The potential role of ocular and otolaryngological mucus proteins in myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness associated with a constellation of other symptoms. While the most common symptom is unrelenting fatigue, many individuals also report suffering from rhinitis, dry eyes and a sore throat. Mucin proteins are responsible for contributing to the formation of mucosal membranes throughout the body. These mucosal pathways contribute to the body's defense mechanisms involving pathogenic onset. When compromised by pathogens the epithelium releases numerous cytokines and enters a prolonged state of inflammation to eradicate any particular infection. Based on genetic analysis, and computational theory and modeling we hypothesize that mucin protein dysfunction may contribute to ME/CFS symptoms due to the inability to form adequate mucosal layers throughout the body, especially in the ocular and otolaryngological pathways leading to low grade chronic inflammation and the exacerbation of symptoms.

Associations Among Trajectories of Sleep Disturbance, Depressive Symptomology and 24-Hour Urinary Cortisol in HIV+ Women Following a Stress Management Intervention.

Objective: The burden of sleep disturbance and depressive symptomology is high for persons living with HIV and particularly so for women. While cognitive behavioral stress management (CBSM) is shown to reduce symptoms of depression and 24-hr urinary free cortisol output (CORT) in HIV+ men, less is known about the effects of CBSM on mood and concomitant sleep disturbance in HIV+ women. The study aim is to model longitudinal change in sleep disturbance, depressive symptomology, and CORT for HIV+ women exposed to a 12-week CBSM intervention or control condition. Methods: Self-reported sleep quality and depressive symptomology, along with CORT, was collected from surveys at baseline and approximately every three months thereafter for nine months from 130 HIV+ women (Mage = 38.44, SD = 7.73). The data was used to specify a parallel process latent growth model with CORT as a time-varying covariate. Results: The model showed acceptable fit. There was a linear decline in sleep disturbance (ß = -0.32, p < .05) and logarithmic decline in depressive symptomology (ß = -0.33, p < .05) for those receiving the intervention. Decline in sleep disturbance predicted lower CORT at nine months. Furthermore, having less depressive symptoms at baseline was associated with lower initial levels of sleep disturbance and greater improvement in sleep quality over time. There was no discernible association between sleep and mood disturbance in the control group. Across groups, there was a consistent association between older age and greater sleep disturbance (r = 0.34, p < .01). Conclusion: Sleep disturbance appears to be a behavioral target for CBSM in HIV+ women although older age, preintervention levels of depressive mood, and time-varying levels of CORT output may limit improvement in sleep quality over time.

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

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.

Change in urinary cortisol excretion mediates the effect of angry/hostile mood on 9 month diastolic blood pressure in HIV+ adults.

Cardiovascular disease is a growing concern in HIV disease management and nearly 1 out of 3 persons living with the virus is hypertensive. Biobehavioral factors such as anger, hostility, and HPA axis reactivity are emperically linked to blood pressure regulation. Whether HPA axis or mood disturbance increases risk for hypertension remains unclear in HIV disease. The aim of this study was to determine whether 9-month change in angry/hostile mood predicts alterations in systolic (SBP) or diastolic blood pressure (DBP), and whether this change is mediated by 24-h urinary cortisol (CORT) output. Sixty-one HIV positive adults, aged 41.1 ± 8.6 years, assigned to the control condition of a stress management intervention provided blood samples, 24-h urine specimens, blood pressure in-office, and self-reported mood at baseline and a 9-month follow-up. CORT was tested as a mediator in two separate models controlling for baseline BP, CD4 count, HIV-1 viral load, protease inhibitor use, body mass index, smoking status, and family history of cardiometabolic disease. Increase in angry/hostile mood was associated with greater SBP (ß = 0.33, CI 0.09, 0.56, p = 0.01) and DBP (ß = 0.39, CI 0.16, 0.62, p < 0.001) at follow-up. CORT partially mediated the effect of angry/hostile mood on DBP (ß = 0.28, CI 0.03, 0.54, p = 0.03). Change in CORT was not related to SBP (ß = 0.12, CI -0.20, 0.44, p = 0.46). The final mediation model accounted for 41.2% of the variance in 9-month DBP. Angry or hostile mood may contribute to increased risk for hypertension in persons treated for HIV via disturbance of the HPA-axis.

