Buchwald – American ME and CFS Society

Longitudinal associations of lymphocyte subsets with clinical outcomes in chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by prolonged fatigue and other physical and neurocognitive symptoms. Some studies suggest that CFS is accompanied by disruptions in the number and function of various lymphocytes. However, it is not clear which lymphocytes might influence CFS symptoms.

PURPOSE: To determine if patient reported fatigue symptoms and physical functioning scores significantly changed across time with lymphocyte counts as evidence of a relation among chronic fatigue symptoms and the immune response.

METHODS: The current longitudinal, naturalistic study assessed the cellular expression of three lymphocyte subtypes — natural killer (NK) cells (CD3-CD16+ and CD3-CD56+) and naïve T cells (CD4+CD45RA+) — to determine whether changes in lymphocytes at 4 time points across 18 months were associated with clinical outcomes, including CFS symptoms, physical functioning, and vitality, among patients with chronic fatigue.. Latent growth curve models were used to examine the longitudinal relationship between lymphocytes and clinical outcomes.

RESULTS: Ninety-three patients with Fukuda-based CFS and seven with non-CFS fatigue provided study data. Results indicated that higher proportions of naïve T cells and lower proportions of NK cells were associated with worse physical functioning, whereas higher proportions of NK cells (CD3-CD16+) and lower proportions of naïve T cells were associated with fewer CFS symptoms.

CONCLUSION: These findings suggest that lymphocytes are modestly related to clinical outcomes over time.

Source: Mehalick ML, Schmaling KB, Sabath DE, Buchwald DS. Longitudinal associations of lymphocyte subsets with clinical outcomes in chronic fatigue syndrome. Fatigue. 2018;6(2):80-91. doi: 10.1080/21641846.2018.1426371. Epub 2018 Jan 12. https://www.ncbi.nlm.nih.gov/pubmed/30112249

Longitudinal associations of lymphocyte subsets with clinical outcomes in chronic fatigue syndrome

Abstract:

Background: Chronic fatigue syndrome (CFS) is characterized by prolonged fatigue and other physical and neurocognitive symptoms. Some studies suggest that CFS is accompanied by disruptions in the number and function of various lymphocytes. However, it is not clear which lymphocytes might influence CFS symptoms.

Purpose: To determine if patient reported fatigue symptoms and physical functioning scores significantly changed across time with lymphocyte counts as evidence of a relation among chronic fatigue symptoms and the immune response.

Methods: The current longitudinal, naturalistic study assessed the cellular expression of three lymphocyte subtypes – natural killer (NK) cells (CD3 − CD16+ and CD3 − CD56+) and naïve T cells (CD4 + CD45RA+) – to determine whether changes in lymphocytes at 4 time points across 18 months were associated with clinical outcomes, including CFS symptoms, physical functioning, and vitality, among patients with chronic fatigue. Latent growth curve models were used to examine the longitudinal relationship between lymphocytes and clinical outcomes.

Results: Ninety-three patients with Fukuda-based CFS and seven with non-CFS fatigue provided study data. Results indicated that higher proportions of naïve T cells and lower proportions of NK cells were associated with worse physical functioning, whereas higher proportions of NK cells (CD3 − CD16+) and lower proportions of naïve T cells were associated with fewer CFS symptoms.

Conclusion: These findings suggest that lymphocytes are modestly related to clinical outcomes over time.

Source: Melissa L. Mehalick, Karen B. Schmaling, Daniel E. Sabath & Dedra S.Buchwald. Longitudinal associations of lymphocyte subsets with clinical outcomes in chronic fatigue syndrome. Fatigue: Biomedicine, Health & Behavior, Published online: 12 Jan 2018. http://www.tandfonline.com/action/showCitFormats?doi=10.1080%2F21641846.2018.1426371

The comorbidity of self-reported chronic fatigue syndrome, post-traumatic stress disorder, and traumatic symptoms

Abstract:

BACKGROUND: Data from primary care and community samples suggest higher rates of post-traumatic stress disorder (PTSD) among individuals with chronic fatigue syndrome (CFS).

OBJECTIVE: This study investigated the co-occurrence of CFS, PTSD, and trauma symptoms and assessed the contribution of familial factors to the association of CFS with lifetime PTSD and current traumatic symptoms.

