptoms during the year preceding chronic fatigue syndrome (CFS): an examination of CFS patients and subjects with a nonspecific life crisis.. Psychosom Med. 61 (3): 304-10. PMID 10367610.
- ↑ Heim C, Wagner D, Maloney E, Papanicolaou DA, Solomon L, Jones JF, Unger ER, Reeves WC (2006). Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study.. Arch Gen Psychiatry 63 (11): 1258-66. PMID 17088506.
- ↑ Kato K, Sullivan PF, Evengard B, Pedersen NL (2006). Premorbid predictors of chronic fatigue.. Arch Gen Psychiatry 63 (11): 1267-72. PMID 17088507.
- ↑ T Chalder, R Goodman, S Wessely, M Hotopf, H Meltzer (2003). Epidemiology of chronic fatigue syndrome and self reported myalgic encephalomyelitis in 5-15 year olds: cross sectional study.. BMJ 327: 654-655. DOI 10.1136/bmj.327.7416.654.
- ↑ 102.0 102.1 102.2 Reeves W, Vernon S Press Briefing on Chronic Fatigue Syndrome. (HTM) Centers for Disease Control and Prevention. URL accessed on 2008-01-27.
- ↑ Roberts AD, Wessely S, Chalder T, Papadopoulos A, Cleare AJ (2004). Salivary cortisol response to awakening in chronic fatigue syndrome.. Br J Psychiatry 184: 136-41. PMID 14754825.
- ↑ Gaab J, Huster D, Peisen R, Engert V, Heitz V, Schad T, Schurmeyer TH, Ehlert U (2002). Hypothalamic-pituitary-adrenal axis reactivity in chronic fatigue syndrome and health under psychological, physiological, and pharmacological stimulation.. Psychosom Med 64 (6): 951-62. PMID 12461200.
- ↑ Gaab J, Engert V, Heitz V, Schad T, Schurmeyer TH, Ehlert U (2004). Associations between neuroendocrine responses to the Insulin Tolerance Test and patient characteristics in chronic fatigue syndrome.. J Psychosom Res 56 (4): 419-24. PMID 15094026.
- ↑ Margutti P, Delunardo F, Ortona E (2006). Autoantibodies associated with psychiatric disorders.. Curr Neurovasc Res 3 (2): 149-57. PMID 16719797.
- ↑ Vollmer-Conna U, Lloyd A, Hickie I, Wakefield D (1998). Chronic fatigue syndrome: an immunological perspective.. Aust N Z J Psychiatry 32 (4): 523-7. PMID 9711366.
- ↑ Tanaka S, Kuratsune H, Hidaka Y, Hakariya Y, Tatsumi KI, Takano T, Kanakura Y, Amino N (2003). Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome.. Int J Mol Med 12 (2): 225-30. PMID 12851722.
- ↑ Nijs J, Van de Velde B, De Meirleir K (2005). Pain in patients with chronic fatigue syndrome: does nitric oxide trigger central sensitisation?. Med Hypotheses 64 (3): 558-62. PMID 15617866.
- ↑ Cho HJ, Skowera A, Cleare A, Wessely S (2006). Chronic fatigue syndrome: an update focusing on phenomenology and pathophysiology. Curr Opin Psychiatry 19 (1): 67-73.
- ↑ 111.0 111.1 Smith AK, Dimulescu I, Falkenberg VR, et al (2008). Genetic evaluation of the serotonergic system in chronic fatigue syndrome. Psychoneuroendocrinology 33 (2): 188-97.
- ↑ Demitrack MA, Dale JK, Straus SE, et al (1991). Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J. Clin. Endocrinol. Metab. 73 (6): 1224–34.
- ↑ Cleare AJ (2003). The neuroendocrinology of chronic fatigue syndrome. Endocr. Rev. 24 (2): 236–52.
- ↑ 114.0 114.1 Van Den Eede F, Moorkens G, Van Houdenhove B, Cosyns P, Claes SJ (2007). Hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome. Neuropsychobiology 55 (2): 112–20.
