Skip to main content

Advertisement

SpringerLink
Log in

Environmental, Neuro-immune, and Neuro-oxidative Stress Interactions in Chronic Fatigue Syndrome

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS) is a complex, multisystem disease that is characterized by long-term fatigue, exhaustion, disabilities, pain, neurocognitive impairments, gastrointestinal symptoms, and post-exertional malaise, as well as lowered occupational, educational, and social functions. The clinical and biomarker diagnosis of this disorder is hampered by the lack of validated diagnostic criteria and laboratory tests with adequate figures of merit, although there are now many disease biomarkers indicating the pathophysiology of CFS. Here, we review multiple factors, such as immunological and environmental factors, which are associated with CFS and evaluate current concepts on the involvement of immune and environmental factors in the pathophysiology of CFS. The most frequently reported immune dysregulations in CFS are modifications in immunoglobulin contents, changes in B and T cell phenotypes and cytokine profiles, and decreased cytotoxicity of natural killer cells. Some of these immune aberrations display a moderate diagnostic performance to externally validate the clinical diagnosis of CFS, including the expression of activation markers and protein kinase R (PKR) activity. Associated with the immune aberrations are activated nitro-oxidative pathways, which may explain the key symptoms of CFS. This review shows that viral and bacterial infections, as well as nutritional deficiencies, may further aggravate the immune-oxidative pathophysiology of CFS. Targeted treatments with antioxidants and lipid replacement treatments may have some clinical efficacy in CFS. We conclude that complex interactions between immune and nitro-oxidative pathways, infectious agents, environmental factors, and nutritional deficiencies play a role in the pathophysiology of CFS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Fukuda K, Strauss SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A (1995) The chronic fatigue syndrome: a comprehensive approach to its definition and study. J Chronic Fatigue Syndr 1(2):67–84

    Google Scholar 

  2. Campling F, Sharpe M (2000) Chronic fatigue syndrome (CFS/ME). Oxford University Press, Oxford

    Google Scholar 

  3. Prins J, van der Meer JWM, Bleijenberg G (2006) Chronic fatigue syndrome (review). Lancet 367:346–355

    PubMed  Google Scholar 

  4. Clayton EW (2015) Beyond myalgic encephalomyelitis/chronic fatigue syndrome: an IOM report on redefining an illness. Jama 313(11):1101–1102

    CAS  PubMed  Google Scholar 

  5. Janssens KA, Zijlema WL, Joustra ML, Rosmalen JG (2015) Mood and anxiety disorders in chronic fatigue syndrome, fibromyalgia, and irritable bowel syndrome: results from the LifeLines Cohort Study. Psychosom Med 77(4):449–457. https://doi.org/10.1097/PSY.0000000000000161

    Article  PubMed  Google Scholar 

  6. Daniels J, Brigden A, Kacorova A (2017) Anxiety and depression in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): examining the incidence of health anxiety in CFS/ME. Psychol Psychother Theory Res Pract 90(3):502–509

    Google Scholar 

  7. Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK et al (2009) Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science 326(5952):585–589. https://doi.org/10.1126/science.1179052

    Article  CAS  PubMed  Google Scholar 

  8. Naviaux RK, Naviaux JC, Li K, Bright AT, Alaynick WA, Wang L, Baxter A, Nathan N et al (2016) Metabolic features of chronic fatigue syndrome. Proc Natl Acad Sci U S A 113(37):E5472–E5480. https://doi.org/10.1073/pnas.1607571113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sotzny F, Blanco J, Capelli E, Castro-Marrero J, Steiner S, Murovska M, Scheibenbogen C, European Network on MC (2018) Myalgic encephalomyelitis/chronic fatigue syndrome - evidence for an autoimmune disease. Autoimmun Rev 17(6):601–609. https://doi.org/10.1016/j.autrev.2018.01.009

    Article  CAS  PubMed  Google Scholar 

  10. Dadar M, Shahali Y, Whatmore AM (2018) Human brucellosis caused by raw dairy products: a review on the occurrence, major risk factors and prevention. Int J Food Microbiol 292:39–47

  11. Gaudino EA, Coyle P, Krupp LB (1997) Post-Lyme syndrome and chronic fatigue syndrome: neuropsychiatric similarities and differences. Arch Neurol 54(11):1372–1376

