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Comorbidity
Symptoms, Conditions,
Behavior and Treatments
Edited by
Rhonda Brown
Einar Thorsteinsson
Comorbidity
Rhonda Brown · Einar Thorsteinsson
Editors
Comorbidity
Symptoms, Conditions, Behavior
and Treatments
Editors
Rhonda Brown Einar Thorsteinsson
Research School of Psychology School of Psychology
Australian National University University of New England
Canberra, ACT, Australia Armidale, NSW, Australia
ISBN 978-3-030-32544-2 ISBN 978-3-030-32545-9 (eBook)

https://doi.org/10.1007/978-3-030-32545-9
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature
Switzerland AG 2020
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether
the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse
of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and
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The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specific statement, that such names are exempt
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The publisher, the authors and the editors are safe to assume that the advice and information in this
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Cover illustration: Gregory Davies/Stockimo/Alamy Stock Photo
This Palgrave Macmillan imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Preface
Collectively, as co-authors, we have extensive clinical and research expe-

rience related to the various clinical disorders, symptoms, behaviour and
biology covered in the book. Furthermore, as research collaborators, we
can provide a unique perspective on the likely evolution and nature of
disease comorbidity, which integrates biological, medical and psycho-
logical perspectives. The book was written with an academic audience in
mind, although other interested individuals may appreciate the explora-
tion of possible mechanisms underpinning disease comorbidity. To be
clear, this is not a self-help book that reflects upon the way in which
people should live a better life or which reflects upon the way that we as
individuals live our own lives.
The stimulus for the book was research conducted by Laird
Birmingham, Rhonda Brown and others, related to low body temper-
ature and infection in anorexia nervosa patients, which later gave rise
to discussions around the possible role played by body temperature in
mediating some of the adverse health outcomes related to overweight/
obesity. However, more broadly, the co-authors have worked collec-
tively, in several different research groups, to answer the following ques-
tions related to disease comorbidity: What is causing the comorbidity
v
vi Preface
between different medical and psychological conditions? What role (if any)
is played by the shared (or overlapping) medical and psychological
symptoms? Or is a common factor more likely to cause the co-occurrences?
Finally, why is a similar profile of risk factors detected for a range of
different but frequently comorbid illnesses and conditions?
As argued in this book, there is a crucial need to more fully inte-
grate a broader range of comorbid illnesses and conditions, and their
often overlapping risk factors, into the same disease models; to arrive
at a more complex real-world understanding of comorbid illness causa-
tion. If such a clinical model could be developed, it might be used to
test complex hypotheses related to the evolution and nature of disease
comorbidity as well as evaluate potential new therapies.
Finally, as co-authors, we wish to thank the various researchers and
clinicians we have worked with over many years, who each have con-
tributed to the evolution of the thoughts that are collectively advanced
in this book.
Canberra, Australia Rhonda Brown

Armidale, Australia Einar Thorsteinsson
Contents
1 Comorbidity: What Is It and Why Is It Important? 1

Rhonda Brown and Einar Thorsteinsson
1.1 What Is Comorbidity? 1
1.2 Why Is Comorbidity Important? 4
1.3 What Is the Cost of Comorbidity? 8
References 16
2 Models of Comorbidity 23
2.1 Computational and Clinical Models
of Concurrent Symptom Development 23
2.2 Sleep, Body Temperature, and Circadian
Rhythm Function 30
References 36
vii
viii Contents
3 Overweight/Obesity and Concurrent Disorders,

Symptoms, Behaviour, and Body Temperature 43
Rhonda Brown and Yasmine Umar
3.1 Overweight/Obesity and Comorbid Disorders 43
3.2 Overweight/Obesity, Sleep Disorders,
and Impaired Sleep 47
3.3 Overweight/Obesity, Disordered Eating, and Sleep 51
3.4 Overweight/Obesity, Disordered Eating, Sleep,
and Body Temperature 58
References 64
4 Overview of the Comorbidity Between Medical

Illnesses and Overweight/Obesity 79
Christopher J. Nolan
4.1 Medical Illnesses and Overweight/Obesity 80
4.2 Overweight/Obesity Comorbidities
and Causal Linkages 91
4.3 Lessening the Burden of Comorbid Illnesses
in Overweight and Obese Individuals 97
References 98
5 Comorbid Eating Disorders 115

C. Laird Birmingham
5.1 Anorexia Nervosa and Bulimia Nervosa 115
5.2 Eating Disorders and Medical Comorbidities 118
5.3 Eating Disorders and Anxiety and Mood Disorders 119
5.4 Can Comorbid Psychiatric Disorders Prevent
Recovery from Eating Disorders? 121
5.5 Anorexia Nervosa, Body Temperature,
Hyperactivity, and Clinical Outcomes 122
5.6 Body Warming to Treat Anorexia Nervosa,
Hyperactivity, and Exercise Addiction 124
5.7 Other Medical Treatments for Anorexia Nervosa 126
References 129
Contents ix
6 Comorbid Psychiatric Illnesses 139

Einar Thorsteinsson and Rhonda Brown
6.1 Comorbidity Between Anxiety and Depressive
Disorder 139
6.2 Relationships Between Stress, Depression, Anxiety,
and Impaired Sleep 143
6.3 Risk and Protective Factors for Mental Ill-Health 145
6.4 Causal Models for the Development of Depression
and Anxiety 149
References 161
7 Arousal States, Symptoms, Behaviour, Sleep and Body

Temperature 179
7.1 Arousal States and Elevated Body Temperature 179
7.2 Symptoms and Elevated Body Temperature 181
7.3 Exercise, Sleep, Affective Distress, Overweight/Obesity
and Body Temperature 191
7.4 Behaviour Linked to Impaired Sleep and Elevated Body
Temperature 197
References 202
8 Design, Statistical and Methodological Considerations:

Comorbidity 221
Einar Thorsteinsson and Rhonda Brown
8.1 Methodological Approaches 221
8.2 Statistical Approaches 228
8.3 Overlapping Risk and Protective Factors 232
8.4 Other Research and Data-Handling Approaches 234
8.5 Summary 236
References 237
x Contents
9 Typing It All Together 241

9.1 What Causes Comorbidity? 241
9.2 Comorbidity—Where to from Here? 248
9.3 Possible Existing, Repurposed, and Novel
Treatments for Comorbid Illness 255
References 264
Notes on Contributors
C. Laird Birmingham, M.D. is a Specialist in Internal Medicine,

Epidemiologist and Biostatistician and a Professor of Psychiatry at the
University of British Columbia, where he was previously Professor of
Medicine. He was Leader of the BC Eating Disorders Epidemiology
Project in the Centre for Health Evaluation and Outcome Sciences
until 2008 and then Medical Director of the Woodstone Residential
Treatment Centre for Eating Disorders until December 2013. He is a
Member of the Brain Research Centre at UBC and Senior Associate
Clinician Scientist at the Children and Family Research Institute. He
has more than 40 years of experience in eating disorder research and
treatment and has 280 publications including 131 refereed articles, 23
invited chapters and 9 books. Dr. Birmingham’s research has focused on
nutrition and the brain, the effect of ambient temperature on anorexia
nervosa and the medical management of eating disorders. He is focused
now on LORETA imaging and neurofeedback of patients with disorder.
Rhonda Brown started her career as a lab-based researcher, develop-
ing an animal model for immune-mediated polyneuropathies during
her Ph.D. and exploring the overlap between neurochemical, neuroen-
docrine and immune responses to stress and infective illness, including
xi
xii Notes on Contributors
bacterial translocation (i.e. leaky gut), during her post-doctoral fellow-

ship. She works as an Associate Professor in the Research School of
Psychology, Australian National University. She teaches health psychol-
ogy and her research examines predictive relationships between stress,
affective distress (e.g. anxiety, depression), sleep, fatigue, other symp-
toms, and illness outcomes in patients (e.g. cancer, overweight/obesity,
sleep apnoea, multiple sclerosis) and community-well individuals. She
also collaborates with other researchers to examine work-stress, burnout,
communication performance and empathy in medical staff and medical
and psychology students as well as immune function, fever response and
infection in patients with anorexia nervosa. Over the past 20-years, she
has worked extensively with each of the co-authors of this book.
Christopher J. Nolan is a clinician scientist and policy advisor in
the field of diabetes and metabolic diseases. He recently stepped
down as Director of Diabetes Services (2011–2018) and Director of
Endocrinology (2016–2018) for ACT Health to take up a new position
as Associate Dean of Research for the Medical School at the Australian
National University. He is currently a Board Member of the Australian
Diabetes Society (2018–) and an Associate Editor for Diabetologia
(2016–). He directs an active diabetes research laboratory focusing on
islet beta-cell failure in type 1 and 2 diabetes and the role of insulin
hypersecretion in metabolic syndrome and related conditions. He is a
lead investigator for the ANU Grand Challenges Project, Our Health in
Our Hands, which includes research into improving the care of people
with type 1 diabetes using a personalised medicine approach.
Einar Thorsteinsson works as Associate Professor at the University of
New England, Australia. He worked on his Ph.D., the effects of social
support on changes in cortisol and cardiovascular reactivity in response
to stressful situations, at La Trobe University in Melbourne. He was
awarded a Ph.D. in 1999 and then worked at La Trobe University in a
fire fighting decision-making lab for two years before he moved back to
focus on health psychology at the University of New England where he
has built national and international research collaborations covering
areas such as stress, social support, depression, anxiety, adolescent cop-
ing and health, and psychological well-being.
Notes on Contributors xiii
Yasmine Umar is a Doctoral Candidate at the Australian National

University, extensively researching the predictors of disrupted sleep,
obesity and affective distress in the general Australian population. She
has also explored the relationships between stress, infection symptoms
and chronic fatigue. She currently practises as a clinical psychologist,
specialising in youth oncology.
List of Figures
Fig. 2.1 Symptoms, states, and behaviour that can increase

nocturnal body temperature, and if practiced at night,
thereby potentially interfere with sleep onset 30
Fig. 2.2 Original caption reads: “Diagrammatic representation
of normally entrained endogenous rhythms of core body
temperature (solid curve), plasma melatonin (dotted curve),
and objective sleep propensity (dashed curve) placed
in the context of the 24-h clock time and normal sleep
period (shaded area).” Figure is from Lack et al. [25] 31
Fig. 2.3 Original caption reads: “Fitted Fourier curves
to the control group and insomniac group mean
24-h temperature data in the constant routine relative
to subjects’ usual sleep onset times (vertical solid line).
The usual mean lights out times (LOT) for each group
are indicated as vertical dashed lines. The estimated
mean wake maintenance zone (WMZ) for each group
is indicated as shaded area.” Figure is from Morris et al. [30] 33
xv
1
Comorbidity: What Is It and Why Is It
Important?
1.1 What Is Comorbidity?