- ↑  The Centers For Disease Control and Prevention (website): CFS Home > Publications > Molecular Epidemiology Program - Date: July 25 2005 - Content source: National Center for Infectious Diseases
- ↑ Whistler T, Jones JF, Unger ER, Vernon SD (2005). Exercise responsive genes measured in peripheral blood of women with chronic fatigue syndrome and matched control subjects.. BMC Physiol 5 (1): 5. PMID 15790422.
- ↑ Whistler T, Unger ER, Nisenbaum R, Vernon SD (2003). Integration of gene expression, clinical, and epidemiologic data to characterize Chronic Fatigue Syndrome.. J Transl Med 1 (1): 10. PMID 14641939.
- ↑ Vernon SD, Unger ER, Dimulescu IM, Rajeevan M, Reeves WC (2002). Utility of the blood for gene expression profiling and biomarker discovery in chronic fatigue syndrome.. Dis Markers 18 (4): 193-9. PMID 12590173.
- ↑ Kaushik N, Fear D, Richards SC, McDermott CR, Nuwaysir EF, Kellam P, Harrison TJ, Wilkinson RJ, Tyrrell DA, Holgate ST, Kerr JR (2005). Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome.. J Clin Pathol 58 (8): 826-32. PMID 16049284.
- ↑ Fang H, Xie Q, Boneva R, Fostel J, Perkins R, Tong W (2006). Gene expression profile exploration of a large dataset on chronic fatigue syndrome.. Pharmacogenomics 7 (3): 429-40. PMID 16610953.
- ↑ BBC News (28 May 2005) - Scientists 'unlock ME genetics' (study still in its early stages)
- ↑ Fostel J, Boneva R, Lloyd A (2006). Exploration of the gene expression correlates of chronic unexplained fatigue using factor analysis.. Pharmacogenomics 7 (3): 441-54. PMID 16610954.
- ↑ Kerr J, Burke B, Petty R, et al (2007). Seven genomic subtypes of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME): a detailed analysis of gene networks and clinical phenotypes. J Clin Pathol.
- ↑ Narita M, Nishigami N, Narita N, Yamaguti K, Okado N, Watanabe Y, Kuratsune H (2003). Association between serotonin transporter gene polymorphism and chronic fatigue syndrome. Biochem. Biophys. Res. Commun. 311 (2): 264-6.
- ↑ Goertzel BN, Pennachin C, de Souza Coelho L, Gurbaxani B, Maloney EM, Jones JF (2006). Combinations of single nucleotide polymorphisms in neuroendocrine effector and receptor genes predict chronic fatigue syndrome. Pharmacogenomics 7 (3): 475-83.
- ↑ Smith AK, White PD, Aslakson E, Vollmer-Conna U, Rajeevan MS (2006). Polymorphisms in genes regulating the HPA axis associated with empirically delineated classes of unexplained chronic fatigue. Pharmacogenomics 7 (3): 387-94.
- ↑ Torpy DJ, Bachmann AW, Gartside M, Grice JE, Harris JM, Clifton P, Easteal S, Jackson RV, Whitworth JA (2004). Association between chronic fatigue syndrome and the corticosteroid-binding globulin gene ALA SER224 polymorphism. Endocr. Res. 30 (3): 417-29.
- ↑ Kerr JR (2005). Pathogenesis of parvovirus B19 infection: host gene variability, and possible means and effects of virus persistence. J. Vet. Med. B Infect. Dis. Vet. Public Health 52 (7-8): 335-9.
- ↑ Carlo-Stella N, Badulli C, De Silvestri A, Bazzichi L, Martinetti M, Lorusso L, Bombardieri S, Salvaneschi L, Cuccia M (2006). A first study of cytokine genomic polymorphisms in CFS: Positive association of TNF-857 and IFNgamma 874 rare alleles. Clin. Exp. Rheumatol. 24 (2): 179-82.
- ↑ Vladutiu GD, Natelson BH (2004). Association of medically unexplained fatigue with ACE insertion/deletion polymorphism in Gulf War veterans. Muscle Nerve 30 (1): 38-43.
- ↑ Wyller VB (2007). The chronic fatigue syndrome - an update. Acta Neurol Scand Suppl 187: 7-14. PMID 17419822.