    CAS  PubMed  Google Scholar 

  12. Anderson G, Berk M, Maes M (2014) Biological phenotypes underpin the physio-somatic symptoms of somatization, depression, and chronic fatigue syndrome. Acta Psychiatr Scand 129(2):83–97. https://doi.org/10.1111/acps.12182

    Article  CAS  PubMed  Google Scholar 

  13. Collin SM, Nikolaus S, Heron J, Knoop H, White PD, Crawley E (2016) Chronic fatigue syndrome (CFS) symptom-based phenotypes in two clinical cohorts of adult patients in the UK and The Netherlands. J Psychosom Res 81:14–23. https://doi.org/10.1016/j.jpsychores.2015.12.006

    Article  PubMed  Google Scholar 

  14. Chia JK, Chia AY (2008) Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. J Clin Pathol 61(1):43–48

    CAS  PubMed  Google Scholar 

  15. Montoya JG, Kogelnik AM, Bhangoo M, Lunn MR, Flamand L, Merrihew LE, Watt T, Kubo JT et al (2013) Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome. J Med Virol 85(12):2101–2109

    CAS  PubMed  Google Scholar 

  16. Meeus M, Nijs J, McGregor N, Meeusen R, De Schutter G, Truijen S, Fremont M, Van Hoof E et al (2008) Unravelling intracellular immune dysfunctions in chronic fatigue syndrome: interactions between protein kinase R activity, RNase L cleavage and elastase activity, and their clinical relevance. In Vivo 22(1):115–121

    PubMed  Google Scholar 

  17. Shetzline SE, Martinand-Mari C, Reichenbach NL, Buletic Z, Lebleu B, Pfleiderer W, Charubala R, De Meirleir K et al (2002) Structural and functional features of the 37-kDa 2-5A-dependent RNase L in chronic fatigue syndrome. J Interf Cytokine Res 22(4):443–456

    CAS  Google Scholar 

  18. Frémont 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):239–246

    PubMed  Google Scholar 

  19. Vojdani A, Choppa PC, Lapp CW (1998) Downregulation of RNase L inhibitor correlates with upregulation of interferon-induced proteins (2-5A synthetase and RNase L) in patients with chronic fatigue immune dysfunction syndrome. J Clin Lab Immunol 50(1):1–16

    CAS  PubMed  Google Scholar 

  20. Martinand C, Salehzada T, Silhol M, Lebleu B, Bisbal C (1998) The RNase L inhibitor (RLI) is induced by double-stranded RNA. J Interf Cytokine Res 18(12):1031–1038. https://doi.org/10.1089/jir.1998.18.1031

    Article  CAS  Google Scholar 

  21. Nijs J, Nicolson G, De Becker P, Coomans D, De Meirleir K (2002) Prevalence of mycoplasmal infections in European CFS patients. Examination of four mycoplasma species. FEMS Immunol Med Microbiol 34:209–214

    CAS  PubMed  Google Scholar 

  22. Launer-Felty K, Cole JL (2014) Domain interactions in adenovirus VAI RNA mediate high-affinity PKR binding. J Mol Biol 426(6):1285–1295

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Dey M, Mann BR, Anshu A, Mannan MA-U (2014) Activation of protein kinase PKR requires dimerization-induced cis-phosphorylation within the activation loop. J Biol Chem 289(9):5747–5757

    CAS  PubMed  Google Scholar 

  24. Mensah FKF, Bansal AS, Ford B, Cambridge G (2017) Chronic fatigue syndrome and the immune system: where are we now? Neurophysiol Clin 47(2):131–138. https://doi.org/10.1016/j.neucli.2017.02.002

    Article  PubMed  Google Scholar 

  25. Maes M, Twisk FN, Kubera M, Ringel K (2012) Evidence for inflammation and activation of cell-mediated immunity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin. J Affect Disord 136(3):933–939

    CAS  PubMed  Google Scholar 

  26. Maes M, Twisk FN, Ringel K (2012) Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome and depression: inflammatory markers are higher in myalgic encephalomyelitis/chronic fatigue syndrome than in depression. Psychother Psychosom 81(5):286–295

