Suzanne Ashton

A twin study of chronic fatigue.

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 ≥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 ≥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 ≥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.

Comorbid Clinical Conditions in Chronic Fatigue

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 three 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 ≥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.

Markers of Viral Infection in Monozygotic Twins Discordant for Chronic Fatigue Syndrome

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.

Monozygotic twins discordant for chronic fatigue syndrome: Objective measures of sleep

Abstract Purpose Chronic fatigue syndrome (CFS) is characterized by profound fatigue accompanied by disturbances of sleep, cognition, mood, and other symptoms. Our objective was to describe sleep architecture in CFS-discordant twin pairs. Methods We conducted a co-twin control study of 22 pairs of monozygotic twins where one twin met criteria for CFS and the co-twin was healthy. Twins underwent two nights of polysomnography. Results The percentage of Stage 3 and REM sleep was greater among the CFS twins than their healthy co-twins ( P ≤.05 for both), but no other differences in sleep architecture including sleep latency, REM latency, and total sleep time were observed. Compared to their co-twins, CFS twins had higher values for the apnea–hypopnea index and apnea–hypopnea arousal index ( P ≤.05 for both). Conclusion These results do not provide strong evidence for a major role for abnormalities in sleep architecture in CFS. Respiration appears impaired in CFS, but these clinical abnormalities cannot alone account for the prominence of sleep complaints in this illness. The co-twin control methodology highlights the importance of selecting well-matched control subjects.

Cellular Immunity in Monozygotic Twins Discordant for Chronic Fatigue Syndrome

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.

Cognitive compromise following exercise in monozygotic twins discordant for chronic fatigue syndrome: fact or artifact?

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 (VO2 max) 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.

Use of alternative treatments by Chronic Fatigue Syndrome discordant twins

Background: Patients with chronic fatigue syndrome (CFS) have been faced with difficulties in diagnosis and lack of effective treatments. Anecdotal evidence suggests that use of alternative treatments may be common in these patients. Our primary objective was to compare the prevalence and patterns of alternative medicine use among twins who met the Centers for Disease Control and Prevention (CDC) CFS criteria to that of their non-CFS co-twins. Secondary goals were to assess how often alternative medicine use was discussed with physicians and the perceived benefit of these therapies. Methods: Sixty-three twin pairs discordant for CFS completed a survey about their use of 22 alternative therapies. Matched pair odds ratios and 95% confidence intervals were used to examine differences in the use between CFS twins and their non-CFS co-twins. Results: 91% of twins with CFS and 71% of non-CFS twins had used at least 1 alternative treatment in their lifetime. Twins with CFS were more likely to use homeopathy, mega-vitamins, herbal therapies, biofeedback, relaxation/meditation, guided imagery, massage therapy, energy healing, religious healing by others, and self-help groups than their non-CFS counterparts. A large proportion of all twins found alternative therapies helpful; however, only 42% of those with CFS and 23% of those without CFS discussed their use of alternative medicine with a physician. Conclusions: Individuals with CFS frequently used alternative medical treatments yet rarely communicated this use to their medical doctor. Future research should ascertain the usefulness of alternative practices in the management of CFS.

Preventive care of older urban American Indians and Alaska natives in primary care.

Little is known about prevention among elderly or urban American Indian/Alaska Native (AI/AN) populations. We reviewed the medical records of 550 older urban AI/AN primary care patients to evaluate how frequently preventive measures were received. Adherence to guidelines was examined by a culturally appropriate (≥50 years) and standard age threshold (≥65 years), and by performance of preventive measures at any time (“ever”) and in the past year. Lifetime performance was inadequate for the many measures, including mammograms (56%), fecal occult blood testing (37%), audiometry (33%), visual acuity testing (50%), smoking cessation counseling (50%), and pneumococcal (22%) and influenza (49%) vaccinations. Performance of the measures was less frequent in the prior year, but did not differ by age threshold. Predictors of adherence included female gender, having insurance, and having more health problems and medications. Nonadherence infrequently resulted from patients’ failure to comply with recommendations. We conclude that use of most preventive services among elderly urban AI/ANs is suboptimal and should be improved.