risk factors – Page 8 – American ME and CFS Society

Genetic Risk Factors of ME/CFS: A Critical Review

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex multisystem illness that lacks effective therapy and a biomedical understanding of its causes. Despite a prevalence of approximately 0.2-0.4% and its high public health burden, and evidence that it has a heritable component, ME/CFS has not yet benefited from the advances in technology and analytical tools that have improved our understanding of many other complex diseases.

Here we critically review existing evidence that genetic factors alter ME/CFS risk before concluding that most ME/CFS candidate gene associations are not replicated by the larger CFS cohort within UK Biobank. Multiple genome-wide association studies of this cohort also have not yielded consistently significant associations. Ahead of upcoming larger genome-wide association studies we discuss how these could generate new lines of enquiry into the DNA variants, genes and cell-types that are causally involved in ME/CFS disease.

Source: Dibble JJ, McGrath SJ, Ponting CP. Genetic Risk Factors of ME/CFS: A Critical Review [published online ahead of print, 2020 Aug 3]. Hum Mol Genet. 2020;ddaa169. doi:10.1093/hmg/ddaa169 https://pubmed.ncbi.nlm.nih.gov/32744306/

Associations of physical and psychiatric conditions with chronic fatigue syndrome in Germany: an exploratory case-control study

Abstract:

Background: Only a few studies have analyzed the effects of physical and psychiatric conditions on the risk of chronic fatigue syndrome (CFS). Therefore, the goal of this exploratory case-control study was to investigate the associations of physical and psychiatric conditions with CFS in almost 19 800 adults from Germany.

Methods: This study included patients diagnosed for the first time with CFS in one of 1238 general practices in Germany between 2010 and 2017 (index date). Controls without CFS were matched (1:1) to cases with CFS by sex, age, index year, and practice. Physical and psychiatric conditions diagnosed in the year prior to the index date were included if they were present in at least 3% of patients with CFS. Associations between physical and psychiatric conditions (33 potential independent variables) and CFS (dependent variable) were analyzed in an adjusted conditional logistic regression model, and physical and psychiatric disorders were included in the model using forward stepwise selection.

Results: This study included 9896 cases with CFS and 9896 controls without CFS [65.1% women; mean (standard deviation) age 49.5 (18.3) years]. Seven conditions were associated with CFS in the adjusted regression model. The disorders displaying the strongest relationship with CFS were cancer [odds ratio (OR) = 2.57, 95% confidence interval (CI) = 2.24-2.95], sleep disorders (OR = 1.88, 95% CI = 1.66-2.12) and depression (OR = 1.77, 95% CI = 1.61-1.95).

Conclusions: Cancer, sleep disorders, and depression were strongly and positively associated with CFS. Additional studies are needed to gain a better understanding of the mechanisms underlying these relationships.

Source: Jacob L, Haro JM, Kostev K. Associations of physical and psychiatric conditions with chronic fatigue syndrome in Germany: an exploratory case-control study [published online ahead of print, 2020 Jul 20]. Psychol Med. 2020;1-7. doi:10.1017/S0033291720002470 https://pubmed.ncbi.nlm.nih.gov/32686638/

Risk Factors for Suicide in Chronic Fatigue Syndrome

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) includes symptoms such as post-exertional malaise, unrefreshing sleep, and cognitive impairments. Several studies suggest these patients have an increased risk of suicidal ideation and early mortality, although few have published in this area.

This study explores risk factors for suicide among 64 individuals with ME/CFS using archival data, 17 of which died from suicide. Results indicated an increased risk of suicide for those for those utilizing the label CFS, for those with limited overall functioning, and for those without comorbid illnesses. Findings suggest that stigma and functional impairments limit access to care and social supports.

Source: Johnson ML, Cotler J, Terman JM, Jason LA. Risk factors for suicide in chronic fatigue syndrome [published online ahead of print, 2020 Jun 12]. Death Stud. 2020;1‐7. doi:10.1080/07481187.2020.1776789

Associations of occupational stress, workplace violence and organizational support on chronic fatigue symptoms among nurses

Abstract:

AIMS: Chronic fatigue syndrome is an agnogenic disease worldwide. Nurses are at a high risk of chronic fatigue syndrome. However, no research has been done to examine the associations of workplace violence, organizational support and occupational stress with chronic fatigue syndrome among Chinese nurses. This study aimed to examine effects of these factors on chronic fatigue syndrome in this occupational group.

DESIGN: Cross-sectional. All participants voluntarily completed a questionnaire survey.