- ↑ Kennedy G, Spence VA, McLaren M, Hill A, Underwood C, Belch JJ (2005). Oxidative stress levels are raised in CFS and are associated with clinical symptoms.. Free Radic Biol Med 39 (5): 584-9. PMID 16085177.
- ↑ Jammes Y, Steinberg JG, Mambrini O, Bregeon F, Delliaux S (2005). Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise.. J Intern Med 257 (3): 299-310. PMID 15715687.
- ↑ Richards RS, Wang L, Jelinek H (2007). Erythrocyte oxidative damage in chronic fatigue syndrome.. Arch Med Res 38 (1): 94-8. PMID 17174731.
- ↑ Vecchiet J, Cipollone F, Falasca K, Mezzetti A, Pizzigallo E, Bucciarelli T, De Laurentis S, Affaitati G, De Cesare D, Giamberardino MA (2003). Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome.. Neurosci Lett 335 (3): 151-4. PMID 12531455.
- ↑ Fulle S, Mecocci P, Fano G, Vecchiet I, Vecchini A, Racciotti D, Cherubini A, Pizzigallo E, Vecchiet L, Senin U, Beal MF (2000). Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome.. Free Radic Biol Med 29 (12): 1252-9. PMID 11118815.
- ↑ Richards RS, Roberts TK, McGregor NR, Dunstan RH, Butt HL (2000). Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome.. Redox Rep 5 (1): 35-41. PMID 10905542.
- ↑ Nijs J, Meeus M, De Meirleir K (2006). Chronic musculoskeletal pain in chronic fatigue syndrome: recent developments and therapeutic implications.. Man Ther 11 (3): 187-91. PMID 16781183.
- ↑ Maes M, Mihaylova I, Bosmans E (2007). Not in the mind of neurasthenic lazybones but in the cell nucleus: patients with chronic fatigue syndrome have increased production of nuclear factor kappa beta. Neuro Endocrinol. Lett. 28 (4): 456–62.
- ↑ Maes M, Mihaylova I, Leunis JC (2006). Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins. Neuro Endocrinol. Lett. 27 (5): 615–21.
- ↑ Broderick G, Craddock RC, Whistler T, Taylor R, Klimas N, Unger ER (2006). Identifying illness parameters in fatiguing syndromes using classical projection methods. Pharmacogenomics 7 (3): 407–19.
- ↑ van de Glind G, de Vries M, Rodenburg R, Hol F, Smeitink J, Morava E (2007). Resting muscle pain as the first clinical symptom in children carrying the MTTK A8344G mutation. Eur. J. Paediatr. Neurol. 11 (4): 243–6.
- ↑ Behan WM, More IA, Behan PO (1991). Mitochondrial abnormalities in the postviral fatigue syndrome. Acta Neuropathol. 83 (1): 61–5.
- ↑ 144.0 144.1 Vernon SD, Whistler T, Cameron B, Hickie IB, Reeves WC, Lloyd A (2006). Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr virus. BMC Infect. Dis. 6: 15.
- ↑ Klimas NG, Koneru AO (2007). Chronic fatigue syndrome: inflammation, immune function, and neuroendocrine interactions. Curr Rheumatol Rep 9 (6): 482–7.
- ↑ 146.0 146.1 Kaushik N, Fear D, Richards SC, et al (2005). Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome. J. Clin. Pathol. 58 (8): 826–32.
- ↑ Pieczenik SR, Neustadt J (2007). Mitochondrial dysfunction and molecular pathways of disease. Exp. Mol. Pathol. 83 (1): 84–92.
- ↑ Lundell K, Qazi S, Eddy L, Uckun FM. Clinical activity of folinic acid in patients with chronic fatigue syndrome. Arzneimittelforschung. 2006;56(6):399-404.
- ↑ Jacobson W, Saich T, Borysiewicz LK, Behan WM, Behan PO, Wreghitt TG. Serum folate and chronic fatigue syndrome. Neurology 1993 Dec;43(12):2645-7.
- ↑ Horrobin, David F. (1990). Omega-6 essential fatty acids: pathophysiology and roles in clinical medicine, 275-282, New York: Wiley-Liss.
