Inflammation correlates with symptoms in chronic fatigue syndrome

Komaroff, Anthony L.

doi:10.1073/pnas.1712475114

Cited by 52 publications

(48 citation statements)

References 18 publications

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“…Dysfunction of NVC is closely related to neuroinflammation, which is another neurological disease process proposed to underly ME/CFS [85,86]. Dysfunction of NVC may trigger neuroinflammation.…”

Section: Discussionmentioning

confidence: 99%

Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review

et al. 2020

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Background: Since the 1990s, neuroimaging has been utilised to study Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a debilitating illness with unknown aetiology. While brain abnormalities in ME/CFS have been identified, relatively little is known regarding which specific abnormalities are consistently observed across research groups and to what extent the observed abnormalities are reproducible. Method: To identify consistent and inconsistent neuroimaging observations in ME/CFS, this retrospective and systematic review searched for studies in which neuroimaging was used to investigate brain abnormalities in ME/CFS in Ovid MEDLINE, PubMed (NCBI), and Scopus from January 1988 to July 2018. A qualitative synthesis of observations was performed to identify brain abnormalities that were consistently and inconsistently reported. Results: 63 full-text articles were included in the synthesis of results from 291 identified papers. Additional brain area recruitment for cognitive tasks and abnormalities in the brain stem are frequent observations in 11 and 9 studies using different modalities from different research teams respectively. Also, sluggish blood oxygenation level-dependent (BOLD) signal responses to tasks, reduced serotonin transporters, and regional hypometabolism are consistent observations by more than two research teams. Single observations include abnormal brain tissue properties, regional metabolic abnormalities, and association of brain measures with ME/CFS symptoms. Reduced resting cerebral blood flow and volumetric brain changes are inconsistent observations across different studies. Conclusion: Neuroimaging studies of ME/CFS have frequently observed additional brain area recruitment during cognitive tasks and abnormalities in the brain stem. The frequent observation of additional brain area recruitment and consistent observation of sluggish fMRI signal response suggest abnormal neurovascular coupling in ME/CFS.

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Section: Discussionmentioning

confidence: 99%

Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review

et al. 2020

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“…For example, patients diagnosed with post-traumatic stress disorder (PTSD) present with low basal CORT levels but higher levels of circulating pro-inflammatory cytokines including IL-1β, TNFα, and IL-6 (85). Similarly, patients diagnosed with chronic fatigue syndrome have low urinary free CORT levels (86) and severity of symptoms is highly correlated with increased levels of ROS and IFN-γ (87). Together, these studies demonstrate that stress influences immune processes and dysregulation of the HPA axis results in maladaptive inflammation.…”

Section: Stress Influences Inflammation Through Glucocorticoidsmentioning

confidence: 99%

A Tilted Axis: Maladaptive Inflammation and HPA Axis Dysfunction Contribute to Consequences of TBI

2019

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Each year approximately 1.7 million people sustain a traumatic brain injury (TBI) in the US alone. Associated with these head injuries is a high prevalence of neuropsychiatric symptoms including irritability, depression, and anxiety. Neuroinflammation, due in part to microglia, can worsen or even cause neuropsychiatric disorders after TBI. For example, mounting evidence demonstrates that microglia become “primed” or hyper-reactive with an exaggerated pro-inflammatory phenotype following multiple immune challenges. Microglial priming occurs after experimental TBI and correlates with the emergence of depressive-like behavior as well as cognitive dysfunction. Critically, immune challenges are various and include illness, aging, and stress. The collective influence of any combination of these immune challenges shapes the neuroimmune environment and the response to TBI. For example, stress reliably induces inflammation and could therefore be a gateway to altered neuropathology and behavioral decline following TBI. Given the increasing incidence of stress-related psychiatric disorders after TBI, the degree in which stress affects outcome is of particular interest. This review aims to highlight the role of the hypothalamic-pituitary-adrenal (HPA) axis as a key mediator of stress-immune pathway communication following TBI. We will first describe maladaptive neuroinflammation after TBI and how stress contributes to inflammation through both anti- and pro-inflammatory mechanisms. Clinical and experimental data describing HPA-axis dysfunction and consequences of altered stress responses after TBI will be discussed. Lastly, we will review common stress models used after TBI that could better elucidate the relationship between HPA axis dysfunction and maladaptive inflammation following TBI. Together, the studies described in this review suggest that HPA axis dysfunction after brain injury is prevalent and contributes to the dynamic nature of the neuroinflammatory response to brain injury. Experimental stressors that directly engage the HPA axis represent important areas for future research to better define the role of stress-immune pathways in mediating outcome following TBI.

