Chronic Fatigue Syndrome: Michigan

Balon R. · Department of Psychiatry and Behavioral Neurosciences Wayne State University School of Medicine, Detroit, Mich., USA. · Psychother Psychosom. · Pubmed #17570958 No free full text.

Abstract: This article reviews several areas of new and interesting development in the fields of psychosomatics and psychotherapy published in the literature during 2006. These areas are: (1) cardiovascular illness and its interplay with depression; (2) risks and predisposing factors in the areas of mental illness and physical illness; (3) new developments in chronic fatigue syndrome, and (4) new or newly explored/modified (psycho)therapies, especially cognitive-behavioral therapy. In addition, an important area of conflict of interest in psychiatry in particular and in biomedical science in general is discussed, as this issue has reached prominence in the biomedical literature.

Glass JM. · University of Michigan, Institute for Social Research and Department of Psychiatry, 426 Thompson Street, Room 5256, Ann Arbor, MI 48106-1248, USA. · Curr Rheumatol Rep. · Pubmed #17092441 No free full text.

Abstract: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) patients often have memory and cognitive complaints. Objective cognitive testing demonstrates long-term and working memory impairments. In addition, CFS patients have slow information-processing, and FM patients have impaired control of attention, perhaps due to chronic pain. Neuroimaging studies demonstrate cerebral abnormalities and a pattern of increased neural recruitment during cognitive tasks. Future work should focus on the specific neurocognitive systems involved in cognitive dysfunction in each syndrome.

Dadabhoy D, Clauw DJ. · Chronic Pain and Fatigue Research Center, The University of Michigan, 24 Frank Lloyd Wright Drive, Box 385, Ann Arbor, MI 48106, USA. · Nat Clin Pract Rheumatol. · Pubmed #16932722 No free full text.

Abstract: In the past decade, we have made tremendous progress in our understanding of fibromyalgia, which is now recognized as one of many 'central' pain syndromes that are common in the general population. Specific genes that might confer an increased risk of developing fibromyalgia syndrome are beginning to be identified and the environment (in this case exposure to stressors) might also have a significant effect on triggering the expression of symptoms. After developing the syndrome, the hallmark aberration noted in individuals with fibromyalgia is augmented central pain processing. Insights from research suggest that fibromyalgia and related syndromes require a multimodal management program that is different from the standard used to treat peripheral pain (i.e. acute or inflammatory pain). Instead of the nonsteroidal anti-inflammatory drugs and opioids commonly used in the treatment of peripheral pain, the recommended drugs for central pain conditions are neuroactive compounds that downregulate sensory processing. The most efficacious compounds that are currently available include the tricyclic drugs and mixed reuptake inhibitors that simultaneously increase serotonin and norepinephrine concentrations in the central nervous system. Other compounds that increase levels of single monoamines (serotonin, norepinephrine or dopamine), and anticonvulsants also show efficacy in this condition. In addition to these pharmacologic therapies, which are useful in improving symptoms, nonpharmacologic therapies such as exercise and cognitive behavioral therapy are useful treatments for restoring function to an individual with fibromyalgia.

Crofford LJ. · Division of Rheumatology, University of Michigan, Room 5510, MSRB-I, 1150 W. Medical Center Dr., Ann Arbor, MI 48109-0680, USA. · Curr Rheumatol Rep. · Pubmed #15251075 No free full text.

Abstract: Fibromyalgia syndrome (FMS) is a chronic multisymptom illness characterized by widespread pain and associated with neuropsychological symptoms including fatigue, unrefreshing sleep, cognitive dysfunction, anxiety, and depression. A discreet cause of FMS has not been identified. It is likely that multiple mechanisms give rise to symptom expression. Understanding specific etiologic factors and pathogenic mechanisms in individual patients will allow clinicians to determine treatments that are most effective for a given patient. Available evidence implicates the central nervous system as key in maintaining pain and other core symptoms of FMS. The approach to treatment of pain will typically address these central mechanisms. Nonpain symptoms may be treated by drugs affecting similar central neurochemicals. This paper will review the rationale for the different types of pharmaceutical treatments that may be useful for the treatment of FMS and issues regarding new drug development for this indication.

Ambrose K, Lyden AK, Clauw DJ. · Chronic Pain and Fatigue Research Program, University of Michigan, 24 Frank Lloyd Wright Drive, PO Box 385, Ann Arbor, MI 48109-0483, USA. · Curr Pain Headache Rep. · Pubmed #12946287 No free full text.

Abstract: Fibromyalgia, chronic fatigue syndrome, and related illnesses fall under the spectrum of chronic multisymptom illnesses (CMI). This constellation of syndromes often is defined by chronic pain, unremitting fatigue, cognitive difficulties, and various other symptoms. In treating these illnesses, pharmacotherapy generally is the mode of choice, with exercise being overlooked often. However, research has shown that exercise is quite beneficial in reducing pain and fatigue in this population and should be included as part of a multimodal therapy regimen. This article reviews the exercise and CMI literature and provides a model for applying these evidence-based guidelines to a clinical population.

