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Chronic fatigue books

Environmental and other risk factors affecting Chronic fatigue, fibromyalgia or myalgic encephalomyelitis

Chronic fatigue associations and societies worldwide ME/CFS Worldwide Patient Alliance

Ongoing clinical trails, worldwide, can be interrogated at ClinicalTrials.Gov a service of the US National Institutes of Health

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Genes ACE ADRB2 AGER APOE BDNF COMT CRHR1 DISC1 DRD3 GRIK2 . HLA-DRB1 HLA-DQA1 HTR2A IFNG IL4 IL17 IL17F HDAC7A. HOXA1 . HTR2A KIR3DL1 KIR3DS1 KIRREL MAOA MAOB NPAS2 .NR3C1 NUP98 .OPRM1

PKN1 .POMC PRUNE .SCN9A SERPINA6 SLC6A4 SLC25A40 TH TNF TNK2 . TNFRSF1B . TPH2 WASF3

GWAS from Genome.gov AFAP1 ARHGAP20 C10ORF59 CFLP1 CLYBL DGKH (BG220650.1 blasted) DTX4 FBXO42 FLJ41278 FRA10AC1 GRIK2 GRIN2B HS6ST3 KCNJ6 KLHL32 KRTHA3A LILRB4 LOC100131813 LOC100507140 LOC642587 MAGI3 MSH3 MTAP NLRP11 NLRP13 NPAS2 OTOG PIP5K1B PPFIBP1 RASGRF2 SCN8A SIX6 SLC5A12 TCERG1 TECTB Smith et al, 2011

KEGG pathway analysis of these genes

Need KEGG mapping CNR1 GABRB3 GBP1 GRIA4 RGS4 TAAR1 MEFV SLC25A40 PKN1 PSMA3

Infectious agents

Dietary, lifestyle factors and toxins

Hormonal effects

Association with other diseases/conditions

  • Chronic Fatigue is associated with Gulf War syndrome Coughlin et al, 2011 itself tentatively associated with excessive vaccination
  • Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is characterized by myalgia, myositis, muscle weakness, arthralgia, arthritis, chronic fatigue, sleep disturbances, cognitive impairment and memory loss, and occasionally a demyelinating autoimmune disease caused by systemic exposure after vaccines and adjuvants Barros and Carvalho, 2011.
  • Fibromyalgia is common in patients with rheumatoid arthritis Kapoor et al, 2011
  • Chronic fatigue has been associated with irritable bowel syndrome Wojczynski et al, 2007
  • Postural Tachycardia Syndrome (standing up increases heart rate) is commonly associated with chronic fatigue Ocon et al, 2011
  • Interstitial cystitis / painful bladder syndrome has been associated with chronic fatigue Nickel et al, 2010
  • Fatigue is associated with Primary biliary cirrhosis, a chronic, autoimmune, cholestatic liver disease Abbass et al, 2010
  • Fatigue is associated with interstitial pneumonia which was treated with megadose vitamin C with dehydroepiandrosterone/cortisol supplementation Kodama and Kodama 2005.
  • Chronic fatigue has been associated with low blood pressure, more extensible skin and stiffer arteries Van de Putte et al, 2005
  • Chronic fatigue has been associated with the metabolic syndrome Maloney et al, 2010
  • Chronic fatigue associated with Systemic lupus erythematosus Urbanska-Krawiec and Hrycek, 2011
  • Chronic fatigue has been observed as a consequence of breast cancer treatment Reinertsen et al, 2011
  • Fibromyalgia has been associated with ankylosing spondylitis Almodovar et al, 2010
  • Fatigue precedes the onset of multiple sclerosis by several years Medscape (requires registration)
  • Major depression has been associated with chronic fatigue in women Ciccone and Natelson, 2003
  • Interferon-alpha treatment of viral infections has been associated with chronic fatigue and depression Felger et al, 2011
  • ß-thalassemia has been associated with fibromyalgia Altinoz et al, 2011
  • Chronic fatigue has been associated with Ehlers-Danlos syndrome a group of inherited disorders caused by problems with collagen synthesis Castori et al, 2011
  • Chronic fatigue can be a consequence of traumatic brain injury Reeves and Panguluri, 2011
  • Chronic fatigue has been associated with prior premorbid psychopathology Goodwin et al, 2011
  • attention-deficit hyperactivity disorder may be common in chronic fatigue patients Sáez-Francàs et al, 2012
  • The prevalence of chronic fatigue is higher in women Evangard et al, 2005
  • Women with chronic fatigue reported higher levels of pelvic pain unrelated to menstruation, endometriosis and periods of amenorrhea The number of pregnancies and gynecological surgeries was also higher Boneva et al, 2010
  • Smoking , allergies, and a history of extreme morning sickness may be related to the development of fibromyalgia in women Choi et al, 2010.
  • Obesity and low levels of exercise have been associated with fibromyalgia in women Mork et al, 2010
  • Older age, retirees, housewife status , existing long-term health problems, higher Hospital Anxiety and Depression Scale scores, poor quotient of living , and low self-perceived health associated with increased risk of chronic fatigue: Regular exercise was associated with decreased risk of chronic fatigue Wong and Fielding 2010
  • Parental physical abuse has been associated with chronic fatigue Clark et al, 2011
  • "Chronic fatigue symptoms overlap with systemic hyperalgesia (fibromyalgia), autonomic dysfunction (irritable bowel syndrome and migraine headaches), sensory hypersensitivity (dyspnea; congestion; rhinorrhea; and appreciation of visceral nociception in the esophagus, gastrointestinal tract, bladder, and other organs), and central nervous system maladaptations (central sensitization) recorded by functional magnetic resonance imaging (fMRI). Neurological dysfunction may account for the overlap with idiopathic nonallergic rhinopathy" Baraniuk and Zheng, 2010.
  • Chronic fatigue has been associated with an increased risk of non-Hodgkin lymphoma and certain other cancers Chang et al, 2012
  • Chronic fatigue syndrome is relatively common in patients with Ehlers-Danlos syndrome (Connective tissue disorder) Castori et al, 2011
  • Fatigue is commonly reported in patients with immune-mediated neuropathies, (Guillain-Barré syndrome, chronic immune-mediated demyelinating polyradiculoneuropathy, monoclonal gammopathy of undetermined significance related polyneuropathy, and multifocal motor neuropathy Merkies and Faber, 2012.
  • There appears to be a link between a number of functional somatic syndromes including interstitial cystitis/painful bladder syndrome, fibromyalgia , chronic fatigue syndrome , irritable bowel syndrome, chronic pelvic pain, migraine, sicca / Sjogren syndrome and panic disorder, whereby antecedence of one syndrome predisposes to the subsequent development of another, suggesting a potential common underlying cause Warren et al, 2013
    .

