Chronic Fatigue Syndrome: Washington

Smith MS, Martin-Herz SP, Womack WM, Marsigan JL. · Children's Hospital & Regional Medical Center, Department of Pediatrics, University of Washington, Seattle 98105, USA. · Pediatrics. · Pubmed #12671155 links to  free full text

Abstract: OBJECTIVE: To compare adolescents with migraine, unexplained profound chronic fatigue of >6 months duration, and normal school controls on measures of anxiety, depression, somatization, functional disability, and illness attribution. METHODS: Adolescents referred to Children's Hospital and Regional Medical Center for behavioral treatment of migraine (n = 179) or evaluation of chronic fatigue (n = 97) were compared with a group of healthy controls of similar age and sex from a middle school (n = 32). Subjects completed the Spielberger State-Trait Anxiety Inventory-Trait Form, the Children's Depression Inventory, the Childhood Somatization Inventory, and estimated the number of school days missed in the past 6 months because of illness. Migraine and fatigued subjects completed an illness attribution questionnaire. RESULTS: Subjects in the 3 groups were 56% to 70% female and ranged from 11 years old to 18 years old with a mean age of 14.0 +/- 2.0. Forty-six of the 97 chronically fatigued adolescents met 1994 Centers for Disease Control and Prevention (CDC) criteria for chronic fatigue syndrome (CDC-CFS), while 51 had idiopathic chronic fatigue syndrome (I-CFS) that did not meet full CDC criteria. Adolescents with migraine had significantly higher anxiety scores than those with I-CFS or controls and higher somatization scores than controls. Adolescents with CDC-CFS had significantly higher anxiety scores than those with I-CFS or controls, and higher depression and somatization scores than all other groups. There were significant differences between all groups for school days missed with CDC-CFS more than I-CFS more than migraine more than controls. Parents of adolescents with unexplained I-CFS had significantly lower attribution scores relating illness to possible psychological or stress factors than parents of adolescents with CDC-CFS or migraine. CONCLUSIONS: Adolescents referred to an academic center for evaluation of unexplained chronic fatigue had greater rates of school absenteeism than adolescents with migraine or healthy controls. Those meeting CDC-CFS criteria had higher anxiety scores than controls and higher depression and somatization scores than migraineurs or controls. Parents of adolescents with I-CFS were less likely to endorse psychological factors as possibly contributing to their symptoms than parents of adolescents with CDC-CFS or migraine.

Aaron LA, Arguelles LM, Ashton S, Belcourt M, Herrell R, Goldberg J, Smith WR, Buchwald D, Buchwald D. · Department of Oral Medicine, University of Washington, Seattle, Washington 98195, USA. · J Rheumatol. · Pubmed #12415604 No free full text.

Abstract: OBJECTIVE: To examine the independent effects of chronic regional and widespread pain syndromes on health and functional status after accounting for comorbid chronic fatigue using a co-twin control design. METHODS: We identified 95 twin pairs discordant for pain in which one twin had chronic regional or widespread pain and the other denied chronic pain. Demographic data, functional and psychological status, health behaviors, and symptoms based on the 1994 criteria for chronic fatigue syndrome (CFS) were assessed by questionnaire. Psychiatric diagnoses were based on structured interview. Random effects regression modeling estimated associations between chronic regional and widespread pain and each health measure with and without adjustment for CFS. RESULTS: Significant differences (p </= 0.05) were found within twin pairs discordant for chronic regional and widespread pain, for general health perception, and physical and mental health functioning as measured by summary scores from the Short Form-36. In addition, differences were observed within pain discordant pairs in psychological distress as measured by the General Health Questionnaire as well as the number of psychiatric diagnoses. Adjustment for CFS eliminated the association between chronic pain and mental health, but the association between chronic pain and poor general health, physical functioning, and sleep quality persisted (p </= 0.01). Only the intra-pair difference in physical functioning distinguished twins with regional vs widespread pain (p </= 0.05). CONCLUSION: Both chronic regional and widespread pain exact debilitating effects on perceived general health, physical functioning, and sleep quality independent of CFS. However, the psychological and psychiatric influence of chronic pain appears closely tied to CFS. Research should examine the additive role of CFS-like illnesses in patients with chronic pain, and its influence on treatment and outcome.

