Feelings of fatigue and psychopathology: A conceptual history

Feelings of fatigue and psychopathology: A conceptual history

Feelings of Fatigue and Psychopathology: A Conceptual History GE. Berrios T HE medical concept of fatigue has been defined as: a condition resultin...

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Feelings of Fatigue and Psychopathology: A Conceptual History GE. Berrios

T

HE medical concept of fatigue has been defined as:

a condition resulting from previous stress which leads to reversible impairment of performance and function, affects the organic interplay of the functions and finally may lead to disturbance of the functional structure of the personality; it is generally accompanied by a reduction in readiness to work and a heightened sensation of strain (p. 369)’

The performance aspects of fatigue are defined physiologically as “a failure to maintain a required force or output of power during sustained or repeated muscle contraction. . . .” (p 1014)2; and behaviorally as time-related deteriorations in the ability to perform certain mental tasks3 Gubser’s “heightened sensation” of strain includes what historically has been called “feeling of fatigue.” Piiron was referring to the same experience when he wrote: together with progressive fatigue, as reflected by a diminution of performance during work on an ergograph, afeeling ensues, which is unpleasant, gets worse with time, and leads to abandoning the task. This general feeling is based on vague coenesthetic sensations, and on localized muscular sensations that can sometimes be painful in nature. . . (p. 167).4 (Italics added.)

The feeling of fatigue has received much less attention in the medical literature than the general phenomenon of fatigue. Feeling of fatigue features prominently in some current diagnostic systems; e.g., it does so in relation to about 20 different clinical categories in DSM-111-R’ in which, however, no operational definition of feeling of fatigue is included. Books on descriptive psychopathology fare no better. 6-11This article specifically deals with the concept and history of feeling of fatigue. EPIDEMIOLOGY

Unexplained feeling of fatigue is a common complaint in clinical practice.12 Thus, Sugarman and Berg13 reported fatigue as having a prevalence of 9.1 per 1,000, with a sex and age distribution equal to that of the parent population; 50% of subjects thus affected received a psychosocial diagnosis, 22% a medical diagnosis, and 24% had no diagnosis. Kroenke et al.14 reported feeling of fatigue to be a major problem in 24% of a sample of 1,159 subjects: Females were overrepresented, laboratory investigations were of little value in determining underlying diagnosis, depression and anxiety were common accompaniments, and feeling of fatigue subjects showed Dr. Berrios is a Consulrant and University Lecturer in Psychiatry; Director of Medical Studies and Fellow, Robinson College, Cambridge, England; and Librarian, Royal College of Psychiatrists of the UK. Address reprint requests to G.E. Berrios. M.D., Department of Psychiatry, University of Cambridge, Addenbrooke’s Hospital (Level 4), Hills Rd., Cambridge CB2 ZQQ, England. 0 1990 by W.B. Saunders Company. 0010-440X/90/3102-0004$03.00/0 140

Comprehensive

Psychiatry,

Vol. 3 1, No. 2 (March/April),

1990: pp 140-15 1

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little improvement. Valdini et a1.15 compared 115 fatigued subjects with 139 controls in a l-year follow-up: Cross-over was considerable: 42% of their subjects improved, and 20% of the controls became fatigued. Subjects complaining of feeling of fatigue attended the surgery more often and received “psychological” diagnoses more frequently. Cheni6 reported that feelings of depression and anxiety were correlated with feeling of fatigue, particularly in physically inactive subjects under stress; females were more prone to feeling of fatigue; weight showed little correlation with the symptom. Hoehn-Saric and McLeod” reported that subjects with an “external locus” of control complain of feeling of fatigue more often than those with an internal locus of control. CLINICAL