Lerner AM, Beqaj SH, Deeter RG, Dworkin HJ, Zervos M, Chang CH, Fitzgerald JT, Goldstein J, O'Neill W. · School of Medicine, Wayne State University, Detroit, MI, USA. · Drugs Today (Barc). · Pubmed #12582420 No free full text.

Abstract: This study was designed to determine safety and efficacy of a 6-month trial of valacyclovir in single-virus Epstein-Barr virus (EBV) persistent infection. Phase I of this study used four specific criteria to define a subset of patients with chronic fatigue syndrome (CFS). In the second phase, myocardial dynamics were measured by MUGA rest/stress radionuclide ventriculographic (RVG) examinations pre- and posttreatment with valacyclovir. In phase I, a trial was performed in 19 consecutive CFS patients with the following diagnostic conditions: patients met criteria for diagnosis of CFS; they had had CFS for less than 1 year. They demonstrated repetitively abnormal oscillating T waves (ischemic or flat) at 24-h Holter monitoring; and they had elevated serum IgM antibody titers to EBV viral capsid antigen and/or total diffuse early antigen as measured by the enzyme-linked immunosorbent assay method. The treatment group comprised 10 CFS patients with no serum antibodies to human cytomegalovirus, but the control group (nine CFS patients) had, additionally, high titers of serum antibodies (IgG) to conformational structural antigens of human cytomegalovirus. Both the parallel treatment and control CFS groups received valacyclovir 1.0-1.5 gm q.6.h. for 6 months. This valacyclovir dose achieved serum acyclovir C(max) of > 7 microm and high antiviral activity versus EBV (IC(50) of 4.4-13.3 m). In phase II, six additional CFS patients met the same four criteria as the 19 CFS patients in phase I. They had, however, been ill for a mean of 55.8 months. Thus, 25 CFS patients comprise this study. The studies were carried out at a single outpatient practice in Birmingham, MI, U.S.A. Before initiating valacyclovir, and after 6 months of treatment, clinical and laboratory observations were made. The CFS Energy Index point score (Table I) was used to record each CFS patient's functional capacity at baseline and after 1, 3 and 6 months of valacyclovir. Energy Index point scores, as well as EBV and human cytomegalovirus serum antibody titers were assessed. In the second phase, left ventricular dynamics were repeated after 6 months of treatment with valacyclovir. We concluded that the 16 CFS patients (included in both phases of this study) with EBV-persistent infection (EBV single-virus subset) are improved after 6 months of continuous pharmacokinetic dosing with valacyclovir. Nine CFS patients with EBV/human cytomegalovirus co-infection did not benefit from 6 months of similar treatment. Valacyclovir is not an effective anti-human cytomegalovirus antiviral drug. Unimproved CFS patients with co-infections EBV and human cytomegalovirus may require combined treatment with valacyclovir and another drug more active against human cytomegalovirus. This preliminary trial, with a small number of patients, may be critical to an appropriately designed larger, double-blind, placebo-controlled trial.

Crofford LJ, Appleton BE. · University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI, 48109-0680, USA. · Curr Rheumatol Rep. · Pubmed #11286671 No free full text.

Abstract: Fibromyalgia (FM) is a syndrome of chronic widespread musculoskeletal pain that is accompanied by sleep disturbance and fatigue. Clinical treatment usually includes lifestyle modifications and pharmacologic interventions meant to relieve pain, improve sleep quality, and treat mood disorders. These therapies are often ineffective or have been shown in clinical studies to have only short-term effectiveness. Pharmacologic treatments have considerable side effects. Patients may have difficulty complying with exercise-based treatments. Thus, patients seek alternative therapeutic approaches and physicians are routinely asked for advice about these treatments. This article reviews nontraditional treatment alternatives, from use of nutritional and herbal supplements to acupuncture and mind-body therapy. Little is known about efficacy and tolerance of complementary and alternative therapies in FM and other chronic musculoskeletal pain syndromes. Most studies on these treatments have been performed for osteoarthritis, rheumatoid arthritis, or focal musculoskeletal conditions. Clinical trials are scarce; the quality of these trials is often criticized because of small study population size, lack of appropriate control interventions, poor compliance, or short duration of follow-up. However, because of widespread and growing use of alternative medicine, especially by persons with chronic illnesses, it is essential to review efficacy and adverse effects of complementary and alternative therapies.

Korszun A. · Department of Psychological Medicine, University of Wales College of Medicine, Heath Park Cardiff CF4 4XN, UK. · Curr Rheumatol Rep. · Pubmed #11123049 No free full text.