Koelle DM, Barcy S, Huang ML, Ashley RL, Corey L, Zeh J, Ashton S, Buchwald D. · Department of Laboratory Medicine, University of Washington, Seattle, WA, USA. · Clin Infect Dis. · Pubmed #12173124 No free full text.

Abstract: To estimate the prevalence of viruses associated with chronic fatigue syndrome (CFS) and to control for genetic and environmental factors, we conducted a co-twin control study of 22 monozygotic twin pairs, of which one twin met criteria for CFS and the other twin was healthy. Levels of antibodies to human herpesvirus (HHV)-8, cytomegalovirus, herpes simplex virus 1 and 2, and hepatitis C virus were measured. Polymerase chain reaction (PCR) assays for viral DNA were performed on peripheral blood mononuclear cell specimens to detect infection with HHV-6, HHV-7, HHV-8, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, varicella zoster virus, JC virus, BK virus, and parvovirus B19. To detect lytic infection, plasma was tested by PCR for HHV-6, HHV-8, cytomegalovirus, and Epstein-Barr virus DNA, and saliva was examined for HHV-8 DNA. For all assays, results did not differ between the group of twins with CFS and the healthy twins.

Sabath DE, Barcy S, Koelle DM, Zeh J, Ashton S, Buchwald D. · Department of Laboratory Medicine, Chronic Fatigue Syndrome Cooperative Research Center, University of Washington, Seattle, Washington 98195-7110, USA. · J Infect Dis. · Pubmed #11920301 No free full text.

Abstract: Studies elsewhere have suggested that immune dysfunction may be common in patients with chronic fatigue syndrome (CFS). The objective of this study was to assess the nature and extent of abnormalities in lymphocyte cell surface markers and NK cell activity in patients with CFS while controlling for genetic factors. A co-twin control study of immune system parameters was conducted for 22 pairs of monozygotic twins discordant for CFS and 9 healthy pairs of twins. The CFS twins had greater numbers of CD62L(+) T cells in several T cell subsets, although these differences did not achieve statistical significance. Significantly greater variability was noted in twins discordant for CFS than in the concordant healthy twins for 20 of 48 variables examined. The monozygotic co-twin control design is of unique value because of its ability to control for genetic influences on CFS; however, additional studies will be required to further assess immune dysregulation in this illness.

Lustyk MK, Jarrett ME, Bennett JC, Heitkemper MM. · Department of Psychology, Seattle Pacific University, WA 98119, USA. · Gastroenterol Nurs. · Pubmed #11847862 No free full text.

Abstract: It has been proposed that physical activity moderates physiological or psychological responses to chronic conditions. The purpose of this study was to determine if women with a chronic functional gastrointestinal (GI) disorder, irritable bowel syndrome, had less active lifestyles than healthy controls and to test whether active women with irritable bowel syndrome had less severe recalled or daily reports of GI, psychological, and somatic symptoms than inactive women with irritable bowel syndrome. Questionnaires were used to measure GI and psychological distress and somatic symptoms in 89 women who participated in this study. A daily symptom and activity diary was kept for one menstrual cycle. Women with irritable bowel syndrome were significantly less likely to be active (48%) than control women (71%) (X2 = 3.4, p = .05). Within the irritable bowel syndrome group, active women were less likely to report a feeling of incomplete evacuation following a bowel movement than inactive women (p < .04), yet active women did not have less severe recalled psychological or somatic symptoms than inactive women. Active women with irritable bowel syndrome reported less severe daily somatic symptoms, which were accounted for by a lower level of fatigue (p = .003), but not daily GI or psychological symptoms. These results suggest that physical activity may produce select symptom improvement in women with irritable bowel syndrome.