ASSOCIATIONS

Feeling of fatigue can be found associated with chemotherapy for breast carcinoma,‘* hypercortisolaemia,” hypophosphataemia,20 postviral syndromes,21*22 plasma levels of diazepam, 23 alterations in energy metabolites in muscle,24 high carbohydrate intake in obese subjects with noncarbohydrate craving,25 multiple sclerosis, 26 diabetes mellitus,27 brainstem lesions in children,28 and other disease states.2g Feeling of fatigue can also be prodromal to many conditions. Appels and Mulder3’ reported it to herald myocardial infarction, and Harrigan et a131 reported it to predict onset of migraine headaches. Christensen et a1.32reported feeling of fatigue to correlate with both preoperative trait- and state-anxiety; it increased in some subjects up to day 30 after operation, when it no longer correlated with traitanxiety; they concluded that postoperative feelings of fatigue depend less on psychological makeup than on cardiovascular and neuromuscular status. None of the above studies made use of a refined measurement of feeling of fatigue. TERMINOLOGY

AND CONCEPTUAL

ASPECTS

The feeling of fatigue is common and is associated with numerous physical and psychiatric conditions. In addition, it forms part of the experiential meaning of many technical and vulgar terms: asthenia, anergy, tiredness, weariness, languor, lassitude, depression, melancholia, acedia, apathy, inertia, abulia, lethargy, exhaustion, vecordia, tediousness, ennui, debility, lack of vitality, lack of vigor, pusillanimity, adynamia, boredom, feebleness, failing of strength, hyperesthesis, irritability, anhedonia, “being out of sorts,” “ feeling knackered,” and “down in the dumps.” To clarify the semantic field of the feeling of fatigue, five questions can be asked. The first is whether the terms listed above include a common denominator in the form, e.g., of a primary sensation or of its attending somatic experiences. They appear to have such an experiential link. Indeed, this common sensation may confer on the set of terms a “family resemblance.“33 The second question is whether the sensation that constitutes the feeling of fatigue is distinctive enough to be qualitatively separated from mild pain or discomfort. In this respect, we show that fatigue historically, has been considered both as a primary and a composite experience. The third question is whether, regardless of whether fatigue is a primary sensation, it can be recognized independently from its usual causal associations, e.g., when experienced in situations not preceded by any exertion. Clinical observation

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appears to show that it can; i.e., subjects respond with alarm to the presence of feeling of fatigue when it has not been preceded by physical or intellectual work or by disease (i.e., when is “unexplained”). The fourth question is whether this unexplained feeling of fatigue is phenomenologically identical to the feeling experienced after exercise. The answer to this question must be sought in empirical research. The fifth question is whether-if the feeling of fatigue is considered a primary experience-it is related to a common neurobiological structure or mechanism, e.g., to putative “fatigue receptors” whose activation by exogenous or endogenous agonists would trigger the experience of feeling of fatigue.2g*34 HISTORICAL

ASPECTS

OF FATIGUE

AND THE FEELING OF FATIGUE

The objective phenomenon of fatigue, as opposed to the feeling of fatigue, was well studied during the nineteenth century. This knowledge was summarized by MOSSO,~~ a professor at Turin, who had trained under Hugo Kronecker in Leipzig in 1873. Kronecker36 had then been working on the muscle of the frog, and like other physiologists of the period (Ludwig, Schmidt, Aducco, and Maggiora), was interested in the “laws of fatigue.” Because most of these studies involved animal models, such laws were perforce based on interpretation of curves of muscle performance obtained by means of dynamometers and myographs. These researchers rarely if ever considered the feeling of fatigue as a measurable dependent variable. Mosso’s originality lay in his efforts to develop a unitary view of fatigue, including both physical and intellectual (mental) aspects. He also pondered the feeling of fatigue: Humboldt, when showing how the living environment can enrich language, tells us that the Arabs have more than 20 words to refer to the desert. But we have only one term to refer to fatigue. The reason for this is easy to understand. . . fatigue is toofeatureless nn internal sensation to distinguish any varieties (p. 1 19).35(Italics added.)

He further emphasized this lack of definition: What fatigue, pleasure, hunger, or thirst means can be understood and their intensity qualified by the use of adjectives, but they cunnor compete in precision with the image that the desert can impress on us (p. 119).

