Perceptualand Motor Skills, 1992, 74, 1123-1136. O Perceptual and Motor Skills 1992
PSYCHOLOGICAL ASPECTS O F CHRONIC FATIGUE SYNDROME ' JOHN B. MURRAY St. John's University Summary.-Research on Chronic Fatigue Syndrome has not identified a definitive cause or treatment but psychological aspects have been noted.
The incidence of Chronic Fatigue Syndrome has increased and treatment centers have opened in Anaheim, Charlotte, Houston, and Providence (Harvey, 1989). The term is currently applied to a strange group of flu-like symptoms that have been known for 50 years by a variety of names (Holmes, Kaplan, Gantz, Komaroff, Schonberger, Straus, Jones, Dubois, CunninghamRundles, Pahwa, Tosato, Zegans, Purtilo, Brown, Schooley, & Brus, 1988; Straus, 1991; Swartz, 1988). Chronic fatigue is the most striking characteristic of a curious iUness that has surfaced sporadically with a range of neurological, psychological, and somatic symptoms (Dawson, 1987; Harvey, 1989; Hickie, Lloyd, & Wakefield, 1991; Manu, Lane, & Matthews, 1988). Outbreaks sometimes reached epidemic proportions in different countries and were given names such as, neurasthenia, Iceland Disease, Royal Free disease, benign myalgic encephalomyelitis, Akureyri disease, and more recently, chronic mononucleosis, chronic Epstein-Barr virus (EBV) disease, and chronic mononucleosis-like syndrome (Abbey & Garfinkel, 1991; Acheson, 1959; A new clinical entity?, 1956; Galpine & Macrae, 1953; Henderson & Shelokov, 1959; Manu, Lane, & Matthews, 1988; Outbreak at the Royal Free, 1955; Palca, 1991). Some of the disorders listed above are acute diseases that usually are resolved in two months, whereas only chronic forms of these illnesses appear to resemble Chronic Fatigue Syndrome (Gantz & Holmes, 1989). Chronic Fatigue Syndrome is an heterogeneous disorder that appears more frequently in women, often runs a protracted course, but rarely is fatal (Barnes, 1986; Harvey, 1989). A series of reports in the early 1980s rekindled research interest and investigators at the Centers for Disease Control renamed this disorder Chronic Fatigue Syndrome and published criteria for it (Holmes, et al., 1988; Lloyd, Wakefield, Boughton, & Dwyer, 1988). The Centers for Disease Control set up four surveillance sites in Atlanta, Grand Rapids, Reno, and Wichita (Palca, 1991). Human fatigue is a baffling symptom that may result normally from intense ~hysicalactivity or mental effort or it may be symptomatic of a variety of specific illnesses (Cherfas, 1990; Kennedy, 1987; Poteliakhoff, 1981;
'Address correspondence to John B. Murray, Ph.D., Psychology Department, St. John's University, Jamaica, NY 11439.