Roy-Byrne P, Afari N, Ashton S, Fischer M, Goldberg J, Buchwald D. · Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98104, USA. · Br J Psychiatry. · Pubmed #11772848 links to  free full text

Abstract: BACKGROUND: Up to three-quarters of patients with fatigue syndromes have comorbid mood or anxiety disorders, suggesting that chronic fatigue is a forme fruste of anxiety or depressive states. AIMS: To establish whether the association of chronic fatigue with psychological distress is causal or due to a common genetic or environmental factor. METHOD: 69 monozygotic (MZ) and 31 dizygotic (DZ) female twin pairs, with only one co-twin reporting at least 6 months of fatigue, completed questions on fatigue, the General Health Questionnaire (GHQ) and a structured psychiatric interview. We examined the effects of three progressively more stringent definitions of chronic fatigue on four GHQ sub-scales. RESULTS: Fatigued MZ and DZ twins by all definitions were significantly more depressed, anxious, somatically preoccupied and socially dysfunctional than their non-fatigued co-twins. Intrapair differences were similar in DZ and MZ twins, but non-significant differences were observed for the somatic symptoms and anxiety/insomnia sub-scales. CONCLUSIONS: In this sample, chronic fatigue and psychological distress are strongly associated without evidence for genetic covariation, implying that the association is environmental, or due to overlapping definitions. Any genetic covariation missed is likely to involve anxiety rather than depression.

Buchwald D, Herrell R, Ashton S, Belcourt M, Schmaling K, Sullivan P, Neale M, Goldberg J. · Department of Medicine, University of Washington, Seattle, WA, USA. · Psychosom Med. · Pubmed #11719632 links to  free full text

Abstract: OBJECTIVE: The etiology of chronic fatigue syndrome is unknown, but genetic influences may be important in its expression. Our objective was to assess the role of genetic and environmental factors in unexplained chronic fatigue. METHODS: A classic twin study was conducted using 146 female-female twin pairs, of whom at least one member reported > or =6 months of fatigue. After completing questionnaires on symptoms, zygosity, physical health, and a psychiatric interview, twins were classified using three increasingly stringent definitions: 1) chronic fatigue for > or =6 months, 2) chronic fatigue not explained by exclusionary medical conditions, and 3) idiopathic chronic fatigue not explained by medical or psychiatric exclusionary criteria of the chronic fatigue syndrome case definition. Concordance rates in monozygotic and dizygotic twins were calculated for each fatigue definition along with estimates of the relative magnitude of genetic and environmental influences on chronic fatigue. RESULTS: The concordance rate was higher in monozygotic than dizygotic twins for each definition of chronic fatigue. For idiopathic chronic fatigue, the concordance rates were 55% in monozygotic and 19% in dizygotic twins (p =.042). The estimated heritability in liability was 19% (95% confidence interval = 0-56) for chronic fatigue > or =6 months, 30% (95% confidence interval = 0-81) for chronic fatigue not explained by medical conditions, and 51% (95% confidence interval = 7-96) for idiopathic chronic fatigue. CONCLUSIONS: These results provide evidence supporting the familial aggregation of fatigue and suggest that genes may play a role in the etiology of chronic fatigue syndrome.

Pall ML. · School of Molecular Biosciences and Program in Medical Sciences, Washington State University, Pullman, 99164-4660, USA. · Med Hypotheses. · Pubmed #11461161 No free full text.