Mosso related this to the vagueness of propioception: Fatigue, which can be considered as a sort of poisoning, can alter the composition of the blood and biological homoeostasis; however, we just feel it as a vague sensation of tiredness. . . .35

Since the work of Mosso, and particularly that of the French SchooL3’ it has been a common belief that intellectual fatigue reflects a decline in the energy metabolism of neurons and that behavioral and cognitive variables must be examined to detect its presence.38 Yet Mosso’s views on the vagueness and inaccessibility of feelings of fatigue itself were also influential; e.g., MacDougall” suggested that “a sharp distinction must be drawn between objective and subjective exhaustion, between fatigue (Ermtidung) and weariness (Mtidigkeit).” He defined weariness as: a superficial fact of attention, which may appear, disappear and reappear many times in a day . . [it] can be induced in a fresh subject by dull work, monotony, stale familiarity. . . [it] can abate as

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. . . weariness is a fluctuating personal attitude which is scarcely susceptible oj

record in any form (Italics added).

Mosso also influenced the work of Ioteyko whose research on fatigue had started with her doctoral thesis of 1896 on “fatigue and muscle respiration.” By the time her excellent book on fatigue4’ appeared, she had already moved from Brussels to Paris and had completed about 10 important research publications. Ioteyko considered the feeling of fatigue as a separate although vague experience and justified its inclusion in evolutionary terms: “In higher species, particularly in man, a third condition is essential to define fatigue: this is a sensation of ‘malaise’ known as feeling of fatigue.” Other investigators took a more “composite view” of the nature of fatigue: [FJeeling of fatigue is not a simple act, but a psychological state made out of a number of simpler elements which include changes in affect or sentiment corresponding to obscure and sometimes subconscious tactile and muscular sensations. Feeling of fatigue is but a form of coenesthesis4

Views such as these precluded development of an adequate phenomenology of the feeling of fatigue and placed it beyond measurement. MacDougall himself suggested: [In] the study of fatigue we have to seek for the phenomena of actual reduction in capacity for productive work; and from its effects we must discriminate the factors of interest and weariness (p 203.39

because weariness did not have a linear, or even monotonic correlation with fatigue, a study of the latter could shed little light on the feeling of fatigue.3g A second line of research into fatigue during the nineteenth century related to the concept of intellectual fatigue among school children and to its relevance to teaching methods. Kraepelin4* Ebbinghaus,“3 and Griesbach did much of the earlier work in this area. By the end of the century, however, MacDougal13’ was able to celebrate the fact that schoolmasters, such as Kensies44 and Wagner,45 had showed interest. Most of this research was based on the “work curve” paradigm developed by Kraepelin46 and later completed by Pauli and Arnold. This methodology of analysis did not include the feeling of fatigue. The history of fatigue in education is beyond the scope of this article. Early work on the objective aspects of fatigue was marred by a conceptual confusion that impeded comparison of research results: Fatigue was defined by some researchers as a process, i.e., as the interaction between stress (and other covariates) and the dependent variables, and by others as the e@ct itself.’ The analysis of feeling of fatigue, on the other hand, was caught up in the parallel etiological debate of whether it was a truly central and primary experience (preceding all physiological concomitants) or whether it was the introspective reading of peripheral somatic changes (as suggested by Williams and Lange) (pp. 93-94).40*47Other investigators compromised and suggested that the feeling of fatigue only magnified peripheral sensations.48 After World War II, Bartley and Chute49 suggested that the “experience of fatigue” might be evaluated by “psychological methods.” Even then, they did not include among these methods the measurement of feeling of fatigue. Bugard,34 in a book that represents the culmination of the old approach, dedicated little space to But

