Tag: etiology

Herpesviruses Serology Distinguishes Different Subgroups of Patients From the United Kingdom Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Biobank

Abstract:

The evidence of an association between Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and chronic herpesviruses infections remains inconclusive. Two reasons for the lack of consistent evidence are the large heterogeneity of the patients’ population with different disease triggers and the use of arbitrary cutoffs for defining seropositivity. In this work we re-analyzed previously published serological data related to 7 herpesvirus antigens. Patients with ME/CFS were subdivided into four subgroups related to the disease triggers: S0-42 patients who did not know their disease trigger; S1-43 patients who reported a non-infection trigger; S2-93 patients who reported an infection trigger, but that infection was not confirmed by a lab test; and S3-48 patients who reported an infection trigger and that infection was confirmed by a lab test.

In accordance with a sensitivity analysis, the data were compared to those from 99 healthy controls allowing the seropositivity cutoffs to vary within a wide range of possible values. We found a negative association between S1 and seropositivity to Epstein-Barr virus (VCA and EBNA1 antigens) and Varicella-Zoster virus using specific seropositivity cutoff. However, this association was not significant when controlling for multiple testing. We also found that S3 had a lower seroprevalence to the human cytomegalovirus when compared to healthy controls for all cutoffs used for seropositivity and after adjusting for multiple testing using the Benjamini-Hochberg procedure. However, this association did not reach statistical significance when using Benjamini-Yekutieli procedure. In summary, herpesviruses serology could distinguish subgroups of ME/CFS patients according to their disease trigger, but this finding could be eventually affected by the problem of multiple testing.

Source: Domingues TD, Grabowska AD, Lee JS, Ameijeiras-Alonso J, Westermeier F, Scheibenbogen C, Cliff JM, Nacul L, Lacerda EM, Mouriño H, Sepúlveda N. Herpesviruses Serology Distinguishes Different Subgroups of Patients From the United Kingdom Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Biobank. Front Med (Lausanne). 2021 Jul 5;8:686736. doi: 10.3389/fmed.2021.686736. PMID: 34291062; PMCID: PMC8287507. https://pubmed.ncbi.nlm.nih.gov/34291062/

The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multi-system disease whose etiological basis has not been established. Enteroviruses (EVs) as a cause of ME/CFS have sometimes been proposed, as they are known agents of acute respiratory and gastrointestinal infections that may persist in secondary infection sites, including the central nervous system, muscle, and heart. To date, the body of research that has investigated enterovirus infections in relation to ME/CFS supports an increased prevalence of chronic or persistent enteroviral infections in ME/CFS patient cohorts than in healthy individuals. Nevertheless, inconsistent results have fueled a decline in related studies over the past two decades.

This review covers the aspects of ME/CFS pathophysiology that are consistent with a chronic enterovirus infection and critically reviews methodologies and approaches used in past EV-related ME/CFS studies. We describe the prior sample types that were interrogated, the methods used and the limitations to the approaches that were chosen. We conclude that there is considerable evidence that prior outbreaks of ME/CFS were caused by one or more enterovirus groups. Furthermore, we find that the methods used in prior studies were inadequate to rule out the presence of chronic enteroviral infections in individuals with ME/CFS. Given the possibility that such infections could be contributing to morbidity and preventing recovery, further studies of appropriate biological samples with the latest molecular methods are urgently needed.

Source: O’Neal AJ, Hanson MR. The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review. Front Med (Lausanne). 2021 Jun 18;8:688486. doi: 10.3389/fmed.2021.688486. PMID: 34222292; PMCID: PMC8253308. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253308/  (Full text)

A Molecular network approach reveals shared cellular and molecular signatures between chronic fatigue syndrome and other fatiguing illnesses

Abstract:

The molecular mechanisms of chronic fatigue syndrome (CFS, or Myalgic encephalomyelitis), a disease defined by extreme, long-term fatigue, remain largely uncharacterized, and presently no molecular diagnostic test and no specific treatments exist to diagnose and treat CFS patients. While CFS has historically had an estimated prevalence of 0.1-0.5% [1], concerns of a “long hauler” version of Coronavirus disease 2019 (COVID-19) that symptomatically overlaps CFS to a significant degree (Supplemental Table-1) and appears to occur in 10% of COVID-19 patients[2], has raised concerns of a larger spike in CFS [3].

Here, we established molecular signatures of CFS and a corresponding network-based disease context from RNA-sequencing data generated on whole blood and FACs sorted specific peripheral blood mononuclear cells (PBMCs) isolated from CFS cases and non-CFS controls. The immune cell type specific molecular signatures of CFS we identified, overlapped molecular signatures from other fatiguing illnesses, demonstrating a common molecular etiology. Further, after constructing a probabilistic causal model of the CFS gene expression data, we identified master regulator genes modulating network states associated with CFS, suggesting potential therapeutic targets for CFS.

Source: Comella PH, Gonzalez-Kozlova E, Kosoy R, Charney AW, Peradejordi IF, Chandrasekar S, Tyler SR, Wang W, Losic B, Zhu J, Hoffman GE, Kim-Schulze S, Qi J, Patel M, Kasarskis A, Suarez-Farinas M, Gümüş ZH, Argmann C, Merad M, Becker C, Beckmann ND, Schadt EE. A Molecular network approach reveals shared cellular and molecular signatures between chronic fatigue syndrome and other fatiguing illnesses. medRxiv [Preprint]. 2021 Feb 2:2021.01.29.21250755. doi: 10.1101/2021.01.29.21250755. PMID: 33564792; PMCID: PMC7872387.  https://pubmed.ncbi.nlm.nih.gov/33564792/

Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

The etiology and pathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are unknown, and autoimmunity is one of many proposed underlying mechanisms. Human Leukocyte Antigen (HLA) associations are hallmarks of autoimmune disease, and have not been thoroughly investigated in a large ME/CFS patient cohort.

