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Chronic Fatigue Syndrome: HELP
Articles from Miami
Based on 27 articles published since 2010
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These are the 27 published articles about Fatigue Syndrome, Chronic that originated from Miami during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Biomarkers for chronic fatigue. 2012

Klimas, Nancy G / Broderick, Gordon / Fletcher, Mary Ann. ·Miami Veterans Affairs Medical Center, Miami, FL, USA. Nancy.Klimas@va.gov ·Brain Behav Immun · Pubmed #22732129.

ABSTRACT: Fatigue that persists for 6 months or more is termed chronic fatigue. Chronic fatigue (CF) in combination with a minimum of 4 of 8 symptoms and the absence of diseases that could explain these symptoms, constitute the case definition for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Inflammation, immune system activation, autonomic dysfunction, impaired functioning in the hypothalamic-pituitary-adrenal axis, and neuroendocrine dysregulation have all been suggested as root causes of fatigue. The identification of objective markers consistently associated with CFS/ME is an important goal in relation to diagnosis and treatment, as the current case definitions are based entirely on physical signs and symptoms. This review is focused on the recent literature related to biomarkers for fatigue associated with CFS/ME and, for comparison, those associated with other diseases. These markers are distributed across several of the body's core regulatory systems. A complex construct of symptoms emerges from alterations and/or dysfunctions in the nervous, endocrine and immune systems. We propose that new insight will depend on our ability to develop and deploy an integrative profiling of CFS/ME pathogenesis at the molecular level. Until such a molecular signature is obtained efforts to develop effective treatments will continue to be severely limited.

2 Clinical Trial Tracking post-infectious fatigue in clinic using routine Lab tests. 2016

Harvey, Jeanna M / Broderick, Gordon / Bowie, Alanna / Barnes, Zachary M / Katz, Ben Z / O'Gorman, Maurice R G / Vernon, Suzanne D / Fletcher, Mary Ann / Klimas, Nancy G / Taylor, Renee. ·Department of Medicine, University of Miami, Miami, FL, USA. · Department of Medicine, University of Miami, Miami, FL, USA. gbroderick@nova.edu. · Institute for Neuro Immune Medicine, Nova Southeastern University, University Park Plaza, 3440 South University, Fort Lauderdale, 33328, FL, USA. gbroderick@nova.edu. · University of Alberta, Edmonton, AB, Canada. gbroderick@nova.edu. · University of Alberta, Edmonton, AB, Canada. · Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA. · Children's Hospital Los Angeles, Los Angeles, CA, USA. · Solve ME/CFS Initiative, Charlotte, NC, USA. · Institute for Neuro Immune Medicine, Nova Southeastern University, University Park Plaza, 3440 South University, Fort Lauderdale, 33328, FL, USA. · University of Illinois at Chicago, Chicago, IL, USA. ·BMC Pediatr · Pubmed #27118537.

ABSTRACT: BACKGROUND: While biomarkers for chronic fatigue syndrome (CFS) are beginning to emerge they typically require a highly specialized clinical laboratory. We hypothesized that subsets of commonly measured laboratory markers used in combination could support the diagnosis of post-infectious CFS (PI-CFS) in adolescents following infectious mononucleosis (IM) and help determine who might develop persistence of symptoms. METHODS: Routine clinical laboratory markers were collected prospectively in 301 mono-spot positive adolescents, 4 % of whom developed CFS (n = 13). At 6, 12, and 24 months post-diagnosis with IM, 59 standard tests were performed including metabolic profiling, liver enzyme panel, hormone profiles, complete blood count (CBC), differential white blood count (WBC), salivary cortisol, and urinalysis. Classification models separating PI-CFS from controls were constructed at each time point using stepwise subset selection. RESULTS: Lower ACTH levels at 6 months post-IM diagnosis were highly predictive of CFS (AUC p = 0.02). ACTH levels in CFS overlapped with healthy controls at 12 months, but again showed a trend towards a deficiency at 24 months. Conversely, estradiol levels depart significantly from normal at 12 months only to recover at 24 months (AUC p = 0.02). Finally, relative neutrophil count showed a significant departure from normal at 24 months in CFS (AUC p = 0.01). Expression of these markers evolved differently over time between groups. CONCLUSIONS: Preliminary results suggest that serial assessment of stress and sex hormones as well as the relative proportion of innate immune cells measured using standard clinical laboratory tests may support the diagnosis of PI-CFS in adolescents with IM.

3 Article Post-exertional malaise is associated with greater symptom burden and psychological distress in patients diagnosed with Chronic Fatigue Syndrome. 2020

May, Marcella / Milrad, Sara F / Perdomo, Dolores M / Czaja, Sara J / Fletcher, Mary Ann / Jutagir, Devika R / Hall, Daniel L / Klimas, Nancy / Antoni, Michael H. ·Department of Psychology, University of Miami, USA. Electronic address: mmay@med.miami.edu. · Florida Atlantic University, USA. · Department of Psychology, University of Miami, USA. Electronic address: dperdomo@med.miami.edu. · Weill Cornell Medical College, USA. Electronic address: sjc7004@med.cornell.edu. · Nova Southeastern University, USA. Electronic address: mfletcher@nova.edu. · Memorial Sloan Kettering Cancer Center, USA. Electronic address: jutagird@mskcc.org. · Massachusetts General Hospital/Harvard Medical School, USA. Electronic address: dhall7@mgh.harvard.edu. · Nova Southeastern University, USA. Electronic address: nklimas@nova.edu. · Department of Psychology, University of Miami, USA. Electronic address: mantoni@miami.edu. ·J Psychosom Res · Pubmed #31884303.

ABSTRACT: OBJECTIVE: Post-exertional malaise (PEM) is often considered a cardinal symptom of Chronic Fatigue Syndrome (CFS). There is no gold standard diagnostic method for CFS, however, and the Centers for Disease Control (CDC) Fukuda case definition does not require PEM. Research has identified differences in symptom burden between patients according to PEM, but whether it is associated with psychological distress has not been investigated. METHODS: The CDC CFS Inventory, Fatigue Symptom Inventory, Profile of Mood States, Center for Epidemiologic Studies Depression Scale, Perceived Stress Scale, and subscales of the Sickness Impact Profile were administered to 261 patients diagnosed with the Fukuda criteria. PEM status (loPEM/hiPEM) was determined via self-reported post-exertional fatigue severity. Analyses of covariance (ANCOVA), controlling for age and gender, assessed cross-sectional group differences, and cross-sectional linear regressions using the continuous PEM severity predictor paralleled these analyses. RESULTS: hiPEM patients reported greater symptom intensity, frequency, and interference than loPEM counterparts (p's < .001). hiPEM patients also reported greater social disruption, depressive symptoms, and mood disturbance (p's ≤ .011). Groups did not differ in recent negative life experiences, perceived stress, or demographic variables. The results of regression analyses mirrored those of ANCOVAs. CONCLUSION: This study replicates the association between PEM and symptom burden and additionally associates PEM with psychological distress; psychological distress could, however, be a consequence of symptom burden. Differences between hiPEM and loPEM CFS patients highlight the heterogeneity of diagnoses resulting from the Fukuda criteria. It is also possible that PEM identifies particularly distressed patients for whom psychological intervention would be most beneficial.