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feeling of fatigue, although he echoed Coirault’s view that “fatigue is a state of nervous suffering, which, together with insomnia, constitutes the common denominator of the prodromal phase of many mental diseases.” Bugard34 preferred to concentrate on visual and sensory changes as the best indicators of central nervous system fatigue. Such concepts prevailed, although since early in the twentieth century a definition of fatigue as “lassitude or weariness resulting from either bodily or mental exertion”50 had already been established, and although Jasper? had called for a distinction between objective and subjective fatigue (feeling of weariness or fatigue). Clinicians (particularly alienists), however, were forced to pay attention to the feeling of fatigue because since the late nineteenth century they increasingly evaluated a population of subjects whose only complaint was unexplained feeling of fatigue and needed to develop techniques that might differentiate simulators from real patients.51 FEELINGS OF FATIGUE IN THE HISTORY PSYCHOPATHOLOGICAL CONCEPTS

OF

A source of writings on feeling of fatigue can be found in the work of late nineteenth century alienists, e.g., on the concept of “nervous prostration” or neurasthenia.52 This clinical category, supported by a newly developed theory of functional nervous disorder,53-56 became a fashionable diagnosis in the hands of writers such as Beard57*58and was to engulf, toward the end of the century, most functional disorders having feeling of fatigue as a common denominator.59-62 The concept of neurasthenia was the final stage in the evolution of an older notion, “asthenia,” that had played a crucial role in Brunonianism during the late 18th century. 63*64Brownj3 wrote: “Asthenic disease is a state of the living body characterized by a weakening, occasionally disordered, of all functions.” All asthenic diseases were not accompanied by fatigue, because some included states of defective excitation that distorted their symptomatology; others, like emaciation or extenuation, were. One of the important offshoots of Brunonian theory was that bleeding was discredited as a treatment of asthenic diseases (p. 104). By the end of the nineteenth century “asthenia” had lost its theoretical role and become a simple description for “a lack or impairment of strength. r’38Tuke65 did not even include the term in his dictionary. A derivative category was adynamia66 defined as “a state of impotence, of lack of force of the organism.” By this period, the concept had become a hypothetical construct: [Sltrictly appearance, as a direct Adynamias

speaking, adynamia accompanies all diseases . . . adynamia is little else than an a phenomenon which can be attached to different diseases. . . pathologists conceive of it reduction in vital force or in the functional rhythms, as a form of asthenia. .“9’ could result from excessive or insufficient stimulation.

Another related category was irritability, still defined during the middle of the nineteenth century as it had been by Von Haller67 a century earlier: “a property peculiar to muscle substance by which it contracts on the application of stimuli.“68 Glisson had first used irritability during the 17th century to name a property of all the body fibers which was independent of consciousness and of the nervous system.69 This concept (together with sensibility) was to undergo major elaboration during

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the following century, and in its British version (particularly in the hands of Cullen and Whytt) it became related to the nervous system. In the end, both concepts were to become properties of the cell.“*” Irritation, a modality of irritability, played an important role in the development of the concept of neurasthenia, through the mediating notions of nervous and spinal irritation (pp. 64-76).53 Asthenia, now defined as “a state of spinal nervous exhaustion caused by excessive irritation following over-stimulation,53 was to reappear as one of the forms of presentation of the spinal irritation syndrome and be termed “spinal neurasthenia.” Beard54 extended the concept and explanatory mechanism from the spinal cord to the brain. Charcot legitimatized neurasthenia as a “major neurosis” in 1887, 72 but developed a narrow view of the disorder. This allowed him to suggest that neurasthenia and hysteria might be found in combination.73 Fatigue and feeling of fatigue were central symptoms of neurasthenia. For example, Savil16’ included “mental exhaustion and inability to think and study . . . easily tired, easily startled, state of debility and exhaustion,” and Cobb62 supported this view in one of the last great books to be published on the subject. Fatigue and feeling of fatigue were, however, also present in other “psychonevroses.” Dubois61 one the most important writers on these groups of disorders, showed much interest in “fatigabilitt” (feeling of fatigue), a term which he complained was not in the French dictionary and which named a “gradual diminution of functional power, a difficulty to persist on the task at hand . . . etc.” He quoted extensively from TissiC who had performed research in cyclists and agreed that fatigue could lead to “transient, experimental psychosis” (p. 139). More important, he also quoted the work of F&C:on the mental symptoms of fatigue. According to FCr&,37,74 fatigue after severe exercise could produce symptoms similar to those exhibited by neurasthenia sufferers. These included nihilistic and paranoid ideas, selfish attitudes, rekindling of obsessional thoughts and compulsions, and depression. . . . F&-t” linked proneness to fatigue with the theory of degeneration.75-78 He also saw an association between a tendency to nervousness and high arousal (p 185). Hecke17’ wrote at length on the complex interaction between the feeling of fatigue and psychiatric symptoms (pp. 215-218), as did Spanish writers: [T]he subject presents depression and apathy, there is a weakness of the will, and sometimes abulia, there are illusions and increased susceptibility to suggestion.4’

