Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome

Abstract:

Abnormalities in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis are a well recognised feature of endogenous depression. The mechanism underlying this phenomenon remains obscure although there is strong evidence suggesting excessive CRH activity at the level of the hypothalamus.

We propose a novel hypothesis in which we suggest that the aetiological antecent to CRH hyperactivity is cytokine activation in the brain. It is now well established both that interleukins -1 and -6 are produced in a number of central loci and that cytokines are potent stimulators of the HPA axis.

Hence, we suggest that activation of IL-1 and IL-6 by specific mechanisms (such as neurotropic viral infection) in combination with the consequent CRH-41 stimulation, may (via their known biological effects) underly many of the features found in major depression and other related disorders, particularly where chronic fatigue is a prominent part of the symptom complex.

This theory has considerable heuristic value and suggests a number of experimental stratagems which may employed in order to confirm or reject it.

 

Source: Ur E, White PD, Grossman A. Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome. Eur Arch Psychiatry Clin Neurosci. 1992;241(5):317-22. http://www.ncbi.nlm.nih.gov/pubmed/1606197

 

Chronic fatigue syndromes in clinical practice

Abstract:

Chronic fatigue is a common and difficult challenge in clinical practice. The majority of patients with this chief complaint have treatable mood or anxiety disorders, complicated by a tendency toward somatization. A minority of patients suffer from sleep disorders, endocrinologic abnormalities, or chronic inflammatory conditions. Prolonged recovery after viral infections is only rarely the cause of chronic fatigue. Specific pharmacologic interventions and cognitive-behavioral therapy are effective in an environment that is sensitive to the patient’s interpretation of symptoms and avoids unproven medical investigations and therapies.

 

Source: Manu P, Lane TJ, Matthews DA. Chronic fatigue syndromes in clinical practice. Psychother Psychosom. 1992;58(2):60-8. http://www.ncbi.nlm.nih.gov/pubmed/1484921

 

The pathophysiology of chronic fatigue syndrome: confirmations, contradictions, and conjectures

Abstract:

OBJECTIVE: To examine published data regarding patient cohorts with the recently defined chronic fatigue syndrome.

METHOD: Review of thirty-two peer-assessed research publications that included full disclosure of the methodology employed; classification of the findings as confirmed, contradictory, or non-duplicated.

RESULTS: Research studies have confirmed that the majority of patients with the chronic fatigue syndrome: 1) are white middle-aged women, 2) have a high prevalence of current major depression and somatization disorder, 3) have abnormal personality traits, 4) believe that their fatigue has a physical cause, and 5) show mild abnormalities of humoral immunity. Contradictory data have been presented with regard to: 1) the time of onset of depressive disorders, 2) the etiologic role of herpetic and enteroviral infections, 3) the presence of abnormal cellular immunity, and 4) the clinical utility of immunoglobulin therapy. Non-duplicated research has indicated 1) hypothalamic-pituitary-adrenal axis dysfunction, 2) abnormalities on magnetic resonance images of the brain, 3) altered cytokine production, and 4) the possibility of retroviral infection.

CONCLUSIONS: As presently defined, the chronic fatigue syndrome has many of the clinical and biological features associated with depressive and somatoform disorders. A specific etiologic role for infections or immune dysfunction has not been confirmed.

 

Source: Manu P, Lane TJ, Matthews DA. The pathophysiology of chronic fatigue syndrome: confirmations, contradictions, and conjectures. Int J Psychiatry Med. 1992;22(4):397-408. http://www.ncbi.nlm.nih.gov/pubmed/1338059

 

Evaluation and management of patients with chronic fatigue

Abstract:

Chronic fatigue is a common and disabling problem in primary care practice. The differential diagnosis of chronic fatigue is extensive and includes medical disorders, altered physiologic states (eg, pregnancy, exertion), psychiatric disorders, lifestyle derangements, drugs, and controversial entities (eg, chronic candidiasis, food allergies, environmental illness, and chronic fatigue syndrome). The most common diagnoses are psychiatric disorders, including mood, anxiety, and somatoform disorders.