Abstract: Fibromyalgia (FM) is a syndrome of generalized muscle pain that is also associated with equally distressing symptoms of sleep disturbance and fatigue. FM shows clinical overlap with other stress-associated disorders, including chronic fatigue syndrome (CFS) and depression. All of these conditions have the features of disrupted sleep patterns and dysregulated biologic circadian rhythms, such as stress hormone secretion. This review focuses on the role of sleep and circadian rhythm disorders in FM and, in the absence of any specific treatment for FM, presents a pragmatic therapeutic approach aimed at identifying and treating comorbid sleep and depressive disorders, optimizing sleep habits, and judicious use of pharmacologic agents.

Glass JM, Lyden AK, Petzke F, Stein P, Whalen G, Ambrose K, Chrousos G, Clauw DJ. · Department of Psychiatry and Institute for Social Research, University of Michigan, Ann Arbor, MI, USA. · J Psychosom Res. · Pubmed #15518675 No free full text.

Abstract: OBJECTIVE: Abnormalities of the biological stress response (hypothalamic-pituitary-adrenal axis and the autonomic nervous system) have been identified in both fibromyalgia (FM) and chronic fatigue syndrome (CFS). Although these changes have been considered to be partly responsible for symptom expression, we examine an alternative hypothesis that these HPA and autonomic changes can be found in subsets of healthy individuals in the general population who may be at risk of developing these conditions. Exposure to "stressors" (e.g., infections, trauma, etc.) may lead to symptom expression (pain, fatigue, and other somatic symptoms) in part by precipitating lifestyle changes. In particular, we focus on the effect of deprivation of routine aerobic exercise on the development of somatic symptoms. METHODS: Eighteen regularly exercising (>/=4 h/week) asymptomatic, healthy adults refrained from physical activity for 1 week. We predicted that a subset of these individuals would develop symptoms of FM/CFS with exercise deprivation, and this manuscript focuses on the baseline HPA axis, immune, and autonomic function measures that may predict the development of symptoms. RESULTS: Eight of the subjects reported a 10% increase in one or more symptoms (pain, fatigue, mood) after 1 week of exercise deprivation. These symptomatic subjects had lower HPA axis (baseline cortisol prior to VO2max testing), immune (NK cell responsiveness to venipuncture), and autonomic function (measured by heart rate variability) at baseline (prior to cessation of exercise) when compared to the subjects who did not develop symptoms. CONCLUSIONS: A subset of subjects developed symptoms of pain, fatigue, or mood changes after exercise deprivation. This cohort was different from the individuals who did not develop symptoms in baseline measures of HPA axis, immune, and autonomic function. We speculate that a subset of healthy individuals who have hypoactive function of the biological stress response systems unknowingly exercise regularly to augment the function of these systems and thus suppress symptoms. These individuals may be at risk for developing chronic multisymptom illnesses (CMIs) (e.g., FM or CFS among others) when a "stressor" leads to lifestyle changes that disrupt regular exercise.

Crofford LJ, Young EA, Engleberg NC, Korszun A, Brucksch CB, McClure LA, Brown MB, Demitrack MA. · Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA. · Brain Behav Immun. · Pubmed #15157948 No free full text.

Abstract: The objective of this study was to evaluate and compare the basal circadian and pulsatile architecture of the HPA axis in groups of patients with FMS, CFS, or both syndromes with individually matched control groups. Forty patients with either FMS (n = 13), FMS and CFS (n = 12), or CFS (n = 15) were matched by age (18-65), sex, and menstrual status to healthy controls. Subjects were excluded if they met criteria for major Axis I psychiatric disorders by structured clinical interview (SCID). Subjects were admitted to the General Clinical Research Center where meals and activities were standardized. Blood was collected from an intravenous line every 10 min over 24 h for analysis of ACTH and cortisol. Samples were evaluable for ACTH in 36 subject pairs and for cortisol in 37 subject pairs. There was a significant delay in the rate of decline from acrophase to nadir for cortisol levels in patients with FMS (P <.01). Elevation of cortisol in the late evening quiescent period was evident in half of the FMS patients compared with their control group, while cortisol levels were numerically, but not significantly, lower in the overnight period in patients with CFS compared with their control group. Pulsatility analyses did not reveal statistically significant differences between patient and control groups. We conclude that the pattern of differences for basal circadian architecture of HPA axis hormones differs between patients with FMS and CFS compared to their matched control groups. The abnormalities in FMS patients are consistent with loss of HPA axis resiliency.

Harris RE, Clauw DJ. · Department of Anesthesiology, The University of Michigan, Ann, Arbor, MI, USA. · Ther Clin Risk Manag. · Pubmed #19337439 links to  free full text

Abstract: Fibromyalgia syndrome is a common chronic pain disorder of unknown etiology. The lack of understanding of the pathophysiology of fibromyalgia has made this condition frustrating for patients and clinicians alike. The most common symptoms of this disorder are chronic widespread pain, fatigue, sleep disturbances, difficulty with memory, and morning stiffness. Emerging evidence points towards augmented pain processing within the central nervous system (CNS) as having a primary role in the pathophysiology of this disorder. Currently the two drugs that are approved by the United States Food and Drug Administration (FDA) for the management of fibromyalgia are pregabalin and duloxetine. Newer data suggests that milnacipran, a dual norepinephrine and serotonin reuptake inhibitor, may be promising for the treatment of fibromyalgia. A double-blind, placebo-controlled trial of milnacipran in 125 fibromyalgia patients showed significant improvements relative to placebo. Milnacipran given either once or twice daily at doses up to 200 mg/day was generally well tolerated and yielded significant improvements relative to placebo on measures of pain, patient's global impression of change in their disease state, physical function, and fatigue. Future studies are needed to validate the efficacy of milnacipran in fibromyalgia.