Fatigue and feeling of fatigue also featured prominently in the notion of “psychasthenia,” a fragment of the old neurasthenia concept.8h82 The creation of psychasthenia, in Cobb’s view,62 was a theoretical reaction against the “organic” view of neurasthenia: [I]t is small wonder that a reaction to this view should set in, and a school arise which loudly declaimed the opposite-namely, that neurasthenia was caused by abnormal mental processes, which produced the disorder by means of mental mechanisms the work of Janet marked the first step towards the recognition of the psychical etiology of this disease. Janetg3 wrote: [Tliredness and a horrible sense of fatigue is caused in psychastenics by the least physical or psychological effort . fatigue rapidly affects sensations and perceptions, intellect and movement.

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One of his patients once complained of “a blanket of fatigue falling over me.” Janet created his category based on the theoretical view that psychasthenics showed a reduction in psychological energy which, inter alia, led to a “loss of the sense of the real” a “feeling of incompletion,” obsessions, compulsions, and phobias.*’ Ribot84 was interested in the experiential quality of the feeling of fatigue which he classified as an internal sensation of the same type as hunger and disgust. Answers given by respondents to his field research included various “modes” of representation: [S]ome feel it (ideally) in the muscles; others mentally. . . muscular twitchings in the calves of the legs . . , the eyes feel swollen . . . a feeling of relaxation . . . slowness of movement . . . general lassitude of a diffuse kind . . . mental weariness. _ heavy feeling in the brain.

Ribot added: “[Allthough all my correspondents can revive the feeling of fatigue, three or four can only succeed in doing so with difficulty.” Dechamps” reported that fatigue and feeling of fatigue did not often “correlate.” Thus, in some diseases, such as tabes or chorea, feeling of fatigue “was not experienced even after severe work” whereas in others, such as neurasthenia, feeling of fatigue “was intense without having done any work.” For Dechamps, fatigue “resulted from chemical and anatomical change,” whereas the feeling of fatigue resulted from the “synthesis of tactile sensations, both peripheral and internal (coanesthesis).” The notions of neurasthenia and psychasthenia were themselves disaggregated, disappearing after the Great War. Their remains were included into the new forms of neuroses generated by the psychodynamic and behavioral views. For example, the feeling of fatigue found a new home with the anxiety and affective disorders,86 wherein it became entangled with anhedonia, a term coined by Ribot84 to name situations when: like pain, pleasure is separable from the complex of which it forms part, and under certain conditions may totally disappear. Anhedonia (if I may coin a counterdesignation to analgesia) has been little studied but it exists.

Anhedonia was incorporated by Kraepelin and Bleuler into the symptomatology of depression and schizophrenia, respectively.86a Fatigue continued to being investigated in occupational psychology and medicine; feeling of fatigue was investigated much less. This is surprising because in work-orientated societies unexplained feelings of fatigue are likely to be reported as interloping and undesirable mental states in urgent need of diagnosis and treatment. Indeed, moralistic treatment of fatigue began in the 192O~.~l In addition to being found in isolation, feeling of fatigue remains in clinical circulation as a hidden experiential component in other “symptoms” such as anhedonia, lethargy, lack of drive, abulia, and amotivation, considered by some as “negative” features of schizophrenia,87*88or as side effect of neuroleptics.89 Of late, the feeling of fatigue has become the central symptom of the postviral syndromes.2’*22.90 PHENOMENOLOGY