Abstract: Three types of overlap occur among the disease states chronic fatigue syndrome (CFS), fibromyalgia (FM), multiple chemical sensitivity (MCS) and posttraumatic stress disorder (PTSD). They share common symptoms. Many patients meet the criteria for diagnosis for two or more of these disorders and each disorder appears to be often induced by a relatively short-term stress which is followed by a chronic pathology, suggesting that the stress may act by inducing a self-perpetuating vicious cycle. Such a vicious cycle mechanism has been proposed to explain the etiology of CFS and MCS, based on elevated levels of nitric oxide and its potent oxidant product, peroxynitrite. Six positive feedback loops were proposed to act such that when peroxynitrite levels are elevated, they may remain elevated. The biochemistry involved is not highly tissue-specific, so that variation in symptoms may be explained by a variation in nitric oxide/peroxynitrite tissue distribution. The evidence for the same biochemical mechanism in the etiology of PTSD and FM is discussed here, and while less extensive than in the case of CFS and MCS, it is nevertheless suggestive. Evidence supporting the role of elevated nitric oxide/peroxynitrite in these four disease states is summarized, including induction of nitric oxide by common apparent inducers of these disease states, markers of elevated nitric oxide/peroxynitrite in patients and evidence for an inductive role of elevated nitric oxide in animal models. This theory appears to be the first to provide a mechanistic explanation for the multiple overlaps of these disease states and it also explains the origin of many of their common symptoms and similarity to both Gulf War syndrome and chronic sequelae of carbon monoxide toxicity. This theory suggests multiple studies that should be performed to further test this proposed mechanism. If this mechanism proves central to the etiology of these four conditions, it may also be involved in other conditions of currently obscure etiology and criteria are suggested for identifying such conditions.

Claypoole K, Mahurin R, Fischer ME, Goldberg J, Schmaling KB, Schoene RB, Ashton S, Buchwald D. · Departments of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA. · Appl Neuropsychol. · Pubmed #11388121 No free full text.

Abstract: This study examined the effects of exhaustive exercise on cognitive functioning among 21 monozygotic twin pairs discordant for chronic fatigue syndrome (CFS). The co-twin control design adjusts for genetic and family environmental factors not generally accounted for in more traditional research designs of neuropsychological function. Participants pedaled a cycle ergometer to exhaustion; maximum oxygen output capacity (VO2max) as well as perceived exertion were recorded. Neuropsychological tests of brief attention and concentration, speed of visual motor information processing, verbal learning and recognition memory, and word and category fluency were administered with alternate forms to participants pre- and postexercise. The preexercise neuropsychological test performance of CFS twins tended to be slightly below that of the healthy twin controls on all measures. However, twins with CFS did not demonstrate differential decrements in neuropsychological functioning after exercise relative to their healthy co-twins. Because exercise does not appear to diminish cognitive function, rehabilitative treatment approaches incorporating exercise are not contraindicated in CFS.

Lewis DH, Mayberg HS, Fischer ME, Goldberg J, Ashton S, Graham MM, Buchwald D. · Departments of Radiology, University of Washington, Seattle, USA. · Radiology. · Pubmed #11376266 links to  free full text

Abstract: PURPOSE: To evaluate the relationship between regional cerebral blood flow (rCBF) and chronic fatigue syndrome (CFS) in monozygotic twins discordant for CFS. MATERIALS AND METHODS: The authors conducted a co-twin control study of 22 monozygotic twins in which one twin met criteria for CFS and the other was healthy. Twins underwent a structured psychiatric interview and resting technetium 99m-hexamethyl-propyleneamine oxime single photon emission computed tomography of the brain. They also rated their mental status before the procedure. Scans were interpreted independently by two physicians blinded to illness status and then at a blinded consensus reading. Imaging fusion software with automated three-dimensional matching of rCBF images was used to coregister and quantify results. Outcomes were the number and distribution of abnormalities at both reader consensus and automated quantification. Mean rCBF levels were compared by using random effects regression models to account for the effects of twin matching and potential confounding factors. RESULTS: The twins with and those without CFS were similar in mean number of visually detected abnormalities and in mean differences quantified by using image registration software. These results were unaltered with adjustments for fitness level, depression, and mood before imaging. CONCLUSION: The study results did not provide evidence of a distinctive pattern of resting rCBF abnormalities associated with CFS. The described method highlights the importance of selecting well-matched control subjects.

