The Psychopathology of Functional Somatic Syndromes

Neurobiology and Illness Behavior in Chronic Fatigue

Syndrome, Fibromyalgia, Gulf War Illness, Irrit, 1st Edition

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Published by

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PUBLISHER’S NOTE
This book has been published solely for educational purposes and is not intended to substitute
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search and clinical experience broaden our knowledge, changes in treatment may be required.
While many potential treatment options are made herein, some or all of the options may not be ap-
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Cover design by Marylouise E. Doyle.

Library of Congress Cataloging-in-Publication Data

Manu, Peter, 1947-

The psychopathology of functional somatic syndromes : neurobiology and illness behavior in
chronic fatigue syndrome, fibromyalgia, Gulf War illness, irritable bowel, and premenstrual
dysphoria / Peter Manu.
p. cm.
Includes bibliographical references and index.
ISBN 0-7890-1259-6 (hard : alk. paper)—ISBN 0-7890-1260-X (pbk. : alk. paper)
1. Somatoform disorders. I. Title.
[DNLM: 1. Somatoform Disorders—physiopathology. 2. Colonic Diseases, Functional—
physiopathology. 3. Fatigue Syndrome, Chronic—physiopathology. 4. Fibromyalgia—physiopathology.
5. Persian Gulf Syndrome—physiopathology. 6. Premenstrual Syndrome—physiopathology. WM 170
M294p 2004]
RC552.S66M36 2004
616.85'24—dc21

2003001540
Polonius.
I will be brief. Your noble son is mad.
Mad call I it, for, to define true madness,
What is’t but to be nothing else but mad?

Queen.
More matter with less art.
Hamlet, Act 2, Scene 2
 ABOUT THE AUTHOR

Peter Manu, MD, is Professor of Clinical Medicine and Professor of

Clinical Psychiatry at Albert Einstein College of Medicine at Yeshiva
University in New York. He practices and teaches at Long Island
Jewish Medical Center, where he is Director of Medical Services at
the Zucker Hillside Hospital. Dr. Manu is the author of The Pharm-
acotherapy of Common Functional Syndromes: Evidence-Based Guide-
lines for Primary Care Practice (Haworth) and editor of Functional
Somatic Syndrome: Etiology, Diagnosis, and Treatment (Cambridge).
 CONTENTS

Introduction 1

PART I: THE CLINICAL MANIFESTATIONS

OF FUNCTIONAL SYNDROMES

Chapter 1. The Modern Conceptualization

of Unexplained Symptoms 9
Chronic Fatigue Syndrome 9
Fibromyalgia 12
Premenstrual Syndrome 16
Irritable Bowel Syndrome 17
Gulf War Illness 19
Chapter 2. A Tight-Knit Family of Syndromes 23

PART II: PSYCHIATRIC MORBIDITY

IN FUNCTIONAL SOMATIC ILLNESS

Chapter 3. Depression and Somatization in Chronic

Fatigue Syndrome 35
Mood Disorders and Chronic Fatigue Syndrome 35
Somatization Disorder and Chronic Fatigue Syndrome 42
Psychopathology and Chronic Fatigue: Environmental
or Genetic Covariation? 48
Chapter 4. Somatization and Depression in Fibromyalgia 51
Chapter 5. The Spectrum of Mood Disorders Associated
with Premenstrual Dysphoria 65
Chapter 6. Anxiety, Depression, and Somatization
in Irritable Bowel Syndrome 73
Chapter 7. Somatization and Posttraumatic Stress
in Gulf War Illness 83
PART III: THE PSYCHOBIOLOGY OF FUNCTIONAL
SOMATIC SYNDROMES

Chapter 8. Neuroanatomy and Brain Perfusion

in Functional Somatic Syndromes 97
Magnetic Resonance and Single Photon Emission Imaging
in Chronic Fatigue Syndrome 97
Cerebral Perfusion in Fibromyalgia 109
Magnetic Resonance Imaging and Premenstrual Brain
Volume 112
Functional Magnetic Resonance in Irritable Bowel
Syndrome 113
Magnetic Resonance and Single Photon Emission
Tomography in Gulf War Syndrome 115
Conclusion 116