OF THE FEELING OF FATIGUE

Several factors explain the dearth of studies into the phenomenology of feeling of fatigue: first, the fact that a sort of emotional experience appears to be an important

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aspect of feeling of fatigue, and that the semiology of affectivity is notoriously crude.” Second, feeling of fatigue constitutes by all accounts a poorly defined experience, whose recognition, like others in the area of experiential mental states, vary according to cultural background.92 Third, feeling of fatigue is ambiguously poised with regard to its referent: When used in the first person (i.e., “I feel fatigued.“), it names an experiential state; when used in the third person (i.e., “He is fatigued.“), it ordinarily includes reference to objective signs of fatigue. Fourth, whether feeling of fatigue refers to a primary32 or to a composite feeling-state is unclear. Fifth, it is unclear whether the peripheral or somatic manifestations of fatigue (e.g., breathlessness, nausea, muscular tiredness, aching) are essential parts of the concept as, e.g., the somatic aspects of anxiety appear to be part of the definition of anxiety. As a consequence, whether it is possible to deal with the subjective and objective components of feeling of fatigue independently is unknown. If feeling of fatigue names (like pain) a primary feeling-state,93 irrespective of whether it is preceded by exertion, we can hypothesize that it should be the same for all clinical situations: i.e., the fatigue of Addison’s disease should be the same as that of multiple sclerosis,26 depressive illness, neoplasm, anxiety disorders, myalgic encephalomyelitis,22*94*95or glandular fever. 21 This question must be answered by empirical research, for which however, an evaluative instrument is required. Development of such scale is not an easy matter, and pessimism in this regard was expressed early.96 The semantic construct underlying feeling of fatigue (from which scale items will have to be obtained)97,98 includes sensory, emotional, cognitive, and even evaluative components. In practice, this means that feeling of fatigue, like fatigue itself, is a multidimensional state.99 These dimensions require sorting out and then translation into scale items susceptible to quantification. Furthermore, to avoid contamination from organic symptomatology or distorted propioceptive information, it is important that a scale for feeling of fatigue be based mostly on the psychological attributes of the experience, particularly when there is evidence that objective measures of fatigue correlate poorly with feeling of fatigue.“’ Current scales of fatigue are unidimensional and do not explore the composite nature of the concept.“’ The first stage in identification of the semantic construct of feeling of fatigue is to tease out its meaning systems. Four are apparent: 1. Feeling of fatigue after work. In feeling of fatigue after work, the experience is explained by its antecedent and is often associated with the cognition of not wishing to continue performing. This constitutes the typical, anchor meaning. 2. Premature feelings of fatigue. Premature feelings of fatigue obtain when the experience is reached too quickly or when recovery takes too long. 3. Unexplained feelings of fatigue. Unexplained feelings of fatigue cause alarm because they have no relevant antecedent. The experience may also be accompanied by a feeling of not wishing to begin any task. This meaning is common in relation to physical and psychiatric disease. 4. Feeling like not embarking on any activity. Feeling as though one does not wish to begin any activity may occur in the absence of a feeling of fatigue and probably is an independent phenomenon. Historically and clinically, however, the two sensations have been lumped together. Examples are anhedonia, abulia, inertia, lack of drive, amotivation, mild irritability, lack of concentration, boredom, and the “can’t be bothered” feeling.

