Sickness & behavior in ME/CFS (Chronic Fatigue Syndrome)

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic debilitating condition characterized by physical and mental fatigue with a heightened sensitivity to exertion. To date, the causes are unknown. However, recently the condition has been implicated as a chronic sickness behavior state. That is, the adaptive changes in brain and behavior commonly following acute infection (experiences of malaise, fatigue, brain fog and so forth) seem to have become chronic and thus maladaptive, since no infectious agent is present. The condition is often debilitating, but no effective treatments are available, which implies that interventions are normally aimed at reducing symptoms and/or restoring or improving functioning. Furthermore, classifications are multiple and not empirically based. As such, there is a need for: (1) empirical investigations of how symptoms present and relate to each other and other measures of clinical importance; (2) evaluations of behavior medicine treatment approaches aimed at improving functioning and quality of life, and; (3) studies investigating sickness behavior processes in ME/CFS on both subjective and objective levels. Aims: The overarching aims of the present thesis were to: (a) investigate factors of importance in ME/CFS, including; (b) symptom patterns and their relationships to health and functioning (Study I); (c) inflammatory markers implicated in sickness behavior and fatigue and their associations with common symptoms (Study III); (d) the level of subjective sickness behavior in ME/CFS, compared to chronic pain, primary care patients and the general population (Study IV), and; (e) evaluate the acceptability, safety and preliminary efficacy of an Acceptance and Commitment Therapy(ACT)-based behavior medicine treatment protocol aimed at increasing functioning and quality of life in ME/CFS (Study II). Methods: All ME/CFS patients in the four studies were included after referral and diagnostic assessment (CDC and CCC or ICC criteria) at a tertiary specialist clinic. In Study I (n=106), a total of 14 common ME/CFS symptoms were quantified and latent symptom subgroups were explored. The relationship between latent symptom subgroups and measures of health and functioning were investigated. In Study II (n=40), the effects of the ACT treatment on measures of disability, symptoms and health-related functioning were investigated. In Study III (n=53), associations between inflammatory markers and common symptoms in ME/CFS were investigated. In Study IV, levels of subjective sickness behavior were investigated in, and compared between: patients with ME/CFS (n=40); patients with chronic pain (n=193); patients in primary care (n=168), and; individuals from the general population (n=163). The associations between sickness behavior and self-rated health, mental and physical health-related functioning were also explored. Results: The results in Study I showed four distinct subgroups in which differentiated symptoms gathered representing inflammatory, pain, neurocognitive and autonomic symptoms respectively. The symptom subgroups overall showed significant correlations with important clinical measures, although rarely exceeding .50, indicating the importance of other factors. ACT-based behavior medicine treatment can be considered acceptable, safe and preliminary effective for patients with ME/CFS (Study II). In Study III, several inflammatory markers (β-NGF; CCL11; CXCL10; IL-7; TGF-β-1 and; TNF- ) significant associations with common symptoms (post-exertional fatigue; impaired cognitive processing; musculoskeletal pain, and; recurrent flu-like symptoms). The level of sickness behavior was similar between ME/CFS and chronic pain patients, and significantly higher than in patients from primary care and individuals from the general population (p’s <.001). Conclusions: Symptoms in ME/CFS seem to present in distinct patterns, underlining the importance of the further study of symptom but also illness subtypes. However, factors other than criteria symptoms, such as experiential avoidance and cognitive fusion, are likely more accessible targets in behavior medicine treatment. The results from the ACT-based feasibility study indicate the utility of conceptualizing disability in ME/CFS from a modern learning theory perspective, and the ACT-based behavior medicine treatment format should be further investigated in randomized controlled studies. Finally, sickness behavior processes may guide future research in the differentiation of ME/CFS illness subtypes, as indicated by the level of subjective sickness behavior reported in ME/CFS which is equal to the level found when healthy human subjects are injected with bacterial endotoxin to cause transient sickness behavior in an experimental setting