Chapter 9. Neuropsychological Deficits in Functional

Somatic Illness 117
Chronic Fatigue Syndrome 117
Gulf War Illness 124

Chapter 10. The Hypothalamic-Pituitary-Adrenal Axis

in Functional Somatic Illness 131
Hypothalamic-Pituitary-Adrenal Axis Dysfunction
in Chronic Fatigue Syndrome 131
The Reactivity of the Hypothalamic-Pituitary-Adrenal
Axis in Fibromyalgia 141
Cortisol Levels in Irritable Bowel Syndrome 147
Assessment of the Hypothalamic-Pituitary-Adrenal Axis
in Premenstrual Syndrome 149

Chapter 11. Serotonin Metabolism in Functional Somatic

Illness 153
Serotonergic Neurotransmission in Chronic Fatigue
Syndrome 153
Serotonin Metabolism in Fibromyalgia 157
Serotonergic Function in Premenstrual Syndrome 161
PART IV: ABNORMAL PERSONALITY AND ILLNESS
BEHAVIOR IN FUNCTIONAL SOMATIC
SYNDROMES
Chapter 12. Abnormal Personality in Functional Somatic
Syndromes 171
Chronic Fatigue Syndrome 171
Fibromyalgia 184
Irritable Bowel Syndrome 186
Premenstrual Syndrome 188
Gulf War Illness 193
Conclusion 197
Chapter 13. The Sexual Victimization of Patients
with Functional Somatic Syndromes 199
Fibromyalgia 199
Irritable Bowel Syndrome 204
Chronic Fatigue Syndrome 210
Chapter 14. Somatic Attributions in Functional Illness 213
Chronic Fatigue Syndrome 213
Fibromyalgia 218
Premenstrual Syndrome 220
Chapter 15. Maladaptive Coping in Functional Somatic
Syndromes 221
Chronic Fatigue Syndrome 221
Fibromyalgia 230
Irritable Bowel Syndrome 238
References 245
Index 285
 Introduction
Introduction

Chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome,

premenstrual syndrome, and Gulf War illness are common illnesses
that lack demonstrable structural or biochemical abnormalities and
are characterized by medically unexplained symptoms such as fa-
tigue, myalgias, abdominal pain, difficulty with concentration, mood
lability, and sleep disturbance (Manu, 1998).
The way in which these entities have been explained has varied,
and some clinicians have interpreted and managed them as physical
disorders. However, most physicians have understood them to be
mental illnesses (Sharpe and Carson, 2001). This pattern continues,
as shown by a recent survey of 400 physicians in the South Thames
area of England (Reid et al., 2001). More than half of the respondents
(63 percent) thought that the symptoms were best explained by a psy-
chiatric disorder. An even greater proportion of this physician sample
(83 percent) believed that patients with medically unexplained symp-
toms have a personality disorder. Most of the respondents (93 per-
cent) felt that patients with such symptoms are difficult to manage. A
solid majority (75 percent) of these physicians rejected the possibility
that the symptoms represented evidence of an undiagnosed physical
illness. These beliefs were not related to the physicians’ training in
psychiatry or to the availability of mental health resources in the area
they served. Consistent with these beliefs, most of the physicians felt
that their main role in managing these patients was to provide reas-
surance (99 percent of the respondents), act as gatekeepers to prevent
inappropriate consultations and laboratory investigations (94 per-
cent), and provide counseling and psychological management (84
percent). The individual comments add support to the strong feelings
evoked by these patients in their primary care providers. One physi-
cian indicated a frustration possibly felt by many, writing “I would
like to have enough courage to tell them that nothing is wrong; you
are wasting my time and your time. You must try to learn to live with
your symptoms.” Another reflected distrust, suggesting that “most of
medically unexplained symptoms are related to not wanting to go
back to work, and sick benefits usually help to keep away symptoms.”
The third expressed a degree of annoyance with the fact that “having
excluded the impossible as far as one can, the medically unexplained
symptom usually has a personality/psychiatric aspect but patients
will not be persuaded of this” (Reid et al., 2001, p. 521).
Recent conceptualizations of functional somatic syndromes as
mental disorders have proposed four empirical constructs. The first
suggested that these syndromes are part of the affective spectrum dis-
order, together with major depression, bulimia, panic disorder, obses-
sive-compulsive disorder, and attention deficit disorder with hyper-
activity (Hudson and Pope, 1990). The second proposed that patients
with functional illnesses are chronic somatizers who present with a
large array of complaints, are familiar with the definitions of func-
tional syndromes, have a past history of psychiatric disorders, and
tend to embrace poorly documented disease mechanisms such as en-
vironmental allergies, overgrowth of Candida albicans, and reactiva-
tion of dormant herpetic viruses (Stewart, 1990). The third frame of
reference encouraged an individualized approach to these syndromes
and suggested a variety of explanations such as serotonin deficiency
for the pain symptoms in fibromyalgia and physical inactivity for the
postexercise malaise of patients with chronic fatigue syndrome (Kellner,
1994). The fourth theory emphasized abnormal illness behavior and
focused on these patients’ belief that they have a serious problem,
their sense that the illness is disabling and catastrophic, and their sus-
picion of physicians’ expertise and motivation (Barsky and Borus,
1999). These constructs have remained largely unproven.
The origin of this book is a cluster of observations made by Tom
Lane, Dale Matthews, Victor Hesselbrock, Howard Tennen, Glenn
Affleck, Rich Mendola, Javier Escobar, Priscilla Morse, Micha
Abeles, Rich Castriotta, the late Bob Watson, and me in a large num-
ber of patients with medically unexplainable complaints seen from
1986 through 1993 at the University of Connecticut Health Center,
Farmington, Connecticut. From the outset, the structured data collec-
tion indicated a high prevalence of major depression (Manu, Matthews,
et al., 1989), somatization disorder (Manu, Lane, et al., 1989), and
panic disorder (Manu et al., 1991). However, the severity of psychiat-
ric symptoms did not correlate with myalgias and sleep disturbance
(Manu et al., 1994). The possibility that the psychiatric syndromes
represented reactions to the physical illness appeared unlikely, be-
cause their onset preceded the functional complaint in a majority of
cases (Lane et al., 1991). Moreover, the depressive symptoms com-
monly reported by these patients did not influence their disease con-
viction, disease phobia, and bodily preoccupation (Manu et al., 1996).
The findings challenged the view that functional illnesses were mani-
festations of an affective disorder (Hudson and Pope, 1990), offered
only limited support for the chronic somatization hypothesis (Stew-
art, 1990), and did not confirm the link between depression and
hypochondriasis (Barsky and Borus, 1999).
What is the nature of the association between psychopathology
and functional illness? Is there a biological gradient between the so-
matic and psychological features of these syndromes? Do objective
findings support a relationship? Are psychiatric symptoms the mani-
festations of dysfunctional coping? This book attempts to answer
these questions by studying the best research work of the past two de-
cades. It starts by describing the modern definitions of chronic fa-
tigue, fibromyalgia, irritable bowel, premenstrual dysphoria, and
postcombat ailments and the way in which these entities have evolved
into a tightly knit family of self-standing syndromes with a common
core of somatic symptoms. The second part presents the frequency of
psychiatric disorders in functional syndromes and analyzes the corre-
lation between the burden of psychopathology and the physical fea-
tures of these illnesses. The third part is a review of advances in the
appraisal of the neuroanatomy, neuropsychology, and neurochemis-
try of functional syndromes and an attempt to determine whether the
confirmed abnormalities are similar to those described in psychiatric
disorders. The last part of the book focuses on measurable dimen-
sions of personality, coping, and illness behavior and on their correla-
tion with the severity and prognosis of medically unexplainable ill-
ness. Throughout the book, the sample selection, methodologies, and
findings are described in detail for each of the studies selected. The
meta-analytic temptation was resisted: the works were allowed to
stand alone and the authors’ words permitted to judge the findings.
This book will show that chronic fatigue syndrome, fibromyalgia,
irritable bowel syndrome, premenstrual syndrome, and Gulf War ill-
ness are overlapping conditions with numerous medically unex-
plained complaints. The main somatic descriptors of these illnesses
are chronic musculoskeletal or abdominal pain, persistent fatigue,
sleep disturbance, and cognitive deficits. A past history of mood dis-
orders is common, but only a minority of patients can be diagnosed
with current major depression, dysthymia, panic disorder, or post-
traumatic stress. Depression and anxiety do not correlate well with
the overall severity of functional impairment, but are associated
with the features of somatization and poor long-term outcome. The
cognitive and neurobiological abnormalities are nonspecific, mild,
and variable. No compelling evidence suggests that these syndromes
are serotonin-deficient states. The pattern of activation of the hypo-
thalamic-pituitary axis distinguishes functional syndromes from
melancholic depression and stress-related illnesses. Many patients
with functional syndromes have abnormal personality features, a his-
tory of sexual and physical abuse, a tendency to attribute their illness
to a physical cause, and a catastrophic coping style.
The evidence presented in this book demonstrates that functional
syndromes are not atypical manifestations of mood or anxiety disor-
ders. Their psychopathology centers on production of somatic and
psychological symptoms as expressions of neuroticism, harm avoid-
ance, sexual victimization, and maladaptive coping. This interpreta-
tion of the data accumulated in the past two decades is close to other
important themes about the nature of physical symptoms (Katon and
Walker, 1998). First, functional illnesses are likely to reflect specific
personality traits, prior illness experience, and early family environ-
ment. Second, lifetime psychiatric disorders and psychological dis-
tress correlate with the number of medically unexplained complaints,
a quantitative relationship that highlights the severity of the illness
rather than an etiologic relationship. Third, the severity of symptoms
increases as the evaluation moves from primary to specialized care
settings and creates an unsatisfactory patient-doctor relationship (Katon
and Walker, 1998). The central idea generated by this review is the
coexistence of somatization with personality abnormalities, an area
that has received only scant attention in the research literature. The
personality disorders common in patients with somatization disorder
are histrionic, passive-dependent, and sensitive-aggressive. The in-
teraction between life situations and personality abnormalities leads
to the behavior of complaining, persistence of illness, and resistance
to treatment (Stern et al., 1993).
This work was planned during a visiting professorship in the De-
partment of Psychosomatic Medicine, Heinrich-Heine University,
Düsseldorf, Germany, made possible by John Kane, Matthias Franz,
and Maria Angel. I acknowledge with heartfelt gratitude their sup-
port. The writing of the book, as well as my struggle to decipher the
complexities of functional disorders, would have been much harder
without the clarity brought to this field by Simon Wessely, Michael
Sharpe, Steve Straus, Wayne Katon, and Mark Demitrack. I admire
and respect the insight, wisdom, and discernment of their work.
 PART I:
THE CLINICAL MANIFESTATIONS
OF FUNCTIONAL SYNDROMES
 Chapter 1