4 Article Relationship satisfaction, communication self-efficacy, and chronic fatigue syndrome-related fatigue. 2019

Milrad, Sara F / Hall, Daniel L / Jutagir, Devika R / Lattie, Emily G / Czaja, Sara J / Perdomo, Dolores M / Ironson, Gail / Doss, Brian D / Mendez, Armando / Fletcher, Mary Ann / Klimas, Nancy / Antoni, Michael H. ·Department of Psychology, University of Miami, USA. · Department of Psychiatry, Massachusetts General Hospital/ Harvard Medical School, USA. · Department of Psychiatry & Behavioral Sciences, Memorial Sloan Kettering Cancer Center, USA. · Department of Medical Social Sciences, Northwestern University, Chicago IL, USA. · Department of Psychiatry and Behavioral Sciences, University of Miami, USA. · Institute for Neuro Immune Medicine, Nova Southeastern University, USA. · Department of Psychology, University of Miami, USA. Electronic address: mantoni@miami.edu. ·Soc Sci Med · Pubmed #31377502.

ABSTRACT: RATIONALE: Relationship dissatisfaction has been linked with worse health outcomes in many patient populations, though the mechanism(s) underlying this effect are unclear. Among patients with chronic fatigue syndrome (CFS) and their partners, there is evidence for a bi-directional association between poorer relationship satisfaction and the severity of CFS-related fatigue. OBJECTIVE: Here, we hypothesized that relationship dissatisfaction negatively impacts fatigue severity through greater depression and less patient satisfaction about communication about symptoms to partners. METHOD: Baseline data were drawn from diagnosed CFS patients (N = 150) participating in a trial testing the efficacy of a stress management intervention. Data derived from fatigue severity (Fatigue Symptom Index, FSI), depression (Center for Epidemiologic Survey-Depression, CES-D), relationship quality (Dyadic Adjustment Scale, DAS) and communication satisfaction (Patient Symptom Disclosure Satisfaction, PSDS) questionnaires were used for bootstrapped indirect effect analyses using parallel mediation structural equation modeling in Mplus (v8). Age and BMI were entered as covariates. RESULTS: Greater relationship satisfaction predicted greater communication satisfaction (p < 0.01) and lower CES-D scores (p < 0.01), which in turn were each significantly related to greater fatigue severity (p < 0.05). Tests of the indirect paths indicated that relationship satisfaction had a significant effect on fatigue severity through both constructs, but primarily via depression. There was no direct association between relationship satisfaction and fatigue severity after the intermediate variables (depression, communication satisfaction) were included in the model. CONCLUSION: Results highlight the importance of considering depression and communication-related factors when examining the effects of relationship satisfaction on CFS symptoms such as fatigue. Further mechanism-based, longitudinal research might identify relationship-related mediating variables that can be targeted therapeutically.

5 Article Genetic Predisposition for Immune System, Hormone, and Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study. 2019

Perez, Melanie / Jaundoo, Rajeev / Hilton, Kelly / Del Alamo, Ana / Gemayel, Kristina / Klimas, Nancy G / Craddock, Travis J A / Nathanson, Lubov. ·Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States. · Department of Psychology and Neuroscience, Nova Southeastern University, Fort Lauderdale, FL, United States. · Institute for Neuro Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States. · Veterans Affairs Medical Center, Miami, FL, United States. · Department of Computer Science, Nova Southeastern University, Fort Lauderdale, FL, United States. ·Front Pediatr · Pubmed #31179255.

ABSTRACT:

6 Article Leveraging Prior Knowledge of Endocrine Immune Regulation in the Therapeutically Relevant Phenotyping of Women With Chronic Fatigue Syndrome. 2019

Morris, Matthew C / Cooney, Katherine E / Sedghamiz, Hooman / Abreu, Maria / Collado, Fanny / Balbin, Elizabeth G / Craddock, Travis J A / Klimas, Nancy G / Broderick, Gordon / Fletcher, Mary Ann. ·Center for Clinical Systems Biology, Rochester General Hospital, Rochester, NY, USA. · Institute for Neuro Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA; Miami Veterans Affairs Medical Center, Miami, FL, USA. · Institute for Neuro Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA; Departments of Psychology and Neuroscience, Computer Science, and Clinical Immunology, Nova Southeastern University, Fort Lauderdale, FL, USA. · Center for Clinical Systems Biology, Rochester General Hospital, Rochester, NY, USA; Institute for Neuro Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA; Department of Biomedical Engineering, Rochester Institute of Technology, Rochester, NY, USA. Electronic address: gordon.broderick@rochesterregional.org. ·Clin Ther · Pubmed #30929860.

ABSTRACT: PURPOSE: The complex and varied presentation of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has made it difficult to diagnose, study, and treat. Its symptoms and likely etiology involve multiple components of endocrine and immune regulation, including the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, and their interactive oversight of immune function. We propose that the persistence of ME/CFS may involve changes in the regulatory interactions across these physiological axes. We also propose that the robustness of this new pathogenic equilibrium may at least in part explain the limited success of conventional single-target therapies. METHODS: A comprehensive model was constructed of female endocrine-immune signaling consisting of 28 markers linked by 214 documented regulatory interactions. This detailed model was then constrained to adhere to experimental measurements in a subset of 17 candidate immune markers measured in peripheral blood of patients with ME/CFS and healthy control subjects before, during, and after a maximal exercise challenge. A set of 26 competing numerical models satisfied these data to within 5% error. FINDINGS: Mechanistically informed predictions of endocrine and immune markers that were either unmeasured or exhibited high subject-to-subject variability pointed to possible context-specific overexpression in ME/CFS at rest of corticotropin-releasing hormone, chemokine (C-X-C motif) ligand 8, estrogen, follicle-stimulating hormone (FSH), gonadotropin-releasing hormone 1, interleukin (IL)-23, and luteinizing hormone, and underexpression of adrenocorticotropic hormone, cortisol, interferon-γ, IL-10, IL-17, and IL-1α. Simulations of rintatolimod and rituximab treatment predicted a shift in the repertoire of available endocrine-immune regulatory regimens. Rintatolimod was predicted to make available substantial remission in a significant subset of subjects, in particular those with low levels of IL-1α, IL-17, and cortisol; intermediate levels of progesterone and FSH; and high estrogen levels. Rituximab treatment was predicted to support partial remission in a smaller subset of patients with ME/CFS, specifically those with low norepinephrine, IL-1α, chemokine (C-X-C motif) ligand 8, and cortisol levels; intermediate FSH and gonadotropin-releasing hormone 1 levels; and elevated expression of tumor necrosis factor-α, luteinizing hormone, IL-12, and B-cell activation. IMPLICATIONS: Applying a rigorous filter of known signaling mechanisms to experimentally measured immune marker expression in ME/CFS has highlighted potential new context-specific markers of illness. These novel endocrine and immune markers may offer useful candidates in delineating new subtypes of ME/CFS and may inform on refinements to the inclusion criteria and instrumentation of new and ongoing trials involving rintatolimod and rituximab treatment protocols.