Psychological Distress Mediates the Effect of Alexithymia on 2-Year Change in HIV Viral Load.

PURPOSE: Individuals with trait alexithymia (AL) display poor cognitive assimilation of thoughts, feelings, and emotions. This may result in the persistence of stress, anxiety, and depressive disorders. The cumulative effect of this psychological distress is also linked clinical markers of human immunodeficiency virus (HIV) disease progression. This study examines the indirect effect of AL on HIV viral load as a function of baseline levels and change in psychological distress. METHODS: N = 123 HIV positive adults aged 37.9 ± 9.2 years provided blood samples for HIV-1 viral RNA and CD4 T lymphocytes along with self-reported stress, anxiety, and depression every 6 months for 2 years. A second-order conditional latent growth model was used to represent baseline and 2-year change in cumulative levels of psychological distress and to test the indirect effect of baseline levels of trait AL on change in HIV-1 viral load through this latent measure. RESULTS: AL was associated with baseline and latent change in psychological distress. Furthermore, baseline psychological distress predicted 2-year change in HIV-1 viral RNA after controlling for viral load at baseline. Altogether, trait AL had a significant indirect effect on change in viral load (ß = 0.16, p = 0.03) as a function of baseline levels of distress. CONCLUSION: Identification and communication of thoughts, feelings, and emotions are important for long-term psychological adaptation in HIV. Greater psychological distress, in turn, allows for persistence of peripheral viral replication.

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

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.

Alexithymia, Assertiveness and Psychosocial Functioning in HIV: Implications for Medication Adherence and Disease Severity.

Psychosocial function and adherence to antiretroviral regimen are key factors in human immunodeficiency virus (HIV) disease management. Alexithymia (AL) is a trait deficit in the ability to identify and describe feelings, emotions and bodily sensations. A structural equation model was used to test whether high levels of AL indirectly relate to greater non-adherent behavior and HIV disease severity via psychosocial dysfunction. Blood draws for HIV-1 viral load and CD4 T-lymphocyte, along with psychosocial surveys were collected from 439 HIV positive adults aged 18-73 years. The structural model supports significant paths from: (1) AL to non-active patient involvement, psychological distress, and lower social support, (2) psychological distress and non-active involvement to non-adherent behavior, and (3) non-adherence to greater HIV disease severity (CFI = .97, RMSEA = .04, SRMR = .05). A second model confirmed the intermediary effect of greater patient assertiveness on the path from AL to social support and non-active patient involvement (CFI = .94, RMSEA = .04, SRMR = .05). Altogether, AL is indirectly linked with HIV disease management through it's association with poor psychosocial function, however greater patient assertiveness buffers the negative impact of AL on relationship quality with healthcare providers and members of one's social support network.

Tracking post-infectious fatigue in clinic using routine Lab tests.

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.

Spiritual coping predicts CD4-cell preservation and undetectable viral load over four years.

In this study of 177 people living with HIV, we examined if spiritual coping leads to slower HIV disease progression (CD4 cells, viral load [VL]), and more positive health behaviors (adherence, safer sex, less substance use). Prior research suggests that physicians' assessment of spiritual coping can be an interventional aid in promoting positive spiritual coping. Longitudinal spiritual coping was rated using qualitative content analysis of six-monthly interviews/essays. Positive spiritual coping (65%) was predominant over negative (7%), whereas 28% did not make significant use of spirituality as a means to cope. Spiritual coping was associated with less substance use disorder but not with less sexual risk behavior. Hierarchical linear modeling demonstrated that spiritual coping predicted sustained undetectable VL and CD4-cell preservation over four years, independent of sociodemographics, baseline disease status, and substance use disorder. Achieving undetectable VL significantly increased over time in participants with positive spiritual coping but decreased among those with negative spiritual coping. For every participant with positive spiritual coping achieving undetectable VL, four with negative spiritual coping reported with detectable/transmittable HIV. Notably, even when controlling for the effect of VL suppression, CD4-cell decline was 2.25 times faster among those engaged in negative versus positive spiritual coping. In conclusion, spiritual coping is associated with positive health behaviors, such as maintaining long-term VL suppression and less onset/relapse of substance use disorder over time. Among those who are sexually active, positive spiritual coping reduces the risk of HIV transmission via VL suppression but may not prevent the transmission of other STDs because spiritual coping is not related to safer sexual behavior. Notably, the association between spiritual coping and immune preservation was direct (i.e., not explained by VL suppression), suggesting potential psychoneuroimmunological pathways. Thus, assessment of spiritual coping may be an important area of intervention to achieve undetectable VL, reduce HIV disease progression, and prevent substance use onset/relapse.