Vitamins

Antiviral agents

Protective Drugs, Diets Vitamins and Vaccines (Clinical Trials)

Biochemical effects

  • Low levels of serum acylcarnitine have been reported Kuratsune et al, 1998
  • Chronic fatigue is associated with mitochondrial malfunction Myhill et al, 2009.
  • Reduced levels of ferritin have been reported in fibromyalgia Ortancil et al, 2010
  • Nitric oxide metabolites (nitrates) increase at higher levels than controls after physical exertion in CFS patients Suarez et al, 2010
  • Increased lipid peroxidation (free radical damage) positively correlated with triglyceride levels and lower HDL levels has been observed in female patients Brkic et al, 2010
  • CFS patients have a lower neutrophil respiratory burst and natural killer cell cytotoxic activity Brenu et al, 2010
  • A reduction in natural killer cell associated perforin levels has been noted Maher et al, 2005
  • Genes related to immune modulation, oxidative stress and apoptosis are dysregulated in blood monocytes Gow et al, 2009
  • Serum Immunoglobulin M levels directed against oleic, palmitic and myristic acid, malondialdehyde , azelaic acid, S-farnesyl-L-cysteine, and the N-oxide derivates, nitro-tyrosine, nitro-phenylalanine, nitro-arginine, nitro-tryptophan, and nitro-cysteinyl were significantly greater in CFS patients than in normal controls Maes et al, 2006
  • Decreased serum levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation Maes et al, 2005.
  • Reduced mRNA levels of oestrogen receptor beta in blood mononuclear cells Grans et al, 2007
  • Elevated plasma concentrations of neuropeptide Y ( NPY ) have been reported Fletcher et al, 2010
  • Increased oxidative stress as indexed by plasma peroxides and increased serum oxidised LDL Maes et al, 2011.
    • and of thiobarbituric acid reactive substances in certain subgroups Jammes et al, 2012
    • decreased levels CoenzymeQ(10), catalase and ATP and increased lipid peroxide levels in blood mononuclear cells from fibromyalgia patients Cordero et al, 2012
  • CSF proteomic analysis : alpha-1-Antichymotrypsin alpha-2-Macroglobulin APLP1 Autotaxin , BEHAB CDNP1 Ceruloplasmin Chromogranin B Complement components C3 C4A C4B Gelsolin Haptoglobin IgG Hemopexin Keratin 6C Keratin 14 Keratin 16 Keratin 17 Orosomucoid 1 Orosomucoid 2 Secreted phosphoprotein 1 Baraniuk et al, 2005
  • Salivary proteome: calgranulin A, calgranulin C, cyclophilin A, profilin 1, Rho GDP-dissociation inhibitor 2, proteasome subunit-a-type-2 and haptoglobin-related protein precursor: transaldolase and phosphoglycerate mutase I Bazzichi et al, 2009
  • Low blood levels of cortisol have been reported, suggesting dysfunction of the hypothalamic-pituitary-adrenal axis Tak et al, 2011
  • Upregulation of TGF beta expression in peripheral blood mononuclear cells in chronic fatigue patients Zhang et al, 2011.
  • Protein and lipid oxidation levels reportedly higher in female chronic fatigue patients Tomic et al, 2012
  • Chronic fatigue reported to correlate with serum leptin levels Stringer et al, 2013