METHODS: The study was conducted in Liaoning province from December 2017 to January 2018. Self-administered questionnaires were distributed to 1200 nurses, including Effort-Reward-Imbalance, Workplace Violence Scale, Survey of Perceived Organizational Support, together with age, gender, marital status, education levels, physical activities, job rank, monthly income and weekly working hours. Complete responses were obtained from 1080 (90%) participants. Chronic fatigue syndrome was diagnosed by doctors according to the Centers for Disease Control and Prevention criteria. Multivariable logistic regression was performed to examine these independent risk factors.

RESULTS: The prevalence of chronic fatigue syndrome was 6.76%. The results of logistic regression analysis showed that nurses who experienced serious higher levels of overcommitment, workplace violence and less organizational support were more likely to be classified as chronic fatigue syndrome.

CONCLUSION: There was a high prevelence of chronic fatigue syndrome. Lower workplace violence, more organizational support and lower overcommitment could be effective resources for reducing chronic fatigue syndrome.

IMPACT: Workplace violence, organizational support and occupational stress were related to chronic fatigue syndrome, which helped to explain why Chinese nurses suffered higher prevelance of chronic fatigue syndrome. Overcommitment explained chronic fatigue syndrome better than Effort/Reward Ratio, so intrinsic stress played a more critical role than extrinsic stress in chronic fatigue syndrome. Chinese nurses suffered serious sleep disorders and impairment of concentration and memory. These symptoms might also atributed to serious occupational stress, unsafe and unsupportive working environment. Creating a safe and supportive working emvironment, releiving intrinsic occupational stress should be considered as an institutional strategy to early prevent chronic fatigue syndrome.

Source: Li M, Shu Q, Huang H, Bo W, Wang L, Wu H. Associations of occupational stress, workplace violence and organizational support on chronic fatigue symptoms among nurses. J Adv Nurs. 2020 Feb 3. doi: 10.1111/jan.14312. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32011012

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a Hyper-Regulated Immune System Driven by an Interplay Between Regulatory T Cells and Chronic Human Herpesvirus Infections

Abstract:

Autoimmunity and chronic viral infections are recurrent clinical observations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a complex disease with an unknown cause. Given these observations, the regulatory CD4+ T cells (Tregs) show promise to be good candidates for the underlying pathology due to their capacity to suppress the immune responses against both self and microbial antigens. Here, we discussed the overlooked role of these cells in the chronicity of Human Herpes Virus 6 (HHV6), Herpes Simplex 1 (HSV1), and Epstein-Barr virus (EBV), as often reported as triggers of ME/CFS.

Using simulations of the cross-regulation model for the dynamics of Tregs, we illustrated that mild infections might lead to a chronically activated immune responses under control of Tregs if the responding clone has a high autoimmune potential. Such infections promote persistent inflammation and possibly fatigue. We then hypothesized that ME/CFS is a condition characterized by a predominance of this type of infections under control of Tregs. In contrast, healthy individuals are hypothesized to trigger immune responses of a virus-specific clone with a low autoimmune potential.

According to this hypothesis, simple model simulations of the CD4+ T-cell repertoire could reproduce the increased density and percentages of Tregs observed in patients suffering from the disease, when compared to healthy controls. A deeper analysis of Tregs in the pathogenesis of ME/CFS will help to assess the validity of this hypothesis.

Source: Sepúlveda N, Carneiro J, Lacerda E, Nacul L. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a Hyper-Regulated Immune System Driven by an Interplay Between Regulatory T Cells and Chronic Human Herpesvirus Infections. Front Immunol. 2019 Nov 21;10:2684. doi: 10.3389/fimmu.2019.02684. eCollection 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883905/ (Full article)

Intimate Partner Violence and the Risk of Developing Fibromyalgia and Chronic Fatigue Syndrome

Abstract:

Intimate partner violence (IPV) is a global public health issue with a variety of ill health consequences associated with exposure. Due to the stimulation of chronic stress and inflammatory pathways, childhood abuse has been associated with the subsequent development of functional syndromes such as fibromyalgia and chronic fatigue syndrome (CFS). Although IPV in women appears to elicit similar biochemical responses, this association has not been tested thoroughly in IPV survivors. These functional syndromes are complex in etiology and any indication of their risk factors would benefit health care professionals managing this population. Therefore, we aimed to investigate the association between exposure to IPV with functional syndromes: fibromyalgia and CFS.

We conducted a retrospective open cohort study using “The Heath Improvement Network” database between January 1, 1995 and December 1, 2017. A total of 18,547 women who were exposed to IPV were each matched by age to four controls who were not exposed (n = 74,188). The main outcome measures were the risk of developing fibromyalgia and CFS. These were presented as adjusted incidence rate ratios (aIRR) with 95% confidence intervals (CIs).