Alexithymia is linked to neurocognitive, psychological, neuroendocrine, and immune dysfunction in persons living with HIV.

The neuropathological changes resulting from Human Immunodeficiency Virus (HIV) infection may manifest in alexithymia (AL), a multidimensional trait characterized by impairments in the cognitive assimilation of feelings and emotions. A sample of 93 HIV survivors scoring high, i.e., ⩾74 on the 26-item Toronto Alexithymia Scale (TAS-26), were compared to 79 low AL (TAS-26⩽54) survivors on measures of neurocognitive, psychological, neuroendocrine and immune function. Neurocognitive function was evinced by a standardized test of psychomotor speed, cognitive flexibility and task switching ability, HIV Dementia and general cognitive status. Patients were also screened for levels of depression, anxiety and psychological stress. A 24-h urinary norepinephrine (NE) and cortisol (CORT) collection was taken; blood was drawn for T lymphocyte subset counts (CD4+CD3+) and HIV-1 viral load. Alexithymic patients exhibited higher levels of executive dysfunction, psychological distress, norepinephrine-to-cortisol (NE/CORT) ratio and viral load. Linear regression models accounting for sociodemographic and disease-related variables revealed two AL subscales, difficulties identifying and describing feelings, predicted and explained a significant proportion of variance in the outcome measures. Specifically, poorer executive task-switching/cognitive flexibility was associated with greater difficulty describing feelings; dysregulated autonomic response (high NE/CORT ratio) and depressive symptoms were predicted by difficulty identifying feelings; higher levels of anxiety and psychological stress were both predicted by greater difficulty describing and identifying feelings. Overall, the psychoneuroimmunological profile of alexithymia in HIV positive persons at mid-stage of infection suggests a greater vulnerability for disease progression.

Oxytocin, social support, and sleep quality in low-income minority women living with HIV.

Sleep disturbances are highly prevalent in women with HIV, and few studies examine potential protective factors that may reduce risk for sleep disturbances in this high-risk population. This study predicted that HIV-specific social support from various sources (i.e., friends, family members, and spouses), as well as oxytocin (OT), would explain sleep quality in 71 low-income minority women living with HIV. Social support from family members was associated with better sleep quality in women. For women with high OT, support from friends was associated with better sleep quality, whereas for women with low OT, support from friends was associated with poorer sleep quality. Women with low OT may not effectively interpret and utilize available support resources, which may be associated with sleep disturbances.

A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome.

BACKGROUND: Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating condition presenting complex immune, endocrine and neurological symptoms. Here we compared male (n = 20) and female (n = 10) veterans with GWI separately against their healthy counterparts (n = 21 male, n = 9 female) as well as subjects with chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) (n = 12 male, n = 10 female). METHODS: Subjects were assessed using a Graded eXercise Test (GXT) with blood drawn prior to exercise, at peak effort (VO2 max) and 4-hours post exercise. Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFNγ, TNFα and TNFß in plasma samples from each phase of exercise. Linear classification models were constructed using stepwise variable selection to identify cytokine co-expression patterns characteristic of each subject group. RESULTS: Classification accuracies in excess of 80% were obtained using between 2 and 5 cytokine markers. Common to both GWI and CFS, IL-10 and IL-23 expression contributed in an illness and time-dependent manner, accompanied in male subjects by NK and Th1 markers IL-12, IL-15, IL-2 and IFNγ. In female GWI and CFS subjects IL-10 was again identified as a delineator but this time in the context of IL-17 and Th2 markers IL-4 and IL-5. Exercise response also differed between sexes: male GWI subjects presented characteristic cytokine signatures at rest but not at peak effort whereas the opposite was true for female subjects. CONCLUSIONS: Though individual markers varied, results collectively supported involvement of the IL-23/Th17/IL-17 axis in the delineation of GWI and CFS in a sex-specific way.