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Swartz, 1988). Fatigue is a common complaint in primary care patients and chronic fatigue is associated with many medical illnesses and psychiatric disorders, especially anxiety and depression (Abbey & Garfinkel, 1990; Komaroff, Wang, Lee, & Grayston, 1992; Manu, Lane, & Matthews, 1989; Manu, Matthews, Lane, Tennen, Hesselbrock, Mendola, & Affleck, 1989; Mitchell, 1986; Montgomery, 1983; Nelson, Kirk, McHugo, Douglass, Ohler, Wasson, & Zubkoff, 1987; Sugarman & Berg, 1984; Swanson, Moore, & Nobrega, 1978). Because fatigue symptoms may be subjective, quantification has been difficult (Bartley, 1981; Broadbent, 1979; Potempa, Lopez, Reid, & Lawson, 1986). Fatigue may be considered central in depressive states or when motivation for voluntary motor activity is low. Chronic Fatigue Syndrome has been defined as a disorder characterized by debilitating fatigue lasting for at least 6 months along with multiple other symptoms, including fever, recurrent sore throat, lymph node pain, myalgia, arthralgia, headache, postexercise weakness, sleep disorders, and various CNS complaints (Gantz & Holrnes, 1989). Goodnick (1990) described the syndrome as a disorder of immunity with symptoms of frequent infections, fevers, and impaired immunity, combined with fatigue and lack of motivation. The criteria of the Centers for Disease Control required that diagnosed patients have disabling fatigue and other constitutional complaints for at least six months in the absence of other definable immune dysfunctions or medical problems (Holrnes, et al., 1988; Kruesi, Dale, & Straus, 1990). Minor criteria listed by the Centers for Disease Control included neuropsychologic complaints such as forgetfulness, depression, and irritability. These invite psychological investigation; however, the criteria for Chronic Fatigue Syndrome excluded patients with current or past psychiatric disorders or who used major tranquilizers, lithium, antidepressants, or abused or were dependent on drugs, in effect limiting a complete investigation of psychological factors that might be involved (Hickie, et al., 1991). Many Chronic Fatigue Syndrome patients do suffer from psychiatric disorders (Huller & Moser, 1990; Kroenke, Wood, Mangelsdorff, Meier, & Powell, 1988; Manu, Matthews, & Lane, 1988). But, some portion of primary care and neurologic disorder patients also have psychiatric symptoms, usually mood disorders, that accompany their presenting illness (Bridges & Goldberg, 1984, 1985; Rodin & Voshart, 1986). A very common clinical manifestation of chronic Epstein-Barr virus infection according to Jones and Straus (1987) was sporadic neurasthenia, in which patients report fatigue and a list of other complaints with few abnormalities that can be identified on physical examination or routine laboratory tests. Because a variety of symptoms in addition to fatigue are included in the definition and the unknown etiology, laboratory tests have not been able to confirm Chronic Fatigue Syndrome (Gantz & Holmes, 1989; Hefinger, Smith, Van Scoy, Spitzer, Forgaes, & Edson, 1988; Jones, Wilhams, Schooley, Rob-
PSYCHOLOGICAL ASPECTS: CHRONIC FATIGUE
inson, & Glaser, 1988; Komaroff & Buchwald, 1991; Straus, Dale, Peter, & Dinarello, 1989; Sugarman & Berg, 1984; Swartz, 1988). While researchers struggle to identify a specific organic basis for Chronic Fatigue Syndrome, definitive diagnostic and therapeutic tools are unavailable (Buchwald & Komaroff, 1991; Straus, 1987). I n many studies the syndrome appears to have psychological components; these are the main focus of this review of research for their pattern may contribute to better diagnoses and treatment.
ETIOLOGY OF CHRONIC FATIGUE SYNDROME The causes of fatigue are numerous but the basis of the syndrome remains unknown (Gantz & Holmes, 1989). Some patients date their condition to a poorly defined acute respiratory, gastrointestinal, or mononucleosis-like illness that did not resolve. Other patients describe a more insidious onset unrelated to a previous acute illness. A variety of etiologic agents have been investigated. Some findings support the notion that Chronic Fatigue Syndrome may be due to one or more immune disorders that have resulted from exposure to infectious agents (Chao, Gallagher, Phair, & Peterson, 1990; Cheney, 1991; DeFreitas, Hilliard, Cheney, Bell, Kiggundu, Sankey, Wroblewska, Pdadino, Woodward, & Koprowski, 1991; Landay, Jessop, Lennette, & Levy, 1991; Subira, Castilla, Civeira, & Prieto, 