[To read the full text of this free access article, click here. See also the authors’ added explanation, attached as a footnote(1) to this abstract.]
Background: In a recently published paper, Harvey and Wessely put forward a ‘biopsychosocial’ explanatory model for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is proposed to be applicable to (chronic) fatigue even when apparent medical causes are present.
Methods: Here, we review the model proposed by Harvey and Wessely, which is the rationale for behaviorally oriented interventions, such as cognitive behavior therapy (CBT) and graded exercise therapy (GET), and compare this model with a biological model, in which inflammatory, immune, oxidative and nitrosative (IO&NS) pathways are key elements.
Although human and animal studies have established that the pathophysiology of ME/CFS includes IO&NS pathways, these abnormalities are not included in the model proposed by Harvey and Wessely.
• Activation of IO&NS pathways is known to induce fatigue and somatic (F&S) symptoms and can be induced or maintained by viral and bacterial infections, physical and psychosocial stressors, or organic disorders such as (auto)immune disorders.
• Studies have shown that ME/CFS and major depression are both clinical manifestations of shared IO&NS pathways, and that both disorders can be discriminated by specific symptoms and unshared or differentiating pathways.
• Interventions with CBT/GET are potentially harmful for many patients with ME/CFS, since the underlying pathophysiological abnormalities may be intensified by physical stressors.
Conclusions: In contrast to Harvey and Wessely’s (bio)psychosocial model for ME/CFS, a bio(psychosocial) model based upon IO&NS abnormalities is likely more appropriate to this complex disorder.
In clinical practice, we suggest physicians should also explore the IO&NS pathophysiology by applying laboratory tests that examine the pathways involved.
1. Author Commentary. Michael Maes & Frank Twisk wrote in a news release dated Jun 16, 2010 and shared via the Co-Cure Listserv:
We are pleased that BMC has published our critique on the (bio)psychosocial model for ME/CFS put forward by Harvey and Wessely in an article in BMC last year (“Chronic fatigue syndrome: Identifying zebras amongst the horses,” Harvey SB, Wessely S. BMC Medicine 2009, 7:58. doi:10.1186/1741-7015-7-58).
In our commentary (“Chronic fatigue syndrome: Harvey and Wessely’s (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways”) we substantiate why the Harvey and Wessely model for ME/CFS (‘unexplained fatigue’) is incoherent and invalid, and why the label biopsychosocial model is inappropriate.
A pathophysiological model for ME/CFS should incorporate the precipitating and perpetuating factors and the biological aberrations (induced and/or maintained by these factors), which can plausibly explain specific symptoms.
“As an alternative to the model of Harvey and Wessely and other (bio)psychosocial models, we outline a bio(psychosocial) model for ME/CFS, in which (persistent and/or reactivating) infections, immunological abnormalities (inflammation, immune activation, immunosuppression and immune dysfunction), oxidative and nitrosative stress, and their sequels (e.g. mitochondrial dysfunction and channelopathy) are key players.
These biological aberrations account for many of the symptoms characteristic for ME/CFS – e.g. “fatigue”, neurocognitive impairment, and pain.
Since physiological and psychological stress intensify the immunological abnormalities (inflammation, immunosuppression and immune dysfunction) and oxidative and nitrosative stress, it is not surprising that ‘behaviorally oriented programs’, like CBT/GET, as proposed by Harvey and Wessely, amplify many symptoms, as has been observed by various authors.
We conclude that it is about time to leave the (bio)psychosocial explanatory model(s) for ME/CFS and behavorial interventions justified by these models, (CBT/GET) behind us once and for all, and to shift the focus to the organical pathophysiology of ME/CFS (and depression accompanying ME/CFS), subgroups of ME/CFS patients, defined by immunological and other objective markers, and therapies to effectively reverse the biological abnormalities.”