Comorbidity refers to any distinct clinical entity that coexists with or
occurs during the clinical course of another illness or condition [1]. In
other words, it refers to the co-occurrence of two or more distinct illnesses,
disorders or conditions in a single individual. As a result of the comorbidity,
some disorders tend to occur together more often than they occur alone.
For example, anxiety, depressed mood and impaired sleep often co-occur,
and in this instance, the co-occurrence appears to be the rule rather than
the exception [2].
In this book, the term co-occurrence is used to refer to the coexistence
of multiple symptoms (or clinical signs), whereas comorbidity specifically
R. Brown (B)
Australian National University, Canberra, ACT, Australia
e-mail: rhonda.brown@anu.edu.au
E. Thorsteinsson
University of New England, Armidale, NSW, Australia
e-mail: ethorste@une.edu.au
© The Author(s) 2020 1

R. Brown and E. Thorsteinsson (eds.), Comorbidity,
https://doi.org/10.1007/978-3-030-32545-9_1
2 R. Brown and E. Thorsteinsson
refers to the coexistence of multiple illnesses, disorders or conditions. For

simplicity, the terms illness, disease, disorder and condition will be used
interchangeably, as appropriate to the medical or psychological literatures
referenced in each chapter.
It is not possible to provide a comprehensive analysis of all comorbid dis-
orders and concurrent symptoms in this book. Nonetheless, the book rep-
resents a significant step forward in its coverage of a broad range of concur-
rent disorders including overweight/obesity, diabetes mellitus type-II, car-
diovascular disease, sleep-disordered breathing, impaired sleep/insomnia,
disordered eating (e.g. binge-eating disorder), anxiety, depression, fatigue,
anorexia nervosa and bulimia nervosa.
In contrast, prior published books on the topic have tended to examine
a limited number of comorbidities, including that between anxiety and
depression [3–10], depression and other disorders [3], comorbidity with
rheumatic disease [11], epilepsy [12], hypertension [9] and lifetime (or
non-concurrent) comorbidity [4]. However, Sartorius and colleagues [13]
have comprehensively detailed the clinical challenges of managing medical
illnesses (e.g. cardiovascular disease, cancer, infectious disease) that tend
to co-occur with mental and behavioural disorders, including substance
abuse, eating disorders and anxiety; they covered the clinical management
of the comorbidities.
In this book, a focus of attention is the comorbidity between over-
weight/obesity (or proxy measures of it, e.g. high body mass index [BMI] or
weight gain) and impaired sleep/insomnia, which is increasingly observed
in clinical practice, but as yet is not fully understood. Specifically, over-
weight/obese individuals tend to take longer to fall asleep (i.e. longer sleep
onset latency) [14], sleep for a shorter time [15, 16], and have poorer
sleep quality [17], relative to non-obese controls (or lower BMI). How-
ever, little else is known about this common comorbidity, although the
sleep problems do typically resolve once the person loses weight [18]. In
Chapter 3, this comorbidity will be discussed in greater detail as will the
links between the phenomena and certain behaviour, which may play a
causal role in contributing to the disorders. In Chapter 2, existing the-
ories that seek to explain the presence and/or development of comorbid
symptoms and disorders will be discussed.
Additionally, in Chapter 4, comorbidity between overweight/obesity

and diabetes mellitus type-II, sleep-disordered breathing (e.g. obstructive
sleep apnoea [OSA]) and affective distress (e.g. anxiety, depression) will
be discussed. In Chapter 6, the concurrence between anxiety, depression,
insomnia/impaired sleep, fatigue, gut pathology and gut symptoms will
be discussed. In Chapter 5, comorbidity between eating disorders (e.g.
anorexia nervosa, bulimia nervosa) and sleep problems, anxiety, depres-
sion, gut problems and hyperactivity will be examined. In Chapter 7,
symptoms/conditions (e.g. chronic pain, fatigue) that frequently co-occur
with impaired sleep, psychopathology, and other co-occurring conditions
will be briefly discussed, as will the potential role played by unhelpful
behaviour, including sleep-disrupting behaviour.
Statistically, disease comorbidity is typically evidenced by high co-
prevalence estimates between the different diagnoses; symptom concur-
rence is evidenced by moderate to high correlations between two or more
composite measures (e.g. total construct scores), using validated question-
naires [19]. Consistent with this approach, the book chapters will provide
detailed research evidence illustrating the degree of concurrence between
the aforementioned disorders and symptoms, as appropriate to the spe-
cific chapter. Further, where possible, the emphasis will be on present-
ing meta-analytic and prospective longitudinal study results, rather than
cross-sectional correlational results. That is to say, our current conception
of causality typically requires that the cause of an event must precede its’
onset in time. Only longitudinal (and experimental) study results can fulfil
that criterion, to a greater or lesser degree.
However, appreciating the nature of the temporal relationship between
two separate phenomena tells us little about the mechanism/s that under-
pin the relationship. As detailed in Chapter 2, there are few available
theories to help guide the research on disease comorbidity, and as a result,
we currently know little about the true nature of the phenomenon. Fur-
thermore, a number of statistical and methodological (e.g. measurement)
problems complicate our understanding of comorbidity, for example, by
potentially inflating the extent of the observed relationship between the
different phenomena. These methodological and statistical problems will
be discussed in more detail in Chapter 8.
Finally, in Chapter 9, we will tie the threads together from the vari-
ous chapters and reflect upon the most likely mechanism/s underpinning
the development of comorbidity between the aforementioned disorders.
In particular, we will discuss the likely role played by circadian rhythm
dysfunction in the development of the disorders, along with the role played
by sleep-disrupting behaviour and biological processes (e.g. elevated noc-
turnal body temperature). Finally, we will explore a broad range of novel,
existing and repurposed therapy approaches that could show utility in
treating the comorbid conditions.
1.2 Why Is Comorbidity Important?

In the twenty-first century, the tendency of patients to develop multi-
ple disorders or conditions, rather than a single medical or psychologi-
cal problem, is relatively high. For example, in a large study of 198,670
Spanish patients aged over 14 years [20], 42% had at least one chronic
condition, and the prevalence estimate for comorbidity was one-quarter
(24.5%) although the prevalence was higher in women (28.1%) than in
men (19.4%), and it increased with advancing age until 69 years, when
it stabilised. Of the 26 chronic health conditions surveyed, three distinct
comorbidity burden patterns were detected, including high comorbidity
(pattern B), intermediate comorbidity (patterns A and D) and low comor-
bidity (pattern C). Pattern B conditions included ischemic heart disease,
congestive heart failure, cerebrovascular diseases and chronic renal fail-
ure, mostly in older patients (>70 years). Pattern A conditions included
cardiac arrhythmias, hypertension (with/without complications), dia-
betes (with/without complications) and hyperlipidaemia, mostly in older
patients. Pattern D included 14 conditions, for example, obesity, osteo-
porosis, dementia, and cancer, whereas pattern C included asthma, thy-
roid disease, anxiety, depression and schizophrenia, mostly in younger
(<30 years) patients. Thus, several distinct comorbidity patterns were evi-
dent reflecting that different medical and psychological disorders tended
to cluster together, in different general practice patients.
Similarly, high comorbidity prevalence estimates have been obtained
in GP record-based studies in other countries. For example, a prevalence
estimate of 20% was obtained in an Australian study [21]; 29.7% had

acute and/or chronic conditions in a sample from the Netherlands [22];
and 30% had comorbid illnesses in a Spanish population-based sample
[23]. In the USA, about 25% of the population are reported to suffer from
multiple chronic conditions and this percentage increases with advancing
age [24]. Thus, it is evident that disease comorbidity is common in clinical
practice and more broadly in the global community.
Comorbidity substantially increases the burden of illness in chronic ill-
ness patients. For example, the Global Burden of Disease Study [25] eval-
uated chronic and acute illness and injury burden on patients across 188
countries (1990–2013) using years lived with disability (YLD). Globally,
from 1990 to 2013, disability rates were shown to rise, as people tended to
live longer and experienced more illness. Additionally, comorbidity preva-
lence estimates rose substantially in absolute terms and also with increasing
age; for example, the number of people with 10 or more disorders increased
by 52% over that time. Further, in total, one-third of the participants had
>5 chronic or acute illnesses, of whom 81% were <65 years of age [25].
Thus, it is evident that comorbidity occurs in younger as well as older
individuals.
However, few studies have explicitly compared the degree to which
different disorders are comorbid with each other, although higher comor-
bidity rates are reported in patients with heart (e.g. heart failure) and
cerebrovascular conditions and lower rates are reported in patients with
asthma and mental health conditions [21, 26, 27]. Nonetheless, depres-
sion is known to be a leading cause of Global Burden of Disease (GBD)
based on years lived with disability (YLD) and disability-adjusted life
years (DALYs); it may contribute to suicide and cardiovascular disease
[28]. However, expanding this examination to cover other mental health
problems including substance use/abuse and the combined effects of the
disorders is required; as the conditions are leading causes of DALY and
YLD worldwide [29]. Furthermore, as shown in a UK study, nearly one-
half (46%) of people with a mental health problem also had a chronic
physical health problem/s, whereas fewer (30%) people with a chronic
physical condition also had a mental health problem [30], suggesting that
mental ill-health is a common comorbid health problem which may have
implications for physical health.
Taken together, it appears that comorbidity is present in at least one-

quarter to one-third of the population, including in general practice
patients. Furthermore, comorbidity prevalence estimates have significantly
increased over time and they tend to increase with advancing age, as do dis-
ability prevalence estimates [31]. Thus, as the global population ages, the
extent to which we will be affected by comorbid disease burden is expected
to substantially rise, although a substantial proportion of younger people
are also affected by comorbidities. Therefore, there is an urgent need to bet-
ter understand the nature of disease comorbidity and its likely causation,
so that effective multi-modal therapies can be developed (or re-purposed)
to treat the individual patients who have multiple comorbid illnesses.
Comorbidity tends to be associated with impaired daily functioning
and low health-related quality of life (QOL), including the physical and
mental health components of QOL [23]. More broadly, chronic illness
patients often experience severe and/or debilitating symptoms; will likely
undertake fear-provoking, painful or otherwise demanding investigations
and treatments; experience a high degree of uncertainty related to the
condition/s and their treatment; and about one-quarter of them will go
on to develop clinically significant psychological distress. Adherence may
also be reduced due to such severe symptoms and painful and demanding
treatments reducing the efficiency of treatment and increasing costs. Even
without a psychological disorder, patients will still need to psychologically
adjust to their illness, which will require them to regulate their thoughts,
feelings and behaviour; acquire new skills to manage their psychologi-
cal symptoms; adopt a new lifestyle of self-care; establish collaborative
relationships with their healthcare team/s; and, even then, sub-clinical
affective distress (e.g. anxiety, depression) may occur [32]. Nevertheless,
the impact of multiple different comorbid disorders (e.g. disability) tends
to be greater than for a single disorder, as are the costs associated with it
(e.g. financial, personal), as discussed in detail below.
However, despite the high prevalence of comorbidity and its con-
siderable impact on individual patients, most medical and psychologi-
cal researchers have tended to focus on single disorders or conditions,
rather than (or in addition to) disorders that coexist with them; irrespec-
tive of whether the subjects are medical patients, psychological clients or
community-derived non-clinical samples. For example, researchers may
investigate the relationship between certain risk factors (e.g. physical inac-
tivity) and depressed mood, without examining their relationship to other
coexisting symptoms (e.g. impaired sleep, fatigue), despite the common
propensity of depression to coexist with anxiety [33], impaired sleep [34]
and fatigue [33, 35]. However, many researchers will at least statistically
control for the potential effects of the concurrent symptoms. For exam-
ple, they may assess the predictive relationship between risk factors and
depressed mood, and partial out the effects of anxiety on the outcome mea-
sure, to obtain a purer estimate of the risk factor–depression relationship.
Such an approach can assist researchers to better understand the extent
to which particular risk factors and depressed mood are related, but this
approach potentially ignores the possibility that anxiety is functionally
related to depression via a number of possible mechanisms, as discussed
in Chapter 6.
Additionally, few theories of disease comorbidity exist to help guide the
comorbidity research. Specifically, as discussed in detail in Chapter 2, there
are few available clinical theories with any utility in explaining the way
in which different-but-related disorders and symptoms are likely to coex-
ist and the mechanisms by which they will develop. Such a theoretical
model would greatly assist researchers and clinicians to better understand
the likely complex causal relationships that exist between different risk
factors, medical illnesses and psychological disorders; it might also facili-
tate the evidence-based co-treatment of different comorbid disorders and
conditions.
However, most existing therapies have not been designed to treat
different-but-related disorders. Nor have they been examined for their
utility in treating coexisting conditions. Similarly, clinical practice guide-
lines and disease management programs typically focus on single diseases
but fail to take comorbidities into account; instead, they tend to deal with
the disorders as if they are isolated clinical entities [36]. Thus, there is
a clear need to update the clinical practice guidelines and patient man-
agement approaches to take disease comorbidity into account, especially
in the case of highly comorbid disorders and conditions. Furthermore,
there is a need to develop and evaluate novel (or repurposed) evidence-
based therapies to more effectively treat the aforementioned comorbid
conditions.
However, as discussed in Chapter 9, there appear to be few novel ther-