Landis CA, Lentz MJ, Rothermel J, Riffle SC, Chapman D, Buchwald D, Shaver JL. · Biobehavioral Nursing and Health Systems, University of Washington, Seattle, Washington 98195, USA. · J Clin Endocrinol Metab. · Pubmed #11297602 links to  free full text

Abstract: Fibromyalgia (FM) is a complex syndrome, primarily of women, characterized by chronic pain, fatigue, and sleep disturbance. Altered function of the somatotropic axis has been documented in patients with FM, but little is known about nocturnal levels of PRL. As part of a laboratory study of sleep patterns in FM, we measured the serum concentrations of GH and PRL hourly from 2000--0700 h in a sample of 25 women with FM (mean, 46.9 +/- 7.6 yr) and in 21 control women (mean, 42.6 +/- 8.1 yr). The mean (+/-SEM ) serum concentrations (micrograms per L) of GH and of PRL during the early sleep period were higher in control women than in patients with FM [GH, 1.6 +/- 0.4 vs. 0.6 +/- 0.2 (P < 0.05); PRL, 23.2 +/- 2.2 vs. 16.9 +/- 2.0 (P < 0.025)]. The mean serum concentrations of GH and PRL increased more after sleep onset in control women than in patients with FM [GH, 1.3 +/- 0.4 vs. 0.3 +/- 0.2 (P < 0.05); PRL, 16.2 +/- 2.4 vs. 9.7 +/- 1.5 (P < 0.025)]. Sleep efficiency and amounts of sleep or wake stages on the blood draw night were not different between groups. There was a modest inverse relationship between sleep latency and PRL and a direct relationship between sleep efficiency and PRL in FM. There was an inverse relationship between age and GH most evident in control women. Insulin-like growth factor I levels were not different between the groups. These data demonstrate altered functioning of both the somatotropic and lactotropic axes during sleep in FM and support the hypothesis that dysregulated neuroendocrine systems during sleep may play a role in the pathophysiology of FM.

Aaron LA, Herrell R, Ashton S, Belcourt M, Schmaling K, Goldberg J, Buchwald D. · Division of General Internal Medicine, Department of Medicine, University of Washington, Seattle, WA 98104, USA. · J Gen Intern Med. · Pubmed #11251747 links to  free full text

Abstract: OBJECTIVES: Chronically fatiguing illness, defined as fatigue for at least 6 months, has been associated with various physical health conditions. Our objective was to determine whether there is a significant relationship between chronically fatiguing illness and 10 clinical conditions that frequently appear to be associated with fatigue, adjusting for the potentially confounding effects of psychiatric illness. DESIGN: A co-twin control study controlling for genetic and many environmental factors by comparing chronically fatigued twins with their nonfatigued co-twins. SETTING: A nationally distributed volunteer twin registry. PARTICIPANTS: The study included 127 twin pairs in which one member of the pair experienced fatigue of at least 6 months' duration and the co-twin was healthy and denied chronic fatigue. Fatigued twins were classified into 3 levels using increasingly stringent diagnostic criteria. MEASUREMENTS AND MAIN RESULTS: Twins reported on a history of fibromyalgia, irritable bowel syndrome, multiple chemical sensitivities, temporomandibular disorder, interstitial cystitis, postconcussion syndrome, tension headache, chronic low back pain, chronic pelvic pain (women), and chronic nonbacterial prostatitis (men). The prevalence of these comorbid clinical conditions was significantly higher in the fatigued twins compared to their nonfatigued co-twins. Most notably, compared to their nonfatigued co-twins, the chronically fatigued twins had higher rates of fibromyalgia (> 70% vs < 10%) and irritable bowel syndrome (> 50% vs < 5%). The strongest associations were observed between chronic fatigue and fibromyalgia (odds ratios > 20), irritable bowel syndrome, chronic pelvic pain, multiple chemical sensitivities, and temporomandibular disorder (all with odds ratios > or = 4). Regression analysis suggested that the number of comorbid clinical conditions associated with chronic fatigue could not be attributed solely to psychiatric illness. CONCLUSIONS: Chronically fatiguing illnesses were associated with high rates of many other clinical conditions. Thus, patients with chronic fatigue may present a complex clinical picture that poses diagnostic and management challenges. Nonetheless, clinicians should assess such patients for the presence of comorbid clinical conditions. Future research should provide a better understanding of the temporal relationship of the onset of fatigue and these conditions, and develop strategies for early intervention.