We found that 97 women in the exposed group developed fibromyalgia (incidence rate [IR] = 1.63 per 1,000 person-years) compared to 239 women in the unexposed group (IR = 0.83 per 1,000 person-years). Following adjustment, this translated to an IRR of 1.73 (95% CI = [1.36, 2.22]). Similarly, 19 women developed CFS in the exposed group (IR = 0.32 per 1,000 person-years), compared to 53 in the unexposed group (0.18 per 1,000 person-years), which translates to an aIRR of 1.92 (95% CI = [1.11, 3.33]).

Therefore, we have identified an association between a history of IPV in women and the development of these functional syndromes, which may provide more information to inform the biopsychosocial pathway precipitating the development of fibromyalgia and CFS.

Source: Chandan JS, Thomas T, Raza K, Bradbury-Jones C, Taylor J, Bandyopadhyay S1, Nirantharakumar K. Intimate Partner Violence and the Risk of Developing Fibromyalgia and Chronic Fatigue Syndrome. J Interpers Violence. 2019 Dec 6:886260519888515. doi: 10.1177/0886260519888515. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31805821

A logistic regression analysis of risk factors in ME/CFS pathogenesis

Abstract:

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease, whose exact cause remains unclear. A wide range of risk factors has been proposed that helps understanding potential disease pathogenesis. However, there is little consistency for many risk factor associations, thus we undertook an exploratory study of risk factors using data from the UK ME/CFS Biobank participants. We report on risk factor associations in ME/CFS compared with multiple sclerosis participants and healthy controls.

METHODS: This was a cross-sectional study of 269 people with ME/CFS, including 214 with mild/moderate and 55 with severe symptoms, 74 people with multiple sclerosis (MS), and 134 healthy controls, who were recruited from primary and secondary health services. Data were collected from participants using a standardised written questionnaire. Data analyses consisted of univariate and multivariable regression analysis (by levels of proximity to disease onset).

RESULTS: A history of frequent colds (OR = 8.26, P <= 0.001) and infections (OR = 25.5, P = 0.015) before onset were the strongest factors associated with a higher risk of ME/CFS compared to healthy controls. Being single (OR = 4.41, P <= 0.001), having lower income (OR = 3.71, P <= 0.001), and a family history of anxiety is associated with a higher risk of ME/CFS compared to healthy controls only (OR = 3.77, P < 0.001). History of frequent colds (OR = 6.31, P < 0.001) and infections before disease onset (OR = 5.12, P = 0.005), being single (OR = 3.66, P = 0.003) and having lower income (OR = 3.48, P = 0.001), are associated with a higher risk of ME/CFS than MS. Severe ME/CFS cases were associated with lower age of ME/CFS onset (OR = 0.63, P = 0.022) and a family history of neurological illness (OR = 6.1, P = 0.001).

CONCLUSIONS: Notable differences in risk profiles were found between ME/CFS and healthy controls, ME/CFS and MS, and mild-moderate and severe ME/CFS. However, we found some commensurate overlap in risk associations between all cohorts. The most notable difference between ME/CFS and MS in our study is a history of recent infection prior to disease onset. Even recognising that our results are limited by the choice of factors we selected to investigate, our findings are consistent with the increasing body of evidence that has been published about the potential role of infections in the pathogenesis of ME/CFS, including common colds/flu.

Source: Lacerda EM, Geraghty K, Kingdon CC, Palla L, Nacul L. A logistic regression analysis of risk factors in ME/CFS pathogenesis. BMC Neurol. 2019 Nov 7;19(1):275. doi: 10.1186/s12883-019-1468-2. https://www.ncbi.nlm.nih.gov/pubmed/31699051

Increased risk of chronic fatigue syndrome following psoriasis: a nationwide population-based cohort study

Abstract:

BACKGROUND: The onset of chronic fatigue syndrome (CFS) has been shown to be associated with several immunological conditions such as infections or atopy. The aim of this study was to clarify the risk of chronic fatigue syndrome following the diagnosis of psoriasis, an immune-related dermatological disease, by analyzing the National Health Insurance Research Database of Taiwan.

METHOD: 2616 patients aged 20 years or older with newly diagnosed psoriasis during 2004-2008 and 10,464 participants without psoriasis were identified. Both groups were followed up until the diagnoses of CFS were made at the end of 2011.

RESULTS: The relationship between psoriasis and the subsequent risk of CFS was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 2.27 and 3.58 per 1000 person-years among the non-psoriasis and psoriasis populations, respectively (adjusted hazard ratio [HR] = 1.48, with 95% confidence interval [CI] 1.07-2.06). In the stratified analysis, the psoriasis group were consistently associated with a higher risk of CFS in male sex (HR = 2.05, 95% CI 1.31-3.20) and age group of ≥ 60 years old (HR = 2.32, 95% CI 1.33-4.06). In addition, we discovered that the significantly increased risk of CFS among psoriasis patients is attenuated after they receive phototherapy and/or immunomodulatory drugs.