    PubMed  Google Scholar 

  27. Marcusson JA, Lindh G, Evengård B (2000) Chronic fatigue syndrome and nickel allergy. Contact Dermatitis 42(1):56–57

    Google Scholar 

  28. Sterzl I, Procházková J, Hrdá P, Bártová J, Matucha P, Stejskal VD (1999) Mercury and nickel allergy: risk factors in fatigue and autoimmunity. Neuroendocrinol Lett 20(3):221–228

    PubMed  Google Scholar 

  29. Lucas K, Maes M (2013) Molecular mechanisms underpinning laser printer and photocopier induced symptoms, including chronic fatigue syndrome and respiratory tract hyperresponsiveness: pharmacological treatment with cinnamon and hydrogen. Neuroendocrinol Lett 34(8):723–737

  30. Semenova Y, Zhunussov Y, Pivina L, Abisheva A, Tinkov A, Belikhina T, Skalny A, Zhanaspayev M et al (2019) Trace element biomonitoring in hair and blood of occupationally unexposed population residing in polluted areas of East Kazakhstan and Pavlodar regions. J Trace Elem Med Biol 56:31–37. https://doi.org/10.1016/j.jtemb.2019.07.006

    Article  CAS  PubMed  Google Scholar 

  31. Stejskal VD, Danersund A, Lindvall A, Hudecek R, Nordman V, Yaqob A, Mayer W, Bieger W et al (1999) Metal-specific lymphocytes: biomarkers of sensitivity in man. Neuroendocrinol Lett 20(5):289–298

    PubMed  Google Scholar 

  32. Yaqob A, Danersund A, Stejskal VD, Lindvall A, Hudecek R, Lindh U (2006) Metal-specific lymphocyte reactivity is down-regulated after dental metal replacement. Neuroendocrinol Lett 27(1–2):189–197

    PubMed  Google Scholar 

  33. Shin S-R, Han A-L (2012) Improved chronic fatigue symptoms after removal of mercury in patient with increased mercury concentration in hair toxic mineral assay: a case. Korean J Fam Med 33(5):320–325

    PubMed  PubMed Central  Google Scholar 

  34. Lerner AM, Ariza ME, Williams M, Jason L, Beqaj S, Fitzgerald JT, Lemeshow S, Glaser R (2012) Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and deoxyribonucleotide polymerase in a chronic fatigue syndrome subset. PLoS One 7(11):e47891

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Patarca-Montero R, Mark T, Fletcher MA, Klimas NG (2000) Immunology of chronic fatigue syndrome. J Chronic Fatigue Synd 6(3–4):69–107

    Google Scholar 

  36. Roerink ME, Knoop H, Bronkhorst EM, Mouthaan HA, Hawinkels LJ, Joosten LA, Meer JW (2017) Cytokine signatures in chronic fatigue syndrome patients: a case control study and the effect of anakinra treatment. J Transl Med 15(1):267

    PubMed  PubMed Central  Google Scholar 

  37. Chen X, Zhu YH, Cheng XY, Zhang ZW, Xu SW (2012) The protection of selenium against cadmium-induced cytotoxicity via the heat shock protein pathway in chicken splenic lymphocytes. Molecules 17(12):14565–14572. https://doi.org/10.3390/molecules171214565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wang M, Fu H, Xiao Y, Ai B, Wei Q, Wang S, Liu T, Ye L et al (2013) Effects of low-level organic selenium on lead-induced alterations in neural cell adhesion molecules. Brain Res 1530:76–81. https://doi.org/10.1016/j.brainres.2013.07.028

    Article  CAS  PubMed  Google Scholar 

  39. Leonarduzzi G, Gamba P, Sottero B, Kadl A, Robbesyn F, Calogero RA, Biasi F, Chiarpotto E et al (2005) Oxysterol-induced up-regulation of MCP-1 expression and synthesis in macrophage cells. Free Radic Biol Med 39(9):1152–1161. https://doi.org/10.1016/j.freeradbiomed.2005.06.024

    Article  CAS  PubMed  Google Scholar 

  40. Reddi AS, Bollineni JS (2001) Selenium-deficient diet induces renal oxidative stress and injury via TGF-beta1 in normal and diabetic rats. Kidney Int 59(4):1342–1353. https://doi.org/10.1046/j.1523-1755.2001.0590041342.x