METHOD: Data on lifetime CFS and PTSD, as measured by self-report of a doctor’s diagnosis of the disorder, and standardized questionnaire data on traumatic symptoms, using the Impact of Events Scale (IES), were obtained from 8544 female and male twins from the community-based University of Washington Twin Registry.

RESULTS: Lifetime prevalence of CFS was 2% and lifetime prevalence of PTSD was 4%. Participants who reported a history of PTSD were over eight times more likely to report a history of CFS. Participants with scores ≥ 26 on the IES were over four times more likely to report CFS than those who had scores ≤ 25. These associations were attenuated but remained significant after adjusting for familial factors through within-twin pair analyses.

CONCLUSION: These results support similar findings that a lifetime diagnosis of CFS is strongly associated with both lifetime PTSD and current traumatic symptoms, although familial factors, such as shared genetic and environmental contributions, played a limited role in the relationship between CFS, PTSD, and traumatic symptoms. These findings suggest that future research should investigate both the familial and the unique environmental factors that may give rise to both CFS and PTSD.

Published by Elsevier Inc.

Source: Dansie EJ, Heppner P, Furberg H, Goldberg J, Buchwald D, Afari N. The comorbidity of self-reported chronic fatigue syndrome, post-traumatic stress disorder, and traumatic symptoms. Psychosomatics. 2012 May-Jun;53(3):250-7. doi: 10.1016/j.psym.2011.08.007. Epub 2012 Jan 31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343192/ (Full article)

Conditions comorbid with chronic fatigue in a population-based sample

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) has been found to be comorbid with various medical conditions in clinical samples, but little research has investigated CFS comorbidity in population-based samples.

OBJECTIVE: This study investigated conditions concurrent with a CFS-like illness among twins in the population-based Mid-Atlantic Twin Registry (MATR), including chronic widespread pain (CWP), irritable bowel syndrome (IBS), and major depressive disorder (MDD).

METHOD: A survey was mailed to participants in the MATR in 1999. Generalized estimating equations were used to estimate odds ratios to assess associations between CFS-like illness and each comorbid condition.

RESULTS: A total of 4590 completed surveys were collected. Most participants were female (86.3%); mean age was 44.7 years. Among participants with a CFS-like illness, lifetime prevalences of CWP, IBS, and MDD were 41%, 16%, and 57% respectively. Participants reporting at least one of the three comorbid conditions were about 14 times more likely to have CFS-like illness than those without CWP, IBS, or MDD (95% confidence interval 8.1%-21.3%). Only MDD showed a temporal pattern of presentation during the same year as diagnosis of CFS-like illness. Age, gender, body mass index, age at illness onset, exercise level, self-reported health status, fatigue symptoms, and personality measures did not differ between those reporting CFS-like illness with and without comorbidity.

CONCLUSION: These results support findings in clinically based samples that CFS-like illness is frequently cormorbid with CWP, IBS, and/or MDD. We found no evidence that CFS-like illnesses with comorbidities are clinically distinct from those without comorbidities.

Source: Dansie EJ, Furberg H, Afari N, Buchwald D, Edwards K, Goldberg J, Schur E, Sullivan PF. Conditions comorbid with chronic fatigue in a population-based sample. Psychosomatics. 2012 Jan-Feb;53(1):44-50. doi: 10.1016/j.psym.2011.04.001. Epub 2011 Sep 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3254018/ (Full article)

Xenotropic murine leukemia virus-related virus in monozygotic twins discordant for chronic fatigue syndrome

Abstract:

A recent report suggested an association between xenotropic murine leukemia virus-related virus (XMRV) and chronic fatigue syndrome (CFS). If confirmed, this would suggest that antiretroviral therapy might benefit patients suffering from CFS. We validated a set of assays for XMRV and evaluated the prevalence of XMRV in a cohort of monozygotic twins discordant for CFS. Stored peripheral blood mononuclear cell (PBMC) samples were tested with 3 separate polymerase chain reaction (PCR) assays (one of which was nested) for XMRV DNA, and serum/plasma was tested for XMRV RNA by reverse transcription (RT)-PCR. None of the PBMC samples from the twins with CFS or their unaffected co-twins was positive for XMRV, by any of the assays. One plasma sample, from an unaffected co-twin, was reproducibly positive by RT-PCR. However, serum from the same day was negative, as was a follow-up plasma sample obtained 2 days after the positive specimen. These data do not support an association of XMRV with CFS.