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These four meaning-systems should generate different questions and must be clearly separated. They also may lead to different predictions with regard to correlations between the experience of feeling of fatigue and objective measures of fatigue. A preliminary version of such a scale has now been developed and is undergoing field trials (a specimen is available on request). SUMMARY

Since the 19th century, fatigue has received far more attention in the medical literature than feeling of fatigue. The latter is defined as a primary, sui generis feeling, which can be studied (and is experienced) independently of physical phenomena such as tiredness, and cognitive concomitants such as “not wanting to continue or initiate a task.” The unexplained feeling of fatigue is a common medical complaint, and accompanies various medical and psychiatric conditions. Several meaning systems can be identified in relation to feeling of fatigue and provide material for construction of a measuring instrument. Such a scale will allow us to answer four questions: Is the feeling of fatigue a unitary and primary experience or sensation? Is it the same regardless of the clinical or social context in which it occurs? Are the somatic and cognitive accompaniments of feeling of fatigue an essential part of its definition? Does feeling of fatigue have a neurobiological basis? REFERENCES 1. Gubser A: Fatigue, in Eysenck HJ, Arnold W, and Meili R (eds): Encyclopaedia of Psychology, vol 1. London, Search, 1972, p 369 2. Stokes MJ, Cooper RG, and Edwards RHT: Normal muscle strength and fatigability in patients with effort syndromes. Br Med J 297:1014-1016, 1988 3. Broadbent D: Decision and Stress. Academic Press, London, 1971 4. Pitron H: Sentiment de fatigue, in Pitron H (ed): Vocabulaire de la Psychologie. Paris, Presses Universitaires de France, 1968, p 167 5. American Psychiatric Association: Diagnostic and Statistical Manual of Mental disorder, 3rd ed., revised, Washington, DC, American Psychiatric Association Press, 1987 6. Bash KW: Introduction to General Clinical Psychopathology. Berne, Hans Huber, 1961 7. Scharfetter C: General Psychopathology (translated by Marshall H). Cambridge, Cambridge University Press, 1980 8. Hamilton M: Fish’s Clinical Psychopathology. Bristol, Wright, 1975 9. Simms A: Symptoms of the Mind. London, Bailliire Tindall, 1988 10. Bernard P, Trouve S: Stmiologie Psychiatrique. Paris, Masson, 1977 11. Reed G: The Psychology of Anomalous Experience. Buffalo, Prometheus, 1988 12. Bass C: Fatigue states. Br J Hosp Med 41:315, 1989 13. Sugarman JR, Berg AO: Evaluation of fatigue in a family practice. J Fam Pratt 19:643-647,1984 14. Kroenke K, Wood DR, Mangelsdorff AD, et al: Chronic fatigue in primary care. Prevalence, patient characteristics, and outcome. JAMA 260:929-934,1988 15. Valdini AF, Steinhardt S, Valicenti J, et al: A one-year follow up of fatigued patients. J Fam Prac 26:33-38, 1988 16. Chen MK: The epidemiology of self-perceived fatigue among adults. Prev Med 15:74-81, 1986 17. Hoehn-Saric R, McLeod DR: Locus of control in chronic anxiety disorders. Acta Psychiatr Stand 72:529-535,1985 18. Knobf MT: Physical and psychological distress associated with adjuvant chemotherapy in women with breast cancer. J Clin Oncol4:678-684, 1986 19. Krishnan R, Ellinwood EH, Laszlo J, et al: Effect of gamma interferon on the hypothalamicpituitary-adrenal system. Biol Psychiatry 22:1163-l 166, 1987 20. Waldholtz BD, Andersen AE: Hypophosphatemia during starvation in anorexia nervosa. Int J Eating Dis 7:551-555, 1988

