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Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways

Maes M, Twisk FN. (2010) BMC Medicine 8 35. doi: 10.1186/1741-7015-8-35. 

Web URL: View this and related abstracts via PubMed here. Free full text of this article is available online.



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.


Here, we review the model proposed by Harvey and Wessely, which is the rationale for behaviourally oriented interventions, such as cognitive behaviour 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.


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.


This article sets out a very clear rationale for appropriate biomedical assessment of patients with Chronic Fatigue Syndrome (CFS), pointing out the limitations of standard approaches to this highly debilitating condition, which currently emphasise purely psychosocial factors. 

The authors acknowledge the variability within 'CFS' (which is a broad and purely descriptive diagnosis), but explain how CFS and depression (while often sharing some features) can be distinguished.  They explain the role of inflammtory, oxidative stress and nitrosative stress pathways in each condition, provide models to simplify potential diagnostic and treatment pathways.

They also explain why they believe current management approaches such as Cognitive Behavioural Therapy and Graded Exercise Therapy can be effective for some patients, but why the latter in particular may be harmful to others with Chronic Fatigue Syndrome.

Importantly, the paper includes a list of the biomedical laboratory tests that clinicians can use in order to plan and monitor individual clinical management of patients with CFS.