    Article  CAS  PubMed  Google Scholar 

  41. Roy S, Dontamalla SK, Mondru AK, Sannigrahi S, Veerareddy PR (2011) Downregulation of apoptosis and modulation of TGF-beta1 by sodium selenate prevents streptozotocin-induced diabetic rat renal impairment. Biol Trace Elem Res 139(1):55–71. https://doi.org/10.1007/s12011-010-8635-z

    Article  CAS  PubMed  Google Scholar 

  42. Lu Y, Wahl LM (2005) Oxidative stress augments the production of matrix metalloproteinase-1, cyclooxygenase-2, and prostaglandin E2 through enhancement of NF-κB activity in lipopolysaccharide-activated human primary monocytes. J Immunol 175(8):5423–5429

    CAS  PubMed  Google Scholar 

  43. Simopoulos AP (2004) Omega-6/omega-3 essential fatty acid ratio and chronic diseases. Food Rev Int 20(1):77–90

    CAS  Google Scholar 

  44. Edin S, Wikberg ML, Dahlin AM, Rutegard J, Oberg A, Oldenborg PA, Palmqvist R (2012) The distribution of macrophages with a M1 or M2 phenotype in relation to prognosis and the molecular characteristics of colorectal cancer. PLoS One 7(10):e47045. https://doi.org/10.1371/journal.pone.0047045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Nakanishi M, Menoret A, Tanaka T, Miyamoto S, Montrose DC, Vella AT, Rosenberg DW (2011) Selective PGE2 suppression inhibits colon carcinogenesis and modifies local mucosal immunity. Cancer Prev Res 4(8):1198–1208

    CAS  Google Scholar 

  46. Obermajer N, Kalinski P (2012) Key role of the positive feedback between PGE2 and COX2 in the biology of myeloid-derived suppressor cells. Oncoimmunology 1(5):762–764

    PubMed  PubMed Central  Google Scholar 

  47. Whiteside TL, Jackson EK (2013) Adenosine and prostaglandin e2 production by human inducible regulatory T cells in health and disease. Front Immunol 4:212

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Glover EI, Phillips SM (2010) Resistance exercise and appropriate nutrition to counteract muscle wasting and promote muscle hypertrophy. Curr Opin Clin Nutr Metab Care 13(6):630–634

    PubMed  Google Scholar 

  49. Morris G, Maes M (2013) A neuro-immune model of myalgic encephalomyelitis/chronic fatigue syndrome. Metab Brain Dis 28(4):523–540

    CAS  PubMed  Google Scholar 

  50. Scrimshaw NS (2003) Historical concepts of interactions, synergism and antagonism between nutrition and infection. J Nutr 133(1):316S–321S

    PubMed  Google Scholar 

  51. Morris G, Maes M (2014) Oxidative and nitrosative stress and immune-inflammatory pathways in patients with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). Curr Neuropharmacol 12(2):168–185

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Nicolson GL, Nasralla M, De Meirleir K (2002) Bacterial and viral co-infections in chronic fatigue syndrome (CFS/ME) patients. In: Proc Clin Sci Conference on Myalgic Encephalopathy/Chronic Fatigue Syndrome, pp. 1–12

    Google Scholar 

  53. Haier J, Nasralla M, Franco AR, Nicolson GL (1999) Detection of mycoplasmal infections in blood of patients with rheumatoid arthritis. Rheumatology (Oxford, England) 38(6):504–509

    CAS  Google Scholar 

  54. Nicolson GL, Gan R, Haier J (2004) Evidence for Brucella spp. and Mycoplasma spp. co-infections in blood of chronic fatigue syndrome patients. J Chronic Fatigue Syndr 12(2):5–17

    Google Scholar 

  55. Castaño MJ, Solera J (2009) Chronic brucellosis and persistence of Brucella melitensis DNA. J Clin Microbiol 47(7):2084–2089

    PubMed  PubMed Central  Google Scholar 

  56. Bjørklund G, Dadar M, Pen JJ, Chirumbolo S, Aaseth J (2019) Chronic fatigue syndrome (CFS): suggestions for a nutritional treatment in the therapeutic approach. Biomed Pharmacother 109:1000–1007