Lerner AM, Beqaj SH, Fitzgerald JT. · Department of Medicine, Wayne State University School of Medicine and William Beaumont Hospital, Royal Oak, MI, USA. · In Vivo. · Pubmed #19181009 No free full text.

Abstract: BACKGROUND: A simple quantitative accurate method for assessing the degree of fatigue in patients with chronic fatigue syndrome (CFS) is necessary for physicians and patients. Severity of the disease and recovery can, thus, be assayed. PATIENT AND METHODS: From February 1-27, 2007, fifty-six consecutive CFS patients at a single treatment center were simultaneously evaluated by the patient with the fatigue severity score (FSS), and by consensus of both patient and physician by the energy index (EI) point score. RESULTS: The FSS and EI correlated well, 0.67, p<0.001. CONCLUSION: The El point score is a validated reliable method to assess fatigue in CFS patients.

Armitage R, Landis C, Hoffmann R, Lentz M, Watson N, Goldberg J, Buchwald D. · Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. · J Psychosom Res. · Pubmed #19073294 No free full text.

Abstract: OBJECTIVE: The purpose of the study was to evaluate quantitative sleep electroencephalogram (EEG) frequencies in monozygotic twins discordant for chronic fatigue syndrome. METHODS: Thirteen pairs of female twins underwent polysomnography. During the first night, they adapted to the sleep laboratory, and during the second night, their baseline sleep was assessed. Visual stage scoring was conducted on sleep electroencephalographic records according to standard criteria, and power spectral analysis was used to quantify delta through beta frequency bands, processed in 6-s blocks. Data were averaged across sleep stage within each twin and coded for sleep stage and the presence or absence of chronic fatigue syndrome (CFS). A completely within-subjects repeated measure multivariate analysis of variance evaluated twin pairs by frequency band by sleep stage interactions and simple effects. The relationship between alpha and delta EEG was also assessed across twin pairs. RESULTS: No significant differences in spectral power in any frequency band were found between those with CFS and their nonfatigued cotwins. Phasic alpha activity, coupled with delta was noted in five subjects with CFS but was also present in 4/5 healthy twins, indicating this finding likely reflects genetic influences on the sleep electroencephalogram rather than disease-specific sleep pathology. CONCLUSIONS: The genetic influences on sleep polysomnography and microarchitecture appear to be stronger than the disease influence of chronic fatigue syndrome, despite greater subjective sleep complaint among the CFS twins. EEG techniques that focus on short duration events or paradigms that probe sleep regulation may provide a better description of sleep abnormalities in CFS.

Geisser ME, Strader Donnell C, Petzke F, Gracely RH, Clauw DJ, Williams DA. · Chronic Pain and Fatigue Research Center, Dept. of Internal Medicine, Div. of Rheumatology, Univ. of Michigan, Ann Arbor, MI 48108, USA. · Psychosomatics. · Pubmed #18448779 links to  free full text

Abstract: BACKGROUND: Somatic symptoms are common in conditions such as fibromyalgia (FM) and chronic fatigue syndrome (CFS). OBJECTIVE: Authors investigated a potential shared pathologic mechanism: a generalized perceptual abnormality where there is heightened responsiveness to varied sensory stimulation, including pain. METHOD: A composite measure of sensory sensitivity was created and compared with measures of somatic symptoms, comorbid psychological disturbances, and self-reported physical functioning in 38 patients with FM and/or CFS. RESULTS: Sensory amplification influenced physical functioning indirectly through pain intensity, and physical symptoms and fatigue also independently contributed to physical functioning. CONCLUSION: Sensory amplification may be an underlying pathophysiologic mechanism in these disorders that is relatively independent of depression and depressive symptoms.

Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT. · Department of Medicine, William Beaumont Hospital, Royal Oak, MI, USA. · In Vivo. · Pubmed #18019402 No free full text.