The Modern
The Modern Conceptualization
Conceptualization of Unexplained Symptoms
of Unexplained Symptoms

Functional syndromes characterized by malaise, widespread or lo-

calized pain, cognitive abnormalities, anxiety, depression, and so-
matic preoccupation have been identified for more than two centu-
ries. They have received many names and have had many proposed
but unproved etiologies (Feinstein, 2001; Sharpe and Carson, 2001).
In the past two decades, common illnesses such as chronic fatigue
syndrome, fibromyalgia, and irritable bowel have been defined as
“medical syndromes” highlighting patterns of somatic distress thought
to originate from specific bodily systems (Mayou and Farmer, 2002).
The road toward a crisp nosology of functional ailments has been a
difficult one, primarily because those involved in the effort have had
to abandon traditional demands for appropriate correlation of symp-
toms and objective abnormalities (Feinstein, 2001).

CHRONIC FATIGUE SYNDROME

Since the early 1980s, a syndrome of persistent fatigue and symp-

toms resembling those of common viral infections has captured
widespread medical and public attention. Initially, the syndrome was
etiologically linked to immunological stigmata of Epstein-Barr virus
infection (Tobi et al., 1982; Dubois et al., 1984; Jones et al., 1985;
Straus et al., 1985) and the illness came to be known as chronic Ep-
stein-Barr virus infection or chronic mononucleosis-like syndrome.
However, attempts to confirm the role of Epstein-Barr virus infection
in the production of the symptoms refuted a causal relationship
(Holmes et al., 1987; Hellinger et al., 1988; Straus et al., 1988). This
reality led an interdisciplinary group assembled by the Centers for