Goodwin SS. · Pacific Lutheran University, Tacoma, WA 98447, USA. · Issues Ment Health Nurs. · Pubmed #11249354 No free full text.

Abstract: The purpose of this descriptive correlational study was to describe the differences in couples' perceptions of wives' Chronic Fatigue Syndrome (CFS) symptoms and to describe the relationship between changing symptoms and the marital relationship. The convenience sample of 131 wives with CFS and their spouses reported symptom changes similarly. However, wives reported significantly higher problem levels for constitutional, fatigue, cognition, central nervous system (CNS), musculoskeletal, and allergy symptom domains and significantly less problem levels of mood disturbance domain than their husbands. Husbands who reported more symptom changes also reported lower marital adjustment, less empathy and support from their wives, and more conflict within the relationship. Wives who reported more symptom changes reported lower marital adjustment, less empathy for their husbands, and more conflict within the relationship and had husbands who reported lower marital adjustment and less empathy and support by the wives.

Poole J, Herrell R, Ashton S, Goldberg J, Buchwald D. · Harborview Medical Center, 325 Ninth Ave, Box 359780, Seattle, WA 98104, USA. · Arch Intern Med. · Pubmed #11112240 links to  free full text

Abstract: BACKGROUND: The pathogenesis of chronic fatigue syndrome (CFS) is unknown. Neurally mediated hypotension (NMH) has been suggested as a common comorbid condition or a potential underlying cause. METHODS: We conducted a cotwin control study of 21 monozygotic twins who were discordant for CFS. One twin met the 1994 Centers for Disease Control and Prevention criteria for CFS, and the other twin was healthy and denied chronic fatigue. The twins were selected from a volunteer twin registry in which at least 1 member reported persistent fatigue. As part of a 7-day clinical evaluation, all 21 twin pairs were evaluated with a 3-stage tilt table test with isoproterenol hydrochloride for the assessment of NMH. The presence of NMH was defined as syncope or presyncope associated with a decrease of 25 mm Hg in blood pressure and no associated increase in heart rate. RESULTS: A positive tilt table test result was observed in 4 twins with CFS (19%) and in 4 healthy twins (19%). This difference was not statistically significant (matched pair odds ratio, 1.0; 95% confidence interval, 0.2-5.4; P>.90). Compared with the healthy twins, the twins with CFS reported more severe symptoms of CFS and NMH both in the week before and during the tilt table test. CONCLUSIONS: These results do not support a major role for NMH in CFS. They highlight the importance of selecting well-matched control subjects, as well as the unique value of the monozygotic cotwin control design in the study of this illness. Arch Intern Med. 2000;160:3461-3468.

Brace MJ, Scott Smith M, McCauley E, Sherry DD. · Department of Psychiatry, University of Washington, Seattle, USA. · J Dev Behav Pediatr. · Pubmed #11064960 No free full text.

Abstract: Parental encouragement of illness behavior is hypothesized to correlate with psychosocial dysfunction in adolescents with chronic illness. To explore this hypothesis, adolescents aged 11 to 17 years with chronic fatigue syndrome (CFS) (n = 10), juvenile rheumatoid arthritis (JRA) (n = 16), and healthy adolescents (n = 14) were recruited for the study. Measures included the Achenbach parent and youth self report forms, the Family Adaptability and Cohesion Evaluation Scale-II (FACES II), the Children's Depression Rating Scale, and number of days absent from school. The Illness Behavior Encouragement Scale (IBES) generated measures of parental reinforcement of illness behavior. As predicted, the teens with CFS scored statistically higher on measures of depression, total competence, and number of days of school missed in the previous 6 months (mean = 40). Children with JRA scored significantly lower than the CFS group on the measure of parental reinforcement of illness behavior. The healthy group produced intermediate scores. Results and implications for future clinical and research activity are discussed.