Source: Jerome KR, Diem K, Huang ML, Selke S, Corey L, Buchwald D.Xenotropic murine leukemia virus-related virus in monozygotic twins discordant for chronic fatigue syndrome. Diagn Microbiol Infect Dis. 2011 Sep;71(1):66-71. doi: 10.1016/j.diagmicrobio.2011.06.003. Epub 2011 Jul 26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158821/ (Full article)

Comment on “Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome”

Abstract:

Lombardi et al. (Reports, 23 October 2009, p. 585) reported a significant association between the human retrovirus XMRV and chronic fatigue syndrome (CFS). However, the cases with CFS and the control subjects in their study are poorly described and unlikely to be representative. Independent replication is a critical first step before accepting the validity of this finding.

Comment on: Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. [Science. 2009]

You can read the full comment here: http://science.sciencemag.org/content/328/5980/825.2.full

Source: Lloyd A, White P, Wessely S, Sharpe M, Buchwald D. Comment on “Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome”. Science. 2010 May 14;328(5980):825; author reply 825. doi: 10.1126/science.1183706. http://science.sciencemag.org/content/328/5980/825.2.full (Full article)

Adolescent offspring of mothers with chronic fatigue syndrome

Abstract:

PURPOSE: The goal of this study was to determine whether adolescent offspring of mothers with chronic fatigue syndrome(CFS) have higher prevalence of CFS and report more fatigue, greater pain sensitivity, more sleep problems, and poorer cardiopulmonary fitness in comparison with offspring with no exposure to maternal CFS.

METHODS: A total of 26 adolescent offspring of 20 mothers diagnosed with CFS were compared with 45 adolescent offspring of 30 age-matched healthy control mothers. Study measures included structured interviews and medical and laboratory examinations for CFS; tender point examination; maximum oxygen uptake and perceived exertion; dolorimetry pain ratings; and questionnaires on fatigue severity and sleepiness.

RESULTS: In comparison with offspring of healthy mothers, those exposed to mothers with CFS reported higher prevalence of fatigue of at least 1-month duration (23% vs. 4%), fatigue of 6 months or longer (15% vs. 2%), and met criteria for CFS (12% vs. 2%), although these differences only approached statistical significance. CFS and healthy mothers differed on almost all study outcomes, but offspring groups did not differ on measures of current fatigue severity, pain sensitivity, sleep, mean number of tender points, and cardiopulmonary fitness.

CONCLUSIONS: The higher prevalence of fatiguing states in offspring of CFS mothers, despite the lack of statistical significance, suggests that familial factors may potentially play a role in developing chronically fatiguing states. Alternately, perturbations in pain sensitivity and cardiopulmonary fitness may be consequences of CFS. Future studies should focus on examining the impact of maternal CFS and associated disability on psychosocial functioning of offspring.

Source: Smith MS, Buchwald DS, Bogart A, Goldberg J, Smith WR, Afari N. Adolescent offspring of mothers with chronic fatigue syndrome. J Adolesc Health. 2010 Mar;46(3):284-91. doi: 10.1016/j.jadohealth.2009.08.001. Epub 2009 Oct 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824612/ (Full article)

Power spectral analysis of sleep EEG in twins discordant for chronic fatigue syndrome

Abstract:

OBJECTIVE: The purpose of the study was to evaluate quantitative sleep electroencephalogram (EEG) frequencies in monozygotic twins discordant for chronic fatigue syndrome.

METHODS: Thirteen pairs of female twins underwent polysomnography. During the first night, they adapted to the sleep laboratory, and during the second night, their baseline sleep was assessed. Visual stage scoring was conducted on sleep electroencephalographic records according to standard criteria, and power spectral analysis was used to quantify delta through beta frequency bands, processed in 6-s blocks. Data were averaged across sleep stage within each twin and coded for sleep stage and the presence or absence of chronic fatigue syndrome (CFS). A completely within-subjects repeated measure multivariate analysis of variance evaluated twin pairs by frequency band by sleep stage interactions and simple effects. The relationship between alpha and delta EEG was also assessed across twin pairs.

RESULTS: No significant differences in spectral power in any frequency band were found between those with CFS and their nonfatigued cotwins. Phasic alpha activity, coupled with delta was noted in five subjects with CFS but was also present in 4/5 healthy twins, indicating this finding likely reflects genetic influences on the sleep electroencephalogram rather than disease-specific sleep pathology.

