VIDEO: Discovery Forum 2017 Highlights: ME/CFS and Gulf War Illness

The Solve ME/CFS Initiative presents highlights from Discovery Forum 2017 addressing the connections between Gulf War Illness and ME/CFS, featuring the presentation of Dr. Nancy Klimas of Nova Southeastern University. Dr. Klimas has more than 30 years of professional experience and has achieved international recognition for her research and clinical efforts in Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Gulf War Illness (GWI).

Autonomic nervous system function, activity patterns, and sleep after physical or cognitive challenge in people with chronic fatigue syndrome

Abstract:

OBJECTIVE: To explore changes in autonomic functioning, sleep, and physical activity during a post-exertional symptom exacerbation induced by physical or cognitive challenge in participants with chronic fatigue syndrome (CFS).

METHODS: Thirty-five participants with CFS reported fatigue levels 24-h before, immediately before, immediately after, and 24-h after the completion of previously characterised physical (stationary cycling) or cognitive (simulated driving) challenges. Participants also provided ratings of their sleep quality and sleep duration for the night before, and after, the challenge. Continuous ambulatory electrocardiography (ECG) and physical activity was recorded from 24-h prior, until 24-h after, the challenge. Heart rate (HR) and HR variability (HRV, as high frequency power in normalized units) was derived from the ECG trace for periods of wake and sleep.

RESULTS: Both physical and cognitive challenges induced an immediate exacerbation of the fatigue state (p<0.001), which remained elevated 24-h post-challenge. After completing the challenges, participants spent a greater proportion of wakeful hours lying down (p=0.024), but did not experience significant changes in sleep quality or sleep duration. Although the normal changes in HR and HRV during the transition from wakefulness to sleep were evident, the magnitude of the increase in HRV was significantly lower after completing the challenge (p=0.016).

CONCLUSION: Preliminary evidence of reduced nocturnal parasympathetic activity, and increased periods of inactivity, were found during post-exertional fatigue in a well-defined group of participants with CFS. Larger studies employing challenge paradigms are warranted to further explore the underlying pathophysiological mechanisms of post-exertional fatigue in CFS.

Copyright © 2017 Elsevier Inc. All rights reserved.

Source: Cvejic E, Sandler CX, Keech A, Barry BK, Lloyd AR, Vollmer-Conna U.Autonomic nervous system function, activity patterns, and sleep after physical or cognitive challenge in people with chronic fatigue syndrome. J Psychosom Res. 2017 Dec;103:91-94. doi: 10.1016/j.jpsychores.2017.10.010. Epub 2017 Oct 19. https://www.ncbi.nlm.nih.gov/pubmed/29167053

Neuroendocrine disorder in chronic fatigue syndrome

Abstract:

Background/aim: Neuroendocrine disorders are considered a possible pathogenetic mechanism in chronic fatigue syndrome (CFS). The aim of our study was to determine the function of the hypothalamic-pituitary-adrenal axis (HPA) and thyroid function in women of reproductive age suffering from CFS.

Materials and methods: The study included 40 women suffering from CFS and 40 healthy women (15-45 years old). Serum levels of cortisol (0800 and 1800 hours), ACTH, total T4, total T3, and TSH were measured in all subjects. The Fibro Fatigue Scale was used for determination of fatigue level.

Results: Cortisol serum levels were normal in both groups. The distinctively positive moderate correlation of morning and afternoon cortisol levels that was observed in healthy women was absent in the CFS group. This may indicate a disturbed physiological rhythm of cortisol secretion. Although basal serum T4, T3, and TSH levels were normal in all subjects, concentrations of T3 were significantly lower in the CFS group.

Conclusion: One-time hormone measurement is not sufficient to detect hormonal imbalance in women suffering from CFS. Absence of a correlation between afternoon and morning cortisol level could be a more representative factor for detecting HPA axis disturbance.

Source: Tomic S, Brkic S, Lendak D, Maric D, Medic Stojanoska M, Novakov Mikic A. Neuroendocrine disorder in chronic fatigue syndrome. Turk J Med Sci. 2017 Aug 23;47(4):1097-1103. doi: 10.3906/sag-1601-110. https://www.ncbi.nlm.nih.gov/pubmed/29154201

Decreased connectivity and increased BOLD complexity in the default mode network in individuals with chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome / myalgic encephalomyelitis (CFS) is a debilitating disease with unknown pathophysiology and no diagnostic test. This study investigated the default mode network (DMN) in order to understand the pathophysiology of CFS and to identify potential biomarkers.