Abstract: BACKGROUND: We hypothesized that subset classification of Epstein-Barr virus (EBV) in chronic fatigue syndrome (CFS) is required. At first, a blinded-random placebo-controlled trial of valacyclovir in EBV CFS subset was performed (Group 1), and this EBV subset was followed for thirty-six months (Group 2). Patients were given valacyclovir at 14.3 mg/kg every 6 hours. The validated Energy Index (EI) point score assessing physical functional capacity, Holter monitor, multigated (radionuclide) MUGA rest/stress ventriculographic examination, EBV serum IgM viral capsid antibodies (VCA), and EBV early antigen diffuse (EA) were followed. After six-months, Group 1 CFS patients receiving valacyclovir experienced an increased mean least square EI point score +1.12 units (122 kcal/day), while the placebo cohort increased +0.42 EI units (65 kcal/day). EI point scores at Group 2 increased progressively. Sinus tachycardias decreased and abnormal cardiac wall motion improved. Serum antibody titers to EBV VCA IgM decreased. Patients resumed normal activities.

Armitage R, Landis C, Hoffmann R, Lentz M, Watson NF, Goldberg J, Buchwald D. · Department of Psychiatry, University of Michigan, Ann Arbor, MI 48105, USA. · Sleep. · Pubmed #17552382 No free full text.

Abstract: OBJECTIVES: Chronic fatigue syndrome (CFS) has been associated with altered amounts of slow wave sleep, which could reflect reduced delta electroencephalograph (EEG) activity and impaired sleep regulation. To evaluate this hypothesis, we examined the response to a sleep regulatory challenge in CFS. DESIGN: The first of 3 consecutive nights of study served as laboratory adaptation. Baseline sleep was assessed on the second night. On the third night, bedtime was delayed by 4 hours, followed by recovery sleep. Total available sleep time was held constant on all nights. SETTING: A research sleep laboratory. PARTICIPANTS: 13 pairs of monozygotic twins discordant for CFS. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Power spectral analysis quantified slow wave activity (SWA) in the 0.5-3.9 Hz band in successive NREM periods (stage 2, 3, or 4) on each night. To ensure comparability, analyses were restricted to the first 4 NREM periods on each night. Data were coded for NREM period and twin pair. Repeated-measures analysis of variance (ANOVA) contrasted sleep delay effects across NREM periods between twin pairs. A second ANOVA calculated the SWA in each NREM period in recovery sleep relative to baseline SWA. The 2 groups of twins were similar on baseline SWA power. After sleep delay, CFS twins exhibited significantly less SWA power in the first NREM period of recovery sleep and accumulated a smaller percentage of SWA in the first NREM period than their co-twins. CONCLUSIONS: CFS is associated with a blunted SWA response to sleep challenge, suggesting that the basic sleep drive and homeostatic response are impaired.

Young JL, Redmond JC. · Rochester Center for Behavioral Medicine, Rochester Hills, MI. · Psychopharmacol Bull. · Pubmed #17285103 No free full text.

Abstract: Adult attention deficit hyperactivity disorder (ADHD) may share common features with fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS). In an outpatient psychiatric clinic, a number of adult patients who presented primarily with symptoms of ADHD, predominately inattentive type, also reported unexplained fatigue, widespread musculoskeletal pain or a pre-existing diagnosis of CFS or FMS. As expected, ADHD pharmacotherapy usually attenuated the core ADHD symptoms of inattention, distractibility, hyperactivity, and impulsivity. Less expected was the observation that some patients also reported amelioration of pain and fatigue symptoms. The utility of ADHD medications in FMS and CFS states may be their innate arousal and enhanced filtering properties. This model supposes that FMS and CFS are central processing problems rather than peripheral disorders of muscles and joints.

Gillis ME, Lumley MA, Mosley-Williams A, Leisen JC, Roehrs T. · Department of Psychoogy, Wayne State University, Detroit, MI 48202, USA. · Ann Behav Med. · Pubmed #16972811 No free full text.

Abstract: BACKGROUND: The presence and severity of the chronic pain syndrome fibromyalgia (FM) is associated with unresolved stress and emotional regulation difficulties. Written emotional disclosure is intended to reduce stress and may improve health of people with FM. PURPOSE: This study tests the effects of at-home, written emotional disclosure about stressful experiences on the health of people with FM and uses multiple follow-ups to track the time course of effects of disclosure. METHODS: Adults with FM (intention-to-treat, n=83; completers, n=72) were randomized to write for 4 days at home about either stressful experiences (disclosure group) or neutral time management (control group). Group differences in immediate mood effects and changes in health from baseline to 1-month and 3-month follow-ups were examined. RESULTS: Written disclosure led to an immediate increase in negative mood, which did not attenuate across the 4 writing days. Repeated-measures analyses from baseline to each follow-up point were conducted on both intention-to-treat and completer samples, which showed similar outcomes. At 1 month, disclosure led to few health benefits, but control writing led to less negative affect and more perceived support than did disclosure. At 3-month follow-up, these negative affect and social support effects disappeared, and written disclosure led to a greater reduction in global impact, poor sleep, health care utilization, and (marginally) physical disability than did control writing. Interpretation of these apparent benefits needs to be made cautiously, however, because the disclosure group had somewhat poorer health than controls at baseline and the control group showed some minor worsening over time. CONCLUSIONS: Written emotional disclosure can be conducted at home, and there is tentative evidence that disclosure benefits the health of people with FM. The benefits, however, may be delayed for several months after writing and may be of limited clinical significance.