CONCLUSIONS: The data from this population-based retrospective cohort study revealed that psoriasis is associated with an elevated risk of subsequent CFS, which is differentiated by sex and age.

Source: Tsai SY, Chen HJ, Chen C, Lio CF, Kuo CF, Leong KH, Wang YT, Yang TY, You CH, Wang WS. Increased risk of chronic fatigue syndrome following psoriasis: a nationwide population-based cohort study. J Transl Med. 2019 May 14;17(1):154. doi: 10.1186/s12967-019-1888-1. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-1888-1 (Full article)

A Validated Scale for Assessing the Severity of Acute Infectious Mononucleosis

Abstract:

OBJECTIVES: To develop a scale for the severity of mononucleosis.

STUDY DESIGN: One to 5 percent of college students develop infectious mononucleosis annually, and about 10% meet criteria for chronic fatigue syndrome (CFS) 6 months following infectious mononucleosis. We developed a severity of mononucleosis scale based on a review of the literature. College students were enrolled, generally when they were healthy. When the students developed infectious mononucleosis, an assessment was made as to the severity of their infectious mononucleosis independently by 2 physicians using the severity of mononucleosis scale. This scale was correlated with corticosteroid use and hospitalization. Six months following infectious mononucleosis, an assessment is made for recovery from infectious mononucleosis or meeting 1 or more case definitions of CFS.

RESULTS: In total, 126 severity of mononucleosis scales were analyzed. The concordance between the 2 physician reviewers was 95%. All 3 hospitalized subjects had severity of mononucleosis scores ≥2. Subjects with severity of mononucleosis scores of ≥1 were 1.83 times as likely to be given corticosteroids. Students with severity of mononucleosis scores of 0 or 1 were less likely to meet more than 1 case definition of CFS 6 months following infectious mononucleosis.

CONCLUSIONS: The severity of mononucleosis scale has interobserver, concurrent and predictive validity for hospitalization, corticosteroid use, and meeting criteria for CFS 6 months following infectious mononucleosis.

Source: Katz BZ, Reuter C, Lupovitch Y, Gleason K, McClellan D, Cotler J, Jason LA. A Validated Scale for Assessing the Severity of Acute Infectious Mononucleosis. J Pediatr. 2019 Mar 7. pii: S0022-3476(19)30123-4. doi: 10.1016/j.jpeds.2019.01.035. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30853204

Increased risk of chronic fatigue syndrome in patients with inflammatory bowel disease: a population-based retrospective cohort study

Abstract:

BACKGROUND: Similarities in the symptoms of chronic fatigue syndrome (CFS) and inflammatory bowel disease (IBD) have been observed as follows: severe disease activity in IBD correlates with severe fatigue, major psychiatric signs, the common use of medication, and bacterial translocation. One of several hypotheses for explaining the mechanisms underlying CFS suggests a similarity to the impaired intestinal mucosa of IBD. “This study investigated the risk of incident CFS among patients with IBD”.

METHODS: We conducted a population-based retrospective cohort study by using Taiwan’s National Health Insurance Research Database to evaluate the subsequent risk of CFS in patients with IBD, according to demographic characteristics and comorbidities. The exposure cohort comprised 2163 patients with new diagnoses of IBD. Each patient was randomly selected and frequency matching according to gender and age with four participants from the general population who had no history of CFS at the index date (control cohort). Cox proportional hazards regression analysis was conducted to estimate the relationship between IBD and the subsequent risk of CFS.

RESULTS: The exposure cohort had a significantly higher overall risk of subsequent CFS than that of the control group [adjusted hazard ratio (Christophi in Inflamm Bowel Dis 18(12):2342-2356, 2012) = 2.25, 95%, confidence interval (Aaron and Buchwald in Ann Intern Med 134(9 Pt 2):868-881, 2001; Farraye et al. in Am J Gastroenterol 112:241, 2017) 1.70-2.99]. Further analysis indicated a significantly higher risk of CFS in patients who were male (HR = 3.23, 95% CI 2.12-4.91), were older than 35 years, and had IBD but without comorbidity status, e.g. Cancers, diabetes, obesity, depression, anxiety, sleep disorder, renal disease (HR = 2.50, 95% CI 1.63-3.84) after adjustment.

CONCLUSION: The findings from this population-based retrospective cohort study suggest that IBD, especially Crohn’s disease, is associated with an increased risk of subsequent CFS.

Source: Tsai SY, Chen HJ, Lio CF, Kuo CF, Kao AC, Wang WS, Yao WC, Chen C, Yang TY. Increased risk of chronic fatigue syndrome in patients with inflammatory bowel disease: a population-based retrospective cohort study. J Transl Med. 2019 Feb 22;17(1):55. doi: 10.1186/s12967-019-1797-3. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-1797-3 (Full article)