Using functional MRI (fMRI) collected from 72 subjects (45 CFS and 27 controls) with a temporal resolution of 0.798s, we evaluated the default mode network using static functional connectivity (FC), dynamic functional connectivity (DFC) and DFC complexity, blood oxygenation level dependent (BOLD) activation maps and complexity of activity. General linear model (GLM) univariate analysis was used for inter group comparison to account for age and gender differences. Hierarchical regression analysis was used to test whether fMRI measures could be used to explain variances of health scores.

BOLD signals in the posterior cingulate cortex (PCC), the driving hub in the DMN, were more complex in CFS in both resting state and task (P < 0.05). The FCs between medial prefrontal cortex (mPFC) and both inferior parietal lobules (IPLs) were weaker (P < 0.05) during resting state, while during task mPFC – left IPL and mPFC – PCC were weaker (P < 0.05). The DFCs between the DMN hubs were more complex in CFS (P < 0.05) during task. Each of these differences accounted for 7 – 11% variability of health scores. This study showed that DMN activity is more complex and less coordinated in CFS, suggesting brain network analysis could be potential used as a diagnostic biomarker for CFS.

Source: Shan ZY, Finegan K, Bhuta S, Ireland T, Staines DR, Marshall-Gradisnik SM, Barnden LR. Decreased connectivity and increased BOLD complexity in the default mode network in individuals with chronic fatigue syndrome. Brain Connect. 2017 Nov 20. doi: 10.1089/brain.2017.0549. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29152994

Can physical assessment techniques aid diagnosis in people with chronic fatigue syndrome/myalgic encephalomyelitis? A diagnostic accuracy study

Abstract:

Objective: To assess five physical signs to see whether they can assist in the screening of patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and potentially lead to quicker treatment.

Methods: This was a diagnostic accuracy study with inter-rater agreement assessment. Participants recruited from two National Health Service hospitals, local CFS/ME support groups and the community were examined by three practitioners on the same day in a randomised order. Two allied health professionals (AHPs) performed independent examinations of physical signs including: postural/mechanical disturbances of the thoracic spine, breast varicosities, tender Perrin’s point, tender coeliac plexus and dampened cranial flow. A physician conducted a standard clinical neurological and rheumatological assessment while looking for patterns of illness behaviour. Each examination lasted approximately 20 min.

Results: Ninety-four participants were assessed, 52 patients with CFS/ME and 42 non-CFS/ME controls, aged 18–60. Cohen’s kappa revealed that agreement between the AHPs was substantial for presence of the tender coeliac plexus (k=0.65, p<0.001) and moderate for postural/mechanical disturbance of the thoracic spine (k=0.57, p<0.001) and Perrin’s point (k=0.56, p<0.001). A McNemar’s test found no statistically significant bias in the diagnosis by the experienced AHP relative to actual diagnosis (p=1.0) and a marginally non-significant bias by the newly trained AHP (p=0.052). There was, however, a significant bias in the diagnosis made by the physician relative to actual diagnosis (p<0.001), indicating poor diagnostic utility of the clinical neurological and rheumatological assessment.

Conclusions: Using the physical signs appears to improve the accuracy of identifying people with CFS/ME and shows agreement with current diagnostic techniques. However, the present study concludes that only two of these may be needed. Examining for physical signs is both quick and simple for the AHP and may be used as an efficient screening tool for CFS/ME. This is a small single-centre study, and therefore, further validation in other centres and larger populations is needed.

Source: Lucy Hives, Alice Bradley, Jim Richards, Chris Sutton, James Selfe, Bhaskar Basu, Kerry Maguire, Gail Sumner, Tarek Gaber, Annice Mukherjee, Raymond N Perrin. Can physical assessment techniques aid diagnosis in people with chronic fatigue syndrome/myalgic encephalomyelitis? A diagnostic accuracy study. BMJ Open, Volume 7, Issue 11.   http://bmjopen.bmj.com/content/7/11/e017521 (Full article)

Exercise – induced changes in cerebrospinal fluid miRNAs in Gulf War Illness, Chronic Fatigue Syndrome and sedentary control subjects

Abstract:

Gulf War Illness (GWI) and Chronic Fatigue Syndrome (CFS) have similar profiles of pain, fatigue, cognitive dysfunction and exertional exhaustion. Post-exertional malaise suggests exercise alters central nervous system functions. Lumbar punctures were performed in GWI, CFS and control subjects after (i) overnight rest (nonexercise) or (ii) submaximal bicycle exercise. Exercise induced postural tachycardia in one third of GWI subjects (Stress Test Activated Reversible Tachycardia, START). The remainder were Stress Test Originated Phantom Perception (STOPP) subjects. MicroRNAs (miRNA) in cerebrospinal fluid were amplified by quantitative PCR. Levels were equivalent between nonexercise GWI (n = 22), CFS (n = 43) and control (n = 22) groups. After exercise, START (n = 22) had significantly lower miR-22-3p than control (n = 15) and STOPP (n = 42), but higher miR-9-3p than STOPP. All post-exercise groups had significantly reduced miR-328 and miR-608 compared to nonexercise groups; these may be markers of exercise effects on the brain. Six miRNAs were significantly elevated and 12 diminished in post-exercise START, STOPP and control compared to nonexercise groups. CFS had 12 diminished miRNAs after exercise. Despite symptom overlap of CFS, GWI and other illnesses in their differential diagnosis, exercise-induced miRNA patterns in cerebrospinal fluid indicated distinct mechanisms for post-exertional malaise in CFS and START and STOPP phenotypes of GWI.

Source: James N. Baraniuk & Narayan Shivapurkar. Exercise – induced changes in cerebrospinal fluid miRNAs in Gulf War Illness, Chronic Fatigue Syndrome and sedentary control subjects. Scientific Reports 7, Article number: 15338 (2017) doi:10.1038/s41598-017-15383-9    https://www.nature.com/articles/s41598-017-15383-9 (Full article)

Studies and surveys implicate potential iatrogenic harm of cognitive behavioral therapy and graded exercise therapy for myalgic encephalomyelitis and chronic fatigue syndrome patients

Abstract:

Cognitive behavorial therapy (CBT) and graded exercise therapy (GET) are declared to be effective and safe therapies for Myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Medical policies in various countries, e.g. the UK and the Netherlands, recommend CBT and GET as evidence-based treatments. But studies and patient surveys in several countries indicate that CBT often has no effect at all and that GET has detrimental effects in a large subgroup of patients.

Editorial

ME is a disease characterized by distinctive muscular symptoms, including muscle weakness and myalgia after minor exertion lasting for days, neurological symptoms implicating cerebral dysfunction, symptoms indicating circulatory impairment and other symptoms [1,2]. CFS is primarily defined by (unexplained) chronic fatigue, which must be accompanied by at least four out of eight ‘additional’’ symptoms [3]. ME and CFS are incorrectly conceived as ‘similar disorders’ [4]. But the case criteria define three patient groups: ME and/or CFS patients [5], labeled as ME/CFS patients within this context.

Cognitive behavioral therapy (CBT) and graded exercise therapy (GET) are declared to be effective [6,7] and safe [7,8] therapies for Myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Medical policies in various countries, e.g. the UK [9] and the Netherlands [10], recommend CBT and GET as evidence-based treatments.

However various studies implicate that CBT, GET and other behavioral interventions, including graded activity, have negative effects on (subgroups of) ME/CFS patients.

Núñez and co-workers [11] observed that adding CBT and GET to pharmacological treatment had a negative effect on SF-36 physical functioning and pain scores. Jason and others [12,13] found that ‘non-pharmacologic therapies’ had a negative effect on the mean SF- 36 physical functioning score (changes from 5 to -35) of a large subgroup of CFS patients, with lymphocyte subsets data suggesting an elevated humoral immune response (Th2/B Cell). Although ‘Guided graded Exercise Self-help’ (GET) was qualified as “a moderately effective and safe intervention” [14], the investigators acknowledged that a patient subgroup had deteriorated after the GET trial, possibly due to “a worse exacerbation of symptoms in response to GET” [15].