McLean SA, Williams DA, Stein PK, Harris RE, Lyden AK, Whalen G, Park KM, Liberzon I, Sen A, Gracely RH, Baraniuk JN, Clauw DJ. · Department of Emergency Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA. · Neuropsychopharmacology. · Pubmed #16936702 links to  free full text

Abstract: Previous studies have identified stress system dysregulation in fibromyalgia (FM) patients; such dysregulation may be involved in the generation and/or maintenance of pain and other symptoms. Corticotropin-releasing factor (CRF) is the principal known central nervous system mediator of the stress response; however, to date no studies have examined cerebrospinal fluid (CSF) CRF levels in patients with FM. The relationship between CSF CRF level, heart rate variability (HRV), and pain, fatigue, and depressive symptoms was examined in patients with FM. Among participants (n=26), CSF CRF levels were associated with sensory pain symptoms (r=0.574, p=0.003) and affective pain symptoms (r=0.497, p=0.011), but not fatigue symptoms. Increased HRV was also strongly associated with increased CSF CRF and FM pain. In multivariate analyses adjusting for age, sex, and depressive symptoms, the association between CSF CRF and sensory pain symptoms (t=2.54, p=0.027) persisted. Women with FM who reported a history of physical or sexual abuse had lower CSF CRF levels than women who did not report such a history. CSF CRF levels are associated with both pain symptoms and variation in autonomic function in FM. Differences in CSF CRF levels among women with and without a self-reported history of physical or sexual abuse suggest that subgroups of FM patients may exist with different neurobiological characteristics. Further studies are needed to better understand the nature of the association between CSF CRF and pain symptoms in FM.

Geisser ME, Gracely RH, Giesecke T, Petzke FW, Williams DA, Clauw DJ. · Chronic Pain and Fatigue Research Center, Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA. · Eur J Pain. · Pubmed #16546424 No free full text.

Abstract: Evoked or experimental pain is often used as a model for the study of clinical pain, yet there are little data regarding the relationship between the two. In addition, there are few data regarding the types of stimuli and stimulus intensities that are most closely related to clinical pain. In this study, 36 subjects with fibromyalgia (FM), chronic fatigue syndrome (CFS), or both syndromes were administered measures of clinical pain and underwent a dolorimetry evaluation. Subjects also underwent experimental pain testing utilizing heat and pressure stimulation. Stimulation levels evoking low, moderate and high sensory intensity, and comparable levels of unpleasantness, were determined for both types of stimuli using random staircase methods. Clinical pain was assessed using visual analogue ratings and the short form of the McGill Pain Questionnaire (MPQ). Ratings of heat pain sensation were not significantly associated with clinical pain ratings, with the exception of unpleasantness ratings at high stimulus intensities. Pain threshold and tolerance as assessed by dolorimetry were significantly associated with average measures of clinical pain. Both intensity and unpleasantness ratings of pressure delivered using random staircase methods were significantly associated with clinical pain at low, moderate and high levels, and the strength of the association was greater at increasingly noxious stimulus intensities. These findings suggest that random pressure stimulation as an experimental pain model in these populations more closely reflects the clinical pain for these conditions. These findings merit consideration when designing experimental studies of clinical pain associated with FM and CFS.

Seng JS, Graham-Bermann SA, Clark MK, McCarthy AM, Ronis DL. · Institute for Research on Women and Gender, University of Michigan, Ann Arbor, MI 48109-1290, USA. · Pediatrics. · Pubmed #16322133 links to  free full text