    PubMed  Google Scholar 

  57. Maggi RG, Mozayeni BR, Pultorak EL, Hegarty BC, Bradley JM, Correa M, Breitschwerdt EB (2012) Bartonella spp. bacteremia and rheumatic symptoms in patients from Lyme disease–endemic region. Emerg Infect Dis 18(5):783–791

    PubMed  PubMed Central  Google Scholar 

  58. Nicolson GL, Nicolson NL, Haier J (2007) Chronic fatigue syndrome patients subsequently diagnosed with Lyme disease Borrelia burgdorferi: evidence for mycoplasma species coinfections. J Chronic Fatigue Syndr 14(4):5–17

    Google Scholar 

  59. Salit IE (1997) Precipitating factors for the chronic fatigue syndrome. J Psychiatr Res 31(1):59–65. https://doi.org/10.1016/s0022-3956(96)00050-7

    Article  CAS  PubMed  Google Scholar 

  60. Nicolson G, Gan R, Haier J (2003) Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. Apmis 111(5):557–566

    CAS  PubMed  Google Scholar 

  61. Panchenko OA, Tabachnikov SI, Kut'ko II (1996) Mental disorders in the participants in the cleanup of the aftermath of the accident at the Chernobyl Atomic Electric Power Station. Zh Nevrol Psikhiatr Im S S Korsakova 96(5):34–37

    CAS  PubMed  Google Scholar 

  62. Loganovsky KN, Zdanevich NA (2013) Cerebral basis of posttraumatic stress disorder following the Chernobyl disaster. CNS Spectr 18(2):95–102. https://doi.org/10.1017/S109285291200096X

    Article  PubMed  Google Scholar 

  63. Loganovsky KN (2000) Chronic fatigue syndrome as a characteristic aftermath of a radioecological disaster: the Chernobyl accident experience [poster]. Int J Phsychophysiol 35(1):69

    Google Scholar 

  64. Loganovsky KN (2000) Vegetative-vascular dystonia and osteoalgetic syndrome or chronic fatigue syndrome as a characteristic after-effect of radioecological disaster. The Chernobyl accident experience. Journal of Chronic Fatigue Syndrome 7(3):3–16. https://doi.org/10.1300/J092v07n03_02

    Article  Google Scholar 

  65. Pastel RH (2002) Radiophobia: long-term psychological consequences of Chernobyl. Mil Med 167(2 Suppl):134–136

    PubMed  Google Scholar 

  66. Semenova Y, Pivina L, Manatova A, Bjørklund G, Glushkova N, Belikhina T, Dauletyarova M, Zhunussova T (2019) Mental distress in the rural Kazakhstani population exposed and non-exposed to radiation from the Semipalatinsk Nuclear Test Site. J Environ Radioact 203:39–47. https://doi.org/10.1016/j.jenvrad.2019.02.013

    Article  CAS  PubMed  Google Scholar 

  67. Missailidis D, Annesley SJ, Fisher PR (2019) Pathological mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome. Diagnostics (Basel) 9(3). https://doi.org/10.3390/diagnostics9030080

  68. Bjørklund G, Pivina L, Dadar M, Semenova Y, Rahman MM, Chirumbolo S, Aaseth J (2020) Depleted uranium and Gulf War illness: updates and comments on possible mechanisms behind the syndrome. Environ Res 181:108927. https://doi.org/10.1016/j.envres.2019.108927

    Article  CAS  PubMed  Google Scholar 

  69. Bolton JP, Foster CR (2002) Battlefield use of depleted uranium and the health of veterans. J R Army Med Corps 148(3):221–229. https://doi.org/10.1136/jramc-148-03-01

    Article  CAS  PubMed  Google Scholar 

  70. Dyussenova L, Pivina L, Semenova Y, Bjørklund G, Glushkova N, Chirumbolo S, Belikhina T (2018) Associations between depression, anxiety and medication adherence among patients with arterial hypertension: comparison between persons exposed and non-exposed to radiation from the Semipalatinsk Nuclear Test Site. J Environ Radioact 195:33–39. https://doi.org/10.1016/j.jenvrad.2018.09.016