CONCLUSIONS: The genetic influences on sleep polysomnography and microarchitecture appear to be stronger than the disease influence of chronic fatigue syndrome, despite greater subjective sleep complaint among the CFS twins. EEG techniques that focus on short duration events or paradigms that probe sleep regulation may provide a better description of sleep abnormalities in CFS.

Source: Armitage R, Landis C, Hoffmann R, Lentz M, Watson N, Goldberg J, Buchwald D. Power spectral analysis of sleep EEG in twins discordant for chronic fatigue syndrome. J Psychosom Res. 2009 Jan;66(1):51-7. doi: 10.1016/j.jpsychores.2008.08.004. Epub 2008 Nov 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634600/ (Full article)

Twin analyses of fatigue

Abstract:

Prolonged fatigue equal to or greater than 1 month duration and chronic fatigue equal to or greater than 6 months duration are both commonly seen in clinical practice, yet little is known about the etiology or epidemiology of either symptom. Chronic fatigue syndrome (CFS), while rarer, presents similar challenges in determining cause and epidemiology. Twin studies can be useful in elucidating genetic and environmental influences on fatigue and CFS. The goal of this article was to use biometrical structural equation twin modeling to examine genetic and environmental influences on fatigue, and to investigate whether these influences varied by gender. A total of 1042 monozygotic (MZ) twin pairs and 828 dizygotic (DZ) twin pairs who had completed the University of Washington Twin Registry survey were assessed for three fatigue-related variables: prolonged fatigue, chronic fatigue, and CFS. Structural equation twin modeling was used to determine the relative contributions of additive genetic effects, shared environmental effects, and individual-specific environmental effects to the 3 fatigue conditions. In women, tetrachoric correlations were similar for MZ and DZ pairs for prolonged and chronic fatigue, but not for CFS. In men, however, the correlations for prolonged and chronic fatigue were higher in MZ pairs than in DZ pairs. About half the variance for both prolonged and chronic fatigue in males was due to genetic effects, and half due to individual-specific environmental effects. For females, most variance was due to individual environmental effects.

Source: Schur E, Afari N, Goldberg J, Buchwald D, Sullivan PF. Twin analyses of fatigue. Twin Res Hum Genet. 2007 Oct;10(5):729-33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953372/ (Full article)

The impact of a 4-hour sleep delay on slow wave activity in twins discordant for chronic fatigue syndrome

Abstract:

OBJECTIVES: Chronic fatigue syndrome (CFS) has been associated with altered amounts of slow wave sleep, which could reflect reduced delta electroencephalograph (EEG) activity and impaired sleep regulation. To evaluate this hypothesis, we examined the response to a sleep regulatory challenge in CFS.

DESIGN: The first of 3 consecutive nights of study served as laboratory adaptation. Baseline sleep was assessed on the second night. On the third night, bedtime was delayed by 4 hours, followed by recovery sleep. Total available sleep time was held constant on all nights.

SETTING: A research sleep laboratory.

PARTICIPANTS: 13 pairs of monozygotic twins discordant for CFS.

INTERVENTIONS: N/A.

MEASUREMENTS AND RESULTS: Power spectral analysis quantified slow wave activity (SWA) in the 0.5-3.9 Hz band in successive NREM periods (stage 2, 3, or 4) on each night. To ensure comparability, analyses were restricted to the first 4 NREM periods on each night. Data were coded for NREM period and twin pair. Repeated-measures analysis of variance (ANOVA) contrasted sleep delay effects across NREM periods between twin pairs. A second ANOVA calculated the SWA in each NREM period in recovery sleep relative to baseline SWA. The 2 groups of twins were similar on baseline SWA power. After sleep delay, CFS twins exhibited significantly less SWA power in the first NREM period of recovery sleep and accumulated a smaller percentage of SWA in the first NREM period than their co-twins.

CONCLUSIONS: CFS is associated with a blunted SWA response to sleep challenge, suggesting that the basic sleep drive and homeostatic response are impaired.

Source: Armitage R, Landis C, Hoffmann R, Lentz M, Watson NF, Goldberg J, Buchwald D. The impact of a 4-hour sleep delay on slow wave activity in twins discordant for chronic fatigue syndrome, Sleep. 2007 May;30(5):657-62. https://www.ncbi.nlm.nih.gov/pubmed/17552382