Abstract: OBJECTIVE: In adults, posttraumatic stress disorder (PTSD) is associated with adverse health outcomes and high medical utilization and cost. PTSD is twice as common in women and is associated with increased risk for a range of diseases, chronic conditions, and reproductive-health problems. Little is known about the health effects of PTSD in children. The purpose of this study was to explore patterns of physical comorbidity in female children and adolescents with PTSD by using population data. METHODS: This study was a cross-sectional, descriptive epidemiologic case-control analysis of a Midwestern state's Medicaid eligibility and paid-claims data for girls (0-8 years old) and teens (9-17 years old). Data were from 1994-1997. All those with the PTSD diagnostic code were compared with randomly selected controls in relation to 3 sets of outcomes: (1) International Classification of Diseases, Ninth Revision (ICD-9) categories of disease; (2) chronic conditions previously associated with sexual trauma and PTSD in women; and (3) reproductive-health problems. Analyses included bivariate odds ratios (OR) and logistic-regression models that control for the extent of insurance coverage and the independent associations of victimization and psychiatric comorbidity with the 3 sets of outcomes. The mental health covariate was categorical to allow consideration of a range of severity. There were 4 categories for the young girls: neither PTSD nor depression, PTSD without depression, depression without PTSD, and PTSD + depression. For the adolescent analysis, a fifth category reflecting a "complex PTSD" was added, defined as having PTSD complicated by a dissociative disorder or borderline personality disorder diagnosis. RESULTS: There were 647 girls and 1025 adolescents with the PTSD diagnosis. Overall, PTSD was associated with adverse health outcomes in both age strata. Victimization was sometimes independently associated with adverse health outcomes, but PTSD often was a mediator, especially in the adolescent age stratum. The importance of PTSD diagnosis as a predictor of the ICD-9 categories of disease or chronic conditions seemed to increase with age. In the younger age stratum, the increased bivariate ORs of significant associations with PTSD ranged from 1.4 for digestive disorders to 3.4 for circulatory disorders. Among younger girls, PTSD diagnosis was associated with significantly greater bivariate odds for 9 of the 12 ICD-9 categories of disease but not for neoplasms, blood disorders, or respiratory disorders and with threefold increased odds for chronic fatigue. They also had 1.8 times greater odds for sexually transmitted infections, some of which could be from congenital transmission in this age group, which includes infants. In the multivariate models for the young girls, the mental health variable seemed to mediate the relationship between victimization and increased odds of infectious and parasitic diseases, endocrine/metabolic/immune disorders, circulatory diseases, skin and cutaneous tissue disorders, and having any 1 of the 5 chronic conditions. The mental health categories that were significantly associated with health outcomes varied across the conditions. There were no health outcomes in which the depression-without-PTSD category was the only one significantly associated with the outcome condition. Circulatory and musculoskeletal disorders were significantly associated with all 3 of the mental health categories. Having any 1 of the 5 chronic conditions was significantly associated only with simple PTSD (PTSD without depression). Genitourinary disorders and signs/symptoms/ill-defined conditions were significantly associated with both simple and comorbid PTSD. PTSD with comorbid depression, the most severe of the mental health categories in this younger age group, was the only category associated with the endocrine/metabolic/immune disorders and skin disorders outcomes. In the adolescent age stratum, the bivariate ORs significantly associated with PTSD ranged from 2.1 for blood disorders to 5.2 for irritable bowel syndrome. Adolescents with PTSD were nearly twice as likely to have a sexually transmitted infection and 60% more likely to have cervical dysplasia. However, their rate of pregnancy was lower (23% vs 31%), a one-fourth decreased odds. In the adolescent group, only 4 outcomes (nervous system/sense organ, digestive, and genitourinary disorders and signs/symptoms/ill-defined conditions) remained statistically significantly associated with victimization after the mental health variable was added, suggesting an additive model of risk for these outcomes but a mediating role for PTSD in relation to the majority of the health outcomes. Among the adolescent girls, the range of ORs for the ICD-9 and chronic-condition diagnoses generally increased across the categories of the mental health variable in a dose-response pattern. Compared with adolescents with neither PTSD nor depression, those with PTSD without depression had statistically significant ORs from 1.5 to 3.6. Those with depression without PTSD had statistically significant ORs from 1.9 to 4.4. The significant ORs for those with PTSD comorbid with depression were from 2.3 to 6.6, and those in the complex-PTSD category had significant ORs of between 2.5 and 14.9. Only blood disorders seemed to be more strongly associated with depression alone than with the comorbid and complex forms of PTSD. The simple-PTSD category was not significantly associated with blood disorders, chronic pelvic pain, fibromyalgia, or dysmenorrhea. Depression without PTSD was not significantly associated with chronic pelvic pain or fibromyalgia. Fibromyalgia was only significantly associated with complex PTSD. CONCLUSIONS: In young girls who receive Medicaid benefits, PTSD was associated with increased odds of a range of adverse health conditions. The pattern and odds of physical comorbidity among adolescent recipients with PTSD was nearly as extensive as that seen in adult women. Overall, the pattern observed suggests that objective disease states (eg, circulatory problems, infections) may be associated with PTSD to an extent nearly as great as that of PTSD with more subjective somatic experience of loss of wellness. Using the concepts of allostatic load and allostatic support, professionals who work with children and adolescents may be able to decrease the toll that traumatic stress takes on health even if available interventions can only be thought of as supportive and fall short of completely preventing trauma exposure or completely healing posttraumatic stress. Clinical research to extend these exploratory findings is warranted.

Schoofs N, Bambini D, Ronning P, Bielak E, Woehl J. · Grand Valley State University, Grand Rapids, MI, USA. · Orthop Nurs. · Pubmed #15682879 No free full text.

Abstract: PURPOSE: The purpose of this study was to investigate how social support and healthcare support affect the quality of life of persons with fibromyalgia and chronic fatigue syndrome. METHOD: A constant comparison method was used for the qualitative portion of the research and descriptive correlational methods were used for the quantitative portion. CONCLUSION: This mixed design research study suggested that social support, unlike healthcare support, is related to Quality of Life (QOL). It was also evident that subjects suffering from CFS and/or FMS do not experience high levels of social support.

