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Reaktie op

[Making Sense of ME/CFS - Wessely et al]

afgewezen voor publikatie.






In een reaktie op een artikel van Newton en Jones, waarin zij betogen dat er meer

nadruk zou moeten liggen op de organische verklaringen voor kenmerkende klachten,

halen Wessely en kollega's in een brief aan de eindredakteur van Occupational Medicine

voor de 381e keer de biopsychosociale "argumenten" (psychoanalyse, CBT etc.) van stal.


Onze brief, waarin wij het betoog van Wessely wederom inhoudelijk bestrijden, (zie onder) werd door de eindredakteur afgewezen voor publikatie op basis van het argument dat wij onze visie reeds elders gepubliceerd hebben (voor die publikatie: klik op onderstaand logo).




Kennelijk mogen Wessely en kollega's hun onhoudbare biopsychosociale argumenten

tot vervelens toe in diverse wetenschappelijke tijdschriften blijven herhalen,

maar is het anderen niet toegestaan om daar bij herhaling op te reageren...


Gelukkig denken een aantal eindredakturen daar anders over.

Maar goed, je kunt niet alle wedstrijden winnen...




Making sense of ME/CFS: the need for a biological-oriented approach.




Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS), a multi­system disease, is declared to be a controversial disease by various others.


In this letter we substantiate why the (bio)psychosocial model of Harvey and Wessely is largely inadequate to explain the pathophysiology of ME/CFS.


Looking at the evidence, biological aberrations (e.g. inflammation, immune dysfunction, infections, oxidative and nitrosatieve stress, and mitochondrial dysfunction) should be key players in a bio(psychosocial) model for ME/CFS.


Since exertion intensifies the underlying pathophysiology, exercise the­ra­py/cognitive and behavioural focused therapies (GET/CBT), as pro­moted by advocates of a bio(psychosocial) model, are potentially harm­ful for many patients.


Future research should therefore be aimed at interventions to reverse the biological abnormalities, thereby promoting recovery or improvement.





Dear Sir,



With interest we have taken notice of the observations raised by Newton and Jones (1); the arguments raised by Harvey, Mykletun and Wessely (2); and the reply by Newton and Jones (3).


We endorse the arguments made by Newton and Jones that the imbalance in the biological and psychosocial aspects of ME/CFS should be addressed; that "fatigue" is accepted by the clinical community to be biological in its origin; that "fatigue" has profound psychological consequences; and that psychological problems are secondary rather than primary phenomena (3,4).


Harvey, Mykletun and Wessely (2) state that "approaches that dichotomize the mind and body ... ignore the current evidence base and are likely to be suboptimal". However, the explanatory variables in the (bio)psychosocial model of Harvey and Wessely (5) are mainly psychosocial ones. The studies cited by Harvey and Wessely (2) used to endorse the argument "that attempts to identity a consistent pattern of biological abnormalities, have failed" are highly selective. As explained (6), Harvey and Wessely’s (bio)psychosocial model does not encapsulate the biological pathophysiology of ME/CFS, despite abundant evidence of various organic abnormalities.


Although ME/CFS is a heterogeneous disorder (7,8), many, if not all, ME/CFS patients suffer from inflammation, immune dysfunction, infections, oxidative and nitrosative stress, intestinal hyperpermeability, etc. These aberrations, demonstrated in many studies (9,10), are encapsulated in the inflammatory and oxidative and nitrosative stress model of ME/CFS (6). Advocates of biopsychosocial models should include these biological pathways in their models.


Harvey and colleagues state that "randomized control studies have established the effectiveness of cognitive and behavioural focused therapies in .. CFS ..". They fail to discuss recent reviews (11), which demonstrate that the evidence base for these cognitive and behavioural focused therapies in ME/CFS is non-existent and that these therapies are even potentially harmful for many patients, because graded exercise treatment intensifies the pathophysiological mechanisms in ME/CFS, such as inflammation, oxidative stress, etc. (11).