apies on the horizon that might remedy the comorbidities; there is no
clarity as to whether existing therapies could be used to concurrently treat
comorbid illnesses or if a sequenced approach to therapy might work best.
Nevertheless, there are a few notable exceptions: for instance, cognitive
behavioural therapy (CBT) can effectively treat depressed mood, fatigue,
insomnia/sleep problems and eating disorders; and there are disorder-
specific variants of CBT to treat depression [37], fatigue [38], insomnia
(CBT-I) [39] and eating disorders (CBT-E) [40]. However, the CBT pro-
tocols do not generally provide any detail about the way in which the
comorbid disorders should be managed together, either concurrently or
sequentially, in a single individual. Additionally, antidepressants have been
used to treat sleep problems in patients with depressed mood, but the
findings are typically mixed, with some studies showing that the drugs
can improve insomnia [41], whereas others show the drugs may worsen
insomnia [42]. Thus, there is a clear need to systematically review the effi-
cacy of antidepressant use in treating insomnia. A Cochrane review that
began in 2013 found that there was little evidence for the effectiveness of
SSRIs in treating impaired sleep and any apparent improvements in sleep
quality were short-lived, although the findings were only preliminary as
insufficient studies could be sourced to examine this issue [43].
1.3 What Is the Cost of Comorbidity?

Disease comorbidity is associated with a range of economic, societal and
personal costs. Economic costs can include the direct costs to the health-
care system of managing multiple health problems (e.g. prolonged recov-
ery time); direct costs to other sectors (e.g. provision of social care); and,
indirect costs such as the lost opportunity to contribute to economic pro-
ductivity (e.g. reduced workforce participation or participation in school,
etc.). The full economic costs of comorbidity are largely unknown, especially
the estimates of the impact beyond the healthcare system; in this case, the
estimates are mostly of indirect costs, including productivity losses due to
under-employment resulting from absenteeism [44].
Nevertheless, it is broadly appreciated that the financial costs of man-

aging two different chronic disease patients, one with diabetes and the
other with heart disease, will be higher than the cost of managing a single
patient with comorbid heart disease and diabetes [45]. This disparity is
due to the need to duplicate certain aspects of services provision to each
individual patient (e.g. administrative costs, clinic attendance), indicat-
ing that there are likely to be potential per capita cost savings associated
with the treatment of patients with comorbidity. However, a single patient
with comorbid illness may require additional health resources (e.g. more
time with the doctor, longer hospital stay) and longer and more intense
treatments, relative to two different patients with a single chronic condi-
tion. As detailed below, relatively few studies have compared the economic
costs of managing multiple comorbid disorders with the uncomplicated
presentation and treatment of single disorders.
However, the costs associated with managing comorbid mental health
disorders (e.g. anxiety disorders, depressive illness) and related conditions
(e.g., sleep problems) are known to be high. For example, at any one
time, about 2% of the Australian population is reported to be affected
by a serious mental health condition; in financial terms, this translates
into an annual societal cost of AU$15 billion in Australia and NZ$3.1
billion in New Zealand [46]. However, the full costs of managing the
separate conditions tend to be underestimated due to the omission of
costs related to the patients’ other comorbidities [47]. Further, a recent
US study showed that if a patient was hospitalised for a non-mental health
condition (i.e. heart failure), the cost was significantly higher if they had a
comorbid mental health condition (e.g. depression); that is, the additional
costs of depression ranged from US$1844 to US$7763 per patient per
psychiatric diagnosis, and it likely resulted in a longer hospital stay [48].
Thus, despite the lack of specific research, it is evident that the financial
costs of managing comorbid mental and physical health problems are high.
Similarly, sleep problems represent a significant cost to the individual
and the wider community, including the cost of therapy and costs asso-
ciated with work-related injuries, motor vehicle accidents and losses to
productivity due to sleep disorders [49]. For example, in four US corpora-
tions, workers who had insomnia and/or insufficient sleep syndrome had
significantly lower productivity, workplace performance and work safety
outcomes than those without a sleep disorder; the loss to productivity due
to sleep problems was estimated at $1967 per employee annually [50].
Similarly, the costs linked to sleep problems in Australia are estimated to
be about $5.1billion per annum, but again, the value excludes the costs
of managing people’s other comorbid conditions [49]. However, Deloitte
Access Economics and the Australian Sleep Health Foundation computed
the direct and indirect costs of several sleep disorders including insomnia,
OSA and restless leg syndrome (RLS), using 2010 data [51]. The indirect
costs of treating OSA included managing any comorbid hypertension,
vascular disease, depression and related motor vehicle and workplace acci-
dents. In total, the sleep disorders cost about AU$818 million which
included sleep disorder treatment ($274 million), treatment of other dis-
orders caused by the sleep problem ($544 million), and non-financial
costs of the disorders, including lost productivity ($3.1 billion/year) [51],
although some researchers have argued that the full costs were underesti-
mated, due to the use of overly conservative prevalence estimates for OSA,
RLS and insomnia [49].
Thus, it is apparent that the financial costs of managing comorbid
illnesses are high. It is certainly higher than the cost of managing the
uncomplicated presentation of a single disorder. However, relatively few
studies have examined the direct and indirect costs of disease comorbid-
ity. Nevertheless, the costs of comorbidity will likely vary depending on
the type and extent of the comorbidities. For example, common disorders
(e.g. insomnia, obesity) will tend to cost the most to manage, in terms of
the total health sector costs. Similarly, conditions that tend to co-occur
the most will tend to contribute more to the costs of managing other dis-
orders; for example, sleep problems are more strongly linked to depressed
mood than anxiety disorders; and [35, 52] thus, the costs of sleep-related
comorbidity will tend to be greater in patients with depressed mood than
in those with a comorbid anxiety disorder.
In contrast, chronic pain is more strongly linked to anxiety than depres-
sion, and so the economic costs of managing anxiety may be higher than
the costs of managing depression in chronic pain patients. For example,
nearly one-half (43.9%) of a sample of Spanish patients with chronic
widespread pain reported anxiety and whereas only one-quarter (27%)
reported depression [53]. Taken together, the results suggest that the costs
(and disability) associated with chronic widespread pain, which is often

concurrent with anxiety, depression and sleep problems, is higher than
the costs of managing matched control patients who do not have chronic
widespread pain [53]. The specific costs associated with managing other
comorbid disorders (e.g. diabetes mellitus type-II) will be described in
greater detail in the relevant book chapters.
Disease comorbidity has been shown to be associated with shorter life
expectancy. For example, the risk of myocardial infarction increases four—
fivefold in the presence of depressive symptoms, even after controlling for
medical factors [54]. Similarly, patients with comorbid depressed mood
and overweight/obesity [55], diabetes [56, 57] and insomnia (i.e. sleep
duration) [58] are more likely to experience an earlier than expected death.
Depression comorbidity also increases the mortality risk in patients with
high mortality illnesses such as OSA [59, 60] and anorexia nervosa [61],
although there is a lack of research on OSA [62]. Similarly, the high
mortality rate in schizophrenia patients has been shown to be at least
partly attributable to comorbid cardiovascular disease and cancer [63]; a
recent meta-analysis that evaluated studies from 25 countries confirmed
this pattern, showing that the high mortality rates linked to schizophrenia
were largely attributable to the presence of comorbid conditions [64].
Similarly, the Royal Australian and New Zealand College of Psychiatrists
[46] reported that comorbidity of a mental and physical health condition
reduced life expectancy in men and women. Patients with anxiety and/or
depression were at greater risk of all-cause mortality and risk of death from
specific illnesses, probably due to the ill-effects of the comorbid physical
health condition/s (e.g. cardiovascular disease, diabetes) [65]. In addition,
hospital inpatients with depressive symptoms are more likely to experience
readmission or increased mortality risk, relative to patients without depres-
sive symptoms [66]. Similarly, using data from the US National Health
Interview Survey (1999–2011), Pederson and colleagues [66] showed that
people with anxiety/depression were likely to die an average 7.9 years ear-
lier and had a doubled mortality risk and risk of hospital readmission,
relative to non-anxious and depressed controls [66]. Finally, in a study of
>5 million US military veterans, of whom 850,000 were depressed, high
baseline depression was linked to a 17% increased risk of all-cause mor-
tality and specific increases in mortality due to heart disease, respiratory
illness, cerebrovascular disease, accidents, diabetes, nephritis, influenza,