    Article  CAS  PubMed  Google Scholar 

  71. Markabayeva A, Bauer S, Pivina L, Bjørklund G, Chirumbolo S, Kerimkulova A, Semenova Y, Belikhina T (2018) Increased prevalence of essential hypertension in areas previously exposed to fallout due to nuclear weapons testing at the Semipalatinsk Test Site, Kazakhstan. Environ Res 167:129–135. https://doi.org/10.1016/j.envres.2018.07.016

    Article  CAS  PubMed  Google Scholar 

  72. Kovalenko AN, Loganovsky KN (2001) Whether chronic fatigue syndrome X in Chernobyl accident survivors are membrane pathology? [in Russian]. Ukrains'kij Medichnij Chasopis 6(26):70–81

    Google Scholar 

  73. Loganovsky K, Perchuk I, Marazziti D (2016) Workers on transformation of the shelter object of the Chernobyl nuclear power plant into an ecologically-safe system show qEEG abnormalities and cognitive dysfunctions: a follow-up study. World J Biol Psychiatry 17(8):600–607. https://doi.org/10.3109/15622975.2015.1042044

    Article  PubMed  Google Scholar 

  74. Bested AC, Marshall LM (2015) Review of myalgic encephalomyelitis/chronic fatigue syndrome: an evidence-based approach to diagnosis and management by clinicians. Rev Environ Health 30(4):223–249. https://doi.org/10.1515/reveh-2015-0026

    Article  PubMed  Google Scholar 

  75. Cortes Rivera M, Mastronardi C, Silva-Aldana CT, Arcos-Burgos M, Lidbury BA (2019) Myalgic encephalomyelitis/chronic fatigue syndrome: a comprehensive review. Diagnostics (Basel) 9(3). https://doi.org/10.3390/diagnostics9030091

  76. Nijs J, De Meirleir K (2004) Oxidative stress might reduce essential fatty acids in erythrocyte membranes of chronic fatigue syndrome patients. Nutr Neurosci 7(4):251–253. https://doi.org/10.1080/10284150400004148

    Article  CAS  PubMed  Google Scholar 

  77. Chaudhuri A, Watson WS, Pearn J, Behan PO (2000) The symptoms of chronic fatigue syndrome are related to abnormal ion channel function. Med Hypotheses 54(1):59–63. https://doi.org/10.1054/mehy.1998.0822

    Article  CAS  PubMed  Google Scholar 

  78. Venter M, Tomas C, Pienaar IS, Strassheim V, Erasmus E, Ng WF, Howell N, Newton JL et al (2019) MtDNA population variation in myalgic encephalomyelitis/chronic fatigue syndrome in two populations: a study of mildly deleterious variants. Sci Rep 9(1):2914. https://doi.org/10.1038/s41598-019-39060-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Chung HC, Kim SH, Lee MG, Cho CK, Kim TH, Lee DH, Kim SG (2001) Mitochondrial dysfunction by gamma-irradiation accompanies the induction of cytochrome P450 2E1 (CYP2E1) in rat liver. Toxicology 161(1–2):79–91. https://doi.org/10.1016/s0300-483x(01)00332-8

    Article  CAS  PubMed  Google Scholar 

  80. Pall ML (2008) Post-radiation syndrome as a NO/ONOO- cycle, chronic fatigue syndrome-like disease. Med Hypotheses 71(4):537–541. https://doi.org/10.1016/j.mehy.2008.05.023

    Article  CAS  PubMed  Google Scholar 

  81. Loganovsky KN, Bomko MO, Abramenko IV, Kuts KV, Belous NI, Masiuk SV, Gresko MV, Loganovska TK et al (2018) Neuropsychobiological mechanisms of affective and cognitive disorders in the Chornobyl clean-up workers taking into account the specific gene polymorphisms. Probl Radiac Med Radiobiol 23:373–409. https://doi.org/10.33145/2304-8336-2018-23-373-409

    Article  CAS  PubMed  Google Scholar 

  82. Logan AC, Wong C (2001) Chronic fatigue syndrome: oxidative stress and dietary modifications. Altern Med Rev 6(5):450–460

    CAS  PubMed  Google Scholar 

  83. Morris G, Anderson G, Maes M (2017) Hypothalamic-pituitary-adrenal hypofunction in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) as a consequence of activated immune-inflammatory and oxidative and nitrosative pathways. Mol Neurobiol 54(9):6806–6819