Chronic fatigue syndromes: real illnesses that people can recover from

The ‘Oslo Chronic Fatigue Consortium’ consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation. Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them

The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms

Background: Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) often present with a range of flu-like symptoms resembling sickness behavior as well as widespread pain and concentration deficits. The aim of this study was to explore the association between inflammatory markers previously shown to be related to fatigue severity in ME/CFS and common ME/CFS symptoms post-exertional fatigue, impaired cognitive processing, musculoskeletal pain and recurrent flu-like symptoms, and the moderating effect of sex on these associations. Methods: 53 adult patients diagnosed with ME/CFS at a specialist clinic were included in the study. Fasting blood plasma was analyzed using the Olink Proseek Multiplex Inflammation panel (beta-NGF, CCL11, CXCL1, CXCL10, IL-6, IL-7, IL-8, IL-10, IL-18, TGF-alpha, TGF-beta-1 and SCF) and BioRad Human Cytokine Type 1 assay (TNF-alpha). Participants rated the average severity of symptoms (0-10) based on the 2011 International Consensus Criteria of ME/CFS during a structured clinical interview. Associations between inflammatory markers and symptom severity were analyzed using bivariate correlations and moderated regression analyses bootstrapped with 5000 repetitions. Results and conclusions: Only beta-NGF was associated with the fatigue severity measure. However, higher levels of CCL11, CXCL10, IL-7, TNF-alpha and TGF-beta-1 were significantly associated with higher levels of impaired cognitive processing and musculoskeletal pain, and sex was a significant moderator for CXCL10, IL-7 and TGF-beta-1. Future studies should investigate the relationship between inflammatory markers and key symptoms in ME/CFS in a longitudinal design in order to explore if and for whom low-grade inflammation may contribute to illness development

Patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation

Background: Chronic sickness behavior is implicated in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain but the level of subjective sickness behavior in these conditions has not been investigated or compared to other clinical and non-clinical samples, or to the level in experimental inflammation. Furthermore, the relationship between sickness behavior and self-rated health and functioning is not known in patients with ME/CFS and chronic pain. The aim of the present study was to investigate how sickness behavior in patients with chronic conditions differs from that in individuals with experimental acute sickness, primary care patients, the general population and healthy subjects. In addition, we wanted to explore how sickness behavior is related to self-rated health and health-related functioning. Methods: Sickness behavior was quantified using the sickness questionnaire (SicknessQ). Self-ratings were collected at one time-point in 6 different samples. Levels of sickness behavior in patients with ME/CFS (n ​= ​38) and patients with chronic pain (n ​= ​190) were compared to healthy subjects with lipopolysaccharide(LPS)-induced inflammation (n ​= ​29), primary care patients (n ​= ​163), individuals from the general population (n ​= ​155) and healthy subjects (n ​= ​48), using linear regression. Correlations and moderated regression analyses were used to investigate associations between sickness behavior and self-rated health and health-related functioning in ME/CFS, chronic pain and the general population. Results: LPS-injected individuals (M ​= ​16.3), patients with ME/CFS (M ​= ​16.1), chronic pain (M ​= ​16.1) and primary care patients (M ​= ​10.7) reported significantly higher SicknessQ scores than individuals from the general population (M ​= ​5.4) and healthy subjects (M ​= ​3.6) all p’s ​< ​0.001). In turn, LPS-injected individuals, patients with ME/CFS and chronic pain reported significantly higher SicknessQ scores than primary care patients (p’s ​< ​0.01). Higher levels of sickness behavior were associated with poorer self-rated health and health-related functioning (p’s ​< ​0.01), but less so in patients with ME/CFS and chronic pain than in individuals from the general population. Conclusions: Patients with ME/CFS and chronic pain report similar high levels of sickness behavior; higher than primary care patients, and comparable to levels in experimental inflammation. Further study of sickness behavior in ME/CFS and chronic pain populations is warranted as immune-to-brain interactions and sickness behavior may be of importance for functioning as well as in core pathophysiological processes in subsets of patients