Altered immune pathway activity under exercise challenge in Gulf War Illness: an exploratory analysis.

Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating illness presenting with a complex constellation of immune, endocrine and neurological symptoms. Here we compared male GWI (n=20) with healthy veterans (n=22) and subjects with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) (n=7). Blood was drawn during a Graded eXercise Test (GXT) prior to exercise, at peak effort (VO2 max) and 4-h post exercise. Affymetrix HG U133 plus 2.0 microarray gene expression profiling in peripheral blood mononuclear cells (PBMCs) was used to estimate activation of over 500 documented pathways. This was cast against ELISA-based measurement of 16 cytokines in plasma and flow cytometric assessment of lymphocyte populations and cytotoxicity. A 2-way ANOVA corrected for multiple comparisons (q statistic <0.05) indicated significant increases in neuroendocrine-immune signaling and inflammatory activity in GWI, with decreased apoptotic signaling. Conversely, cell cycle progression and immune signaling were broadly subdued in CFS. Partial correlation networks linking pathways with symptom severity via changes in immune cell abundance, function and signaling were constructed. Central to these were changes in IL-10 and CD2+ cell abundance and their link to two pathway clusters. The first consisted of pathways supporting neuronal development and migration whereas the second was related to androgen-mediated activation of NF-κB. These exploratory results suggest an over-expression of known exercise response mechanisms as well as illness-specific changes that may involve an overlapping stress-potentiated neuro-inflammatory response.

Stress Management, Depression and Immune Status in Lower Income Racial/Ethnic Minority Women Co-infected with HIV and HPV.

The stress of co-infection with HIV and Human Papillomavirus (HPV), in race/ethnic minority women, may increase depression and immune decrements. Compromised immunity in HIV+ HPV+ women may increase the odds of cervical dysplasia. Thus we tested the efficacy of a 10-wk cognitive behavioral stress management (CBSM) group intervention and hypothesized that CBSM would decrease depression and improve immune status (CD4+ T-cells, natural killer [NK] cells). HIV+HPV+ women (n=71) completed the Beck Depression Inventory (BDI) and provided blood samples, were randomized to CBSM or a control condition, and were re-assessed post-intervention. Women in CBSM revealed less depression, greater NK cells, and marginally greater CD4+ T-cells post-intervention vs. controls. Stress management may improve mood and immunity in HIV+HPV+ lower income minority women.

The Potential Role of Ocular and Otolaryngological Mucus Proteins in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness associated with a constellation of other symptoms. While the most common symptom is unrelenting fatigue, many individuals also report suffering from rhinitis, dry eyes and a sore throat. Mucin proteins are responsible for contributing to the formation of mucosal membranes throughout the body. These mucosal pathways contribute to the body's defense mechanisms involving pathogenic onset. When compromised by pathogens the epithelium releases numerous cytokines and enters a prolonged state of inflammation to eradicate any particular infection. Based on genetic analysis, and computational theory and modeling we hypothesize that mucin protein dysfunction may contribute to ME/CFS symptoms due to the inability to form adequate mucosal layers throughout the body, especially in the ocular and otolaryngological pathways leading to low grade chronic inflammation and the exacerbation of symptoms.

Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue.

BACKGROUND: As Chronic Fatigue Syndrome (CFS) has been known to follow Epstein-Bar virus (EBV) and other systemic infections; our objective was to describe differences in immune activation in post-infective CFS (PI-CFS) patients and recovered controls. We studied 301 adolescents prospectively over 24 months following the diagnosis of monospot-positive infectious mononucleosis (IM). We found an incidence of CFS at 6, 12 and 24 months of 13%, 7% and 4% respectively. METHODS: Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFN-γ, TNF-α and TNF-ß in duplicate plasma samples available in bio-bank from 9 PI-CFS subjects and 12 recovered controls at 24 months post-infection. RESULTS: Standard comparative analysis indicated significant differences in IL-8 and 23 across subject groups. In constructing a linear classification model IL-6, 8 and 23 were selected by two different statistical approaches as discriminating features, with IL-1a, IL-2 and IFN-γ also selected in one model or the other. This supported an assignment accuracy of better than 80% at a confidence level of 0.95 into PI-CFS versus recovered controls. CONCLUSION: These results suggest that co-expression patterns in as few as 5 cytokines associated with Th17 function may hold promise as a tool for the diagnosis of post-infectious CFS.