1989). The dearth of laboratory markers for Chronic Fatigue Syndrome has lent immediate interest to attempts to validate evidence, suggesting that the immune system may be involved in Chronic Fatigue Syndrome (Palca, 1991; Read, Spickett, Harvey, Edwards, & Larson, 1988; Straus, et al., 1989); however, findings appear not to correlate immunological changes with severity of symptoms of Chronic Fatigue Syndrome (Abbey & Garfinkel, 1990). Although virologic studies have not definitively identified a cause of Chronic Fatigue Syndrome, viral infections are characterized by chronic postinfection fatigue and the onset of Chronic Fatigue Syndrome often appears similar to an acute viral infection (Hartnell, 1987; Landay, et al., 1991; Levine, Krueger, & Straus, 1989; Lloyd, Hickie, Brockman, Dwyer, & Wakefield, 1991; Martin, 1991; Morte, Castilla, Civeira, Serrano, & Prieto, 1989; Swartz, 1988). In searching for causes many different viruses have been investigated; enteroviruses, herpes viruses, Coxsackie A and B viruses, and, particularly in the United States, the Epstein-Barr virus (Dale, Straus, Ablashi, Salahuddin, Gallo, Nishibe, & Inoue, 1989; David, Wessel~,& Pelosi, 1988; Galpine & Macrae, 1953). Although Epstein-Barr virus may infect many in the United States, it is asymptomatic in most cases except for infected adolescents and young adults who develop infectious mononucleosis, the symptoms of which are similar to those of Chronic Fatigue Syndrome (Barnes, 1986; Kasl, Evans, & Niederman, 1979; Straus, 1987; Straus, Tosato, Armstrong, Lawley, Preble, Henle, Davey, Pearson, Epstein, Brus, &
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Blaese, 1985). The Epstein-Barr virus persists for life, and some have proposed that small defects in immunoregulation might permit milder forms of Epstein-Barr virus infection to appear as Chronic Fatigue Syndrome. But, recent studies have cast substantial doubt on an etiological relationship between the Epstein-Barr virus and Chronic Fatigue Syndrome (Buchwald, Sullivan, & Komaroff, 1987; Holmes, Kaplan, Steward, Hunt, Pinsky, & Schonberger, 1987; Manu, Lane, & Matthews, 1988; Palca, 1991; Shorter, 1992). Another approach to the study of Chronic Fatigue Syndrome has investigated muscle metabolism abnormalities but results have not been confirmed in large groups of patients (Abbey & Garfinkel, 1990). I n comparisons of subjective complaints of muscle fatigue in Chronic Fatigue Syndrome with objective controlled tests of muscle function, 20 patients who had recovered from viral infection fatigue syndrome s t d experienced fatigue despite relatively normal behavior of their muscles during controlled fatigue tests (Lloyd, Hales, & Gandevia, 1988; Wessely & Powell, 1989). I n still another approach, Straus, et al. (1985) proposed that allergic reactions were the mechanisms involved in the etiology of Chronic Fatigue Syndrome. But, in a blind, placebo-controlled test, half of 27 Chronic Fatigue Syndrome patients reacted positively to 48 routine cutaneous allergic solutions at a higher rate than expected in the general population (Straus, Dale, Wright, & Metcalfe, 1988). Some Chronic Fatigue Syndrome patients appeared to lack lymphocyte cells that play a significant role in defenses against viral infection (Calgiuri, Murray, Buchwald, Levine, Cheney, Peterson, Komaroff, & Ritz, 1987). Mononucleosis has been likened to Chronic Fatigue Syndrome. In a study of 1400 West Point cadets psychosocial factors, such as high motivation coupled with poor academic achievement, correlated with the likelihood of development of clinical mononucleosis rather than asymptomatic infection. I n those who contracted clinical infection the same psychosocial factors correlated with length of hospitalization (Kasl, et al., 1979). Cadie, Nye, and Storey (1976) investigated psychological malaise in infectious mononucleosis in a follow-up of 36 patients, 16 men and 20 women, drawn from a larger sample of 147 Epstein-Barr virus patients. A short self-rating scale of anxiety, phobia, obsessions, somatization, depression, and hysteria indicated considerable depression in the patients with infectious mononucleosis. An interviewer, who was unaware of the self-rating scale results, rated the patients. I n addition, answers to the self-rating scale were compared with the responses of unselected rural groups. Results with female patients with infectious mononucleosis tended to support an association between infectious mononucleosis and depression. The 20 female patients were higher in morbidity before infectious mononucleosis and significantly different in anxiety and depression one year after contracting infectious mononucleosis. Two of