In various surveys [16-18] most ME/CFS patients experienced no improvement after CBT and more than half of the patients reported GET made them worse. A detailed analysis [18] of a large-scale patient survey in the UK [19] shows that, when combinations of therapies are excluded, 73% of the patients they stayed the same after CBT, while 8% of the patients improved and 18% got worse. No less than 74% of the patients reported worsening of their symptoms after GET, 14% of the patients experienced no change and only 12% reported improvement after GET. In a recent patient survey in the Netherlands [20] 11% reported CBT had improved their health situation, 36% experienced no change, and 53% reported CBT had worsened their condition. 63% reported GET had made their symptoms (much) worse and 34% reported no change. Only 3% of the patients experienced improvement after GET. One could argue that patient surveys (through the internet) are potentially prone to many biases, but a study [21] found that ‘’unsolicited’ web-based patient ratings of care correlate well with conventional research findings, i.e. formal measurements.

As affirmed by the medical authorities in the US recently, “ME/CFS is a serious, chronic, complex, multisystem disease” [4] with “strong evidence” indicating that “immunologic and inflammatory pathologic conditions, neurotransmitter signaling disruption, microbiome perturbation, and metabolic or mitochondrial abnormalities are potentially important for the definition and treatment of ME/CFS [22]. Exertion has (prolonged) negative effects in ME/CFS [4]. For that reason studies and surveys indicating potential harm of CBT and GET in large subgroups of ME/CFS patients should be taken seriously. The ‘safety claim’ is at odds with several observations.

References

  1. Dowsett EG, Ramsay AM, McCartney RA, et al. Myalgic Encephalomyelitis – a persistent enteroviral infection? Postgrad. Med. J.66(777), 526-530 (1990).

  2. Ramsay AM, Dowsett EG, Myalgic Encephalomyelitis: Then and now. In Hyde BM, Goldstein J, Levine P, editors. The Clinical and Scientific Basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Ottawa: The Nightingale Research Foundation pp. 81-84 (1992).

  3. Fukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: a comprehen­sive approach to its definition and study. Ann. Intern. Med. 121(12), 953-959 (1994).

  4. Institute of Medicine. Beyond Myalgic Encephalomyelitis/chronic fatigue syn­drome: redefining an illness. Washington, (2015).

  5. Twisk FNM. Replacing Myalgic Encephalomyelitis and chronic fatigue syndrome with Systemic Exercise Intolerance Disease is not the way forward. Diagnostics (Basel). 6(1), 10 (2016).

  6. Malouff JM, Thorsteinsson EB, Rooke SE, et al. Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta-analysis. Clin. Psychol. Rev. 28(5), 736-745 (2008).

  7. Larun L, Brurberg KG, Odgaard-Jensen J, et al. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev. 4, CD003200 (2017).

  8. Bleijenberg G, Knoop H. Chronic fatigue syndrome: where to PACE from here? Lancet. 377(9768), 786-788 (2011)

  9. National Institute for Health and Clinical Excellence. Chronic fatigue syndrome/ myalgic encephalomyelitis (or encephalopathy): diagnosis and management of chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy) in adults and children. London (UK), (2007).

  10. CBO. Richtlijn diagnose, behandeling, begeleiding en beoordeling van patiënten met het chronisch vermoeidheidssyndroom (CVS). Utrecht (NL), (2013).

  11. Núñez M, Fernández-Solà J, Nuñez E, et al. Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up. Clin. Rheumatol. 30(3), 381-389 (2011).

  12. Jason LA, Torres-Harding S, Friedberg F, et al. Non-pharmacologic interventions for CFS: a randomized trial. J. Clin. Psychol. Med. Settings. 14(4), 275-296 (2007).

  13. Jason LA, Torres-Harding S, Brown M, et al. Predictors of change following participation in non-pharmacologic interventions for CFS. Trop. Med. Health. 36(1), 23-32 (2008).

  14. Clark LV, McCrone P, Ridge D, et al. Graded Exercise Therapy guided Self-hElp Treatment (GETSET) for patients with chronic fatigue syndrome: a randomised controlled trial in secondary care. J. Psychosom. Res. 5(2), 59-60 (2016).

  15. Cheshire A, Ridge D, Clark L, et al. Why patients with chronic fatigue syndrome/ Myalgic Encephalomyelitis improve or deteriorate with graded exercise therapy. J. Psychosom. Res. 85, 59 (2016).

  16. Kirke KD. PACE investigators’ response is misleading regarding patient survey results. J. Health. Psych. 22(9), 1168-1176 (2017).

  17. Twisk FNM, Maes M. A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients. Neuro. Endocrinol. Lett. 30(3), 284-299 (2009).