- ↑ Behan PO, Behan WM, Horrobin D (1990). Effect of high doses of essential fatty acids on the postviral fatigue syndrome. Acta Neurol. Scand. 82 (3): 209-16.
- ↑ Ogawa R, Toyama S, Matsumoto H. (1992). Chronic fatigue syndrome--cases in the Kanebo Memorial Hospital. Nippon Rinsho. 50 (11): 2648-52.
- ↑ 153.0 153.1 Liu Z, Wang D, Xue Q, et al (2003). Determination of fatty acid levels in erythrocyte membranes of patients with chronic fatigue syndrome. Nutritional neuroscience 6 (6): 389-92.
- ↑ 154.0 154.1 Maes M, Mihaylova I, Leunis JC (2005). In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation. Neuro Endocrinol. Lett. 26 (6): 745–51.
- ↑ Warren G, McKendrick M, Peet M (1999). The role of essential fatty acids in chronic fatigue syndrome. A case-controlled study of red-cell membrane essential fatty acids (EFA) and a placebo-controlled treatment study with high dose of EFA. Acta Neurol. Scand. 99 (2): 112-6.
- ↑ 156.0 156.1 Puri BK (2007). Long-chain polyunsaturated fatty acids and the pathophysiology of myalgic encephalomyelitis (chronic fatigue syndrome). J. Clin. Pathol. 60 (2): 122–4.
- ↑ 157.0 157.1 Puri BK (2004). The use of eicosapentaenoic acid in the treatment of chronic fatigue syndrome. Prostaglandins Leukot. Essent. Fatty Acids 70 (4): 399–401.
- ↑ Carruthers, BM, Jain AK et. al. (2003). Myalgic Encephomyelitis / Chronic fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols (a Consensus Document). Journal of Chronic Fatigue Syndrome 11 (1): 66.
- ↑ McGregor N.R. Dunstan H.R. et al. 1998 “Alterations in Plasma Lipid Composition in Patients with CFS” presented at Conference; The Clinical and Scientific Basis of CFS, Sydney 1998, P38
- ↑ McGregor N.R. Dunstan H.R. et al. 1998 “Assessment of Lipid Homeostasis in Sudden and Gradual Onset CFS Patients” presented at Conference; The Clinical and Scientific Basis of CFS, Sydney 1998, P39
- ↑ Mihaylova I, DeRuyter M, Rummens JL, Bosmans E, Maes M (2007). Decreased expression of CD69 in chronic fatigue syndrome in relation to inflammatory markers: evidence for a severe disorder in the early activation of T lymphocytes and natural killer cells. Neuro Endocrinol. Lett. 28 (4): 477–83.
- ↑ Fulle S, Mecocci P, Fanó G, et al (2000). Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome. Free Radic. Biol. Med. 29 (12): 1252–9.
- ↑ Kennedy G, Spence VA, McLaren M, Hill A, Underwood C, Belch JJ (2005). Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms. Free Radic. Biol. Med. 39 (5): 584–9.
- ↑ Richards RS, Roberts TK, McGregor NR, Dunstan RH, Butt HL (2000). Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Rep. 5 (1): 35–41.
- ↑ Jenkins, Rachel; Mowbray, James F. (1991). Post-viral fatigue syndrome (Myalgic encephalomyelitis), New York: Wiley.
- ↑ 166.0 166.1 Kuratsune H, Yamaguti K, Takahashi M, Misaki H, Tagawa S, Kitani T (1994). Acylcarnitine deficiency in chronic fatigue syndrome. Clin. Infect. Dis. 18 Suppl 1: S62–7.
- ↑ Plioplys AV, Plioplys S (1995). Serum levels of carnitine in chronic fatigue syndrome: clinical correlates. Neuropsychobiology 32 (3): 132–8.
- ↑ Kuratsune H, Yamaguti K, Lindh G, et al (1998). Low levels of serum acylcarnitine in chronic fatigue syndrome and chronic hepatitis type C, but not seen in other diseases. Int. J. Mol. Med. 2 (1): 51–6.