Lerner AM, Dworkin HJ, Sayyed T, Chang CH, Fitzgerald JT, Beqaj S, Deeter RG, Goldstein J, Gottipolu P, O'Neill W. · Department of Medicine, William Beaumont Hospital, Royal Oak, Michigan, USA. · In Vivo. · Pubmed #15369178 No free full text.

Abstract: We reported unique incomplete herpesvirus (Epstein-Barr Virus (EBV) and/or nonstructural (HCMV) cytomegalovirus) multiplication in 2 distinct subsets of CFS patients. The CFS subsets were identified by: a) presence of IgM serum antibodies to HCMV nonstructural gene products p52 and CM2 (UL44 and UL57), and/or b) IgM serum antibodies to Epstein-Barr virus viral capsid antigen (EBV, VCA IgM). Diagnostic IgM serum antibodies were found in two independent blinded studies involving 49 CFS patients, but the same antibodies were absent in 170 control patients (p<0.05). Abnormal 24 Hr-electrocardiographic monitoring, tachycardias at rest and, in severe chronic cases, abnormal cardiac wall motion (ACWM) were seen in these same CFS patients. We now report a prospective consecutive case control study from 1987--1999 of cardiac dynamics as measured by radionuclide ventriculography in 98 CFS patients from 1987--1999. Controls were patients with various malignancies who were evaluated in protocols requiring radionuclide ventriculography before initiation of cardiotoxic chemotherapeutic agents. The prevalence of abnormal cardiac wall motion (ACWM) at rest in CFS patients was 10 out of 87 patients (11.5%). With stress exercise, 21 patients (24.1%) demonstrated ACWM. Cardiac biopsies in 3 of these CFS patients with ACWM showed a cardiomyopathy. Among the controls, ACWM at rest was present in 4 out of 191 patients (2%) (p=0.0018). A progressive cardiomyopathy caused by incomplete virus multiplication of EBV and/or HCMV in CFS patients is present.

McLean SA, Clauw DJ. · Department of Emergency Medicine, University of Michigan Medical Center, 24 Frank Lloyd Wright Drive, P.O. Box 385, Ann Arbor, MI 48106, USA. · Med Hypotheses. · Pubmed #15325010 No free full text.

Abstract: Stressful events occur in the lives of millions of individuals each year. Such events, or "stressors", are experiences that threaten personal well-being, and include traumatic events such as motor vehicle collision, infectious illness, and situations such as military deployment. While most individuals recover from such events, others develop persistent somatic symptoms, such as chronic pain and fatigue, and/or psychological disturbances, such as posttraumatic stress disorder. Recent findings from the study of risk factors for the development of chronic somatic symptoms after a traumatic, infectious, or situational stressor suggest that similar pre-event, event-related, and post-event risk factors influence the development of chronic symptoms in each condition. Females, and those with pre-event distress or psychological factors, may be at higher risk of developing chronic symptoms after such events. Regarding the event, or "stressor", it appears as though the intensity or specific characteristics of exposure may be a relatively unimportant predictor of patient outcome. Instead, other factors such as the worry, or expectation, of chronicity may increase the risk of chronic symptom development. After the event, inactivity and time off work appear to increase the risk of chronic symptoms. Health care providers have an important role in emphasizing the benefits of resuming usual activities, and downplaying potential benefits of continuing in the sick role (e.g., time off work, increased family attention). While many aspects of the complex interaction of biological, psychological, and social factors that influence patient outcome after a stressful event remain to be elucidated, it appears that for the present, one of the most important interventions is to continue to emphasize to patients the old saying, "rest makes rust".

Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT. · Department of Medicine, William Beaumont Hospital and Wayne State University School of Medicine, Royal Oak, Michigan, USA. · In Vivo. · Pubmed #15113035 No free full text.

Abstract: BACKGROUND: A unique subset of patients with chronic fatigue syndrome (CFS) and IgM serum antibodies to cytomegalovirus (HCMV) non-structural gene products p52 and CM2 (UL 44 and UL 57) has been described. PATIENTS AND METHODS: Fifty-eight CFS patients and 68 non-CFS matched controls were studied. Serum antibodies to EBV viral capsid antigen (VCA) IgM and EBV Early Antigen, diffuse (EA, D) as well HVCMV(V), IgM and IgG; VP (sucrose, density purified V); p52 and CM2 IgM serum antibodies were assayed. RESULTS: Mean age of CFS patients was 44 years (75% women). Control patients were 9 years older (73% women). Serum EBV VCA IgM positive antibody titers were identified in 33 CFS patients (Group A subset EBV VCA IgM 62.3+/-8.3, neg. <20), but were not present in other CFS patients, (Group B subset EBV VCA IgM 6.8+/-0.7) controls (p<0.0001). EBV VCA IgM titers remained positive in CFS patients from Group A for 24-42 months. CONCLUSION: Serum antibody to EBV VCA IgM may be a specific diagnostic test for a second subset of CFS patients.