7 Article Treatment Avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Split-gender Pharmacogenomic Study of Gene-expression Modules. 2019

Jeffrey, Mary G / Nathanson, Lubov / Aenlle, Kristina / Barnes, Zachary M / Baig, Mirza / Broderick, Gordon / Klimas, Nancy G / Fletcher, Mary Ann / Craddock, Travis J A. ·Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA; College of Psychology, Nova Southeastern University, Ft. Lauderdale, FL, USA. · Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA; Department of Clinical Immunology, Nova Southeastern University, Ft. Lauderdale, FL, USA. · Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA; Department of Clinical Immunology, Nova Southeastern University, Ft. Lauderdale, FL, USA; Miami Veterans Affairs Medical Center, Miami, FL, USA. · Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA; Miami Veterans Affairs Medical Center, Miami, FL, USA; Miller School of Medicine, University of Miami, Miami, FL, USA; Diabetes Research Institute, University of Miami, Miami, FL, USA. · Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA. · Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA; College of Psychology, Nova Southeastern University, Ft. Lauderdale, FL, USA; Department of Clinical Immunology, Nova Southeastern University, Ft. Lauderdale, FL, USA; Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Center for Clinical Systems Biology, Rochester General Hospital, Rochester, NY, USA. · Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA; College of Psychology, Nova Southeastern University, Ft. Lauderdale, FL, USA; Department of Clinical Immunology, Nova Southeastern University, Ft. Lauderdale, FL, USA. · Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA; College of Psychology, Nova Southeastern University, Ft. Lauderdale, FL, USA; Department of Clinical Immunology, Nova Southeastern University, Ft. Lauderdale, FL, USA; Department of Computer Science, Nova Southeastern University, Ft. Lauderdale, FL, USA. Electronic address: tcraddock@nova.edu. ·Clin Ther · Pubmed #30851951.

ABSTRACT: PURPOSE: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisymptom illness impacting up to 1 million people in the United States. As the pathogenesis and etiology of this complex condition are unclear, prospective treatments are limited. Identifying US Food and Drug Administration-approved drugs that may be repositioned as treatments for ME/CFS may offer a rapid and cost-effective solution. METHODS: Here we used gene-expression data from 33 patients with Fukuda-defined ME/CFS (23 females, 10 males) and 21 healthy demographically comparable controls (15 females, 6 males) to identify differential expression of predefined gene-module sets based on nonparametric statistics. Differentially expressed gene modules were then annotated via over-representation analysis using the Consensus Pathway database. Differentially expressed modules were then regressed onto measures of fatigue and cross-referenced with drug atlas and pharmacogenomics databases to identify putative treatment agents. FINDINGS: The top 1% of modules identified in males indicated small effect sizes in modules associated with immune regulation and mitochondrial dysfunction. In females, modules identified included those related to immune factors and cardiac/blood factors, returning effect sizes ranging from very small to intermediate (0.147 < Cohen δ < 0.532). Regression analysis indicated that B-cell receptors, T-cell receptors, tumor necrosis factor α, transforming growth factor β, and metabolic and cardiac modules were strongly correlated with multiple composite measures of fatigue. Cross-referencing identified genes with pharmacogenomics data indicated immunosuppressants as potential treatments of ME/CFS symptoms. IMPLICATIONS: The findings from our analysis suggest that ME/CFS symptoms are perpetuated by immune dysregulation that may be approached via immune modulation-based treatment strategies.

8 Article Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy. 2019

Mueller, Christina / Lin, Joanne C / Sheriff, Sulaiman / Maudsley, Andrew A / Younger, Jarred W. ·Department of Psychology, The University of Alabama at Birmingham, 1720 2nd Ave S, Birmingham, AL, 35294, USA. · Department of Radiology, Miller School of Medicine, University of Miami, 1600 NW 10th Ave #1140, Miami, FL, 33136, USA. · Department of Psychology, The University of Alabama at Birmingham, 1720 2nd Ave S, Birmingham, AL, 35294, USA. younger@uab.edu. ·Brain Imaging Behav · Pubmed #30617782.

ABSTRACT: Previous neuroimaging studies have detected markers of neuroinflammation in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Magnetic Resonance Spectroscopy (MRS) is suitable for measuring brain metabolites linked to inflammation, but has only been applied to discrete regions of interest in ME/CFS. We extended the MRS analysis of ME/CFS by capturing multi-voxel information across the entire brain. Additionally, we tested whether MRS-derived brain temperature is elevated in ME/CFS patients. Fifteen women with ME/CFS and 15 age- and gender-matched healthy controls completed fatigue and mood symptom questionnaires and whole-brain echo-planar spectroscopic imaging (EPSI). Choline (CHO), myo-inositol (MI), lactate (LAC), and N-acetylaspartate (NAA) were quantified in 47 regions, expressed as ratios over creatine (CR), and compared between ME/CFS patients and controls using independent-samples t-tests. Brain temperature was similarly tested between groups. Significant between-group differences were detected in several regions, most notably elevated CHO/CR in the left anterior cingulate (p < 0.001). Metabolite ratios in seven regions were correlated with fatigue (p < 0.05). ME/CFS patients had increased temperature in the right insula, putamen, frontal cortex, thalamus, and the cerebellum (all p < 0.05), which was not attributable to increased body temperature or differences in cerebral perfusion. Brain temperature increases converged with elevated LAC/CR in the right insula, right thalamus, and cerebellum (all p < 0.05). We report metabolite and temperature abnormalities in ME/CFS patients in widely distributed regions. Our findings may indicate that ME/CFS involves neuroinflammation.

9 Article Using a Consensus Docking Approach to Predict Adverse Drug Reactions in Combination Drug Therapies for Gulf War Illness. 2018

Jaundoo, Rajeev / Bohmann, Jonathan / Gutierrez, Gloria E / Klimas, Nancy / Broderick, Gordon / Craddock, Travis J A. ·Institute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA. rj426@nova.edu. · Department of Psychology & Neuroscience, Nova Southeastern University, Fort Lauderdale, FL 33314, USA. rj426@nova.edu. · Department of Clinical Immunology, Nova Southeastern University, Fort Lauderdale, FL 33314, USA. rj426@nova.edu. · Pharmaceuticals and Bioengineering Department, Southwest Research Institute, San Antonio, TX 78238, USA. jonathan.bohmann@swri.org. · Pharmaceuticals and Bioengineering, Chemistry and Chemical Engineering Division, Southwest Research Institute, San Antonio, TX 78238, USA. gloria.gutierrez@swri.org. · Institute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA. nklimas@nova.edu. · Department of Clinical Immunology, Nova Southeastern University, Fort Lauderdale, FL 33314, USA. nklimas@nova.edu. · Miami Veterans Affairs Medical Center, Miami, FL 33125, USA. nklimas@nova.edu. · Institute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA. Gordon.Broderick@rochesterregional.org. · Department of Psychology & Neuroscience, Nova Southeastern University, Fort Lauderdale, FL 33314, USA. Gordon.Broderick@rochesterregional.org. · Department of Clinical Immunology, Nova Southeastern University, Fort Lauderdale, FL 33314, USA. Gordon.Broderick@rochesterregional.org. · Centre for Clinical Systems Biology, Rochester General Hospital Research Institute, Rochester, NY 14617, USA. Gordon.Broderick@rochesterregional.org. · Rochester Institute of Technology, Rochester, NY 14623, USA. Gordon.Broderick@rochesterregional.org. · Institute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA. tcraddock@nova.edu. · Department of Psychology & Neuroscience, Nova Southeastern University, Fort Lauderdale, FL 33314, USA. tcraddock@nova.edu. · Department of Clinical Immunology, Nova Southeastern University, Fort Lauderdale, FL 33314, USA. tcraddock@nova.edu. · Department of Computer Science, Nova Southeastern University, Fort Lauderdale, FL 33314, USA. tcraddock@nova.edu. ·Int J Mol Sci · Pubmed #30373189.