A comprehensive approach to diagnosis and management is necessary, including structured psychiatric interviewing, functional assessment, and elicitation of the patient’s diagnostic beliefs. Patients often believe they are suffering from an organic medical disorder (eg, viral or immunologic) and resist psychiatric labelling of their symptoms and referral to mental health practitioners. Establishing and maintaining rapport, having a flexible approach, and demonstrating a personal concern for the patient is essential. Drug therapy for specific psychiatric and medical illnesses and cognitive-behavioral approaches for enhancing coping mechanisms are effective.

 

Source: Matthews DA, Manu P, Lane TJ. Evaluation and management of patients with chronic fatigue. Am J Med Sci. 1991 Nov;302(5):269-77. http://www.ncbi.nlm.nih.gov/pubmed/1750445

 

An overview of chronic fatigue syndrome

Abstract:

BACKGROUND: Psychological and immunologic factors both appear to contribute to chronic fatigue syndrome (CFS). By comparing CFS with other disorders in which fatigue is a prominent symptom, the association between fatigue, psychological vulnerability, depression, and immune function may be further defined. Recent data from psychological, neurologic, and immunologic studies that address these issues are reviewed.

METHOD: Articles and abstracts covering CFS and related topics of fatigue, depression, and postinfectious syndromes were identified through MEDLINE and Index Medicus (1980-1990) and by bibliographic review of pertinent review articles.

RESULTS: The 1988 definition of CFS by the Centers for Disease Control encompasses several conditions in which the major characteristic is severe fatigue associated with constitutional symptoms. Several studies have identified immune dysfunction in CFS patients, but the specificity of these findings remains unclear. Most studies have shown that CFS patients, compared with other patients with chronic medical illness, experience more disabling fatigue. Some investigators have found a higher incidence of concurrent and past psychiatric illness in CFS patients compared with other medical patients, thereby suggesting an underlying psychopathology in CFS. However, other studies have not found a higher than expected incidence of past depression in CFS patients and have further shown that many CFS patients have no identifiable psychopathology.

CONCLUSION: CFS appears to be a heterogenous entity. Although there may be a high coincidence of major depression in CFS, a substantial proportion of patients lack any identifiable DSM-III-R psychiatric disorder yet still manifest the syndrome, thereby suggesting it has an autonomous entity. Despite the evolving nature of our current understanding of CFS, a rational diagnostic and therapeutic approach to CFS is possible.

 

Comment in: Pathogenesis of chronic fatigue syndrome. [J Clin Psychiatry. 1992]

 

Source: Krupp LB, Mendelson WB, Friedman R. An overview of chronic fatigue syndrome. J Clin Psychiatry. 1991 Oct;52(10):403-10. http://www.ncbi.nlm.nih.gov/pubmed/1938975

 

Pain syndromes, disability, and chronic disease in childhood

Abstract:

Childhood disability and chronic disease are common, and their prevalence is increasing as children survive with conditions that were previously fatal. It is important that physicians in training learn about disability and handicap, and the functioning of multidisciplinary teams to manage these problems. Chronic ill-health is often very expensive to manage, and some serious and creative thinking about the best way to fund such health care is urgently needed.

Pediatric rheumatologists are involved with the care of many children with chronic and recurrent musculoskeletal pain; however, they have not perhaps focused enough research effort on the investigation of pain and its management. Whether reflex neurovascular dystrophy, fibromyalgia, and chronic fatigue syndrome are part of a disease continuum is unclear, but it seems probable that psychosocial problems are often important contributing factors in all three conditions.

Immunoglobulin subclass deficiencies are being increasingly delineated, occurring in chronic fatigue syndrome as well as many other disease states. Their clinical relevance still remains, for the most part, uncertain. Short stature occurs in many chronic illnesses, and the role of growth hormone treatment in these conditions is beginning to be investigated.

