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

Abstract

BackgroundIn 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.MethodsHere, 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.DiscussionAlthough 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.ConclusionsIn 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.

Role of physical activity in tumor patients and possible underlying mechanisms

“…Further certain chemotherapeutic drugs (e.g., anthracycline) unfold their therapeutic effect by generating free radicals [20]. A principal involvement of oxidative and nitrosative stress in the development of chronic fatigue was recently described by Maes and Twisk [47] on the basis of a bio(psychosocial) model which describes the pathophysiology of chronic fatigue. Patients that experience chronic fatigue syndrome possess higher peroxide concentrations in their blood plasma [46].…”

What's ‘difficult’? A multi-stage qualitative analysis of secondary care specialists' experiences with medically unexplained symptoms

“…somatisation disorder, somatoform disorder, abnormal illness behaviour or functional symptoms [2]- [7]. The terminological heterogeneity not only mirrors the fact that such conditions often fall between specialities [8], but also reflects the lack of agreement about the conceptual basis of this phenomenon [9]- [11]. This is especially the case regarding questions about mind-body interaction [12].…”

Diagnosis of myalgic encephalomyelitis: where are we now?

“…Some authors [1,2] consider ME/CFS to be a neuro-immune disorder characterized by both a specific symptom profile and a neuro-immune pathophysiology [1,2]. The symptoms comprise fatigue, fatigability, hyperalgesia, sleep disorders, as well as inflammatory, neurological, neurocognitive, and autonomic and gastrointestinal symptoms.…”

“…ME/CFS is accompanied by many neuro-immune abnormalities, including immuno-inflammatory processes, oxidative and nitrosative stress (O&NS), damage to lipids, proteins, and DNA by O&NS, decreased natural killer cell activity, autoimmune responses directed against neuronal and other substances, for example, neurotransmitters and anchorage molecules, and mitochondrial defects and lowered ATP production, and neurological abnormalities, for example, brain metabolic dysfunction and reduced blood flow [1][2][3][4][5][6]. It is hypothesized that a complex interplay between these pathways may underpin the neuro-immune pathophysiology of ME/ CFS [1,2]. Science Watch (Thomson Reuters) regards ME/CFS and the O&NS processes in that illness, as a new emerging research front in the neurosciences and behavioral sciences [7].…”