ABSTRACT: Gulf War Illness (GWI) is a chronic multisymptom illness characterized by fatigue, musculoskeletal pain, and gastrointestinal and cognitive dysfunction believed to stem from chemical exposures during the 1990⁻1991 Persian Gulf War. There are currently no treatments; however, previous studies have predicted a putative multi-intervention treatment composed of inhibiting Th1 immune cytokines followed by inhibition of the glucocorticoid receptor (GCR) to treat GWI. These predictions suggest the use of specific monoclonal antibodies or suramin to target interleukin-2 and tumor necrosis factor α , followed by mifepristone to inhibit the GCR. In addition to this putative treatment strategy, there exist a variety of medications that target GWI symptomatology. As pharmaceuticals are promiscuous molecules, binding to multiple sites beyond their intended targets, leading to off-target interactions, it is key to ensure that none of these medications interfere with the proposed treatment avenue. Here, we used the drug docking programs AutoDock 4.2, AutoDock Vina, and Schrödinger's Glide to assess the potential off-target immune and hormone interactions of 43 FDA-approved drugs commonly used to treat GWI symptoms in order to determine their putative polypharmacology and minimize adverse drug effects in a combined pharmaceutical treatment. Several of these FDA-approved drugs were predicted to be novel binders of immune and hormonal targets, suggesting caution for their use in the proposed GWI treatment strategy symptoms.

10 Article Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns. 2018

Trivedi, Malav S / Oltra, Elisa / Sarria, Leonor / Rose, Natasha / Beljanski, Vladimir / Fletcher, Mary Ann / Klimas, Nancy G / Nathanson, Lubov. ·College of Pharmacy, Nova Southeastern University, Fort Lauderdale, United States of America. · School of Medicine and Dentistry, Catholic University of Valencia, Valencia, Spain. · Institute for Neuro Immune Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, United States of America. · Cell Therapy Institute, Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, United States of America. · Miami VAMC, Miami, Florida, United States of America. ·PLoS One · Pubmed #30036399.

ABSTRACT: BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition involving multiple organ systems and characterized by persistent/relapsing debilitating fatigue, immune dysfunction, neurological problems, and other symptoms not curable for at least 6 months. Disruption of DNA methylation patterns has been tied to various immune and neurological diseases; however, its status in ME/CFS remains uncertain. Our study aimed at identifying changes in the DNA methylation patterns that associate with ME/CFS. METHODS: We extracted genomic DNA from peripheral blood mononuclear cells from 13 ME/CFS study subjects and 12 healthy controls and measured global DNA methylation by ELISA-like method and site-specific methylation status using Illumina MethylationEPIC microarrays. Pyrosequencing validation included 33 ME/CFS cases and 31 controls from two geographically distant cohorts. RESULTS: Global DNA methylation levels of ME/CFS cases were similar to those of controls. However, microarray-based approach allowed detection of 17,296 differentially methylated CpG sites in 6,368 genes across regulatory elements and within coding regions of genes. Analysis of DNA methylation in promoter regions revealed 307 differentially methylated promoters. Ingenuity pathway analysis indicated that genes associated with differentially methylated promoters participated in at least 15 different pathways mostly related to cell signaling with a strong immune component. CONCLUSIONS: This is the first study that has explored genome-wide epigenetic changes associated with ME/CFS using the advanced Illumina MethylationEPIC microarrays covering about 850,000 CpG sites in two geographically distant cohorts of ME/CFS cases and matched controls. Our results are aligned with previous studies that indicate a dysregulation of the immune system in ME/CFS. They also suggest a potential role of epigenetic de-regulation in the pathobiology of ME/CFS. We propose screening of larger cohorts of ME/CFS cases to determine the external validity of these epigenetic changes in order to implement them as possible diagnostic markers in clinical setting.

11 Article Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics. 2018

Nagy-Szakal, Dorottya / Barupal, Dinesh K / Lee, Bohyun / Che, Xiaoyu / Williams, Brent L / Kahn, Ellie J R / Ukaigwe, Joy E / Bateman, Lucinda / Klimas, Nancy G / Komaroff, Anthony L / Levine, Susan / Montoya, Jose G / Peterson, Daniel L / Levin, Bruce / Hornig, Mady / Fiehn, Oliver / Lipkin, W Ian. ·Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY, 10032, USA. · UC Davis Genome Center - Metabolomics, University of California, Davis, CA, 95616, CA, USA. · Bateman Horne Center, Salt Lake City, UT, 84102, USA. · Institute for Neuro Immune Medicine, College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, 33314, USA. · Miami VA Medical Center, Miami, FL, 33125, USA. · Harvard Medical School, Brigham and Women's Hospital, Boston, MA, 02115, USA. · Levine Clinic, New York, NY, 10021, USA. · Stanford University, Palo Alto, CA, 94305, USA. · Sierra Internal Medicine at Incline Village, Incline Village, NV, 89451, USA. · Department of Biostatistics, Columbia University Mailman School of Public Health, New York, NY, 10032, USA. · UC Davis Genome Center - Metabolomics, University of California, Davis, CA, 95616, CA, USA. ofiehn@ucdavis.edu. · Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY, 10032, USA. wil2001@cumc.columbia.edu. ·Sci Rep · Pubmed #29968805.

ABSTRACT: The pathogenesis of ME/CFS, a disease characterized by fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, irritable bowel syndrome (IBS), and lymphadenopathy, is poorly understood. We report biomarker discovery and topological analysis of plasma metabolomic, fecal bacterial metagenomic, and clinical data from 50 ME/CFS patients and 50 healthy controls. We confirm reports of altered plasma levels of choline, carnitine and complex lipid metabolites and demonstrate that patients with ME/CFS and IBS have increased plasma levels of ceramide. Integration of fecal metagenomic and plasma metabolomic data resulted in a stronger predictive model of ME/CFS (cross-validated AUC = 0.836) than either metagenomic (cross-validated AUC = 0.745) or metabolomic (cross-validated AUC = 0.820) analysis alone. Our findings may provide insights into the pathogenesis of ME/CFS and its subtypes and suggest pathways for the development of diagnostic and therapeutic strategies.

