Chronic fatigue syndrome (CFS) has been attributed, in part, to viral illnesses, immune dysfunction, major depression, and hypothalamic- pituitary-adrenal (HPA) axis dysfunction. The role of other co-morbid features such as sleep disorders, signs and symptoms of sicca, and fibromyalgia (FM) remain unclear. Most of the studies describing these abnormalities in CFS have used a case-control methodology. Studies using this methodology have been troubled by the selection of appropriate control subjects, and have not adjusted for the potentially large effects of genetic variability and environmental influences. The use of monozygotic (MZ) twins is one approach that would provide the unique opportunity to control for genetic and environmental factors. In this study we will establish a national twin registry comprised of dizygotic and MZ twin pairs in which at least one twin has CFS. All twins will complete self-report measures of symptoms, psychosocial status and functional level, and undergo a telephone-administered structured psychiatric interview. From this registry, 20 MZ twins, discordant for CFS, will be chosen for more intensive study. They will travel to Seattle and complete additional questionnaires, undergo a physical examination, neuropsychological testing, polysomnography, and be evaluated for HPA axis function. Using these data in a co-twin control design our objectives are to: 1) assess psychiatric, neuropsychological, social, and functional differences in CFS probands compared to their healthy MZ twin; 2) examine the association of sleep symptoms, polysomnographic findings, and HPA axis function; and 3) ascertain the relationship between CFS and clinical features such as FM and sicca. Thus, this Project will answer the following research questions: Are there psychiatric, neuropsychological, social, and functional differences between CFS probands and their non-CFS healthy twins? Is there an association of sleep symptoms, polysomnographic findings, and HPA axis function between CFS probands and their twin? And are CFS probands more likely to have clinical conditions such as FM, sicca, and allergies than their twins?

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