  18. Geraghty K, Hann M, Kurtev S. Myalgic encephalomyelitis/chronic fatigue syndrome patients’ reports of symptom changes following cognitive behavioural therapy, graded exercise therapy and pacing treatments: Analysis of a primary survey compared with secondary surveys. J. Health. Psychol. (2017).

  19. ME Association. “No decisions about me without me”. ME/CFS illness management survey results, part 1. Gawcott, Bucks (England), (2015).

  20. De Kimpe A, Crijnen B, Kuijper J, et al. Zorg voor ME – Enquête onder ME-patiënten naar hun ervaringen met de zorg in Nederland (2016).

  21. Greaves F, Pape UJ, King D, et al. Associations between Internet-based patient ratings and conventional surveys of patient experience in the English NHS: an observational study. BMJ. Qual. Saf. 21(7), 600-605 (2012).

  22. Green CR, Cowan P, Elk R, et al. National Institutes of Health pathways to prevention workshop: Advancing the research on Myalgic Encephalomyelitis/ chronic fatigue syndrome. Ann. Intern. Med. 162(12), 860-865 (2015).

Source: Frank N.M. Twisk. Studies and surveys implicate potential iatrogenic harm of cognitive behavioral therapy and graded exercise therapy for myalgic encephalomyelitis and chronic fatigue syndrome patients. Research on Chronic Diseases. http://www.openaccessjournals.com/articles/studies-and-surveys-implicate-potential-iatrogenic-harm-of-cognitive-behavioral-therapy-and-graded-exercise-therapy-for-myalgic-en-12190.html

Brain chemistry study shows chronic fatigue syndrome, Gulf War illness as unique disorders

WASHINGTON — Researchers at Georgetown University Medical Center have found distinct molecular signatures in two brain disorders long thought to be psychological in origin — chronic fatigue syndrome (CFS) and Gulf War Illness (GWI).

In addition, the work supports a previous observation by GUMC investigators of two variants of GWI. The disorders share commonalities, such as pain, fatigue, cognitive dysfunction and exhaustion after exercise.

Their study, published in Scientific Reports, lays groundwork needed to understand these disorders in order to diagnosis and treat them effectively, says senior investigator, James N. Baraniuk, MD, professor of medicine at Georgetown University School of Medicine. Narayan Shivapurkar, PhD, assistant professor of oncology at the medical school worked with Baraniuk on the research.

The changes in brain chemistry — observed in levels of miRNAs that turn protein production on or off — were seen 24 hours after riding a stationary bike for 25 minutes.

“We clearly see three different patterns in the brain’s production of these molecules in the CFS group and the two GWI phenotypes,” says Baraniuk. “This news will be well received by patients who suffer from these disorders who are misdiagnosed and instead may be treated for depression or other mental disorders.”

Chronic fatigue syndrome affects between 836,000 and 2.5 million Americans, according to a National Academy of Medicine report. The disorder was thought to be psychosomatic until a 2015 review of 9,000 articles over 64 years of research pointed to unspecified biological causes. Still, no definitive diagnosis or treatment is available.

Gulf War Illness has developed in more than one-fourth of the 697,000 veterans deployed to the 1990-1991 Persian Gulf War, Baraniuk and his colleagues have reported in earlier work.

Gulf War veterans were exposed to combinations of nerve agents, pesticides and other toxic chemicals that may have triggered the chronic pain, cognitive, gastrointestinal and other problems, Baraniuk says. Although the mechanisms remain unknown, the study provides significant insights into brain chemistry that can now be investigated.

This study focused on spinal fluid of CFS, GWI and control subjects who agreed to have a lumbar puncture. Spinal taps before exercise showed miRNA levels were the same in all participants. In contrast, miRNA levels in spinal fluid were significantly different after exercise. The CFS, control and two subtypes of GWI groups had distinct patterns of change. For example, CFS subjects who exercised had reduced levels of 12 different mRNAs, compared to those who did not exercise.

The miRNA changes in the two GWI subtypes add to other differences caused by exercise. One subgroup developed jumps in heart rate of over 30 beats when standing up that lasted for two to three days after exercise. Magnetic resonance imaging showed they had smaller brainstems in regions that control heart rate, and did not activate their brains when doing a cognitive task. In contrast, the other subgroup did not have any heart rate or brainstem changes, but did recruit additional brain regions to complete a memory test. The two groups were as different from each other as they were from the control group.