12 Article Psychoneuroimmunology and Natural Killer Cells: The Chromium-Release Whole-Blood Assay. 2018

Fletcher, Mary Ann / Barnes, Zachary / Broderick, Gordon / Klimas, Nancy G. ·Department of Medicine, University of Miami, Miami, FL, USA. MFletche@med.miami.edu. · Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA. MFletche@med.miami.edu. · Department of Medicine, University of Miami, Miami, FL, USA. · Center for Clinical Systems Biology, Rochester General Hospital Research Institute, Rochester, NY, USA. · Department of Medicine, University of Alberta, Edmonton, AB, Canada. · Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA. · Miami Veterans Affairs Medical Center, Miami, FL, USA. ·Methods Mol Biol · Pubmed #29705850.

ABSTRACT: Natural killer (NK) cells are an essential component of innate immunity. These lymphocytes are also sensitive barometers of the effects of endogenous and exogenous stressors on the immune system. This chapter describes a chromium (

13 Article Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model. 2018

Milrad, Sara F / Hall, Daniel L / Jutagir, Devika R / Lattie, Emily G / Czaja, Sara J / Perdomo, Dolores M / Fletcher, Mary Ann / Klimas, Nancy / Antoni, Michael H. ·Department of Psychology, University of Miami, United States. · Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, United States; Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Harvard Medical School, United States. · Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, United States. · Department of Psychiatry and Behavioral Sciences, University of Miami, United States. · Institute for Neuro Immune Medicine, Nova Southeastern University, United States. · Department of Psychology, University of Miami, United States. Electronic address: mantoni@miami.edu. ·Int J Psychophysiol · Pubmed #28918107.

ABSTRACT: INTRODUCTION: Chronic Fatigue Syndrome (CFS) is a poorly understood illness that is characterized by diverse somatic symptoms, hypothalamic pituitary adrenal (HPA) axis dysfunction and heightened inflammatory indicators. These symptoms are often exacerbated and accompanied by psychological distress states and depression. Since depression is known to be associated with HPA axis dysfunction and greater inflammation, a psychoneuroendocrinological (PNE) model of inflammation was examined in persons diagnosed with CFS in order to uncover underlying biopsychosocial mechanisms in this poorly understood chronic illness. METHODS: Baseline data were drawn from two randomized controlled trials testing the efficacy of different forms of psychosocial intervention, and included psychological questionnaires, di-urnal salivary cortisol, and blood samples. Data were analyzed with structural equation modeling (SEM). RESULTS: The sample (N=265) was mostly middle-aged (M DISCUSSION: Results highlight the role of depression, cortisol and inflammation in possible biological mechanisms involved in the pathophysiology of CFS. Time-lagged, longitudinal analyses are needed to fully explore these relationships.

14 Article Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome. 2017

Nagy-Szakal, Dorottya / Williams, Brent L / Mishra, Nischay / Che, Xiaoyu / Lee, Bohyun / Bateman, Lucinda / Klimas, Nancy G / Komaroff, Anthony L / Levine, Susan / Montoya, Jose G / Peterson, Daniel L / Ramanan, Devi / Jain, Komal / Eddy, Meredith L / Hornig, Mady / Lipkin, W Ian. ·Center for Infection and Immunity, Columbia University Mailman School of Public Health, 722 W 168th Street 17th Floor, New York,, NY, 10032, USA. · Fatigue Consultation Clinic, Salt Lake City, UT, 84102, USA. · Institute for Neuro-Immune Medicine, College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, 33314, USA. · Miami VA Medical Center, Miami, FL, 33125, USA. · Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. · Levine Clinic, New York, NY, 10021, USA. · Stanford University, Palo Alto, CA, 94305, USA. · Sierra Internal Medicine at Incline Village, Incline Village, NV, 89451, USA. · Ayasdi, Inc., Menlo Park, CA, 94025, USA. · Center for Infection and Immunity, Columbia University Mailman School of Public Health, 722 W 168th Street 17th Floor, New York,, NY, 10032, USA. wil2001@cumc.columbia.edu. ·Microbiome · Pubmed #28441964.

ABSTRACT: BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. RESULTS: Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. CONCLUSIONS: Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.

15 Article Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology. 2017

Halpin, Peter / Williams, Marshall Vance / Klimas, Nancy G / Fletcher, Mary Ann / Barnes, Zachary / Ariza, Maria Eugenia. ·Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio. · Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio. · NOVA Southeastern University, Institute for Neuro Immune Medicine, Fort Lauderdale, Florida. · Miami VA Medical Center, Miami, Florida. · University of Miami, Miami, Florida. ·J Med Virol · Pubmed #28303641.

ABSTRACT: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) are debilitating diseases with overlapping symptomology and there are currently no validated tests for definitive diagnosis of either syndrome. While there is evidence supporting the premise that some herpesviruses may act as possible triggers of ME/CFS, the involvement of herpesviruses in the pathophysiology of GWI has not been studied in spite of a higher prevalence of ME/CFS in these patients. We have previously demonstrated that the deoxyuridine triphosphate nucleotidohydrolases (dUTPase) encoded by Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), and varicella-zoster virus (VZV) possess novel functions in innate and adaptive immunity. The results of this study demonstrate that a significant percentage of patients with ME/CFS (30.91-52.7%) and GWI (29.34%) are simultaneously producing antibodies against multiple human herpesviruses-encoded dUTPases and/or the human dUTPase when compared to controls (17.21%). GWI patients exhibited significantly higher levels of antibodies to the HHV-6 and human dUTPases than controls (P = 0.0053 and P = 0.0036, respectively), while the ME/CFS cohort had higher anti-EBV-dUTPase antibodies than in both GWI patients (P = 0.0008) and controls (P < 0.0001) as well as significantly higher anti-human dUTPase antibodies than in controls (P = 0.0241). These results suggest that screening of patients' sera for the presence of various combinations of anti-dUTPase antibodies could be used as potential biomarkers to help identify/distinguish patients with these syndromes and better direct treatment.

16 Article Telephone-administered versus live group cognitive behavioral stress management for adults with CFS. 2017

Hall, Daniel L / Lattie, Emily G / Milrad, Sara F / Czaja, Sara / Fletcher, Mary Ann / Klimas, Nancy / Perdomo, Dolores / Antoni, Michael H. ·Department of Psychology, University of Miami, Coral Gables, FL, USA; Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA. Electronic address: dhall7@mgh.harvard.edu. · Department of Psychology, University of Miami, Coral Gables, FL, USA; Center for Behavioral Intervention Technologies (CBITs), Northwestern University, Chicago, IL, USA. · Department of Psychology, University of Miami, Coral Gables, FL, USA. · Department of Psychiatry and Behavioral Sciences, University of Miami, Miami, FL, USA. · Institute for Neuro Immune Medicine, Nova Southeastern University, Davie, FL, USA. · Department of Psychology, University of Miami, Coral Gables, FL, USA; Department of Psychiatry and Behavioral Sciences, University of Miami, Miami, FL, USA. ·J Psychosom Res · Pubmed #28107891.