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“…Chronic system-wide inflammation is thought to be central to ME/CFS in the clinical setting as it is associated with symptom severity [64], but the evidence demonstrating a role for specific proinflammatory cytokines is inconsistent. While there are indeed reports of the elevation of various proinflammatory cytokines in ME/CFS [33,71,[94][95][96][97][98][99] which would tie in with the chronic inflammation in the clinical setting, these findings contrast with reports of reduced expression of pro-inflammatory agents such as interleukin-8 or transforming growth factor-beta1 [100,101].…”

Section: Inflammationmentioning

confidence: 99%

Pathological Mechanisms Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Missailidis¹,

Annesley²,

Fisher³

2019

Preprint

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The underlying molecular basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is not well understood. Characterized by chronic, unexplained fatigue, a disabling payback following exertion ("post-exertional malaise") and variably presenting, multi-system symptoms, ME/CFS is a complex disease which demands a concerted biomedical investigation from disparate fields of expertise. ME/CFS research and patient treatment have been challenged by the lack of diagnostic biomarkers and finding these is a prominent direction of current work. Despite these challenges, modern research demonstrates a tangible biomedical basis for the disorder across many body systems. This evidence is mostly comprised of disturbances to immunological and inflammatory pathways, autonomic and neurological dysfunction, abnormalities in muscle and mitochondrial function, shifts in metabolism, and gut physiology or gut microbiota disturbances. It is possible that these threads are together entangled as parts of an underlying molecular pathology reflecting a farreaching homeostatic shift. Due to the variability of non-overlapping symptom presentation or precipitating events such as infection or other bodily stresses, the initiation of body-wide pathological cascades with similar outcomes stemming from different causes may be implicated in the condition. Patient stratification to account for this heterogeneity is therefore one important consideration during exploration of potential diagnostic developments.compounded by medical guidelines in some developed countries which are out of date regarding ME/CFS clinical practice and require urgent, overdue revision.Case definitions such as the commonly termed Oxford [1] or Fukuda [2] criteria are most often utilized throughout the UK and USA respectively, yet may fail to discriminate between generalized chronic fatigue and ME/CFS which specifically also involves PEM, which aids in characterizing this disorder as a discrete clinical entity. Also in usage are the Canadian Consensus Criteria [3] and International Consensus Criteria [4] which mandate PEM for a diagnosis of ME/CFS and therefore may be considered more specific definitions. While the presence of PEM is an optional component of the Fukuda criteria, PEM is, unfortunately, not required for research participation by all studies using this or other less strict definitions. Consequently, the discovery of a reliable diagnostic biomarker is perhaps the most common recurring theme in modern ME/CFS research. Despite myriad relevant study outcomes [5][6][7][8][9][10][11][12][13][14][15][16], no such discovery has yet been widely validated or implemented as a suitable diagnostic biomarker of ME/CFS. Not only does ME/CFS affect multiple body systems and organs, but it does so with different and time-varying levels of severity and different patterns of comorbidities in different individuals, thereby producing a highly heterogeneous patient population [7,[17][18][19][20][21][22][23]. This complexity represents a major challenge to the task of incrim...

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Inflammation correlates with symptoms in chronic fatigue syndrome

Cited by 52 publications

References 18 publications

Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review

Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review

A Tilted Axis: Maladaptive Inflammation and HPA Axis Dysfunction Contribute to Consequences of TBI

Pathological Mechanisms Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

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