Alzheimer’s disease, septicaemia, suicide, Parkinson’s disease and hyper-
tension [65]. Thus, it is evident that comorbidity between a mental health
and physical health condition is linked to a shorter life expectancy. Specific
details of the mechanisms that may underpin the elevated mortality risk
in patients with comorbid illnesses will be discussed in greater detail in
the relevant book chapters.
Comorbidity is also typically linked to substantial disability. Disability
can limit a person’s ability to function adequately in their current environ-
ment, either mentally or physically [67]; this can adversely impact upon
multiple different aspects of their daily life. For example, a person with
diabetic retinopathy may develop permanent vision impairment and this
may interfere with their ability to perform daily domestic duties (e.g. cook-
ing), care for children and/or do paid work, unless accommodations can
be made in the workplace. Specifically, disabilities such as mobility and
cognitive impairment often result in a change in the patients’ work status,
including withdrawal from work, reducing work hours and/or changing
the type of work performed, for example, as seen in patients with multi-
ple sclerosis [68]. Furthermore, disease comorbidity can limit a person’s
capacity for self-care [32], suggesting that patients with multiple comorbid
disorders may struggle to manage the different illnesses and deal with the
extent of their disabilities. According to 2012 figures, about 4.2 million
Australians were affected by a disability, and compounding this issue, the
unemployment rate was 9.4% among disabled individuals, compared to
4.9% in those who were not disabled [69]. Thus, disability is common in
the community, although it is unclear just how much of this is related to
comorbid disease burden.
In particular, comorbidity between mental and physical health condi-
tions has been shown to more than double the odds that a person will
suffer from severe disability [70]. Several large mental health surveys have
shown that when mental health conditions are compared to physical health
conditions, the mental health conditions are more likely to predict severe
disability burden; specifically, the odds of experiencing a severe disability
were greater (more than additive) in patients with a mental and physi-
cal health condition/s [70]. Further, comorbidity between psychological
disorders has consistently been shown to be related to poorer progno-

sis and greater therapeutic demands from patients [71]. Taken together,
the results suggest that patients with comorbid health problems are more
likely to experience disability, poorer prognosis, and have more complex
health needs than patients with a single disorder, especially if they have a
concurrent medical and psychological problem/s.
Importantly, disability is described as a societal phenomenon inasmuch
as it is typically defined in terms of the extent to which it impairs a
person’s engagement with activities, including work, and the extent and
nature of their social interactions [72]. Thus, the effects of disability will
tend to extend beyond the individual to include their family unit, friends
and social network, and its effects may change over time. For example,
a patient may withdraw from their social network while they are unwell,
but if their health improves, they may need to rebuild the network and/or
make new friends or contacts. Alternately, a spouse may need to take over as
the primary breadwinner or give up work to care for the patient, resulting
in a loss of family income, financial stress and tension related to changes
in family roles and responsibilities and the broader redefinition of social
roles. Thus, it is apparent that comorbid disease burden has important
implications for the broader community, including the possibility that
the affected individual will prematurely withdraw from or reduce their
engagement with important aspects of their world. For example, a person
may need to withdraw from work and/or their social network due to
disability, and additionally, they may become stigmatised because of the
illness or the disability.
Stigma involves labelling an individual or group therefore setting them
apart from others. In nations such as Australia, stigmatised groups typi-
cally include people who are disabled, Indigenous, LGBTQI, unemployed,
homeless, poor, asylum seekers and those with mental health conditions.
Stigma is known to potentially lead to health inequality [73]; the more
a person (or population) is stigmatised, the more likely they are to suffer
disadvantage, although it has not been examined in regard to comorbidity.
Nevertheless, a review examining the mental health of Australian home-
less youth has suggested that homelessness is linked to increased suicidal
behaviour, the presence of psychiatric disorders and psychological distress
[74].
Thus, it is apparent that comorbidity is associated with considerable per-

sonal costs to individual patients, including the physical and psychological
impacts of the conditions. For example, they will likely experience multi-
ple physical and/or psychological symptoms; need to undertake multiple
different therapies, each of which may need to be taken at a different time
of day or under different conditions (e.g. before meals); need to attend
multiple different therapy appointments at different locations, at con-
siderable personal cost; and need to work with multiple different health
practitioners to co-manage their conditions. As a result, the burden of
comorbidity and its treatment is likely to interfere with a patient’s ability
to lead a normal life, derive a sense of personal control and psychological
well-being and maintain important social relationships and social roles
(e.g. parent, worker). Furthermore, certain aspects of the illnesses (e.g.
severity, disability, prognosis, treatment) may increase the likelihood that
they will experience stress, affective distress (e.g. anxiety, depression), grief
and possibly other comorbid conditions (e.g. sleep disorder).
In particular, patients with several different-but-related conditions may
spend many hours seeing various healthcare professionals, each of whom
will separately evaluate and treat the medical and psychological problems,
in an uncoordinated way. For example, a patient with comorbid over-
weight/obesity, binge-eating disorder, diabetes mellitus type-II, OSA and
depressed mood may variously be managed by an obesity clinic, endocri-
nologist, sleep apnoea clinic and clinical psychologist; they may separately
participate in weight loss and exercise programs and be prescribed dia-
betes medication, continuous positive airway pressure (CPAP) therapy
and cognitive behavioural therapy. As mentioned above, this uncoordi-
nated approach to patient care can represent a substantial burden to indi-
vidual patients and their families; for example, it may interfere with their
capacity to earn a living or fulfil important social roles as well adding to
the financial costs of caring for the patient.
Finally, as mentioned in Sect. 1.2, most healthcare services are currently
ill-equipped to treat patients with multiple comorbid conditions [75]. In
most clinical settings, patients tend to be prescribed a single treatment
plan for each separate condition, rather than a single coordinated ther-
apy plan for individual patients. Each treatment plans will typically be
administered by a different medical team or allied health professional;
there is often little communication between the staff, and between health-
care workers and patients [76]. Similarly, in some poor countries, there is
a lack of healthcare providers who have expertise in managing common
comorbid illnesses (e.g. HIV/AIDS and tuberculosis) using an integrated
treatment plan which takes into account the interactions between the dif-
ferent diseases [77]. Furthermore, where clinical practice guidelines exist
for the treatment of comorbidities, they have typically been found to be
less than adequate and may potentially increase the burden to patients
[78].
Thus, it is clear that patients with substantial comorbid illness burden
require an integrated therapy approach, which separately (and together)
addresses each medical and psychological condition. For example, a patient
could receive multiple co-therapies together or sequential therapies that
are co-managed in individual patients, although few comorbidity ther-
apy protocols currently exist. Nevertheless, multidisciplinary treatment
approaches will likely have utility in optimally managing a person’s comor-
bid illnesses, as they tend to permit the provision of coordinated evidence-
based therapy, using co-therapy or sequential therapy protocols.
Multidisciplinary care typically involves patients attending a central
location to see a number of medical and/or allied health staff involved in
their care. Clinicians can communicate with each other about the pre-
cise sequencing of the prescribed evidence-based care and the manage-
ment of the related problems (e.g. therapy side effects, affective distress).
For example, a breast cancer patient may undergo surgery, chemotherapy
and/or radiotherapy, as sequenced by the treatment team, using established
sequential therapy protocols that minimise side effects and maximise the
clinical response to therapy. Her psychological condition can also be man-
aged in the same clinic by allied health staff in coordination with the
medical team. Unfortunately, multidisciplinary care approaches have, for
the most part, not been utilised in the treatment of comorbid illnesses,
except in diabetes patients, who are sometimes managed in the multidisci-
plinary care setting; in which case, diabetes and comorbid conditions (e.g.
depressed mood) can be concurrently treated, as discussed in Chapter 4.
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724. https://doi.org/10.1001/jama.294.6.716.
2
Models of Comorbidity
2.1 Computational and Clinical Models

of Concurrent Symptom Development
Several authors have suggested that unravelling the causes of comorbidity
ranks among the top clinical priorities [1, 2]. However, most existing the-
ories of disease comorbidity provide only a broad overview of the manner
in which comorbidity is likely to arise. Logically, there are several broad
hypotheses that can be advanced to explain the existence of comorbidities,
including that: (i) a causal relationship exists between the coexisting dis-
orders; (b) a common factor(s) increases the likelihood that both disorders
will occur; and/or (c) the relationship is spurious [3]. However, the broad
overarching theories have, for the most part, not been tested empirically.
R. Brown (B)
Australian National University, Canberra, ACT, Australia
e-mail: rhonda.brown@anu.edu.au
E. Thorsteinsson
University of New England, Armidale, NSW, Australia
e-mail: ethorste@une.edu.au
© The Author(s) 2020 23

R. Brown and E. Thorsteinsson (eds.), Comorbidity,
https://doi.org/10.1007/978-3-030-32545-9_2
Further, few comorbidity theories are comprehensive yet specific enough

to help guide the exploration of relationships between specific comorbid
disorders and the likely role played by intervening factors. As a result,
we know little about the extent to which comorbidity is relevant to our
understanding of single disorders and conditions; the mechanisms which
likely underpin the development of comorbidities; and the nature of the
interactions between specific risk factors and comorbid disorders.
Nevertheless, in some instances, there is clarity as to the likely tem-
poral evolution of the clinical co-occurrences (e.g. mood disorders and
insomnia) [4]. However, bidirectional relationships are ubiquitous in the
scientific literature, and they have been documented in regards to most of
the disorders and symptoms covered in this book. For example, anxiety
and depression can predict the later onset and/or worsening of impaired
sleep, but, additionally, sleep problems can predict the later onset or wors-
ening of anxiety and depressed mood [4]. Crucially, we do not yet fully
understand the nature of these so-called bidirectional relationships. In
particular, noting the existence of a bidirectional relationship between
anxiety and depression over time tells us nothing about how the disorders
are functionally related to each other, including whether (or not) they are
causally related. One possibility, as discussed in Chapter 6, is that impaired
sleep and low mood are causally related to each other; such that sleep dis-
turbance can impair a person’s mood and low mood can worsen sleep, but
it is unclear exactly how this occurs and whether the mechanism/s is the
same (or different) in each case.
In contrast, it might be the case that the relationship is spurious. For
instance, anxiety and depression symptoms tend to overlap with each other
(e.g. impaired sleep is characteristic of both states) [5]; and the Diagnos-
tic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria for
the disorders includes a similar range of symptoms (e.g. impaired sleep,
gut problems) [5]. Further, the scales and clinical interviews that exam-
ine these states tend to ask about a similar range of somatic and affective
symptoms. Thus, the observed relationship between anxiety and depres-
sion may at least in part be a by-product of these overlapping symptoms
and/or the double-counting of the symptoms, although this is unlikely to
fully explain the observed relationships [6, 7]. Finally, it is possible that a
common factor (e.g. stressful life-events) can explain the tendency of people
to experience comorbid anxiety and depression; for example, stress may

result in rumination at night which interferes with sleep and, in turn, this
may contribute to anxiety and/or depressed mood [8]. However, it is not
exactly clear how anxiety and depression comorbidity develops, despite
the plethora of research on the topic, and partly this is due to the lack of
complex real-world models of anxiety and depression co-causation.
Outside the context of anxiety and depression comorbidity, even less is
known about the roots of comorbidity, even in the case of disorders that
are highly comorbid with each other (e.g. obesity, insomnia). Relatively
few studies in the scientific literature have specifically sought to address
this comorbidity, and few clinical theories have been developed to explain
the phenomenon. Thus, there is a crucial need to develop a theoretical
model/s that can parsimoniously explain the presence and development
of the comorbidities.
Nevertheless, some specific (but limited) theories of comorbidity do
exist which seek to explain the mechanisms by which specific disorders
can co-occur. For example, anxious and/or depressive rumination [9] and
cognitive and somatic arousal (i.e. stress-diathesis model of insomnia) [10]
are posited to interfere with the onset of sleep in some people (e.g. insom-
niacs), and, over time, this may contribute to shorter sleep duration and
cumulative tiredness, if the hyper-arousal or rumination persists over time.
Additionally, late night-eating has been posited to interfere with sleep onset
and shorten sleep duration, and as a result, people with night-eating syn-
drome are likely to develop sleep problems and be overweight/obese, rela-
tive to unaffected individuals [11, 12]. However, as discussed in Chapter 3,
it is unclear exactly how overweight/obese people will develop comorbid
sleep problems, for example whether the weight or sleep problem develops
first and the exact mechanism/s by which the late night-eating impacts on
sleep and weight.
As detailed in Chapters 3, 4, and 7, overweight/obese people are at an
increased risk of developing a range of other comorbid disorders and con-
current symptoms including stress, anxiety, depression, binge-eating dis-
order, diabetes mellitus type-II, and sleep-disordered breathing, relative to
unaffected individuals, which might also contribute to morbidity and mor-
tality in affected individuals. Thus, it is apparent that overweight/obesity
is highly comorbid with many different disorders, although we know little
about the specific mechanisms underpinning some of the comorbidities.