    CAS  PubMed  Google Scholar 

  84. Morris G, Stubbs B, Köhler CA, Walder K, Slyepchenko A, Berk M, Carvalho AF (2018) The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis. Sleep Med Rev 41:255–265

    PubMed  Google Scholar 

  85. Richards R, Roberts T, McGregor N, Dunstan R, Butt H (2000) Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Rep 5(1):35–41

    CAS  PubMed  Google Scholar 

  86. Wawrzyniak NR, Joseph A-M, Levin DG, Gundermann DM, Leeuwenburgh C, Sandesara B, Manini TM, Adhihetty PJ (2016) Idiopathic chronic fatigue in older adults is linked to impaired mitochondrial content and biogenesis signaling in skeletal muscle. Oncotarget 7(33):52695–52709

    PubMed  PubMed Central  Google Scholar 

  87. Armstrong CW, McGregor NR, Lewis DP, Butt HL, Gooley PR (2015) Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients. Metabolomics 11(6):1626–1639

    CAS  Google Scholar 

  88. Jammes Y, Steinberg J, 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

    CAS  PubMed  Google Scholar 

  89. Maes M, Mihaylova I, Leunis J-C (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. Neuroendocrinol Lett 27(5):615–622

    CAS  PubMed  Google Scholar 

  90. Werbach MR (2000) Nutritional strategies for treating chronic fatigue syndrome. Altern Med Rev 5(2):93–108

    CAS  PubMed  Google Scholar 

  91. Regland B, Forsmark S, Halaouate L, Matousek M, Peilot B, Zachrisson O, Gottfries C-G (2015) Response to vitamin B12 and folic acid in myalgic encephalomyelitis and fibromyalgia. PLoS One 10(4):e0124648

    PubMed  PubMed Central  Google Scholar 

  92. Miwa K, Fujita M (2010) Fluctuation of serum vitamin E (α-tocopherol) concentrations during exacerbation and remission phases in patients with chronic fatigue syndrome. Heart Vessel 25(4):319–323

    Google Scholar 

  93. Maric D, Brkic S, Mikic AN, Tomic S, Cebovic T, Turkulov V (2014) Multivitamin mineral supplementation in patients with chronic fatigue syndrome. Medical science monitor: international medical journal of experimental and clinical research 20:47

    CAS  Google Scholar 

  94. Nicolson GL, Ellithorpe R (2006) Lipid replacement and antioxidant nutritional therapy for restoring mitochondrial function and reducing fatigue in chronic fatigue syndrome and other fatiguing illnesses. J Chronic Fatigue Syndr 13(1):57–68

    Google Scholar 

  95. Houston M (2010) Lipid replacement therapy with a glycophospholipid-antioxidant-vitamin formulation significantly reduces fatigue within one week.

  96. Joustra ML, Minovic I, Janssens KA, Bakker SJ, Rosmalen JG (2017) Vitamin and mineral status in chronic fatigue syndrome and fibromyalgia syndrome: a systematic review and meta-analysis. PLoS One 12(4):e0176631

    PubMed  PubMed Central  Google Scholar 

  97. Fukuda S, Nojima J, Motoki Y, Yamaguti K, Nakatomi Y, Okawa N, Fujiwara K, Watanabe Y et al (2016) A potential biomarker for fatigue: oxidative stress and anti-oxidative activity. Biol Psychol 118:88–93. https://doi.org/10.1016/j.biopsycho.2016.05.005

    Article  PubMed  Google Scholar 

  98. 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):584–589

    CAS  PubMed  Google Scholar 

  99. Klimas NG, Salvato FR, Morgan R, Fletcher MA (1990) Immunologic abnormalities in chronic fatigue syndrome. J Clin Microbiol 28(6):1403–1410

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Nguyen T, Staines D, Nilius B, Smith P, Marshall-Gradisnik S (2016) Novel identification and characterisation of transient receptor potential melastatin 3 ion channels on natural killer cells and B lymphocytes: effects on cell signalling in chronic fatigue syndrome/myalgic encephalomyelitis patients. Biol Res 49(1):27. https://doi.org/10.1186/s40659-016-0087-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Bradley A, Ford B, Bansal A (2013) Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls. Clin Exp Immunol 172(1):73–80