Afari N, Schmaling KB, Herrell R, Hartman S, Goldberg J, Buchwald DS. · Department of Medicine, University of Washington, Seattle, WA 98104, USA. · J Psychosom Res. · Pubmed #11033373 No free full text.

Abstract: OBJECTIVES: Individuals with chronic fatigue and chronic fatigue syndrome (CFS) face debilitating symptoms as well as stressful life situations that may result from their condition. The goal of this study was to examine the coping strategies used by fatigue-discordant twin pairs. METHODS: We utilized a co-twin design to assess how twin pairs discordant for chronic fatigue and CFS cope with stress. All twin pairs were administered the Revised Ways of Coping Checklist. RESULTS: Overall, the pattern of coping strategies was similar for fatigued and non-fatigued twins. However, twins with chronic fatigue or CFS utilized more avoidance strategies than their non-fatigued counterparts; those with chronic fatigue also used more avoidance relative to problem-focused coping than their co-twins. CONCLUSIONS: These results suggest that while fatigue-discordant twins generally exhibit similar behavior patterns in order to cope with stress, there may be an association between fatigue and avoidance coping. Future research should focus on the role of avoidance and its relationship to fatiguing illnesses.

Schmaling KB, Smith WR, Buchwald DS. · University of Washington, Seattle 98195-6560, USA. · Psychosom Med. · Pubmed #10845358 links to  free full text

Abstract: OBJECTIVE: The predictive power of partners' responses to illness behavior for illness outcomes was investigated among couples in which one person had chronic fatigue syndrome (CFS). METHODS: One hundred nineteen participants who met case-definition criteria for CFS and were living with a significant other (SO) completed self-report measures of relationship satisfaction, responses of their SO to fatigue symptoms, and outcome measures of fatigue and functional status. RESULTS: The results indicated that more frequent solicitous SO responses to illness behavior were predictive of greater fatigue-related severity and bodily pain. Solicitous SO responses to fatigue behavior were particularly influential in the context of a satisfactory relationship. In highly satisfactory relationships, solicitous SO responses were associated with significantly greater fatigue severity and fatigue-related disability than in relationships characterized by low or average satisfaction. CONCLUSIONS: Solicitous SO responses to CFS-related symptoms are associated with poorer patient outcomes, especially in the context of a satisfactory intimate relationship. Because of the cross-sectional nature of the study, the direction of effects cannot be interpreted unambiguously. SOs may be inadvertently positively reinforcing illness-related behavior: Solicitous partners may help the patient more with tasks of daily living, thereby decreasing the patient's activity level, which may lead to deconditioning and disability. Alternatively, patients with more severe symptoms and disability may present more opportunities for concerned SO responses, which again may be heightened in the context of a caring, satisfactory relationship. In either case, the results suggest that additional research on the role of solicitous SO responses is warranted.

Pall ML. · Department of Biochemistry/Biophysics and Program in Basic Medical Sciences, Washington State University, Pullman 99164-4660, USA. · Med Hypotheses. · Pubmed #10790736 No free full text.

Abstract: The etiology of chronic fatigue syndrome (CFS) has been both obscure and highly contentious, leading to substantial barriers to both clear diagnosis and effective treatment. I propose here a novel hypothesis of CFS in which either viral or bacterial infection induces one or more cytokines, IL-1beta IL-6, TNF-alpha and IFN-gamma. These induce nitric oxide synthase (iNOS), leading to increased nitric oxide levels. Nitric oxide, in turn, reacts with superoxide radical to generate the potent oxidant peroxynitrite. Multiple amplification and positive feedback mechanisms are proposed by which once peroxynitrite levels are elevated, they tend to be sustained at a high level. This proposed mechanism may lower the HPA axis activity and be maintained by consequent lowered glucocorticoid levels. Similarities are discussed among CFS and autoimmune and other diseases previously shown to be associated with elevated peroxynitrite. Multiple pharmacological approaches to the treatment of CFS are suggested by this hypothesis.