- ↑ Kuratsune H, Yamaguti K, Hattori H, et al (1992). [Symptoms, signs and laboratory findings in patients with chronic fatigue syndrome]. Nippon Rinsho 50 (11): 2665–72.
- ↑ Miwa S, Takikawa O (2007). [Chronic fatigue syndrome and neurotransmitters]. Nippon Rinsho 65 (6): 1005–10.
- ↑ Jones MG, Goodwin CS, Amjad S, Chalmers RA (2005). Plasma and urinary carnitine and acylcarnitines in chronic fatigue syndrome. Clin. Chim. Acta 360 (1-2): 173–7.
- ↑ Li YJ, Wang DX, Bai XL, et al (2005). [Clinical characteristics of patients with chronic fatigue syndrome: analysis of 82 cases]. Zhonghua Yi Xue Za Zhi 85 (10): 701–4.
- ↑ McGregor N.R. Dunstan H.R. et al. 1998 “Classification of CFS Patients by Assessing Plasma lipid Homeostasis” presented at Conference; The Clinical and Scientific Basis of CFS, Sydney 1998, P40
- ↑ Famularo G, De Simone C, Trinchieri V, Mosca L (2004). Carnitines and its congeners: a metabolic pathway to the regulation of immune response and inflammation. Ann. N. Y. Acad. Sci. 1033: 132–8.
- ↑ Saheki T (1999). [Carnitine as a vitamin-like biofactor]. Nippon Rinsho 57 (10): 2270–5.
- ↑ Vermeulen RC, Scholte HR (2006). Azithromycin in chronic fatigue syndrome (CFS), an analysis of clinical data. J Transl Med 4 issue=: 34.
- ↑ Fernández-Solà J, Lluís Padierna M, Nogué Xarau S, Munné Mas P (2005). [Chronic fatigue syndrome and multiple chemical hypersensitivity after insecticide exposure]. Med Clin (Barc) 124 (12): 451–3.
- ↑ Dunstan RH, Donohoe M, Taylor W, et al (1995). A preliminary investigation of chlorinated hydrocarbons and chronic fatigue syndrome. Med. J. Aust. 163 (6): 294–7.
- ↑ Kennedy G, Abbot NC, Spence V, Underwood C, Belch JJ (2004). The specificity of the CDC-1994 criteria for chronic fatigue syndrome: comparison of health status in three groups of patients who fulfill the criteria. Ann Epidemiol 14 (2): 95–100.
- ↑ Viner R, Hotopf M (2003). Childhood predictors of self reported chronic fatigue syndrome/myalgic encephalomyelitis in adults: national birth cohort study.. BMJ 329 (7472): 941. PMID 15469945.
- ↑ Lane RJ, Barrett MC, Taylor DJ, Kemp GJ, Lodi R (1998). Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle. Neuromuscul. Disord. 8 (3-4): 204–9.
- ↑ Lane RJ, Barrett MC, Woodrow D, Moss J, Fletcher R, Archard LC (1998). Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome. J. Neurol. Neurosurg. Psychiatr. 64 (3): 362–7.
- ↑ Lane RJ, Soteriou BA, Zhang H, Archard LC (2003). Enterovirus related metabolic myopathy: a postviral fatigue syndrome. J. Neurol. Neurosurg. Psychiatr. 74 (10): 1382–6.
- ↑ Lamb GD, Stephenson DG (2006). Point: lactic acid accumulation is an advantage during muscle activity. J. Appl. Physiol. 100 (4): 1410–2; discussion 1414.
- ↑ Pedersen TH, Nielsen OB, Lamb GD, Stephenson DG (2004). Intracellular acidosis enhances the excitability of working muscle.. Science 305 (5687): 1144-7. PMID 15326352.
- ↑ Lane RJ, Soteriou BA, Zhang H, Archard LC (2003). Enterovirus related metabolic myopathy: a postviral fatigue syndrome.. J Neurol Neurosurg Psychiatry 74 (10): 1382-6. PMID 14570830.
- ↑ Barron DF, Cohen BA, Geraghty MT, Violand R, Rowe PC (2002). Joint hypermobility is more common in children with chronic fatigue syndrome than in healthy controls.. J Pediatr 141 (3): 421-5. PMID 12219066.
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