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: 7.25). 06/2010; 8(1):35. DOI: 10.1186/1741-7015-8-35
Source: PubMed


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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    • "Currently, fatigue science is a popular field of research, but the molecular mechanisms underlying fatigue are not well understood due to the complicated nature of its causes. Recent studies have suggested the involvement of oxidative stress and systems such as the endocrine, metabolic, autonomic nervous system, and immune system in fatigue (Jason, Porter, Herrington, Sorenson, & Kubow, 2009; Maes & Twisk, 2010). In particular, reactive oxygen species (ROS) cause oxidative damage to proteins, lipids, and DNA, and can contribute to functional disorders in cells and tissues with reduced levels of energy (Fulle et al., 2000; Jason et al., 2009). "
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    ABSTRACT: Sesamin has anti-oxidative functions in vivo. Fatigue is caused in part by oxidative stress. We evaluated whether sesame lignans (sesamin/episesamin = 1/1, 10 mg) with vitamin E (55 mg of alpha-tocopherol) (SVE) could improve subjective statuses and anti-oxidative capacity in humans using questionnaires on fatigue, sleep and physical appearance, as well as low-density lipoprotein oxidation lag time. A placebo-controlled, double-blind, parallel-group study was conducted with subjects experiencing daily fatigue. After a run-in period, subjects were administered oral SVE or a placebo (P) for 8 weeks. A questionnaire regarding fatigue, sleep and physical appearance was conducted at 0, 4, and 8 weeks. Plasma low-density lipoprotein oxidation lag time was measured as an indicator of anti-oxidative capacity. The per-protocol analysis revealed significant improvements in fatigue status at 4 and 8 weeks compared to 0 weeks in both groups (p < 0.01), and sleep and physical appearance at 8 weeks compared to 0 weeks only in the SVE group (p < 0.01). There were no significant differences observed between the groups. According to the 72-subject subgroup analysis (aged 40 and over), the sleep and physical appearance significantly improved compared to the P group (p < 0.05), and fatigue status showed a tendency for improvement compared to the P group. Anti-oxidative capacity in the SVE group significantly increased compared to the P group (p < 0.01). No adverse events relating to SVE supplementation were confirmed. These results suggest SVE supplementation could safely alleviate daily fatigue and oxidative stress.
    Global journal of health science 03/2015; 7(6). DOI:10.5539/gjhs.v7n6p1
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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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    ABSTRACT: Myalgic Encephalomyelitis (ME) was identified as a new clinical entity in 1959 and has been acknowledged as a disease of the central nervous system/neurological disease by the World Health Organisation since 1969. Cognitive impairment, (muscle) weakness, circulatory disturbances, marked variability of symptoms, and, above all, post-exertional malaise: a long-lasting increase of symptoms after minor exertion, are distinctive symptoms of ME.Chronic Fatigue Syndrome (CFS) was introduced in 1988 and was redefined into clinically evaluated, unexplained (persistent or relapsing) chronic fatigue, accompanied by at least four out of a list of eight symptoms, e.g. headaches and unrefreshing sleep, in 1994.Although the labels are used interchangeably, ME and CFS define distinct diagnostic entities. Post-exertional malaise and cognitive deficits e.g. are not mandatory for the diagnosis CFS, while obligatory for the diagnosis ME. “Fatigue” is not obligatory for the diagnosis ME.Since fatigue and other symptoms are subjective and ambiguous, research has been hampered. Despite this and other methodological issues, research has observed specific abnormalities in ME/CFS repetitively, e.g. immunological abnormalities, oxidative and nitrosative
    Frontiers in Physiology 03/2014; 5:109. DOI:10.3389/fphys.2014.00109 · 3.53 Impact Factor
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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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    ABSTRACT: Emissions of laser printers and photocopiers (LP&P) may be associated with health problems. The aim of this review is to describe the clinical picture that is triggered by exposure to LP&P and the molecular mechanisms underpinning the symptoms. Exposure to LP&P to vulnerable subjects may cause a symptom complex consisting of 1) irritation and hyperresponsiveness of the upper and lower respiratory tract; and 2) chronic fatigue (syndrome, CFS). Symptoms occur within hours after L&P exposure and may last for some days or become chronic with exacerbations following LP&P exposure. Substances that can be found in toners or are generated during the printing process are Silica nanoparticles, Titanium Dioxide nanoparticles, Carbon Black, metals, ozone, volatile organic compounds (VOC), etc. The latter may generate oxidative and nitrosative stress (O&NS), damage-associated molecular patterns molecules, pulmonary and systemic inflammation, and modulate Toll Like Receptor 4 (TRL4)‑related mechanisms. It is concluded that LP&P emissions may cause activation of the TLR4 Radical Cycle and thus be associated with the onset of chronic inflammatory and O&NS illnesses, such as CFS, in some vulnerable individuals. Cinnamon, an antagonist of the TLR4 complex, and Hydrogen, a potent antiinflammatory and oxygen radical scavenger, may have efficacy treating LP&P-induced illness.
    Neuro endocrinology letters 12/2013; 34(8):723-37. · 0.80 Impact Factor
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