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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    • "The latter diagnosis was not only more liberal than the NIOF criterion, but also less specific with regard to IO&NS disorders. The clinical NIOF diagnosis is externally validated by IO&NS biomarkers showing that the neuro-psychiatric and physiosomatic-related symptoms are significantly associated with IO&NS pathways, which in fact may explain the pathogenesis of these symptoms (Maes & Twisk 2010; Morris & Maes 2013a; 2013b). Consequently, we showed that a simple algorithm may be used to make the diagnosis " NIOF " (Table 5). "
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    ABSTRACT: Background: Chronic fatigue syndrome (CFS) or Myalgic Encephalomyelitis (ME) is characterized by neuro-psychiatric (e.g. depression, irritability, sleep disorders, autonomic symptoms and neurocognitive defects) and physio-somatic (fatigue, a flu-like malaise, hyperalgesia, irritable bowel, muscle pain and tension) symptoms. New ME/CFS case definitions based on consensus criteria among experts are largely inadequate, e.g. those of the US Institute of Medicine . Objectives: The aim of the present study was to delineate a new case definition of ME/CFS based on pattern recognition methods and using neuro-immune, inflammatory, oxidative and nitrosative stress (neuro-IO&NS) biomarkers as external validating criteria. Methods: We measured the 12-item Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale in 196 subjects with CFS (CDC criteria) and 83 with chronic fatigue. The "Neuro-IO&NS" biomarkers were: IgM / IgA responses against LPS of gut commensal bacteria (leaky gut), IgM responses to O&NS modified neoepitopes, autoimmunity to serotonin, plasma interleukin-1 (IL-1) and serum neopterin. Results: Cluster analysis showed the presence of two well-separated clusters with highly significant differences in symptoms and biomarkers. The cluster with higher scores on all FF items was externally validated against all IO&NS biomarkers and therefore this diagnostic group was labeled "Neuro-IO&NS Fatigue" or "Neuro-Inflammatory and Oxidative Fatigue" (NIOF). An algorithm was constructed which defined NIOF as chronic fatigue and 4 or more of the following 6 symptoms: muscle tension, memory disturbances, sleep disorders, irritable bowel, headache or a flu-like malaise. There was a significant overlap between NIOF and CFS although NIOF criteria were much more restrictive. Factor analysis showed two factors, the first a fatigue-hyperalgesia (fibromyalgic complaints) and the second a fatigue-depression factor.
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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
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