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 Clinics @ TRIA, Piyavate Hospital, Bangkok, Thailand.
BMC Medicine (Impact Factor: 7.28). 06/2010; 8(1):35. DOI: 10.1186/1741-7015-8-35
Source: PubMed

ABSTRACT 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.

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Available from: Michael Maes, Aug 11, 2014
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    • "Immunological aberrations (inflammation, immune activation, immunosuppression and immune dysfunction); Klimas et al., 1990; Fletcher et al., 2009; Lorusso et al., 2009; Meeus et al., 2009; Brenu et al., 2011; Maes et al., 2012b consistent with processes observed during (latent) infection; Lloyd et al., 1993; Kerr et al., 2008a; Broderick et al., 2010 Intestinal dysbiosis, inflammation and hyperpermeability, Maes et al., 2007a; Sheedy et al., 2009; Lakhan and Kirchgessner, 2010; De Meirleir et al., 2013; Frémont et al., 2013 associated with systemic immune system abnormalities; Maes et al., 2012c; Groeger et al., 2013 (reactivating and/or persistent) infections; Hilgers and Frank, 1996; Chia and Chia, 2003; Nicolson et al., 2003; Chia et al., 2010; Chapenko et al., 2012 Elevated oxidative and nitrosative stress; Zhang et al., 1995; Kennedy et al., 2010; Maes and Twisk, 2010; Tomic et al., 2012 Mitochondrial dysfunction and damage to mitochondria; Behan et al., 1991; Pietrangelo et al., 2009; Booth et al., 2012; Meeus et al., 2013 Hypovolemia, diminished cardiac output and Streeten and Bell, 1998; Hurwitz et al., 2009; Miwa and Fujita, 2009; Hollingsworth et al., 2012 blood and oxygen supply deficits to muscles and brain, McCully and Natelson, 1999; Biswal et al., 2011; Ocon, 2013 especially in an upright position and during exercise; LaManca et al., 1999; Peckerman et al., 2003; Wyller et al., 2007; Patrick Neary et al., 2008 Reduced (maximum) oxygen uptake; Farquhar et al., 2002; Weinstein et al., 2009; Vermeulen et al., 2010; Jones et al., 2012 Neurological abnormalities; Lange et al., 2005; Chen et al., 2008; Puri et al., 2012; Natelson, 2013 Hypocortisolism/blunted hypothalamic-pituitary-adrenal (HPA) axis response; Demitrack et al., 1991; Lorusso et al., 2009; Papadopoulos and Cleare, 2011; Tak et al., 2011 Ion channel dysfunction (channelopathy); Watson et al., 1997; Whistler et al., 2005; Broderick et al., 2006; Cameron et al., 2007 A deviant physiological responses to exertion Thambirajah et al., 2008; Jones et al., 2012; Light et al., 2012; Smylie et al., 2013; Snell et al., 2013 (Kindlon, 2012), e.g., oxygen uptake at the anaerobic threshold and maximum oxygen uptake (VO2max), and biomarkers, e.g., (exercise-induced) cytokine levels. "
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    • "We now will discuss the mechanistic explanations underpinning the onset of the symptoms that characterize LP&P-induced illness. 1) Airway hypersensitivity and other impairments of the respiratory tract, including asthma exacerbations, cough, chronic rhinitis, burning eyes, throat and vocal cord discomfort, burning tongue are readily explained by the effects of for example Magnetite, TiO2 nanoparticles , ozone and VOCs inducing increased responses to allergens, increased mucin secretion, local (neutrophilic ) inflammation and inflammasome signaling, O&NS processes, local lung lesions, etc (Pauluhn 2012; Peden, 2011; Chen et al. 2011; Yoon et al. 2010; Mogel et al. 2011). 2) There is now a vast literature that CFS is accompanied by a complex interplay between activated immune-inflammatory (including translocation of gram negative commensal bacteria) and O&NS pathways leading to autoimmune reactions, mitochondrial dysfunctions and brain disorders (Maes and Twisk, 2010; Morris et al. 2013). In those papers, evidence was provided that these pathways may contribute to the onset of specific CFS symptoms, such as chronic fatigue, exhaustion, irritable bowel syndrome, neurocognitive disorders, infectious or inflammatory symptoms (e.g. a flu-like malaise), and fibromyalgic symptoms and hyperalgesia. "
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    • "Farnesylation is required for RAt sarcoma (RAS) protein binding and therefore signal transduction from the outside of the cell membrane to the nucleus, DNA synthesis, cell growth, differentiation, apoptosis and malignant transformation (Elad et al. 1999; Boguski and McCormick 1993; Lowy and Willumsen 1993). As reviewed in the Introduction, dysfunctions in intracellular signaling, cellular differentiation , activation of apoptosis pathways, etc. occur in both depression and ME/CFS (Gow et al. 2009; Kerr et al. 2008) an in ME/CFS are associated with signs of infections (Maes and Twisk 2010; Zhang et al. 2010). "
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