As a result, if an overly specific mechanism (e.g. night-eating syndrome
diagnosis) is examined for its utility in explaining the sleep and weight
problems in overweight/obese individuals, we may learn little about the
extent to which other concurrences (e.g. depression) or related risk factors
(e.g. physical inactivity) will interact together to contribute to the prob-
lems. Clearly, there is a crucial need to employ a more holistic theoretical
approach to the problem of disease comorbidity, which specifies the likely
roles played by multiple different intervening variables.
Currently, there are only two theories that have sought to explain the
presence and development of comorbidity in regards to multiple disorders
and symptoms. The first is a computational model that seeks to explain the
co-occurrence of multiple psychiatric symptoms. Schmittmann and col-
leagues [13] have used a network approach to conceptualise psychological
attributes (e.g. anxiety) as ‘networks of directly related observables’; that
is, a single construct (e.g. anxiety) might be conceptualised as a network of
related variables (e.g. somatic arousal, cognitive arousal, fear cognitions),
which overlaps with other constructs (e.g. somatic arousal, depression).
In another paper, the authors [1] sought to examine the network’s struc-
ture and its dynamics in an effort to replicate the empirical evidence of
psychiatric symptom comorbidity, using simulation methods to evaluate
the plausibility of the network’s properties. This work has resulted in the
network model of psychiatric symptoms that was derived from the analysis
of overlapping symptoms in DSM-4.
In their computational model, individual DSM-listed symptoms were
represented as individual nodes. In the analysis, nearly one-half of the
entire DSM-4 network of psychiatric symptoms (N = 208 symptoms,
across 69 disorders) was shown to be connected in the so-called giant
component. In the computational models, the distances between the
nodes for major depressive episode (MD) and generalised anxiety dis-
order (GAD) were reported to be consistent with the published comor-
bidity rates for the disorders, and model simulations of MD and GAD
reproduced the published population statistics (e.g. prevalence statistics)
for the two disorders [1].
Regarding potential mechanisms, Borsboom and colleagues [1] found

that many of the highly overlapping psychiatric symptoms in their DSM-
4 analysis were linked to basic homeostatic brain functions, including
eating, sleeping, sex and mood regulation. In particular, the four most
highly connected psychiatric symptoms in the analysis were insomnia,
psychomotor-agitation, psychomotor-retardation, and depression, which
were collectively linked to 60–71 other DSM-4 symptoms and 29–35%
of the symptoms in the giant component, for GAD and MD, respectively.
Thus, impaired sleep/insomnia, changes in activity levels, and depression
were the most highly connected symptom groups, which were highly cor-
related with each other, other symptom groups (e.g. anxiety), and changes
in behaviour (e.g. eating, sex). These computational results are generally
consistent with the observation that homeostatic processes are involved
in mediating at least some of the comorbid relationships, for example
between impaired sleep and fatigue, both of which are symptoms of depres-
sion [14].
On the basis of the results, Borsboom and colleagues [1, 15] posited that
the most highly connected symptoms may be ‘causally-coupled variables’
that play a crucial role in maintaining the structure of the psychiatric
symptom network. That is, activating a single node (e.g. anxiety) in the
network may indirectly contribute to the activation of other nodes (e.g.
depression) to cause other symptom group(s). For example, anxiety may
propagate via the network structure to contribute to insomnia, which, in
turn, may contribute to depressed mood, via anxious and/or depressive
rumination, which delays sleep onset and shortens sleep, and over time,
this may contribute to tiredness and depressed mood [9]. Thus, the shared
symptoms of anxiety and depression (e.g. impaired sleep, fatigue) may
‘function as bridge symptoms that transfer symptom activation from one
network to the other, like a virus may spread from one community to
another via people who are in contact with both’ (p. 9) [13].
Taken together, the results suggest that the computational model has
substantial utility in explaining the tendency of people to develop comor-
bid anxiety and depression, either concurrently or sequentially, potentially
via a number of different mechanisms. Several other aspects of the model
are also appealing: (1) there may be several or more potential causal path-
ways contributing to a particular disorder; (2) the symptom networks may
be different in different individuals and they may tend to change over

time; (3) this might result in different comorbidity pathways in different
individuals or in the same person at different times; and/or (4) multiple
different causation events may contribute to comorbid illnesses in some
individuals [1, 13, 15]. That is to say, there may be different possible paths
to comorbidity, and the pathways occurring in particular individuals may
depend upon the characteristics of the person (e.g. life experiences, coping
methods) and their specific life situation.
As detailed above, so-called causally coupled variables or causal chains
have already been posited to underpin the common co-occurrence of anxi-
ety and depression [16] and fatigue and depressed mood [17], via impaired
sleep and rumination [8]; for more discussion, see Chapter 6. Borsboom
and colleagues [1] also posited that comorbidity between depressive and
anxiety disorders will likely arise from causal chains of directly related
symptoms (e.g. impaired sleep). Consistent with this assertion, Kim and
Ahn [18] have shown that clinical psychologists tend to interpret their
clients’ symptom patterns in terms of the particular causal networks in
their clinical practice.
However, most ‘causal chains’ that have been described in the litera-
ture are singular in their focus. For example, they typically investigate a
single specific mechanism (e.g. impaired sleep leading to depression via
rumination) but exclude other clinically relevant factors or comorbidities
(e.g. emotional eating, overweight/obesity), which are also known to be
linked to impaired sleep [19] and affective distress (e.g. depression) [20,
21]. Thus, again, there is a crucial need to employ a more holistic theoret-
ical approach to the problem of disease comorbidity, which incorporates
multiple highly concurrent symptoms, disorders, and behaviour together,
so that a range of coexisting phenomena and potential intervening factors
can be considered together.
To address the aforementioned issues, the authors of this book have
recently developed a new clinical theory of concurrent symptom development
[22] which seeks to explain the mechanisms by which comorbidity is likely
to arise in people with concurrent overweight/obesity, impaired sleep, eat-
ing disorders, affective distress (e.g. anxiety, depression), and other dis-
orders (e.g. diabetes mellitus type-II). A specific biological mechanism—
dysregulation of nocturnal body temperature (BT) and the circadian rhythm
of BT —is proposed to explain comorbidities between the aforementioned

disorders, and throughout the book, we examine the model for its utility in
explaining the co-occurrence of highly connected conditions. A detailed
analysis of the relevant literatures pertaining to the relationships between
the disorders, symptoms, and behaviour, and perturbations in BT will be
provided, as appropriate, in the following chapters.
In short, the clinical theory posits that when certain symptoms (e.g.
anxiety) or sleep-disrupting behaviour (e.g. stress-related eating) are expe-
rienced at night, this can result in an elevated nocturnal BT that is sufficient
to interrupt sleep, occurring via a phase shift in the circadian rhythm of
BT. Furthermore, once a person’s sleep is disrupted, they may tend to
engage in similar (or different) sleep-disrupting behaviour (e.g. night-
eating, electronic device use) while they wait for sleep to come, and over
time, this may worsen their sleep and contribute to new disorders (e.g.
overweight/obesity) [23]. In this way, a person’s late night-eating may con-
tribute to a new disorder (e.g. insomnia, obesity) and/or the worsening or
perpetuation of existing behaviour (e.g. night-eating) via the delayed onset
of sleep at night, and as detailed in Chapter 3, the relationship appears to
be indirect, complex, and bidirectional.
That is, we propose that a bio-psycho-behavioural mechanism—an ele-
vated nocturnal BT that interferes with sleep onset —can parsimoniously
explain the presence and development of highly concurrent disorders
including insomnia/impaired sleep and overweight/obesity, via the prac-
tice of sleep-disrupting behaviour (e.g. late night-eating) at night.That is to
say, sleep-disrupting behaviour may be a behavioural mechanism by which
disease comorbidity occurs, because of its tendency to raise a person’s BT
[22], and the premise is examined in greater detail in Sect. 2.2. Simply put,
we propose that impaired sleep may play a pivotal and bidirectional role
in contributing to the causation, worsening, and/or perpetuation of other
disorders, symptoms, and behaviour, as well as being the consequence of
other disorders, symptoms, and behaviour. A pictorial representation of
our model is presented in Fig. 2.1.
Detailed empirical evidence will be provided to support this assertion
throughout the book, as appropriate to the specific disorders, symptoms,
and behaviour discussed in each chapter. However, it is worthwhile briefly
Fig. 2.1 Symptoms, states, and behaviour that can increase nocturnal body tem-
perature, and if practiced at night, thereby potentially interfere with sleep onset
reiterating that the study results of Borsboom and colleague’s [1] net-
work simulations showed that the most highly connected of all the psy-
chiatric symptoms were insomnia, psychomotor-agitation, psychomotor-
retardation, and depression. It is appreciated that all four of these symptom
groups are substantially correlated with elevated BT, especially high noc-
turnal BT, as indeed are most of the concurrent symptoms, disorders, and
behaviour discussed in this book, including overweight/obesity, night-
eating, and other sleep-disrupting behaviour.
2.2 Sleep, Body Temperature, and Circadian