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21. Tobi M, Straus SE: Chronic mononucleosis-A legitimate diagnosis. Postgrad Med 83:69-78, 1988 22. David AS, Wessely S, Pelosi AJ: Post-viral fatigue syndrome: Time for a new approach. Br Med J 296:696-699,1988 23. Shader RL, Pary RJ, Harmatz JS, et al: Plasma concentrations and clinical effects after simple oral doses of prazepam, clorazepate, and diazepam. J Clin Psychiatry 45:411-413,1984 24. Edwards RHT: Hypotheses of peripheral and central mechanisms underlying occupational muscle pain and injury. Em J Appl Physiol.57:275-281, 1988 25. Lieberman HR, Wurtman JJ, Chew B: Changes in mood after carbohydrate consumption amongst obese individuals. Am J Clin Nutr 44:772-778, 1986 26. Krupp LB, Alvarez LA, LaRocca NC, et al: Fatigue in multiple sclerosis. Arch Neurol 451435-437, 1988 27. Surridge DHC, Williams EDL, Lawson JS, et al: Psychiatric aspects of diabetes mellitus. Br J Psychiatry 145:269-276,1984 28. Osson D, Nzeyimana C, Smelten V, et al: Les sequelles psychiques des traumatismes du tronc cerebral de l’enfant a propos de 18 observations. Neuropsychiatr Enfance Adolesc 34:323-328, 1986 29. Kennedy HG: Fatigue and fatigability. Br J Psychiatry 153:1-5,1988 30. Appels A, Mulder P: Imminent myocardial infarction: A psychological study. J Hum Stress 10:129-134, 1984 31. Harrigan JA, Kues JR, Ricks DF, et al: Moods that predict coming migraine headaches. Pain 20:385-396,1984 32. Christensen T, Hjortso NC, Mortensen E, et al: Fatigue and anxiety in surgical patients. Acta Psychiatry Stand 73:76-79, 1986 33. Wittgenstein L: Philosophical Investigations (translated by Anscombe GEM). Oxford, Basil Blackwell, 1967 34. Bugard P: La fatigue. Physiology- psychologie- et Mtdecine sociale. Paris, Masson, 1960 35. Mosso A: La Fatigue: Intellectuel et Physique, Paris, Alcan, 1903 36. Kronecker H: Uber die Ermtldung und Erholung der quergestreiften Muskeln. Beritche Verhandlungen d.k. saechsisch Gesell Wiss Leipzig 5:710-736, 1871 37. F&C Ch: Sensation y Movimiento (translation of the 1887 French edition by Rubio R). Madrid, Fernando Fe, 1903 38. Baldwin JM: Dictionary of Philosophy and Psychology, vol 1, London, MacMillan, 1901 39. MacDougall R: Fatigue. Psycho1 Rev 6:203-208,1899 40. Ioteyko J: La fatigue. Paris, Flammarion, 1920 41. Anonymous: Fatiga, in Enciclopedia Universal Ilustrada Europeo-Americana, vol 23. Bilbao, Espasa-Calpe, 1924, p 376 42. Kraepelin E: Zur Ueberbtlrdungsfrage. Jena, Fischer, 1898 43. Caparr6s A: H Ebbinhaus. Un Funcionalista Investigador Tipo Dominio. Barcelona, Editions Universitat Barcelona, p 207, 1986 44. Kensies F: Arbeitshygiene der Schule auf Grund von Ermtidungsmessen. Berlin, Reuther und Reichard, 1898 45. Wagner L: Unterricht und Ermildung. Berlin, Reuther und Reichard, 1898 46. Kraepelin E: Die Arbeitskurve. Wundts Philosophischen Studien 19:459-507, 1902 47. Poore G: On fatigue. Lancet 2:163-164, 1895 48. Waterman G: The treatment of fatigue states. J Abnorn Psycho1 4:128-139,1909 49. Bartley SH, Chute E: Fatigue and Impairment in Man. New York, McGraw Hill, 1947 50. Anonymous: Oxford English Dictionary. Oxford, England, Oxford University, 1971 51. Jaspers K: General Psychopathology (translated by Hoenig J, Hamilton MW). Manchester, Manchester University Press, 1963 52. van Deusen EH: Observations on a form of nervous prostration neurasthenia. Am J Insanity 25~447, 1869 53. Ldpez Pifiero JM: Historical Origins of the Concept of Neurosis (translated by Berrios D), Cambridge, Cambridge University Press, 1983 54. Chatel JC, Peel R: The concept of neurasthenia. Int J Psychiatry 9:36-49, 1970 55. Carlson ET: The nerve weakness of the 19th century. Int J Psychiatry 9:50-54, 1970 56. Gosling FG: Before Freud: Neurasthenia and the American medical community 1870-1910. Urbana: University of Illinois Press, 1987

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