ABSTRACT: OBJECTIVE: Chronic fatigue syndrome (CFS) symptoms have been shown to be exacerbated by stress and ameliorated by group-based psychosocial interventions such as cognitive behavioral stress management (CBSM). Still, patients may have difficulty attending face-to-face groups. This study compared the effects of a telephone-delivered (T-CBSM) vs a live (L-CBSM) group on perceived stress and symptomology in adults with CFS. METHODS: Intervention data from 100 patients with CFS (mean age 50years; 90% female) participating in T-CBSM (N=56) or L-CBSM (N=44) in previously conducted randomized clinical trials were obtained. Perceived Stress Scale (PSS) and the Centers for Disease Control and Prevention symptom checklist scores were compared with repeated measures analyses of variance in adjusted and unadjusted analyses. RESULTS: Participants across groups showed no differences in most demographic and illness variables at study entry and had similar session attendance. Both conditions showed significant reductions in PSS scores, with L-CBSM showing a large effect (partial ε CONCLUSIONS: Two different formats for delivering group-based CBSM-live and telephone-showed reductions in perceived stress among patients with CFS. However, only the live format was associated with physical symptom improvements, with specific effects on post-exertional malaise, chills, fever, and restful sleep. The added value of the live group format is discussed, along with implications for future technology-facilitated group interventions in this population.

17 Article Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women. 2017

Milrad, Sara F / Hall, Daniel L / Jutagir, Devika R / Lattie, Emily G / Ironson, Gail H / Wohlgemuth, William / Nunez, Maria Vera / Garcia, Lina / Czaja, Sara J / Perdomo, Dolores M / Fletcher, Mary Ann / Klimas, Nancy / Antoni, Michael H. ·Department of Psychology, University of Miami, 5665 Ponce de Leon Blvd., Miami, FL 33133, USA. · Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, 55 Fruit St., Boston, MA 02114, USA. · Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 N Lake Shore Dr. Suite 1400, Chicago, IL 60611, USA. · Department of Sleep Medicine, Miami Veteran Affairs Hospital, 1201 NW 16th St, Miami, FL 33125, USA. · Institute for Neuro Immune Medicine, Nova Southeastern University, 8501 SW 124th Ave #111, Miami, FL 33183, USA. · Department of Psychiatry and Behavioral Sciences, University of Miami, 1120 NW 14th St., Miami, FL 33136, USA. · Department of Psychology, University of Miami, 5665 Ponce de Leon Blvd., Miami, FL 33133, USA. Electronic address: mantoni@miami.edu. ·J Neuroimmunol · Pubmed #28038892.

ABSTRACT: OBJECTIVE: Poor sleep quality has been linked to inflammatory processes and worse disease outcomes in the context of many chronic illnesses, but less is known in conditions such as chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). This study examines the relationships between sleep quality, pro-inflammatory cytokines, and CFS/ME symptoms. METHODS: Sixty women diagnosed with CFS/ME were assessed using the Pittsburgh Sleep Quality Index (PSQI), Fatigue Symptom Inventory (FSI) and Center for Disease Control and Prevention (CDC)-based CFS/ME symptom questionnaires. Circulating plasma pro-inflammatory cytokine levels were measured by ELISA. Multiple regression analyses examined associations between sleep, cytokines and symptoms, controlling for age, education, and body mass index. RESULTS: Poor sleep quality (PSQI global score) was associated with greater pro-inflammatory cytokine levels: interleukin-1β (IL-1β) (β=0.258, p=0.043), IL-6 (β=0.281, p=0.033), and tumor necrosis factor-alpha (TNF-α) (β=0.263, p=0.044). Worse sleep quality related to greater fatigue severity (β=0.395, p=0.003) and fatigue-related interference with daily activities (β=0.464, p<0.001), and more severe and frequent CDC-defined core CFS/ME symptoms (β=0.499, p<0.001, and β=0.556, p<0.001, respectively). CONCLUSIONS: Results underscore the importance of managing sleep-related difficulties in this patient population. Further research is needed to identify the etiology of sleep disruptions in CFS/ME and mechanistic factors linking sleep quality to symptom severity and inflammatory processes.

18 Article Illness progression in chronic fatigue syndrome: a shifting immune baseline. 2016

Russell, Lindsey / Broderick, Gordon / Taylor, Renee / Fernandes, Henrique / Harvey, Jeanna / Barnes, Zachary / Smylie, AnneLiese / Collado, Fanny / Balbin, Elizabeth G / Katz, Ben Z / Klimas, Nancy G / Fletcher, Mary Ann. ·Department of Medicine, University of Alberta, Edmonton, AB, Canada. · Department of Medicine, University of Alberta, Edmonton, AB, Canada. gbroderick@nova.edu. · Miami Veterans Affairs Medical Center, Miami, FL, USA. gbroderick@nova.edu. · Institute for Neuro-immune Medicine, Nova Southeastern University, Suite 3440 University Park Plaza, 3424 South University Drive, Fort Lauderdale, FL, 33328, USA. gbroderick@nova.edu. · Department of Occupational Therapy, University of Illinois at Chicago, Chicago, IL, USA. · Department of Medicine, University of Miami, Miami, FL, USA. · Miami Veterans Affairs Medical Center, Miami, FL, USA. · Institute for Neuro-immune Medicine, Nova Southeastern University, Suite 3440 University Park Plaza, 3424 South University Drive, Fort Lauderdale, FL, 33328, USA. · Division of Infectious Diseases, Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA. ·BMC Immunol · Pubmed #26965484.

ABSTRACT: BACKGROUND: Validation of biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) across data sets has proven disappointing. As immune signature may be affected by many factors, our objective was to explore the shift in discriminatory cytokines across ME/CFS subjects separated by duration of illness. METHODS: Cytokine expression collected at rest across multiple studies for female ME/CFS subjects (i) 18 years or younger, ill for 2 years or less (n = 18), (ii) 18-50 years of age, ill for 7 years (n = 22), and (iii) age 50 years or older (n = 28), ill for 11 years on average. Control subjects were matched for age and body mass index (BMI). Data describing the levels of 16 cytokines using a chemiluminescent assay was used to support the identification of separate linear classification models for each subgroup. In order to isolate the effects of duration of illness alone, cytokines that changed significantly with age in the healthy control subjects were excluded a priori. RESULTS: Optimal selection of cytokines in each group resulted in subsets of IL-1α, 6, 8, 15 and TNFα. Common to any 2 of 3 groups were IL-1α, 6 and 8. Setting these 3 markers as a triple screen and adjusting their contribution according to illness duration sub-groups produced ME/CFS classification accuracies of 75-88 %. The contribution of IL-1α, higher in recently ill adolescent ME/CFS subjects was progressively less important with duration. While high levels of IL-8 screened positive for ME/CFS in the recently afflicted, the opposite was true for subjects ill for more than 2 years. Similarly, while low levels of IL-6 suggested early ME/CFS, the reverse was true in subjects over 18 years of age ill for more than 2 years. CONCLUSIONS: These preliminary results suggest that IL-1α, 6 and 8 adjusted for illness duration may serve as robust biomarkers, independent of age, in screening for ME/CFS.