Finding two distinct pathophysiological miRNA brain patterns in patients reporting Gulf War disease “adds another layer of evidence to support neuropathology in the two different manifestations of Gulf War disease,” he says.

Baraniuk adds that miRNA levels in these disorders were different from the ones that are altered in depression, fibromyalgia, and Alzheimer’s disease, further suggesting CFS and GWI are distinct diseases.

###

The study was supported by funding from The Sergeant Sullivan Center, Dr. Barbara Cottone, Dean Clarke Bridge Prize, Department of Defense Congressionally Directed Medical Research Program (CDMRP) W81XWH-15-1-0679, and National Institute of Neurological Diseases and Stroke R21NS088138 and RO1NS085131.

Baraniuk and Shivapurkar are named as inventors on a patent application that has been filed by Georgetown University related to the technology described.

Vitamin D status in chronic fatigue syndrome/myalgic encephalomyelitis: a cohort study from the North-West of England

Abstract:

OBJECTIVE: Severe vitamin D deficiency is a recognised cause of skeletal muscle fatigue and myopathy. The aim of this study was to examine whether chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with altered circulating vitamin D metabolites.

DESIGN: Cohort study.

SETTING: UK university hospital, recruiting from April 2014 to April 2015.

PARTICIPANTS: Ninety-two patients with CFS/ME and 94 age-matched healthy controls (HCs).

MAIN OUTCOME MEASURES: The presence of a significant association between CFS/ME, fatigue and vitamin D measures.

RESULTS: No evidence of a deficiency in serum total 25(OH) vitamin D (25(OH)D2 and 25(OH)D3 metabolites) was evident in individuals with CFS/ME. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis revealed that total 25(OH)D was significantly higher (p=0.001) in serum of patients with CFS/ME compared with HCs (60.2 and 47.3 nmol/L, respectively). Analysis of food/supplement diaries with WinDiets revealed that the higher total 25(OH) vitamin D concentrations observed in the CFS/ME group were associated with increased vitamin D intake through use of supplements compared with the control group. Analysis of Chalder Fatigue Questionnaire data revealed no association between perceived fatigue and vitamin D levels.

CONCLUSIONS: Low serum concentrations of total 25(OH)D do not appear to be a contributing factor to the level of fatigue of CFS/ME.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Source: Earl KE, Sakellariou GK, Sinclair M, Fenech M, Croden F, Owens DJ, Tang J, Miller A, Lawton C, Dye L, Close GL, Fraser WD, McArdle A, Beadsworth MBJ. Vitamin D status in chronic fatigue syndrome/myalgic encephalomyelitis: a cohort study from the North-West of England. BMJ Open. 2017 Nov 8;7(11):e015296. doi: 10.1136/bmjopen-2016-015296  https://www.ncbi.nlm.nih.gov/pubmed/29118054

The epigenetic landscape of myalgic encephalomyelitis/chronic fatigue syndrome: deciphering complex phenotypes

By their very nature, complex disease phenotypes are characterized by the dysregulation of multiple physiological systems, polygenic origins and various environmental triggers that result in patient populations with heterogeneous symptom profiles. Less than 10% of the heritability of complex phenotypes and disease traits are due to genetic variation, indicating that other factors play major roles in disease onset and progression [1]. Epigenetic modifications may partly account for this ‘missing heritability’ [2] through mechanisms that regulate transcriptional potential. These mechanisms appear to be, at least to some extent, responsive to environmental exposures or treatments. An improved understanding of the pathophysiology underlying complex phenotypes and new diagnostic tools can help refine and update classification criteria reliant on nonspecific or self-reported symptoms. Consequently, unraveling complex phenotypes depends to a large extent upon an ability to discriminate what are likely many distinct conditions. We and others have argued that epigenetic investigations integrate multiple levels of information (genetic, stochastic and environmental) to enable a better understanding of the dimensions of illness underlying complex phenotypes [2,3]. Here, we turn to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to illustrate progress and future directions in this regard.

You can read the rest of this article HERE

Source: de Vega WC, McGowan PO. The epigenetic landscape of myalgic encephalomyelitis/chronic fatigue syndrome: deciphering complex phenotypes. Epigenomics. 2017 Nov;9(11):1337-1340. doi: 10.2217/epi-2017-0106. Epub 2017 Oct 18. https://www.futuremedicine.com/doi/full/10.2217/epi-2017-0106 (Full article)