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Maes M, Bosmans E, Kubera M (2015) Increased expression of activation antigens on CD8+ T lymphocytes in myalgic encephalomyelitis/chronic fatigue syndrome: inverse associations with lowered CD19+ expression and CD4+/CD8+ ratio, but no associations with (auto) immune, leaky gut, oxidative and nitrosative stress biomarkers. Neuroendocrinol Lett 36(5):439–446

    PubMed  Google Scholar 

  103. Fenouillet E, Vigouroux A, Steinberg JG, Chagvardieff A, Retornaz F, Guieu R, Jammes Y (2016) Association of biomarkers with health-related quality of life and history of stressors in myalgic encephalomyelitis/chronic fatigue syndrome patients. J Transl Med 14(1):251

    PubMed  PubMed Central  Google Scholar 

  104. Rivas JL, Palencia T, Fernandez G, Garcia M (2018) Association of T and NK cell phenotype with the diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Front Immunol 9:1028. https://doi.org/10.3389/fimmu.2018.01028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Petty RD, McCarthy NE, Le Dieu R, Kerr JR (2016) MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c: potential diagnostic biomarkers in natural killer (NK) cells of patients with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME). PLoS One 11(3):e0150904

    PubMed  PubMed Central  Google Scholar 

  106. Lidbury BA, Kita B, Lewis DP, Hayward S, Ludlow H, Hedger MP, Kretser DM (2017) Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study. J Transl Med 15(1):60

    PubMed  PubMed Central  Google Scholar 

  107. Lieberman J, Bell DS (1993) Serum angiotensin-converting enzyme as a marker for the chronic fatigue-immune dysfunction syndrome: a comparison to serum angiotensin-converting enzyme in sarcoidosis. Am J Med 95(4):407–412. https://doi.org/10.1016/0002-9343(93)90310-l

    Article  CAS  PubMed  Google Scholar 

  108. De Luca C, Raskovic D, Pacifico V, Thai JC, Korkina L (2011) The search for reliable biomarkers of disease in multiple chemical sensitivity and other environmental intolerances. Int J Environ Res Public Health 8(7):2770–2797. https://doi.org/10.3390/ijerph8072770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Scheibenbogen C, Freitag H, Blanco J, Capelli E, Lacerda E, Authier J, Meeus M, Castro Marrero J et al (2017) The European ME/CFS biomarker landscape project: an initiative of the European network EUROMENE. J Transl Med 15(1):162. https://doi.org/10.1186/s12967-017-1263-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Maes M, Rodriguez LA, Morris G (2019) Is a diagnostic blood test for chronic fatigue syndrome on the horizon? Expert Rev Mol Diagn 19(12):1049–1051. https://doi.org/10.1080/14737159.2020.1681976

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Council for Nutritional and Environmental Medicine, Toften 24, 8610, Mo i Rana, Norway

    Geir Bjørklund

  2. Agricultural Research, Education and Extension Organization (AREEO), Razi Vaccine and Serum Research Institute, Karaj, Iran

    Maryam Dadar

  3. Semey Medical University, Semey, Kazakhstan

    Lyudmila Pivina & Yuliya Semenova

  4. CONEM Kazakhstan Environmental Health and Safety Research Group, Semey Medical University, Semey, Kazakhstan

    Lyudmila Pivina & Yuliya Semenova

  5. Department of Pharmacology, Faculty of Medicine, Ovidius University of Constanta, Campus, 900470, Constanta, Romania

    Monica Daniela Doşa

  6. Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Michael Maes

  7. Impact Research Center, Deakin University, Geelong, Australia

    Michael Maes

Authors
  1. Geir Bjørklund
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maryam Dadar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lyudmila Pivina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Monica Daniela Doşa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuliya Semenova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael Maes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Geir Bjørklund or Monica Daniela Doşa.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bjørklund, G., Dadar, M., Pivina, L. et al. Environmental, Neuro-immune, and Neuro-oxidative Stress Interactions in Chronic Fatigue Syndrome. Mol Neurobiol 57, 4598–4607 (2020). https://doi.org/10.1007/s12035-020-01939-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-020-01939-w

Keywords

Search

Navigation