19 Article Perceived Fatigue Interference and Depressed Mood: Comparison of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients with Fatigued Breast Cancer Survivors. 2015

Hall, Daniel L / Antoni, Michael H / Lattie, Emily G / Jutagir, Devika R / Czaja, Sara J / Perdomo, Dolores / Lechner, Suzanne C / Stagl, Jamie M / Bouchard, Laura C / Gudenkauf, Lisa M / Traeger, Lara / Fletcher, MaryAnn / Klimas, Nancy G. ·Department of Psychology, University of Miami. · Department of Psychology, University of Miami ; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine ; Department of Psychiatry and Behavioral Sciences, University of Miami. · Department of Psychiatry and Behavioral Sciences, University of Miami. · Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine. · Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School. · Institute for Neuro Immune Medicine, Nova Southeastern University. ·Fatigue · Pubmed #26180660.

ABSTRACT: OBJECTIVE: Persistent fatigue and depressive symptoms are both highly prevalent among patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) as well as breast cancer survivors. This study aimed to assess and directly compare perceptions of fatigue as highly interfering in one's daily functioning in both patient populations to better understand their relationships with depressed mood. METHODS: Participants were 95 female CFS/ME patients and 67 females who were approximately 5 years post-treatment for stage 0-III breast cancer presenting with clinically elevated fatigue severity. Self-report measures were obtained on participants' fatigue-related interference in daily functioning and fatigue severity as well as depressed mood. Hierarchical regression was used to test effects controlling for relevant demographic, psychosocial, and medical covariates. RESULTS: CFS/ME patients endorsed greater depressed mood and fatigue interference than did fatigued breast cancer survivors, CONCLUSIONS: CFS/ME patients reported elevated fatigue symptoms and depression relative to fatigued breast cancer survivors. In the former group, greater depressed mood was highly and significantly associated with greater fatigue-related inference in daily activities. Potential targets for cognitive behavioral interventions are discussed.

20 Article Stress management skills, cortisol awakening response, and post-exertional malaise in Chronic Fatigue Syndrome. 2014

Hall, Daniel L / Lattie, Emily G / Antoni, Michael H / Fletcher, Mary Ann / Czaja, Sara / Perdomo, Dolores / Klimas, Nancy G. ·Department of Psychology, University of Miami, Coral Gables, FL, USA. Electronic address: dhall@psy.miami.edu. · Department of Psychology, University of Miami, Coral Gables, FL, USA. · Institute for Neuro Immune Medicine, Nova Southeastern University, Davie, FL, USA. · Department of Psychiatry and Behavioral Sciences, University of Miami, Miami, FL, USA. ·Psychoneuroendocrinology · Pubmed #25049069.

ABSTRACT: Chronic Fatigue Syndrome (CFS) is characterized in part by debilitating fatigue typically exacerbated by cognitive and/or physical exertion, referred to as post-exertional malaise (PEM). In a variety of populations, the cortisol awakening response (CAR) has stood out as a marker of endocrine dysregulation relevant to the experience of fatigue, and may therefore be particularly relevant in CFS. This is the first study to examine PEM and the CAR in a sample of individuals with CFS. The CAR has also been established as a stress-sensitive measure of HPA axis functioning. It follows that better management of stress could modulate the CAR, and in turn PEM. In this cross-sectional study, we hypothesized that greater Perceived Stress Management Skills (PSMS) would relate to lower reports of PEM, via the impact of PSMS on the CAR. A total of 117 adults (72% female) with a CFS diagnosis completed self-report measures of PSMS and PEM symptomatology and a two-day protocol of saliva collection. Cortisol values from awakening and 30 min post-awakening were used to compute the CAR. Regression analyses revealed that greater PSMS related to greater CAR and greater CAR related to less PEM severity. Bootstrapped analyses revealed an indirect effect of PSMS on PEM via the CAR, such that greater PSMS related to less PEM, via a greater CAR. Future research should examine these trends longitudinally and whether interventions directed at improving stress management skills are accompanied by improved cortisol regulation and less PEM in individuals with CFS.

21 Article A role for homeostatic drive in the perpetuation of complex chronic illness: Gulf War Illness and chronic fatigue syndrome. 2014

Craddock, Travis J A / Fritsch, Paul / Rice, Mark A / del Rosario, Ryan M / Miller, Diane B / Fletcher, Mary Ann / Klimas, Nancy G / Broderick, Gordon. ·Center for Psychological Studies, Nova Southeastern University, Fort Lauderdale, Florida, United States of America ; Graduate School for Computer and Information Sciences, Nova Southeastern University, Fort Lauderdale, Florida, United States of America ; Institute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, Florida, United States of America. · Department of Medicine, Faculty of Dentistry and Medicine, University of Alberta, Edmonton, Alberta, Canada. · Institute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, Florida, United States of America. · Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America. · Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida, United States of America. · Institute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, Florida, United States of America ; College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, Florida, United States of America. · Center for Psychological Studies, Nova Southeastern University, Fort Lauderdale, Florida, United States of America ; Institute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, Florida, United States of America ; Department of Medicine, Faculty of Dentistry and Medicine, University of Alberta, Edmonton, Alberta, Canada ; College of Pharmacy, Nova Southeastern University, Fort Lauderdale, Florida, United States of America. ·PLoS One · Pubmed #24416298.

ABSTRACT: A key component in the body's stress response, the hypothalamic-pituitary-adrenal (HPA) axis orchestrates changes across a broad range of major biological systems. Its dysfunction has been associated with numerous chronic diseases including Gulf War Illness (GWI) and chronic fatigue syndrome (CFS). Though tightly coupled with other components of endocrine and immune function, few models of HPA function account for these interactions. Here we extend conventional models of HPA function by including feed-forward and feedback interaction with sex hormone regulation and immune response. We use this multi-axis model to explore the role of homeostatic regulation in perpetuating chronic conditions, specifically GWI and CFS. An important obstacle in building these models across regulatory systems remains the scarcity of detailed human in vivo kinetic data as its collection can present significant health risks to subjects. We circumvented this using a discrete logic representation based solely on literature of physiological and biochemical connectivity to provide a qualitative description of system behavior. This connectivity model linked molecular variables across the HPA axis, hypothalamic-pituitary-gonadal (HPG) axis in men and women, as well as a simple immune network. Inclusion of these interactions produced multiple alternate homeostatic states and sexually dimorphic responses. Experimental data for endocrine-immune markers measured in male GWI subjects showed the greatest alignment with predictions of a naturally occurring alternate steady state presenting with hypercortisolism, low testosterone and a shift towards a Th1 immune response. In female CFS subjects, expression of these markers aligned with an alternate homeostatic state displaying hypocortisolism, high estradiol, and a shift towards an anti-inflammatory Th2 activation. These results support a role for homeostatic drive in perpetuating dysfunctional cortisol levels through persistent interaction with the immune system and HPG axis. Though coarse, these models may nonetheless support the design of robust treatments that might exploit these regulatory regimes.

22 Article Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Symptom Severity: Stress Management Skills are Related to Lower Illness Burden. 2013

Lattie, Emily G / Antoni, Michael H / Fletcher, Mary Ann / Czaja, Sara / Perdomo, Dolores / Sala, Andreina / Nair, Sankaran / Fu, Shih Hua / Penedo, Frank J / Klimas, Nancy. ·Department of Psychology, University of Miami. ·Fatigue · Pubmed #24278791.