In an evaluation by the Belgian government, the effects of CBT/GET have been analyzed in hundreds of patients with ME/CFS (12). It was found that ME/CFS did not result in any clinical improvement. On the contrary, CBT/GET aggravated the symptoms of many patients (often up to 30-80% of the patients), including fatigue, daily physical and psychological functioning (12).


Harvey, Wessely and Mykletun state that "a simple mental state examination remains one of the most productive investigations in prolonged fatigue" (5). However, even for chronic fatigue this assertion is invalid (6). According to recent study by Jones and colleagues (13) "chronic fatigue" in general is secondary to medical conditions in 71% of the patients and accompanied by psychological/psychiatric illnesses in only 15% of the cases. As explained (6), we strongly reject the recommendation of Harvey and colleagues that "a simple mental state examination remains one of the most productive investigations" in ME/CFS.


Therefore, we recommend that future research should scrutinize the above-mentioned pathways and delineate novel drugs targeting these pathways to treat this complex multisystem disease, instead of iterating on the psychosocial aspects (6).




Frank N.M. Twisk and Michael Maes.






  1. Newton JL, Jones DEJ.
  2. Making sense of fatigue.

    Occup Med (Lond)2010; 60:326-329. doi:10.1093/occmed/kqq014.

  3. Harvey SB, Mykletun A, Wessely S.
  4. Making sense of fatigue: the need for a balanced approach. Occup Med (Lond)

    2010;60:665-666. doi: 10.1093/occmed/kqq166.

  5. Newton JL, Jones DEJ.
  6. Making sense of fatigue. Reply.

    Occup Med (Lond) 2010;60:666-667. doi:10.1093/occmed/kqq169.

  7. Matsuda Y, Matsui T, Kataoka K, Fukada R, Fukuda S, Kuratsune H, et al.
  8. A two-year follow-up study of chronic fatigue syndrome co-morbid with psychiatric disorders.

    Psychiatry Clin Neurosci 2009. doi: 10.1111/j.1440-1819.2009.01954.x.

  9. Harvey SB, Wessely S.
  10. Chronic fatigue syndrome: identifying zebras amongst the horses.

    BMC Med 2009;7:58. doi:10.1186/1741-7015-7-58.

  11. Maes M, Twisk FNM.
  12. Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways.

    BMC Med 2010;8:35. doi:10.1186/1741-7015-8-35.

  13. Wessely S.
  14. Chronic fatigue syndrome. Summary of a report of a joint committee of the Royal Colleges of Physicians, Psychiatrists and General Practitioners.

    J R Coll Physicians Lond 1996;30:497-504.

  15. Zhang L, Goudh J, Christmas D, Mattey D, Richards S, Main J, et al.
  16. Microbial infections in eight genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

    J Clin Pathol 2010;63:156–164. doi:10.1136/jcp.2009.072561.

  17. Gow JW, Hagan S, Herzyk P, Cannon C, Behan PO, Chaudhuri A.
  18. A gene signature for post-infectious chronic fatigue syndrome.

    BMC Medical Genomics 2009;2:38. doi:10.1186/1755-8794-2-38.

  19. Kaushik N, Fear D, Richards SC, McDermott CR, Nuwaysir EF, Kellam P, et al.
  20. Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome.

    J Clin Pathol 2005;58:826-832. doi:10.1136/jcp.2005.025718.

  21. Twisk FNM, Maes M.
  22. A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME)/chro­nic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients.

    Neuro Endocr Lett 2009;30:284-299. NEL300309R02.

  23. Maes M, Twisk FNM.
  24. Chronic fatigue syndrome: la bęte noire of the Belgian health care system.

    Neuro Endocrinol Lett 2009;30:300-311. NEL300309R04.

  25. Newton JL, Mabillard H, Scott A, Hoad A, Spickett G.
  26. The Newcastle NHS Chronic Fatigue Syndrome Service: not all fatigue is the same.

    J R Coll Physicians Edinb 2010;40:304-307. doi:10.4997/JRCPE.2010.404.