Aaron LA, Burke MM, Buchwald D. · Department of Medicine, University of Washington, Seattle, USA. · Arch Intern Med. · Pubmed #10647761 links to  free full text

Abstract: BACKGROUND: Patients with chronic fatigue syndrome (CFS), fibromyalgia (FM), and temporomandibular disorder (TMD) share many clinical illness features such as myalgia, fatigue, sleep disturbances, and impairment in ability to perform activities of daily living as a consequence of these symptoms. A growing literature suggests that a variety of comorbid illnesses also may commonly coexist in these patients, including irritable bowel syndrome, chronic tension-type headache, and interstitial cystitis. OBJECTIVE: To describe the frequency of 10 clinical conditions among patients with CFS, FM, and TMD compared with healthy controls with respect to past diagnoses, degree to which they manifested symptoms for each condition as determined by expert-based criteria, and published diagnostic criteria. METHODS: Patients diagnosed as having CFS, FM, and TMD by their physicians were recruited from hospital-based clinics. Healthy control subjects from a dermatology clinic were enrolled as a comparison group. All subjects completed a 138-item symptom checklist and underwent a brief physical examination performed by the project physicians. RESULTS: With little exception, patients reported few past diagnoses of the 10 clinical conditions beyond their referring diagnosis of CFS, FM, or TMD. In contrast, patients were more likely than controls to meet lifetime symptom and diagnostic criteria for many of the conditions, including CFS, FM, irritable bowel syndrome, multiple chemical sensitivities, and headache. Lifetime rates of irritable bowel syndrome were particularly striking in the patient groups (CFS, 92%; FM, 77%; TMD, 64%) compared with controls (18%) (P<.001). Individual symptom analysis revealed that patients with CFS, FM, and TMD share common symptoms, including generalized pain sensitivity, sleep and concentration difficulties, bowel complaints, and headache. However, several symptoms also distinguished the patient groups. CONCLUSIONS: This study provides preliminary evidence that patients with CFS, FM, and TMD share key symptoms. It also is apparent that other localized and systemic conditions may frequently co-occur with CFS, FM, and TMD. Future research that seeks to identify the temporal relationships and other pathophysiologic mechanism(s) linking CFS, FM, and TMD will likely advance our understanding and treatment of these chronic, recurrent conditions.

Buchwald D, Herrell R, Ashton S, Belcourt M, Schmaling K, Goldberg J. · Department of Medicine, University of Washington, Seattle, USA. · Twin Res. · Pubmed #10555131 No free full text.

Abstract: Chronic fatigue syndrome (CFS) and the symptom of chronic fatigue are conditions of unknown etiology. The Centers for Disease Control and Prevention (CDC) define CFS as an illness characterized by > or = 6 months of disabling fatigue associated with muscle pain, pharyngitis, and alterations in mood, sleep and neurocognition. We constructed a registry of twins with chronic fatigue to facilitate research on the impact of illness, the associated medical and psychosocial factors, and the heterogeneous proposed mechanisms for these conditions. We have recruited 204 twin pairs in which one or both members reported persistent fatigue through patient support group newsletters (60%), clinicians/researchers familiar with CFS (12%), notices placed on electronic bulletin boards for CFS (11%), twin organizations and researchers (6%), relatives and friends (3%) and other sources (8%). Complete data are available for 177 pairs (87%). Twins completed an extensive questionnaire booklet that included measures of physical and mental health, functional status, and psychosocial factors; a structured psychiatric interview was also conducted by telephone. Twins were classified using three increasingly more stringent diagnostic criteria for chronic fatigue: 1) > or = 6 months of fatigue (115 discordant and 61 concordant pairs); 2) chronic fatigue with additional symptoms and application of the medial exclusions of the CDC CFS case definition as obtained by self-report (92 discordant and 41 concordant pairs) and; 3) chronic fatigue with additional symptoms unexplained by self-reported medical conditions and psychiatric diagnoses as determined by the structured interview (69 discordant pairs and 25 concordant pairs). Despite the limitations of a volunteer registry, the Chronic Fatigue Twin Registry promises to be an important resource for research on CFS and chronic fatigue.