ABSTRACT: BACKGROUND: The onset of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) typically involves reductions in PURPOSE: This study aimed to evaluate if perceived stress management skills affect illness burden via emotional distress, independent of ME/CFS symptom severity. METHODS: A total of 117 adults with ME/CFS completed measures of perceived stress management skills, emotional distress, ME/CFS symptom severity and illness burden. RESULTS: Regression analyses revealed that greater perceived stress management skills related to less social and fatigue-related illness burden, via lower emotional distress. This relationship existed independent of the association of symptom severity on illness burden, and was stronger among those not currently employed. CONCLUSIONS: Ability to manage stress is associated with a lower illness burden for individuals with ME/CFS. Future studies should evaluate the efficacy of psychosocial interventions in lowering illness burden by targeting stress management skills.

23 Article Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome. 2012

Lattie, Emily G / Antoni, Michael H / Fletcher, Mary Ann / Penedo, Frank / Czaja, Sara / Lopez, Corina / Perdomo, Dolores / Sala, Andreina / Nair, Sankaran / Fu, Shih Hua / Klimas, Nancy. ·Department of Psychology, University of Miami, Coral Gables, FL 33124, USA. ·Brain Behav Immun · Pubmed #22417946.

ABSTRACT: OBJECTIVES: Stressors and emotional distress responses impact chronic fatigue syndrome (CFS) symptoms, including fatigue. Having better stress management skills might mitigate fatigue by decreasing emotional distress. Because CFS patients comprise a heterogeneous population, we hypothesized that the role of stress management skills in decreasing fatigue may be most pronounced in the subgroup manifesting the greatest neuroimmune dysfunction. METHODS: In total, 117 individuals with CFS provided blood and saliva samples, and self-report measures of emotional distress, perceived stress management skills (PSMS), and fatigue. Plasma interleukin-1-beta (IL-1β, IL-2, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α), and diurnal salivary cortisol were analyzed. We examined relations among PSMS, emotional distress, and fatigue in CFS patients who did and did not evidence neuroimmune abnormalities. RESULTS: Having greater PSMS related to less fatigue (p=.019) and emotional distress (p<.001), greater diurnal cortisol slope (p=.023) and lower IL-2 levels (p=.043). PSMS and emotional distress related to fatigue levels most strongly in CFS patients in the top tercile of IL-6, and emotional distress mediated the relationship between PSMS and fatigue most strongly in patients with the greatest circulating levels of IL-6 and a greater inflammatory (IL-6):anti-inflammatory (IL-10) cytokine ratio. DISCUSSION: CFS patients having greater PSMS show less emotional distress and fatigue, and the influence of stress management skills on distress and fatigue appear greatest among patients who have elevated IL-6 levels. These findings support the need for research examining the impact of stress management interventions in subgroups of CFS patients showing neuroimmune dysfunction.

24 Article A pilot study of cognitive behavioral stress management effects on stress, quality of life, and symptoms in persons with chronic fatigue syndrome. 2011

Lopez, Corina / Antoni, Michael / Penedo, Frank / Weiss, Donna / Cruess, Stacy / Segotas, Mary-Catherine / Helder, Lynn / Siegel, Scott / Klimas, Nancy / Fletcher, Mary Ann. ·University of Miami, Miami, FL, USA. ·J Psychosom Res · Pubmed #21414452.

ABSTRACT: OBJECTIVE: The present pilot study was designed to test the effects of a 12-week group-based cognitive behavioral stress management (CBSM) intervention on stress, quality of life, and symptoms in chronic fatigue syndrome (CFS). We hypothesized that participants randomized to CBSM would report improvements in perceived stress, mood, quality of life, and CFS symptomatology from pre- to postintervention compared to those receiving a psychoeducational (PE) seminar control. METHOD: We recruited 69 persons with a bona fide diagnosis of CFS and randomized 44 to CBSM and 25 to PE. Participants completed the Perceived Stress Scale (PSS), Profile of Mood States (POMS), Quality of Life Inventory (QOLI), and a Centers for Disease Control (CDC)-based CFS symptom checklist pre- and postintervention. RESULTS: Repeated measures analysis of variance revealed a significant Group×Time interaction for PSS, POMS-total mood disturbance (TMD), and QOLI scores, such that participants in CBSM evidenced greater improvements than those in PE. Participants in CBSM also reported decreases in severity of CFS symptoms vs. those in PE. CONCLUSIONS: Results suggest that CBSM is beneficial for managing distress, improving quality of life, and alleviating CFS symptom severity.

25 Article A Comparison of Immune Functionality in Viral versus Non-Viral CFS Subtypes. 2010

Porter, Nicole / Lerch, Athena / Jason, Leonard A / Sorenson, Matthew / Fletcher, Mary Ann / Herrington, Joshua. ·DePaul University. · University of Miami. ·J Behav Neurosci Res · Pubmed #24634898.

ABSTRACT: Participants with CFS were grouped into viral and non-viral onset fatigue categories and assessed for differential immunological marker expression. Peripheral Blood Mononuclear Cells were assessed for differential phenotypic expression of surface adherence glycoproteins on circulating lymphocytes. The flow cytometric analysis employed fluorescent monoclonal antibody labeling. The viral in comparison to the non-viral group demonstrated significant elevations in several Th1 type subsets including: the percentage and number of CD4+ cells, the percentage and number of CD2+CD26+ cells, the percentage and number of CD2+CD4+CD26+ cells, the percentage and number of CD4+ CD26+ cells, and the percentage of Th2 naïve cells (CD4+ CD45RA+CD62L+). Of the remaining significant findings, the non viral group demonstrated significant elevations in comparison to the viral group for the following Th1 type subsets: the percentage of CD8+ cells, the percentage of T-cytotoxic suppressor cells (CD3+8+), and the percentage and number of Th1 memory cells (CD8+CD45RA-CD62L-). The viral group demonstrated a pattern of activation that differed from that of the group with a non-viral etiology, as evidenced by an elevated and out of range percentage and number of CD4+ cells, the percentage of CD2+CD26+, and the percentage of Th2 naïve cells (CD4+CD45RA+CD62L+). Both groups demonstrated reduced and out of range Natural Killer Cell Cytotoxicity and percentage of B-1 cells (CD5+CD19). In addition, both groups demonstrated an elevated and out of range percentage of CD2+CD8+CD26+, percentage of the Th1 memory subset (CD4+CD45RA-CD62L-), the percentage of Th1 memory and naïve cells (CD8+CD45RA-CD62L-, CD8+CD45RA+CD62L-), the percentage and number of Th2 memory cells (CD4+CD45RA-CD62L+), and the percentage of Th2 memory and naïve cells (CD8+CD45RA-CD62L+, CD8+CD45RA+CD62L+). These findings imply that the homeostatic mechanism responsible for the regulation of the Th1 (cell mediated) and Th2 (humoral) immune responses is disturbed in CFS. The implications of these findings are discussed.

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