We performed high resolution HLA -A, -B, -C, -DRB1, -DQB1 and -DPB1 genotyping by next generation sequencing in 426 adult, Norwegian ME/CFS patients, diagnosed according to the Canadian Consensus Criteria. HLA associations were assessed by comparing to 4511 healthy and ethnically matched controls. Clinical information was collected through questionnaires completed by patients or relatives.

We discovered two independent HLA associations, tagged by the alleles HLA-C*07:04 (OR 2.1 [95% CI 1.4-3.1]) and HLA-DQB1*03:03 (OR 1.5 [95% CI 1.1-2.0]). These alleles were carried by 7.7% and 12.7% of ME/CFS patients, respectively. The proportion of individuals carrying one or both of these alleles was 19.2% in the patient group and 12.2% in the control group (OR 1.7 [95% CI 1.3-2.2], pnc = 0.00003). ME/CFS is a complex disease, potentially with a substantial heterogeneity. We report novel HLA associations pointing toward the involvement of the immune system in ME/CFS pathogenesis.

Source: Lande A, Fluge Ø, Strand EB, Flåm ST, Sosa DD, Mella O, Egeland T, Saugstad OD, Lie BA, Viken MK. Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Sci Rep. 2020 Mar 24;10(1):5267. doi: 10.1038/s41598-020-62157-x. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093502/ (Full text)

Assessing somatization disorder in the chronic fatigue syndrome

Abstract:

This study was conducted to examine the rates of somatization disorder (SD) in the chronic fatigue syndrome (CFS) relative to other fatiguing illness groups. It further addressed the arbitrary nature of the judgments made in assigning psychiatric vs. physical etiology to symptoms in controversial illnesses such as CFS.

Patients with CFS (N = 42), multiple sclerosis (MS) (N = 18), and depression (N = 21) were compared with healthy individuals (N = 32) on a structured psychiatric interview. The SD section of the Diagnostic Interview Schedule (DIS) III-R was reanalyzed using different criteria sets to diagnose SD. All subjects received a thorough medical history, physical examination, and DIS interview. CFS patients received diagnostic laboratory testing to rule out other causes of fatigue.

This study revealed that changing the attribution of SD symptoms from psychiatric to physical dramatically affected the rates of diagnosing SD in the CFS group. Both the CFS and depressed subjects endorsed a higher percentage of SD symptoms than either the MS or healthy groups, but very few met the strict DSM-III-R criteria for SD. The present study illustrates that the terminology used to interpret the symptoms (ie, psychiatric or physical) will determine which category CFS falls into. The diagnosis of SD is of limited use in populations in which the etiology of the illness has not been established.

 

Source: Johnson SK, DeLuca J, Natelson BH. Assessing somatization disorder in the chronic fatigue syndrome. Psychosom Med. 1996 Jan-Feb;58(1):50-7. http://www.ncbi.nlm.nih.gov/pubmed/8677289

 

A psychodynamic view of the chronic fatigue syndrome. The role of object relations in etiology and treatment

Abstract:

The chronic fatigue syndrome (CFS) is a constellation of physical and psychological symptoms including incapacitating fatigue associated with a marked reduction in activity. Although the etiology of CFS is unclear, reports in the literature suggest the presence of both physical and psychological dysfunction in this patient population. These findings have led to a debate between those who consider CFS to be primarily organic in origin and those who view CFS as a primary psychiatric disorder characterized by somatic preoccupations.

This debate led the authors to develop a working model for CFS designed to integrate the psychological and physiological findings, based on the hypothesis that early object relations have an etiologic relationship to CFS. This hypothesis then formed the rationale for a psychoanalytic treatment approach which will be described.

There are no published case reports describing psychoanalytic psychotherapy as a primary treatment modality for this patient population. The current paper attempts to fill a void. Two case reports of long-term (> 18 months), intensive (2-3 times per week) psychoanalytic psychotherapy with CFS patients referred by infectious disease specialists at a university teaching hospital will be presented.

The following aspects of the treatment will be highlighted: 1) the unique opportunity afforded by this treatment to view the nature of CFS, namely, the intimate relationship over time of fatigue symptoms to disturbances in object relationships, particularly within the transference; (2) the improvement in symptoms when this relationship is seen and understood by the patient; (3) the importance of the patient-therapist bond as a facilitating medium for clinical improvement; (4) the challenges involved in treating CFS patients with psychotherapy.

Comment in: Childhood abuse, personality disorder and chronic fatigue syndrome. [Gen Hosp Psychiatry. 1998]

 

Source: Taerk G, Gnam W. A psychodynamic view of the chronic fatigue syndrome. The role of object relations in etiology and treatment. Gen Hosp Psychiatry. 1994 Sep;16(5):319-25. http://www.ncbi.nlm.nih.gov/pubmed/7995502

 

Chronic fatigue syndrome

Abstract:

The major and minor diagnostic criteria of the chronic fatigue syndrome are described. The stages of the differential diagnosis, the diagnostic strategies and the controversies, while insisting on certain sleeping disorders are discussed. The cause of the syndrome may be a viral infection, and an anxious-depressive state may increase somatic complaints. Patients with chronic fatigue syndrome did not demonstrate a specific response to therapy. Spontaneous remission after a few years is a typical feature of this syndrome.

 

Source: Sternon J, Decaux G, Hoffmann G. Chronic fatigue syndrome. Rev Med Brux. 1994 Sep-Oct;15(5):311-5. [Article in French] http://www.ncbi.nlm.nih.gov/pubmed/7984848