Clinical Challenges in the Biopsychosocial Interface

R. Balon, T. N. Wise

• Publisher: S. Karger
• Year: 2015
• ISBN:
  9783318029673
• Topic: Medicine
• Subtopic: Urology

Psychosomatic medicine may be considered to be one of the leading approaches to treating comorbid disorders and conditions. The chapters of this volume are written by experts in the field and present the newest developments in psychosomatic medicine, from basic science to clinical approaches and novel treatments. Discussed are communications with patients suffering from serious illness, basic science and management of fibromyalgia and chronic fatigue. Further psychiatric symptomatology in Huntington's disease and its management as well as coping with losses, grief and mourning in prostate cancer are reviewed. Psychocutaneous diseases, the role of telomeres in stress and mental illness, dimensional psychopharmacology in somatizing patients and many other clinically important areas are also covered. Papers in this publication offer new information on the advances of contemporary psychosomatic medicine in variety of areas previously not sufficiently covered and are of valuable reading for psychiatrists, psychologists, internists, oncologists and primary care specialists.

Balon R, Wise TN (eds): Clinical Challenges in the Biopsychosocial Interface. Update on Psychosomatics for the 21st Century. Adv Psychosom Med. Basel, Karger, 2015, vol 34, pp 61-77 (DOI: 10.1159/000369085)

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Fibromyalgia and Chronic Fatigue: The Underlying Biology and Related Theoretical Issues

Graziella F. Romano^a · Simona Tomassi^b · Alice Russell^a · Valeria Mondelli^a · Carmine M. Pariante^a

^aStress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK; ^bSection of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Verona, Italy

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Abstract

There is an increasing interest in understanding the biological mechanism underpinning fibromyalgia (FM) and chronic fatigue syndrome (CFS). Despite the presence of mixed findings in this area, a few biological systems have been consistently involved, and the increasing number of studies in the field is encouraging. This chapter will focus on inflammatory and oxidative stress pathways and on the neuroendocrine system, which have been more commonly examined. Chronic inflammation, together with raised levels of oxidative stress and mitochondrial dysfunction, has been increasingly associated with the manifestation of symptoms such as pain, fatigue, impaired memory, and depression, which largely characterise at least some patients suffering from CFS and FM. Furthermore, the presence of blunted hypothalamic-pituitary-adrenal axis activity, with reduced cortisol secretion both at baseline and in response to stimulation tests, suggests a role for the hypothalamic-pituitary-adrenal axis and cortisol in the pathogenesis of these syndromes. However, to what extent these systems’ abnormalities could be considered as primary or secondary factors causing FM and CFS has yet to be clarified.

© 2015 S. Karger AG, Basel

Introduction

In recent years, an increasing amount of attention has been given to further understanding the biology underlying fibromyalgia (FM) and chronic fatigue syndrome (CFS). CFS is a complex, debilitating disorder that is characterised by persistent fatigue lasting for at least 6 months and is neither related to overexertion nor alleviated by rest. Associated symptoms, such as cognitive impairment, flu-like symptoms, muscle and joint pain in the absence of swelling, and unrefreshing sleep, must also be present to a degree [1-3]. FM is also complex, causing significant disability in those individuals who suffer from the condition. In contrast to CFS, FM is predominantly characterised by widespread pain; however, overlapping symptoms with CFS include cognitive impairment, sleep disturbances, and a persistent lack of energy [4, 5]. Indeed, it has been proposed that such similar disorders be considered on a continuum, as opposed to distinct diagnoses: that is, to be viewed according to a dimensional approach, as opposed to a categorical approach [6].

Biological, psychological, and social factors have been implicated in the pathogenesis and the maintenance of these disorders, although the degree to which each of these factors contributes to these processes has been a source of debate, with more debate arising in recent years as further biological evidence has mounted [7, 8]. Indeed, research in the field has increasingly focussed on the biological processes putatively underlying these disorders, in an attempt to make further progress in understanding the mechanisms that may lead to advances in treatment and improvement of outcomes. The current paucity of treatment options has contributed to the increased level of disability, and without a medical explanation for their symptoms, patients feel increasingly stigmatised. To date, the results of biological studies are mixed, largely due to unclear diagnoses at recruitment, the heterogeneity of the diagnostic criteria applied, small sample sizes, and a small number of studies examining each biological mechanism proposed. Despite this, some replicated findings are emerging, and the increasing number of studies in the field is encouraging. As such, this chapter will focus on the inflammatory and oxidative stress pathways and the neuroendocrine system, as these biological systems are more commonly examined and have somewhat clearer results.

The Role of the Immune System and Its Implication in Chronic Fatigue Syndrome/Fibromyalgia

The main recognised role of the immune system is the defence of the human body against pathogens and infections. It is divided into two subsystems: innate and adaptive/acquired immunity. The innate immune system reacts to pathogen-associated molecular patterns by activating the production and secretion of inflammatory mediators, such as histamines, prostaglandins, brady-kinin, serotonin, and leukotrienes. These factors attract macrophages that release cytokines, namely, tumour necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6, in order to prolong the systemic inflammatory response and stimulate the adaptive/acquired immune system. The latter system principally functions to create and maintain the immune system's memory and is mainly mediated by T and B cells, or lymphocytes playing a central role in cell-mediated immunity [9]. Furthermore, IL-6 stimulates the release of acute-phase proteins such as C-reactive protein (CRP), which originates in the liver. Under normal circumstances, inflammation is accompanied by an anti-inflammatory response. IL-4 and IL-10 are among the factors contributing to decreased production of TNF-α, IL-1, IL-6, and IL-8 and are defined as anti-inflammatory cytokines. However, comorbidities and other factors can influence a patient's ability to respond appropriately [10].

Interestingly, the increased production of pro-inflammatory cytokines can contribute to the development of a range of symptoms and behavioural changes that both humans and animals experience when affected by physical illnesses and that resemble those in CFS/FM. These changes and symptoms are often referred to as ‘sickness behaviour’ and include symptoms such as fatigue, pain, low mood, and cognitive impairment. While this is an evolutionary adaptive response during infection because it facilitates the body's fight against virus or bacteria, more recently, it has been suggested that when such changes occur in the absence of infection, they may contribute to pathology [11]. Administration of TNF-α and IL-1β in rats and mice induces dose- and time-dependent behavioural changes typical of sickness behaviour: the animals tend to stay in a corner of their cage and lose interest in the physical and social environment, and decreased motor activity and reduced food and water intake are also observed. Furthermore, they show increased pain sensitivity and decreased resistance to forced exercise, induced mostly by IL-1 administration [12, 13]. Similarly, cytokine-based immunotherapy with interferon-α in patients affected by hepatitis C virus induces similar symptoms, such as depression; severe fatigue; and somatic symptoms, including pain. In patients undergoing interferon-α treatment, both depression and fatigue show a correlation with high levels of pro-inflammatory cytokines [14, 15] and are influenced by genetic variants in immune genes [16, 17]. Of interest, blocking pro-inflammatory status with medications has been found to alleviate fatigue and pain in patients with rheumatoid arthritis and psoriasis [18, 19]. Such evidence for the role of inflammation in these symptoms forms part of a growing body of research, with several studies reporting activation of the immuno-inflammatory pathway in a considerable number of psychiatric disorders [20, 21] and chronic illnesses characterised by chronic, unexplained fatigue [22-24]. Evidence for increased inflammation in CFS/FM will now be discussed.

Elevated Inflammatory Markers in Chronic Fatigue Syndrome/Fibromyalgia

Increased levels of pro-inflammatory cytokines, suc...