Rhythm Function
We posit that a complex bio-psycho-behavioural mechanism that results
in an elevated nocturnal BT which interferes with sleep onset can explain
the high degree of comorbidity that exists between the aforementioned
disorders, symptoms, and behaviour, as detailed in Fig. 2.1. To more fully
explain this premise, a detailed explanation of the precise relationships that
exist between sleep onset, sleep offset, and BT in clinical and non-clinical
human samples is provided below.
First, changes in core BT are thought to signal the onset and offset of
sleep [24, 25], as shown in Fig. 2.2 [25]. In particular, before a person
can fall asleep, they typically need to cool down; specifically, sleep onset
is putatively triggered by a precipitous fall in core BT that occurs in the
early evening. In people who live a conventional lifestyle, core BT tends
to stabilise between 2:00 PM to 8:00 PM; then it precipitously declines
(on average 41 minutes before elderly people report wanting to go to bed)
[26]; it reaches a minimum at approximately 4:00–5:00 AM, after the
mid-point of sleep; and then it starts to increase before the end of sleep,
reaching its peak in the late afternoon [25–29]. As a result, most sleep
tends to occur in a rather narrow temporal window from 6 hours before
the temperature nadir and 2 hours after it (≈10 PM–7 AM) [25].
Thus, sleep typically begins when the rate of BT drop and body heat
loss is maximal, that is, when BT is falling most precipitously, a process
Fig. 2.2 Original caption reads: “Diagrammatic representation of normally

entrained endogenous rhythms of core body temperature (solid curve), plasma
melatonin (dotted curve), and objective sleep propensity (dashed curve) placed in
the context of the 24-h clock time and normal sleep period (shaded area).” Figure
is from Lack et al. [25]
Another random document with
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haar kamers en gluurde door de stores naar binnen. Niets te zien! In
den gekleurden ballon brandde ’t nachtlichtje; alles stil. Ze sliep, dat
was duidelijk, en aan haar kamer kloppen en haar wakker maken,
durfde hij niet.
In zijn eigen vertrekken teruggekeerd, deed hij moeite om te slapen,

maar ’t gelukte hem niet. Allerlei sombere, nare gedachten hielden
hem bezig en plaagden en vervolgden hem. Dat had men nu van die
vervloekte zijwegjes. En als het nu nog een wezenlijke p e n c h a n t
was, maar zelfs dat niet. Het was pure gewoonte geworden, zijn
gaan naar Lientje Donker, anders niets. Hij ging er heen, zooals men
aan tafel gaat: minder omdat men honger heeft, dan wel omdat het
nu eenmaal een aangenomen gebruik is te acht uren te dineeren.
Wat zou dat den volgenden ochtend een genoeglijke ontmoeting

wezen! Het zweet parelde op zijn voorhoofd, als hij er aan dacht.
Niettemin nam hij zich vast voor den kogel zonder verwijl door de
kerk te schieten. Zaken waren nu eenmaal zaken, en moesten
coulant worden afgedaan. Daar hield hij van, en hij was het zijn
leven lang gewoon geweest.
Tegen den ochtend sluimerde hij in van vermoeidheid en toen zijn

bediende hem tegen acht uren riep, sprong hij verschrikt uit het bed.
Daar zal je de poppen aan het dansen hebben, dacht hij met een
zucht.
De tafel in de achtergalerij stond voor het ontbijt gedekt. Louise was

er niet. Wèl de baboe met het kind; hij nam het van de meid over en
beproefde nog eens of hij den diapason [72]van zijn stemgeluid op
kinderooren streelenden klank kon brengen. Het ging minder goed
dan ooit.
Daar kwam ze aan!

„Goeden morgen,” zei hij op zijn meest gewonen toon. Ze
antwoordde op dezelfde wijze. Van ter zijde begluurde hij haar. Zij
zag er precies uit als altijd. Niets bijzonders.
„Ben je gisteravond nog uit geweest?”
„Ja.”
„Ik geloof dat we elkaar gepasseerd zijn.”
Zij haalde de schouders op, met een onverschillig gezicht, dat zich
geheel niet om zijn geloof scheen te bekommeren.
„’t Is wel mogelijk.”
„Ik meen het zeker te weten. ’t Was in gang.…”
„Och kom! Daar behoefde ik anders volstrekt niet te wezen.”
„Niet?”
„Wel neen. Om naar papa te gaan is het niet noodig dien omweg te
maken.”
„Ben je bij den ouden heer geweest?”
„Ja. Ik heb hem eens opgezocht.”
„Hoe drommel komt die koetsier dan zoo om te rijden?”
„Misschien dacht hij, dat ik het aangenaam vond, of misschien vond

hij ’t zelf pleizierig. Ik heb er niet op gelet.”
„Zoo-o!”
Een s c è n e viel er niet voor, dat was waar, maar Van Velton voelde
zich minder op zijn gemak dan ooit. Hij was zoo’n oude rat, dat hij
om zoo te zeggen de val rook, waarin ze hem naar het scheen wilde
laten loopen.
Er stak iets achter, dat was zeker, en hij moest en hij zou weten, wat
dat was. Met verder vragen kon hij niet doorgaan, [73]en naar dien
brief informeeren was ook niet raadzaam. Ten slotte ging hij naar de
stad met de overtuiging, dat hij aan de eerst zoo gevreesde scène
de voorkeur had gegeven boven deze geheimzinnigheid. Wie weet
of hij, schuld bekennend, onder aanvoering van verzachtende
omstandigheden en met belofte van beterschap, niet.… een kansje
had gehad!
Hortense Van Velton reisde onder de hoede van een predikants-

familie met een der booten van de maatschappij N e d e r l a n d .
Zijzelve was liever met een Fransche boot gegaan, maar de familie
in Holland had dat niet wenschelijk geacht.
Iedereen had de reis erg aangenaam gevonden.
Men had muziek gemaakt, tooneel gespeeld, gedanst en zich het

leven zoo aangenaam mogelijk gemaakt. Doch Hortense had zich
teruggetrokken. Zij vond het ordinair.
Mooi was ze niet, en toch ook niet leelijk, al had ze iets ziekelijks
over zich. Ze was wat lang en wat hoekig voor een jong meisje,
maar zeer blank en erg voornaam. In haar uiterlijk had zij veel van
haar vader. Als hij langs de kali-besar liep, dan had een vreemdeling
allicht kunnen denken, dat alles wat daar stond, gebouwd en
ongebouwd, zijn eigendom was. Welnu, als Hortense op het dek van
den stoomer wandelde, en hij „rolde” niet al te erg, dan stapte zij zoo
voornaam en majestueus van ’t eene eind der kampanje naar ’t
andere, dat de jongelui elkaar aanstieten en haar „mevrouw de
commandant” noemden, wat ze eigenlijk niet zóó zeiden maar op
een andere, meer onder heeren gebruikelijke wijze.
Onder de passagiers was zij niet bemind. Zelfs de predikant en

diens vrouw mochten haar niet, zoo stijf en afgemeten [74]was zij
altijd, en ofschoon haar zee-ouders dat welwillend toeschreven aan
de ziekelijke omstandigheden waarin het meisje verkeerde,—
aangenaam vonden de goede, hartelijke menschen het niet.
Hortense Van Velton haatte haar stiefmoeder, die ze nog nooit had
gezien.
Zij noemde haar vader openlijk een dwaas, en had zich vast
voorgenomen hem dat onder vier oogen te vertellen. Hoe ze „dat
mensch” behandelen moest in haars vaders huis, begreep zij niet.
„Mama” zeggen, dat zou misschien nog het hatelijkste wezen
tegenover dat jonge vrouwtje.
De geheele reis had ze aan niets anders gedacht, dan aan haar
stiefmoeder. Zou ze haar aan boord komen afhalen?
Ze kwam niet.
Toen het schip op de reede van Batavia lag, kwam Van Velton met
een sloep langs zij en klom de trap op. Het was een tamelijk koele
ontvangst. Zij vond, dat papa er veel minder goed uitzag, dan toen
hij een jaar of vijf geleden eens in Europa was geweest; hij vond dat
Hortense leelijk en spichtig was geworden, en dat het heel wat
moeite zou kosten haar aan den man te brengen.
„Hoe heb je het gehad aan boord?” vroeg hij.
„Zoo.… tamelijk.”
„Nu, je kunt thuis je schade inhalen.”
„Thuis bij.… mama?”
„Ja.… noem haar maar zoo.… Als ’t haar niet aanstaat zal ze ’t je
wel zeggen.”
Het gezicht van Hortense klaarde op. Komaan, dat begon

uitstekend! De verhouding was voor haar bijzonder gunstig. [75]Uit de
manier, waarop hij sprak, bleek duidelijk, dat het niet c o u l e u r d e
r o s e was tusschen hem en de tweede vrouw. ’t Kon waarlijk niet
beter. Als papa nu nog niet wist of zij er vrede mee nam, dat de
kinderen haar „mama” noemden.… nu dat scheen in orde te zullen
komen.
„Natuurlijk zou ik haar mama genoemd hebben; zij is uw vrouw en

d u s de „vrouw des huizes.”
„Lieve Hortense,” zei Van Velton op zijn voornaamsten patriarch-

toon, „mevrouw Van Velton-Van der Linden is een zeer eigenaardige
dame. Ik hoop, dat je het goed met haar zult kunnen vinden; maar
als je er misschien op hebt gerekend een.… moeder.…”
„Dank u; m i j n moeder is dood.”
„Of.… een vriendin .…”
„Evenmin.”
„Nu, des te beter dan. Want mijn vrouw zal waarschijnlijk noch het
een, noch het ander voor je zijn. Begin echter met haar te geven,
wat haar wettig toekomt, en noem haar mama.”
Hortense ademde vrijer. Goddank! Geen intimiteit. Op een afstand

en zonder vertrouwelijkheid. Dat was de eenig draaglijke manier.
Nieuwsgierig om te zien hoe „mama” er uitzag, keek ze de
binnengalerij rond nog voor ze uitstapte. Dus kwam „mama” haar
niet te gemoet!
Ze gingen het huis binnen en vonden de vrouw des huizes in de

achtergalerij. Langzaam en met haar commandanten-houding trad
Hortense op het mooie, kleine vrouwtje toe, wier schoonen sierlijken
lichaamsbouw ze met stille woede opmerkte. [76]
„Louise,” zei Van Velton, „dat is mijn dochter Hortense.”
„Dag mama.”
De stiefmoeder begon te lachen.
„Je moet ’t me niet kwalijk nemen, Hortense, maar ’t klinkt zóó gek
om u tegen mij „mama” te hooren zeggen. Noem mij maar
m e v r o u w hoor.”
„Heel goed; dat doe ik ook veel liever.”
„Natuurlijk; ’t was onnoodig het te zeggen. Je kamers zijn klaar. Je

papa zal wel zoo goed zijn om ze je aan te wijzen. Tot ziens.”
Mevrouw Van Velton-Van der Linden keerde zich om en ging heen.

Hortense was er eenigszins van verbluft. Dat overtrof nu alles wat ze
zich bij mogelijkheid had durven voorstellen.
’t Scheen haar hier een huisgezin toe vol storm en onweer.
„Gaat het hier altijd zoo?” vroeg ze haar vader.
„Wat bedoel je?”
„Wel dien vriendelijken toon en die prettige, huiselijke manier van

doen?”
„Mijn vrouw is zeer eigenaardig.”
„O, is het anders niet?”
„Anders niet? Wat zou het dan?”
„Ik dacht dat het misschien.… een ongelukkig huwelijk was.”
„Hoe kom je op dat idée?”
„Och.… zoo maar.”
„’t Gaat hier altijd stil en bedaard toe. Je weet, ik ben een vijand van
rumoer.”
„En altijd op de manier van daareven?” [77]
Wat zou hij zeggen? Waarom het voor haar te verzwijgen? Zij zou
het immers toch spoedig genoeg gewaarworden.
„Ja, zoo ongeveer.”
„Dan heb ik immers gelijk gehad; dan is uw huwelijk ongelukkig, pa.