Biomarkers for chronic fatigue.

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.

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

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-1ß, 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.

The impact of post-traumatic stress on quality of life and fatigue in women with Gulf War Illness.

BACKGROUND: Gulf War Illness (GWI) is a chronic, multi-symptomatic disorder characterized by fatigue, muscle pain, cognitive problems, insomnia, rashes, and gastrointestinal issues affecting an estimated 30% of the ~ 750,000 returning military Veterans of the 1990-1991 Persian Gulf War. Female Veterans deployed to combat in this war report medical symptoms, like cognition and respiratory troubles, at twice the rate compared to non-deployed female Veterans of the same era. The heterogeneity of GWI symptom presentation complicates diagnosis as well as the identification of effective treatments. This is exacerbated by the presence of co-morbidities. Defining subgroups of the illness may help alleviate these complications. One clear grouping is along the lines of gender. Our aim is to determine if women with GWI can be further subdivided into distinct subgroups based on post-traumatic stress disorder (PTSD) symptom presentation. METHODS: Veterans diagnosed with GWI (n = 35) and healthy sedentary controls (n = 35) were recruited through the Miami Veterans Affairs Medical Health Center. Symptoms were assessed via the RAND short form health survey, the multidimensional fatigue inventory, and the Davidson trauma scale. Hierarchal regression modeling was performed on measures of health and fatigue with PTSD symptoms as a covariate. This was followed by univariate analyses conducted with two separate GWI groups based on a cut-point of 70 for their total Davidson trauma scale value and performing heteroscedastic t-tests across all measures. RESULTS: Based on the distinct differences found in PTSD symptomology regarding all health and trauma symptoms, two subgroups were derived within female GWI Veterans. Hierarchical regression models displayed the comorbid effects of GWI and PTSD, as both conditions had measurable impacts on quality of life and fatigue (ΔR2 = 0.08-0.672), with notable differences in mental and emotional measures. Overall, a cut point analysis indicated poorer quality of life and greater fatigue within all measures for women with GWI and PTSD symptoms in comparison to those women with GWI without PTSD symptoms and healthy controls. CONCLUSIONS: Our current findings support the understanding that comorbid symptoms of GWI and PTSD subsequently result in poorer quality of life and fatigue, along with establishing the possibility of varying clinical presentations.

A common language for Gulf War Illness (GWI) research studies: GWI common data elements.

AIMS: The Gulf War Illness programs (GWI) of the United States Department of Veteran Affairs and the Department of Defense Congressionally Directed Medical Research Program collaborated with experts to develop Common Data Elements (CDEs) to standardize and systematically collect, analyze, and share data across the (GWI) research community. MAIN METHODS: A collective working group of GWI advocates, Veterans, clinicians, and researchers convened to provide consensus on instruments, case report forms, and guidelines for GWI research. A similar initiative, supported by the National Institute of Neurologic Disorders and Stroke (NINDS) was completed for a comparative illness, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and provided the foundation for this undertaking. The GWI working group divided into two sub-groups (symptoms and systems assessment). Both groups reviewed the applicability of instruments and forms recommended by the NINDS ME/CFS CDE to GWI research within specific domains and selected assessments of deployment exposures. The GWI CDE recommendations were finalized in March 2018 after soliciting public comments. KEY FINDINGS: GWI CDE recommendations are organized in 12 domains that include instruments, case report forms, and guidelines. Recommendations were categorized as core (essential), supplemental-highly recommended (essential for specified conditions, study types, or designs), supplemental (commonly collected, but not required), and exploratory (reasonable to use, but require further validation). Recommendations will continually be updated as GWI research progresses. SIGNIFICANCE: The GWI CDEs reflect the consensus recommendations of GWI research community stakeholders and will allow studies to standardize data collection, enhance data quality, and facilitate data sharing.