Autoantibodies and immune

  • Anti nuclear antibodies Nishikai, 2007
  • Cardiolipin autoantibodies Hokama et al, 2009
  • Lens epithelium-derived growth factor/transcription co-activator P75 (LEDGF/P75) Kuwabara et al, 2009
  • microtubule-associated protein 2 (MAP2) and single stranded DNA Vernon and Reeves, 2005
  • Muscarinic cholinergic receptor autoantibodies Tanaka et al, 2003
  • Serotonin and phospholipid autoantibodies Klein and Berg, 2002
  • IgM antibodies to palmitic and myristic acid and S-farnesyl-L-cysteine Maes et al, 2012
  • An excess of ligand-free killer lectin KIR3DL1 and KIR3DS1 receptors may hamper the clearance of a pathogens via Natural Killer cells Pasi et al, 2011
  • Evidence for immune activation including increases in IL-10, IFN-gamma, TNF-alpha, CD4+CD25+ T cells Brenu et al, 2011
  • Decreased CD56 natural killer cell activity and increased IL2 receptor levels have been noted Nas et al, 2011
  • A gene expression study in plasma identified a signature of 10 cytokines and chemokines which correctly identifies XMRV infected chronic fatigue patients with 93% specificity and 96% sensitivity Lombardi et al, 2011.
  • Higher interferon gamma (IFNG), and higher IFNG/interleukin (IL)4 ratio, lower tumor necrosis factor-a and lower IL-10 at baseline were related to fatigue severity Ter Wolbeek et al, 2011
  • CFS/ME patients displayed significant increases in IL10, interferon -gamma, TNF-alpha, CD4+CD25+ T cells, and FoxP3 and VPACR2 expression: The cytotoxic activities of natural killer cells were significantly decreased in CFS/ME patients. Additionally granzyme A and granzyme K expression were reduced and expression levels of perforin were significantly increased in CFS/ME Brenu et al, 2011
  • Fibromyalgia is relatively common in primary antiphospholipid syndrome Costa et al, 2011
  • Depression and fatigue during chronic Interferon alpha treatment were associated with alterations in the expression (OAS2) and transcriptional control (CREB/ATF) of genes linked to behavioral disorders including chronic fatigue syndrome and major depression, supporting an immune contribution to these diseases Felger et al, 2011.
  • Co-expression patterns in cytokines (IL6, IL8, IL23, IL2, IL1A and IFNG) associated with Th17 function may act as markers in post-infectious chronic fatigue syndrome Broderick et al, 2012.
  • Proinflammatory cytokine and neopterin levels higher in CFS patients Maes et al, 2012
  • IgM antibodies to palmitic and myristic acid and S-farnesyl-L-cysteine and NO-phenylalanine in CFS sera Maes et al, 2012
  • Reduced expression of microRNA's miR-21, in natural killer and CD8(+)T cells in CFS/ME sufferers and reduced expression of miR-17-5p, miR-10a, miR-103, miR-152, miR-146a, miR-106, miR-223 and miR-191 in natural killer cells Brenu et al, 2012.
  • Atopic diseases can increase the risk of developing chronic fatigue Hunskar et al, 2012
  • Cryoglobulinemia ( immunoglobulins that precipitate in blood ) can cause fatigue Takada et al, 2012

Brain scans and physiology

  • White matter volume was observed to decrease with increasing fatigue duration Barnden et al, 2011
  • Higher Insular cortex reactivity has been associated with pain processing in fibromyalgia Kim et al, 2011
  • Elevated glutamate/creatine levels have been observed in the ventrolateral preforntal cortex Feraco et al, 2011
  • Hyperalgesia (increased sensitivity to pain) is seen for a variety of sensory stimuli, including electrical stimulation, mechanical pressure, heat and histamine. Various tissues are affected by generalised hyperalgesia: the skin, muscle tissue and the lungs. Generalised hyperalgesia is increased by sveral stressors like exercise and noxious heat pain. Nijs et al, 2011
  • Impaired cardiac function is observed in CFS patients: (reduced cardiac mass and blood pool volumes, low end diastolic volume leading to impairments in stroke volume and cardiac output (the heart pumps less blood) Hollingsworth et al, 2011

The PACE trial involving adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and standardised specialist medical care.

Vaccine Adverse Event Reporting System (VAERS database )

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