Hoe bent u ook zoo dom kunnen wezen? Kijk, als dat mensch nu
niet hier in huis was, wat zouden we dan een aangenaam en rustig
leven kunnen hebben. Nu staat zij er tusschen als een hinderpaal; zij
met dat vieze kind.”
„Het is geen vies kind,” zei Van Velton eenigszins verontwaardigd.
„Och, dat zijn die kleine kinderen allemaal. Aan boord.….. bah!”
Van Velton lachte.
„Kom, laat ons er maar over zwijgen. Ik hoop dat de kamers je zullen
bevallen. De meid zal je helpen aan ’t ontpakken van je goed.
Adieu!”
Hij kwam nog even terug.
„Ik ga naar de stad. Straks zal men je wel waarschuwen voor de

rijsttafel.”
De kamers waren keurig ingericht, en al had Hortense het land aan

haar stiefmoeder, ze was verplicht haar in stilte dankbaar te zijn voor
de zorgen, die ze aan het arrangeeren dezer kamers had besteed.
Toch was het geen groote dankbaarheid, die bij het lange, bleeke
jonge meisje opwelde. „Ze heeft smaak,” dacht ze bij zichzelve; „dat
hebben die nona’s meer.”
Verder kwam ze niet. Ze wachtte ook niet, tot ze werd geroepen voor
de rijsttafel. Waarom zou ze wachten? Was [78]het niet evengoed
h a a r huis? Daarom ging ze naar de binnengalerij en bekeek er de
bibelots en de schilderijen, die ze zich van vroeger niet herinnerde.
Een uurtje later kwam een bediende haar zeggen, dat de

„m a k a n a n s o e d a h ” klaar was; ze ging naar achter en vond
haar stiefmoeder reeds aan tafel.
Louise was eenigszins in haar humeur. ’t Had haar aangenaam

getroffen, dat Hortense zooveel minder mooi was, dan zijzelve, en
dat stemde haar tot toegeeflijkheid. „Was je ziek in Holland?” vroeg
ze.
„Ja. Ik kon niet tegen de kou.”
„Hoe is het mogelijk? Ik vond het er heerlijk lekker.”
„Bent u ook in Europa geweest?”

„Natuurlijk,” zei Louise verontwaardigd. „Mijn papa was wel geen
koopman; hij is s l e c h t s geneesheer; maar dat belette hem niet mij
een Europeesche opvoeding te doen geven.”
Hortense voelde het hatelijke, dat in het s l e c h t s stak, maar wist

niet goed wat te zeggen. Zij had ook verstand genoeg om in te zien,
dat ze tegen dit kleine, donkere vrouwtje in een woordenwisseling
niet opgewassen zou zijn, en dat de statigheid en de ernst, die zij
van haar vader had geërfd, het tegen de manieren en de zegswijze
van mevrouw Van Velton-Van der Linden zouden afleggen. En die
overtuiging drong haar nog een andere op. Haar stiefmoeder was de
meesteres in huis en papa had weinig of niets te zeggen. Dàt idée
hinderde haar ’t meest. Zij gaf geen repliek op ’t hatelijke „slechts” en
at stil door. Zij zou met haar vader spreken. Samen zouden zij
sterker zijn. [79]
Zoo liep het diner kalmpjes af. Hortense gaf haar oogen en ooren
meer en beter den kost dan haar mond, terwijl Louise de rijsttafel
groote eer aandeed.
Van Velton zocht, toen hij van ’t kantoor thuis kwam, dadelijk zijn
dochter op.
„Wel, hoe heb je het gehad vandaag?”
„Hartelijk nu juist niet. Aan tafel heeft zij ’n hatelijkheid gedebiteerd

op uw positie.”
„Wat dan?”
Zij vertelde het hem, en hij lachte. Was het anders niet? Hij had
direct gedacht aan zijn positie als echtgenoot.
„Zij schijnt een zeer pertinent en heerschzuchtig schepseltje te zijn,

dat hier geducht den baas speelt.”
„Een vrouw moet meesteres in huis zijn, Stanse. Ik heb je mama ook
’t huishouden laten bestieren, zooals zij dat goed vond.”
„Maar onder de pantoffel zat u niet; dat weet ik wel zeker.”
„Ei?” vroeg hij met saamgetrokken wenkbrauwen. „En wie zegt je,
dat ik er nu onder zit?”
„Dat zeg ik, pa. Aan alles kan ik het merken. Zij, uw tweede vrouw,
bestuurt niet, maar regeert, en feitelijk hebt ge niets te zeggen. Dat
kan zoo niet blijven, en daarom.…”
„En dáárom,” viel haar vader haar in de rede, „dáárom verzoek ik je

om je volstrekt niet te bemoeien met de verhouding tusschen mij en
je stiefmoeder. Ik moet je dat zeer ernstig verzoeken, Hortense! Het
is mijn uitdrukkelijke wil. Je kunt in alles doen wat je goed vindt:
uitgaan, bezoek ontvangen, over geld beschikken voor je toilet,—
maar eens [80]en vooral: houd je dáár buiten. Dat zijn zaken,
waarmee kinderen niets te maken hebben.”
Hij ging terug naar zijn kamer, terwijl Hortense met tranen in de
oogen bleef zitten.
Wat kon haar ’t uitgaan schelen, of bezoek ontvangen? Wat gaf zij
om nog meer toiletten, dan ze reeds had?
Dansen en laat uitblijven veroorloofden haar delicate gezondheid

niet, en trotsch was ze wel, maar die gewone meisjes-ijdelheid en
coquetterie waren haar volkomen vreemd.
’t Zou het ideaal van Hortense geweest zijn, om een stil, rustig leven
te leiden in het mooie huis op ’t Koningsplein, en om daar alles te
regelen en te doen uitvoeren naar haar zin. Het middel om daartoe
te komen, nu eenmaal haar vader zoo onhebbelijk was geweest om
te hertrouwen, bestond in een scheiding tusschen hem en die vrouw.
Ze meende dat het gemakkelijk zou gaan, bij zulk een slechte
verstandhouding en als de oude heer er krachtig toe wilde
meewerken.
Maar dat wilde hij niet. Hij was ook al zoo i n d o l e n t . ’t Was om er
den moed bij te laten zakken!
Louise wist er thans alles van.
Zij had den dag na de ontvangst van den anoniemen brief, het
volgende geschreven aan de weduwe Donker:
„Mevrouw!
U zult mij zeer verplichten met hedenochtend bij mij te komen. Ik

wenschte u in uw eigen belang gaarne te spreken.
Uw Dw.
L. Van Velton-V. d. Linden.”
[81]
Christien Donker moest er om lachen.
Zoo’n nest! zei ze bij zichzelve. „In mijn eigen belang!” O liefje, ik
heb je vast en ik zal je nog wel beter vast krijgen. Maar jij zult bij mij
komen, trotsch diertje, en ik niet bij jou.
In het gevoel harer macht niet verder nadenkend, schreef ze in

dorso van ’t briefje van Louise:
„Als mevrouw Van Velton de weduwe Donker wenscht te spreken,

dan zal zij van het Koningsplein naar gang.… dienen te komen.”
Eerst toen de bediende van Louise, die nog wel van een karretje
gebruik maakte, geruimen tijd was vertrokken, bedacht Christien
Donker, dat zij in haar drift een groote domheid had begaan.
Doch wat kon het haar ten slotte schelen! Zij had nu, meende ze,
toch alle troefkaarten in handen, en ze zou die met het grootste
genot openlijk uitspelen.
Natuurlijk trof Louise onmiddellijk de overeenkomst van het schrift.

Zij haalde den anoniemen brief voor den dag en lei die naast het
antwoord.
Er was geen twijfel mogelijk.
’t Waren dezelfde leelijke, onregelmatige, scheeve letters, met de

ongeoefende hand gezet van iemand, die nooit ’t schrijven goed
heeft geleerd.
Tevergeefs trachtte zij het raadsel op te lossen. Geen

omstandigheden, van welken aard ook, waren in staat geweest haar
tot een bezoek aan die vrouw te bewegen, maar dàt intrigeerde haar
zoo ontzaglijk!
Dat mensch gaf zelf als het ware publiciteit aan de schande [82]harer
dochter, lokte zelf een ontdekking uit, die alleen onaangename
gevolgen voor haar kon hebben. Het ging boven het begrip van
Louise.
Dadelijk liet ze inspannen.
Met de smalle lippen stijf opeen en de wenkbrauwen

samengetrokken, zag Christien Donker het rijtuig haar erf oprijden.
Ze had zich in de voorgalerij eenigszins verdekt opgesteld, zóó, dat,

als Louise binnenkwam, zij als het ware onverwacht voor haar stond.
Ze gevoelde dat ze zenuwachtig was geworden en dat bestreed ze.
Zij was in moeilijke omstandigheden altijd haar zenuwen den baas
gebleven, en zou ze het nu dan niet tegenover „dat nest”?
Maar ze wist hoe „dat nest” wezen kon; ze wist hoe diep minachtend
„dat nest” kon kijken, en welk een hoogen, ijskouden toon, die zelfs
Christien Donker deconcerteerde, datzelfde „nest” kon aanslaan.
Daarom had ze op het effect gerekend.
Toen Louise de paar treden opstapte, die naar de voorgalerij

voerden, zag zij rond of er niemand was. Er was niemand, blijkbaar,
—maar zie, nauwelijks had ze een voet gezet in de voorgalerij of ze
stond tegenover een vrouw van zekeren leeftijd, die met bijzondere
snelheid van achter een pilaar scheen te komen en haar nu strak
aanzag.
Louise nam haar kalmpjes op van ’t hoofd tot de voeten. Wat

beteekende dat? Was het mensch gek?
„Bent u de weduwe Donker?” vroeg ze zeer bedaard.
’t Was voor Christien om uit haar vel te springen. Al het effect van
den c o u p d e t h é â t r e was weg. Zij had er [83]op gerekend dat
Louise haar zou herkennen, en dat ze, haar herkennend, den
geheelen omvang van de verhouding zou begrijpen.
Christien Donker k o n niet gelooven, dat Louise zich harer zelfs niet
meer herinnerde; zij stelde zich altijd op haar eigen standpunt en
nooit op dat van een ander.
„A zoo! Wou mevrouw soms den schijn aannemen, alsof ze me niet

kende?” zei ze op tergend beleefden toon.
En wederom monsterde Louise haar koel en bedaard met haar
groote, zwarte oogen.
„Ik zou niet weten, mensch, waarom ik een schijn zou aannemen. Ik
herinner me niet u ooit gezien te hebben.”
„Och kom? Wil je dat niet te binnen schieten? Zal ik uw memorie dan
eens ’n handje helpen?”
„Wacht even,” zei Louise. „’t Gezicht was ik geheel vergeten, maar
nu herinner ik me die dwaze stem.”
Die dwaze stem! Zij verbeeldde zich, dat ze van allerlei in den klank
harer stem lag, dat zoo’n jong schepsel moest doen rillen en beven,
maar dit „nest” ging alles langs de koude kleeren. Ze voelde, dat ze
terrein kwijt was.
Maar Louise was zeer ernstig geworden.
„Zeker, nu herinner ik me. Je bent die vrouw, die in vroeger jaren

onderhouden werd door papa.”
Het werd zeer eenvoudig gezegd. Zóó eenvoudig en zonder

terughouding, dat Christien Donker ’t gevoel had, als kreeg ze een
klinkenden klap in het gezicht.
„Zoo,” vervolgde mevrouw Van Velton spottend. „En nu vervult uw

dochter dezelfde rol tegenover mijn man! Komaan!”
Daar lag het plan in duigen! Zooveel koele onverschilligheid [84]kon

