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Backgrounds 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 [is greater than] .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

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.

AbstractChronic 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 ? 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) ? 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.