PSYCHOLOGICAL ASPECTS: CHRONIC FATIGUE
16 men were somewhat depressed before infectious mononucleosis and one year after but not significantly more anxious or phobic. The nonspecific nature of important symptoms of fatigue led to the development of criteria for Chronic Fatigue Syndrome (Hickie, Lloyd, Wakefield, & Parker, 1990). The minor criteria in the-Chronic Fatigue Syndrome definition of Holmes, et al. (1988) included neuropsychologic complaints, such as confusion, excessive irritabhty, forgetfulness, difficulty in thnking, inabihty to concentrate, and depression. However, these criteria, since they exclude those who have taken antipsychotic drugs or have received psychiatric help, may prevent an accurate assessment of psychological factors in Chronic Fatigue Syndrome. Depressive symptoms appear along with those of Chronic Fatigue Syndrome in many reports. One of the epidemics of similar symptoms, "benign myalgic encephalomyelitis," occurred at the Royal Free Hospital in London in 1955 (A new clinical entity? 1956; Outbreak at the Royal Free, 1955). A later epidemic outbreak in the Royal Free Hospital affected 292 medical, nursing, and administrative staff. McEvedy and Beard (1973) investigated the records of this epidemic. They compared the records of 100 nurses who contracted the disease with those of 100 nurses who did not contract it and who were similar in height/weight, entrance examination scores, and exposure to the viral infection. Their follow-up study indicated that those who contracted the disease as compared with control subjects had significantly poorer general health and differed also in the amount of psychiatric attention they had received. McEvedy and Beard concluded that the condition came about through a manifestation of anxiety spreading among young women who contracted the disease and referred to "mass hysteria" in their analysis of the data (David, et al., 1988). Medical doctors insisted that organic disease and infection were the causes of this epidemic and the difference in interpretation between infection and psychological explanations persists to the present (Cherfas, 1990; Dawson, 1987). In another early study, Dillon, Marshall, Dudgeon, and Steigman (1974) reported on epidemic neuromyasthenia among the staff, mostly nurses, of a London hospital. The symptomatology, namely, fatigue, headache, and depression, was similar to that in Iceland and the Royal Free outbreak in the authors' judgment. Nurses and medical staff, especially women, have been particularly susceptible to these epidemics of bizarre, clinically similar illnesses reported in many parts of the world (David, et al., 1988; Henderson & Shelokov, 1959; McConnell, 1945; Shelokov, Habel, Verder, & Welsh, 1957). The preponderance of Chronic Fatigue Syndrome in women and its rarity among children argue against acceptance of merely infective causes of Chronic Fatigue Syndrome (David, et al., 1988; Harvey, 1989; Riddle, 1982; Swanson, et al., 1978). General practitioners reported that minor affective illnesses, especial-
J. B. MURRAY
ly depression, often accompany presenting complaints (Bridges & Goldberg, 1985; Goldberg & Blackwell, 1970; SkoInick, 1991). The role of psychosocial features persuaded some general practitioners to regard Chronic Fatigue Syndrome as a psychiatric disorder (Palca, 1991). From 135 consecutive patients referred to a Fatigue Clinic at the University of Connecticut only six met the criteria for Chronic Fatigue Syndrome as opposed to 9 1 (67%) who had clinically active psychiatric disorders (Manu, Lane, & Matthews, 1988). To differentiate between patients whose taclgue was related to affective disorders and those whose fatigue might be indicative of current depression or a residual symptom of affective illness in partial remission, Manu, Matthews, Lane, Tennen, Hesselbrock, Mendola, and Affleck (1989) studied 100 women subjects, whose chronic fatigue had lasted for an average of 13 years. The onset of the first depressive episode appeared to be strongly associated with and previous to the onset of chronic fatigue. Kroenke, et al. (1988), re-examining after a year 102 patients with chronic fatigue out of 1159 consecutive patients, noted that their five psychometric instruments identified fatigue patients more accurately