 

Source: Malleson PN. Pain syndromes, disability, and chronic disease in childhood. Curr Opin Rheumatol. 1991 Oct;3(5):860-6. http://www.ncbi.nlm.nih.gov/pubmed/1836344

 

Postviral fatigue syndrome and psychiatry

Abstract:

The postviral fatigue syndrome overlaps with psychiatry at a number of points. First, there is the influence that some psychological states have on physiological processes, such as immunity. Second, psychological symptoms, particularly depression but also anxiety, are a major feature of the syndrome. Third, difficulties in the doctor-patient relationship are common.

Each of these three areas are discussed in detail. Special attention is given to the possible mechanisms underlying the occurrence of psychological symptoms, which are sufficient to make a psychiatric diagnosis in at least two thirds of cases.

It is concluded that the bulk of the scientific evidence points to psychiatric disturbances being primary but that this does not account for the syndrome in its entirety and other mechanisms probably operate as well. Much of the conflict between doctor and patient arises from misconceptions about the nature and cause of psychological disturbances.

 

Source: David AS. Postviral fatigue syndrome and psychiatry. Br Med Bull. 1991 Oct;47(4):966-88. http://www.ncbi.nlm.nih.gov/pubmed/1794094

 

Post-viral fatigue syndrome. Epidemiology: lessons from the past

Abstract:

This chapter outlines the recorded epidemiological history of PVFS (including the early epidemics of myalgic encephalomyelitis) and the development of the concept, including the realisation that endemic cases also occur.

Cases of PVFS are still not recorded by the Surveillance Centre for Communicable Diseases, so it is very difficult to detect and monitor any outbreak in the community, since each GP may only have two or three such patients and would, therefore, not be aware of an epidemic in the community as a whole if it occurred.

Epidemiological issues raised by the early epidemics, including the delineation of the syndrome, the question of bias, the role of hysteria and the role of depression; the issue of symptom distribution, and its implications for aetiology; and a multiaxial framework for understanding the association with psychological symptoms are discussed. The value of a future multidisciplinary research programme designed to disentangle direct and predisposing causes of PVFS is emphasised.

 

Source: Jenkins R. Post-viral fatigue syndrome. Epidemiology: lessons from the past. Br Med Bull. 1991 Oct;47(4):952-65. http://www.ncbi.nlm.nih.gov/pubmed/1794093

 

Post-viral fatigue syndrome. Epidemiology: a critical review

Abstract:

Numerous reports in medical journals, lay magazines, and newspapers bear witness to the level of interest in the postviral fatigue syndrome and the heated controversy about the true nature of this condition. For many, it represents a ‘rag bag’ diagnosis into which unsolved diagnostic problems are discarded. Others are in no doubt that there is a discrete syndrome, probably with a specific causation.

The real answer almost certainly lies somewhere in between, but the truth can only be established through epidemiological studies designed to answer key questions. Does it exist at all, and, if so, how frequently does it occur? Who is most likely to get it and what is its cause? What is the nature of its implied association with viral infections and what is the role of other frequently postulated factors, such as psychiatric morbidity? What is its natural history and is there any evidence that any of the treatment/management regimes on offer can effectively lead to symptomatic relief or improve prognosis?

In this chapter, we consider the evidence on these key questions, identify some of the deficiencies in our current knowledge and highlight the kind of research which is still required.

 

Source: Wallace PG. Post-viral fatigue syndrome. Epidemiology: a critical review. Br Med Bull. 1991 Oct;47(4):942-51. http://www.ncbi.nlm.nih.gov/pubmed/1794092

 

Treatment of chronic fatigue syndrome

Abstract:

Chronic Fatigue Syndrome is a disorder which is characterised by profound fatigue together with a variety of other subjective clinical features which persist over a prolonged period of time. The aetiology remains at present uncertain and therefore rational therapeutic strategies are difficult to plan. This paper reviews currently used forms of treatment aimed at correcting the possible pathophysiological mechanisms and discusses the problems associated with the management of this condition.

 

Source: McBride SJ, McCluskey DR. Treatment of chronic fatigue syndrome. Br Med Bull. 1991 Oct;47(4):895-907. http://www.ncbi.nlm.nih.gov/pubmed/1794089