Chronic fatigue syndrome (CFS), true to its name, is marked by severe and persistent fatigue, along with a cluster of other symptoms. Fatiguing syndromes, given names such as neurasthenia and DaCosta’s syndrome, were chronicled 100 years ago and greeted thereafter with considerable dissent by the medical establishment (Straus, 1991; Wessely et al., 1998). The recognition and classification of CFS was transformed only in the past decade with the development of a case definition sponsored by the Centers for Disease Control and Prevention. The CDC’s case definition, first published in 1988 and revised in 1994, requires fatigue, dysfunction, and four other defining symptoms at least 6 months’ duration (Holmes et al., 1988; Fukuda et al., 1994). The latter symptoms most commonly include headaches, postexertional malaise, impaired cognition, and muscle pain (Buchwald and Garrity 1994). Established for research and surveillance purposes, the case definition also requires exclusion of several other disorders known to cause fatigue. Less than 1 percent of the population meets the case definition for CFS, although many more patients report chronic fatigue (Komaroff and Buchwald, 1998; Wessely et al., 1998). The etiology of CFS is unknown, and there are no accepted laboratory tests or pathological hallmarks (Epstein, 1995). Several biological correlates of the syndrome have emerged recently, including dysregulation of the hypothalamic–pituitary–adrenal axis, immune activation, and other measures (Goshorn, 1998). While infectious agents may trigger some cases of CFS, a complex, multifactoral etiology is proposed, incorporating biological, psychological, and social factors (Wessely et al., 1998). The degree of disability associated with chronic fatigue syndrome is striking, leaving high rates of unemployment (Bombardier and Buchwald, 1996; Buchwald et al., 1996).
(Hudson and Pope, 1989; Black et al., 1990).12 These views are fueled by the well-documented coexistence of diagnosable mental disorders in a sizable subset of patients with several medically unexplained illnesses. However, many observers have pointed out the difficulty of disentangling cause and effect. Mental disorders such as depression and anxiety may be causes, risk factors, covariates, or consequences of medically unexplained illnesses (Abbey and Garfinkel, 1991; Hyams, 1998). Further, there is some evidence that patients with unexplained illnesses do not satisfy criteria for somatization (Buchwald and Garrity, 1994; Kipen and Fiedler, 1999).
Attempts to systematically study medically unexplained illnesses have been thwarted by problems in case definition and classification of patients (Hyams, 1998). The problems stem not only from the absence of abnormal physical signs