than laboratory tests. Depression and somatic anxiety scores were significantly higher in chronic fatigue patients than in matched control subjects. Fatigue patients' scores on three psychometric measures were significantly different and more suggestive of depression and somatic anxiety than scores of the controls. But, because criteria for Chronic Fatigue Syndrome of the Centers for Disease Control exclude those with a number of psychiatric disorders and those taking psychotropic medication, accurate quantification of the prevalence of psychological factors in patients with Chronic Fatigue Syndrome is difficult to obtain (Hickie, et al., 1990; Holmes, et al., 1988). Symptoms of depression appeared in Gold, Bowden, Sixbey, Riggs, Katon, Ashley, Obrigewitch, and Corey's (1990) prospective investigation of 26 patients, 19 of whom were women, referred to a Viral Disease Clinic with elevated EBV titers. Neither frequency or prevalence of active Epstein-Barr virus differentiated between patients and matched controls. Psychiatric evaluation using the Diagnostic Interview Schedule (Robins, Helzer, Croughan, Williams, & Spitzer, 1981) demonstrated that EBV patients had s i g n i f ~ c a n t l ~ more lifetime episodes of as well as more current major depression. Thirteen of the patients had experienced one or more episodes of major depression that predated chronic fatigue. I n two patients chronic fatigue predated depression. Symptoms of Chronic Fatigue Syndrome decreased in frequency without any medication during the study. The authors proposed that affective illness may be the primary disorder in some patients with Chronic Fatigue Syndrome. A recent investigation of the psychiatric status of patients in Australia indicated that psychological disturbance was likely to be a consequence of - -
PSYCHOLOGICAL ASPECTS: CHRONIC FATIGUE
rather than an antecedent risk factor for Chronic Fatigue Syndrome (Hickie, et al., 1990). The patients were compared with 48 control subjects matched in age and sex. Twenty-two of 48 patients with Chronic Fatigue Syndrome experienced major depression while suffering Chronic Fatigue Syndrome. Rates of psychiatric illness were higher in 28 patients who met the criteria for Chronic Fatigue Syndrome than in the general population or in a control group of patients who were chronically medically ill (Kruesi, et a/., 1990). Lifetime prevalence of psychiatric disorders was 75% in the patients with Chronic Fatigue Syndrome, higher than in either of the two control groups. Psychiatric disorders according to their reports were more likely to precede the onset of Chronic Fatigue Syndrome. The frequency of psychiatric and depressive disorders in these patients also suggested that Chronic Fatigue Syndrome might occur in those who have premorbid vulnerability to depression. In a prospective study undertaken to determine the psychiatric morbidity of patients complaining of chronic fatigue, 100 adults, 65 women and 35 men, who experienced chronic fatigue symptoms for an average of 13 years, received a comprehensive medical examination and responded to the Diagnostic Interview Schedule (Manu, Matthews, & Lane, 1988). Eight months later the patients were re-examined. For 65 patients one or more psychiatric diagnoses were considered the major cause of their chronic fatigue. Mood disorders followed by somatization and anxiety made up most of the psychiatric disorders. In many reports depression and Chronic Fatigue Syndrome have appeared in the same subjects (Cherfas, 1990; Skolnick, 1991). Perhaps 50% to 60% of patients with Chronic Fatigue Syndrome met operational criteria of other psychiatric illness (Kendell, 1991). I n some instances mental health professionals may find the diagnosis of depression easier than to unravel the puzzle of the symptoms of Chronic Fatigue Syndrome. O n the one hand, these patients lack some of the essential characteristics of patients with primary depression (Hickie, et al., 1991). Their symptoms more closely resemble those seen in depressive patients with primary medical disorders. O n the other hand, antidepressant medications have produced improvement in some Chronic Fatigue Syndrome patients (Cherfas, 1990). Finally, whether the depressive symptoms are causative or consequences of Chronic Fatigue Syndrome is difficult to assess (Skolnick, 1991). Greenberg (1990) proposed that Chronic Fatigue Syndrome represented the contemporary equivalent of neurasthenia. The term neurasthenia was introduced in 1869 by Beard, an American neurologist (Kendell, 1991; Straus, 1991). It encompassed much of what is now regarded as neurotic illness but by the early part of the twentieth century had come to mean unexplained exhaustion and fatigue. Neurasthenia remained popular as long as it was
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viewed as a neurological illness caused by environmental factors and more common in educated and professional classes (Abbey & Garfinkel, 1991; Wessely, 1990). In the 1980s those who suffered from unexplained chronic fatigue and from what appeared to be a prolonged bout of mononucleosis were likely to be given the diagnosis of Epstein-Barr virus. Both chronic mononucleosis and Epscein-Barr virus seem to be similar to neurasthenia, one of whose symptoms is fatigue (Greenberg, 1990). Because Chronic Fatigue Syndrome is an heterogeneous disorder, some of the patients are likely to experience multiple psychosomatic and somatic disorders. Chronic Fatigue Syndrome falls at the boundary lines among many medical specialties and psychiatry (Shorter, 1992). The demonstration of persistent infection and immunological abnormalities in Chronic Fatigue Syndrome has supported research on biological factors but the frequency of neuropsychiatric, especially depressive, symptoms in these patients also suggested that Chronic Fatigue Syndrome may occur in some with premorb~d vulnerabdity to depression. Because those who experience anxiety and depression often also have chronic fatigue symptoms and because many of those who receive a diagnosis of Chronic Fatigue Syndrome have symptoms of an affective disorder, assessment of patients with Chronic Fatigue Syndrome needs to be comprehensive. Intervention rarely can be directed toward only one aspect of the problem.
TREATMENT STRATEGIES Because the etiology of Chronic Fatigue Syndrome is unknown, treatment strategies vary (Gantz & Holmes, 1989). The presenting symptoms and those complicating the patients' functioning usually are treated first (Behan, Behan, & Horrobin, 1990; Payne & Sloan, 1989). Acyclovir, which is an antiviral drug that inhibits replication of Epstein-Barr virus, was administered in a double-blind, placebo-controlled investigation. Improvement in the 27 patlencs with Chronic Fatigue Syndrome was about the same with either placebo or acyclovir (Straus, Dale, Tobi, Lawley, Preble, Blaese, Hallahan, & Henle, 1988). The drug and placebo were administered intramuscularly for a week and then orally for a month. Patients were observed before, during, and after the treatment. Changes in mood of patients often were correlated with clinical improvement. In a randomized, double-blind, placebo-controlled investigation for 24 weeks at several centers, 92 patients, who were severely dl with symptoms that met criteria for Chronic Fatigue Syndrome, received intravenously 400 mg of ampligen or placebo (Cotton, 1991). Treated subjects showed improvement in ability to perform daily activities and cognitive tasks and needed fewer pain and anti-inflammatory medications than the controls. An independent analysis indicated the presence of some immunologic disturbance in the patients with Chronic Fatlgue Syndrome. The immunologic changes were
PSYCHOLOGICAL ASPECTS: CHRONIC FATIGUE
consistent with viral infections and one or more viruses may be active together but research has not discovered which virus, if any, is the cause of Chronic Fatigue Syndrome. Tricyclic antidepressants have relieved symptoms of Chronic Fatigue Syndrome especially for those with fibromyalgia (Cherfas, 1990; Gantz & Holmes, 1989). The antidepressant drug phenelzine has improved symptoms of Chronic Fatigue Syndrome but controlled studies have not been reported. The antidepressant Bupropion gave rapid relief of all symptoms to two Chronic Fatigue Syndrome patients (Goodnick, 1990). Nonsteroidal and anti-inflammatory agents have reduced symptoms of patients with Chronic Fatigue Syndrome who show myalgia and symptoms of arthralgia. Cox, Campbell, and Dowson (1991) tested the hypothesis that low red blood cell magnesium might be the causative agent in Chronic Fatigue Syndrome. Their study of 15 patients together with 17 control subjects, matched for age, sex, and socioeconomic class, was randomized, double-blind, and placebo-controlled. During a trial of five weeks magnesium sulfate was injected in the experimental subjects. Twelve of the 15 patients said that the treatment benefitted them as opposed to only three of the 17 control subjects. Energy level, emotional state, and pain symptoms improved with the increase in magnesium. Intravenous injections of immunoglobulin have produced favorable results in one study of patients with Chronic Fatigue Syndrome but not in another (Editorial, 1990). The studies did not include long-term follow-up of their treatment effects. Liver extracts and cyanocobalamin have some immunomodulating effects (Kaslow, Rucker, & Onishi, 1989). Patients with Chronic Fatigue Syndrome were treated with an intramuscular injection of a solution of bovine liver extract containing folic acid and cyanocobalamin in a double-blind, placebo-controlled study of 15 patients whose symptoms of Chronic Fatigue Syndrome met the Centers for Disease Control criteria. Differences between effects of the experimental injection and placebo were not significant, some patients improved on both. Immune g l o b d n therapy has helped some patients diagnosed with Chronic Fatigue Syndrome particularly those with Coxsackie virus infection but no controlled studies have been reported (Gantz & Holmes, 1989). No treatment approach has benefitted all patients with Chronic Fatigue Syndrome. Several different treatment approaches have produced improvement in some symptoms and some patients. The absence of known etiology remains an obstacle to discovery of efficacious treatment procedures.
DISCUSSION There is little consensus about whether Chronic Fatigue Syndrome is psychobiological or physical or whether it even exists. However, results of recent studies as well as of earlier related disorders point to possible involve-
J. B. MURRAY
ment of psychological factors in this troubling condition. Because the incidence is small, a large pool of patients must be drawn to obtain samples of patients with Chronic Fatigue Syndrome and controls large enough that they will provide reliable results. Studies of patients and controls have not accumulated enough to provide a base for consistent findings. I n addition, few studies have employed double-blind placebo controls. Nevertheless, accumulated evidence has indicated that psychological or psychosomatic elements contribute in varying extents to the syndrome. The definition and criteria developed by the Centers for Disease Control included psychological complaints such as irritability, confusion, and inability to concentrate which would usually be transitory. However, investigations that employ these criteria must exclude patients whose symptoms have psychological aspects that may contribute importantly, thereby preventing a complete picture of psychological involvement in the syndrome. Studies of these patients have identified many psychiatric disorders that in some instances may be the major cause of the Chronic Fatigue Syndrome. Analysis of epidemics in the past and impressions of general practitioners, the amount of depression in postviral infection fatigue and infectious mononucleosis, all suggest that diagnosis and treatment of Chronic Fatigue Syndrome include psychological evaluation. More women than men experience Chronic Fatigue Syndrome yet sexes of both patients and controls have been combined in most reports. Chronic Fatigue Syndrome most often has been studied among affected young adults so that age differences have not been explored. Socioeconomic differences in patient or control samples also have not been included in reports. Does Chronic Fatigue Syndrome differ geographically? Populations from the Northeast and the West Coast of the United States have supplied most of the samples. The syndrome has been investigated in England, Canada, Australia, and Germany but international differences have not been examined. Laboratory findings on Chronic Fatigue Syndrome are almost always normal and virologic studies have produced negative results although the syndrome suggests viral causation. I t seems very likely that, along with infectious and immunological factors, psychological components will be found interacting in the syndrome thereby inviting more psychological research. Chronic Fatigue Syndrome is an dusive and complex disease syndrome that probably will prove to have multiple somatic and psychosomatic causes. REFERENCES
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J. B. MURRAY
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PSYCHOLOGICAL ASPECTS: CHRONIC FATIGUE
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J . B . MURRAY
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Accepted May 5, 1992.