niet gehuicheld wezen. Dat was onmogeljjk. Er stak iets achter. Zou
Louise misschien van de gelegenheid gebruik willen maken?.… Had
ze wellicht zelf iets op haar geweten, en vond ze nu een geschikte
gelegenheid om.… Christien Donker dacht niet verder na. Welzeker,
dat moest het wezen.
„Waarom komt u hier?” vroeg ze.
„De eerste vraag is, geloof ik, aan mij. Waarom hebt u me dien brief
geschreven?”
„Daar laat ik me niet over uit.”
Waarom zou ze het zeggen, nu het toch mislukt was?
„Goed, het kan mij ook niet schelen.”
„Nu, wat is uw antwoord? Als het u zoo onverschillig is; als n i e t s u

iets kan schelen, wat doet u dan hier in mijn huis.…”
„Bij manier van spreken.”
„Wat bedoelt u daarmee?”
„Och niets,” zei Louise. Ze keek eens rond en meenend dat Van
Velton de huishuur en ’t meubilair betaalde, was haar dat „bij manier
van spreken” ontsnapt. Ze voelde overigens weinig lust om met
zoo’n wijf in noodeloozen woordentwist te treden.
„Ik heb u een verzoek te doen.”
„Een verzoek?”
„Zeker. Dat u me geschreven hebt, kunt u niet ontkennen, ’t Bewijs

ligt in uw briefje van hedenochtend, ’t Is dus heel natuurlijk dat ik van
uw vriendelijke waarschuwing gebruik maak.”
„Beschouw ’t maar als een vergissing.” [85]
„Toch niet. Ik wenschte dat u nog een stap verder ging en mij in de
gelegenheid stelde te zien.”
„Zoo! Heb je betere bewijzen noodig? Hm! Ik geloof dat ik het
begrijp.”
„Dat geloof ik niet.”
„Zal ik het u maar ronduit zeggen?”
„’t Is onnoodig. Ik zie aan uw gezicht wat u bedoelt. Het schijnt dat
ge u dikwijls vergist in de menschen.—Niets is minder waar dan dàt,
en niets zal ooit minder waar kunnen zijn.”
Al de beleedigde trots der fatsoenlijke vrouw sprak uit haar stem,

haar trekken. Het was zóó onmiskenbaar, dat zelfs Christien Donker
er door in verwarring raakte.
Het was voor deze laatste een zeer gek geval. Weigeren was minder
gemakkelijk dan het scheen, en van toestemmen zag zij het nut niet
in.
Wie weet of zij er niet meer uit zou krijgen, als ze zich bereid
verklaarde om aan het verzoek te voldoen.
„Nu,” zei ze, „het is onnoodig zoo’n hooge borst te zetten. U zoudt de
eerste niet zijn en de laatste evenmin.”
Louise verwaardigde zich niet er op te antwoorden.
„Als u zoo gaarne ’t genoegen wilt smaken van zelf te zien, hoeveel
meneer Van Velton van u houdt, dan wil ik u wel in de gelegenheid
stellen. Kom a. s. Zaterdag.”
„Dan gaat meneer Van Velton zijn partijtje maken.”
„Jawel, dat weten we! Nu maar, kom Zaterdag gerust hier, dan kunt
ge hem zien.”
„Hoe laat?”
„Tegen tien uren.” [86]
„Ik dank u.”
„U behoeft me niet te danken. Ik ben nu eenmaal zoo gek geweest

om u te schrijven, en nu ik in het schuitje zit, dien ik wel mee te
varen.”
„Ik wensch u goeden avond.”
„Dag!” zei Christien Donker kortaf.
En ze was gekomen, en ze had gezien wat haar nominale

echtgenoot bedoelde, als hij Zaterdagsavonds met eenige vrienden
een partijtje ging maken.
Van Velton was in het onzekere gebleven, want op haar volgende

tochten had Louise, instinctmatig voorzichtig, een huurrijtuig
gebruikt. De eerste dagen was hij een beetje bevreesd geweest,
maar hij had het zich, zooals men ’t noemt, ontgeven, en des
Zaterdags toen zij hem bespied had, was hij zijn partijtje gaan
maken met een gerust geweten.
Het ging alles den horizon van Christien Donker te boven. Zij
begreep er alleen van, dat, zoo haar plan was geweest zich door
middel van Lientje te wreken op de wettige dochter van Van der
Linden, dit volkomen was mislukt.
Men hoorde van niets hoegenaamd.
Van geen schandaal, van geen scheiding.

Zij had ook de bedienden van Van Velton uitgehoord, maar die
wisten blijkbaar van niets. Er kwam nooit een heer bij de njonja,
nooit! Zoo ’s morgens een paar getrouwde dames uit de buurt, maar
dàt was ook alles.
Gaarne had zij zich nu gewroken op Van Velton, dien zij in haar
straattaal steeds vereerde met den bijnaam van „het oude varken”,
maar er begon zich voor haar een [87]macht te ontwikkelen; ’t was
het geld dat Van Velton gaf.
Niet dat zij het noodig had,—aan wezenlijk, dadelijk realiseerbaar

eigen kapitaal, bezat ze misschien meer dan hij.
Maar hij kon in een maand meer uitgeven dan zij in een half jaar,
zonder dat er sprake was van zijn kapitaal. Van hetgeen hij gaf,
konden zij en Lientje leven, en zoo hield Christien, die liefde
koesterde voor ’t geld, dat thans haar eenige genegenheid was, zich
liever met Van Velton op een goeden voet.
In die phase was Hortense uit Europa gekomen.
Zij was alreeds een paar dagen thuis, en er begon een pijnlijke
spanning te heerschen.
’t Meisje moest toch uitgaan, moest in families gebracht worden.
Reeds had menig handelsvriend gezegd dat hij gehoord had, dat zijn
dochter was uitgekomen, en gevraagd wanneer men ’t genoegen
zou hebben haar eens te zien.
Van Velton had ontwijkende antwoorden gegeven: vermoeid van de

reis; nog niet op haar gemak; een beetje koortsig,—allemaal
noodleugentjes, want Hortense was volmaakt wel,—maar nu moest
er na een week toch een eind aan komen.
„Hm!.… Louise.…” begon hij op een ochtend.
„Wel, wat wou je?” was het onvriendelijk bescheid.
„Het betreft Hortense. Ze kan niet.… hier in huis blijven zitten.… ze

moet voorgesteld worden.”
„Ja, dat vind ik ook.”
„Als je er dus niets tegen hebt.…”
Zij ging vlak voor hem staan en keek hem zoo recht in [88]de oogen,
dat hij, niet wetend wat daar volgen zou, zich minder op zijn gemak
begon te gevoelen.
„Het verwondert me,” zei ze, „dat je zoo kortzichtig bent. W i j

moeten Hortense niet alleen in de wereld brengen om harentwil,
maar wij, ieder voor zich, zijn dat aan de wereld verplicht. Heb i k me
aan d i e verplichting ooit onttrokken?”
„Volstrekt niet.…”
„Dat ik je niet lijden mag, ja in den laatsten tijd een hekel aan je heb,
is iets waarvan ik onder ons geen geheim maak.”
„Dankje voor de openhartigheid.… ’t Is heel vleiend.…”
„Wees niet jezuïtisch Van Velton. Het is geen nieuws voor je, en ’t
kan je ook niet schelen. D a t w e e t i k .”
Hij hoorde den klemtoon wel, maar vond het geraden Oost-Indisch
doof te wezen. ’t Voornaamste was in orde, en voor het oogenblik
kon men de rest laten rusten.
„Nu,” zei hij vergoelijkend, „laat ons niet twisten. Het spijt me dat ik je
verkeerd heb begrepen, en ik maak er wel mijn excusen over. Het is
dus afgesproken dat we met Stance visites zullen maken?”
„Ja.”
„Zal ik een lijstje opstellen?”
„Och neen! Als ik iets doe, stel ik het zelf vast. Ik zal ’n lijstje maken.”
„O uitstekend.… het is niet.… Ik dacht niet dat je het gaarne deedt.”
Zij haalde de schouders op en ging heen. Hoe had ze toch in

godsnaam ooit er in kunnen toestemmen een man te trouwen, die
zou afschuwelijk b ê t e kon zijn. Dat hij slecht [89]was,—ze wist niet
beter of dat waren zoowat alle mannen. Haar eigen vader, immers!
Maar dat hij zoo’n mal figuur kon maken, vond ze onuitstaanbaar.
Hortense vernam het nieuws met G l e i c h g ü l t i g k e i t . Ze kleedde

zich tegen halfzeven en liep tegen zeven uren slecht gekapt, maar
met een houding als een koningin, de galerij op en neer.
Van Velton zag het, en het hinderde hem.
Dat was nu een meisje, dat een Europeesche opvoeding had

genoten! Ze wist zich nog niet te kleeden!
„Je coiffure is niet bijzonder geslaagd, kindlief,” zei hij, haar hoofd
door zijn lorgnet beschouwend.
„Och, ’t gaat nogal. Ik zal morgenavond een kapper laten komen.”
„Wel ja, doe dat.”
Toen Louise uit haar kamer kwam, trof het hem hoe onberispelijk zij
er in alle opzichten uit zag.

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The Future of Election Administration 1st ed. Edition

Autism in Translation: An Intercultural Conversation on

ISBN 978-3-030-32544-2 ISBN 978-3-030-32545-9 (eBook)

Cover illustration: Gregory Davies/Stockimo/Alamy Stock Photo

Collectively, as co-authors, we have extensive clinical and research expe-

Canberra, Australia Rhonda Brown

1 Comorbidity: What Is It and Why Is It Important? 1

3 Overweight/Obesity and Concurrent Disorders,

4 Overview of the Comorbidity Between Medical

5 Comorbid Eating Disorders 115

6 Comorbid Psychiatric Illnesses 139

7 Arousal States, Symptoms, Behaviour, Sleep and Body

8 Design, Statistical and Methodological Considerations:

9 Typing It All Together 241

C. Laird Birmingham, M.D. is a Specialist in Internal Medicine,

bacterial translocation (i.e. leaky gut), during her post-doctoral fellow-

Yasmine Umar is a Doctoral Candidate at the Australian National

Fig. 2.1 Symptoms, states, and behaviour that can increase

1.1 What Is Comorbidity?

© The Author(s) 2020 1

refers to the coexistence of multiple illnesses, disorders or conditions. For

Additionally, in Chapter 4, comorbidity between overweight/obesity

1.2 Why Is Comorbidity Important?

estimate of 20% was obtained in an Australian study [21]; 29.7% had

Taken together, it appears that comorbidity is present in at least one-

However, as discussed in Chapter 9, there appear to be few novel ther-

1.3 What Is the Cost of Comorbidity?

Nevertheless, it is broadly appreciated that the financial costs of man-

(and disability) associated with chronic widespread pain, which is often

illness, cerebrovascular disease, accidents, diabetes, nephritis, influenza,

disorders has consistently been shown to be related to poorer progno-

Thus, it is apparent that comorbidity is associated with considerable per-

Geriatrics Society. 2007;55(10):1585–1591. https://doi.org/10.1111/j.1532-

2.1 Computational and Clinical Models

© The Author(s) 2020 23

Further, few comorbidity theories are comprehensive yet specific enough

to experience comorbid anxiety and depression; for example, stress may

about the specific mechanisms underpinning some of the comorbidities.

Regarding potential mechanisms, Borsboom and colleagues [1] found

be different in different individuals and they may tend to change over

of BT —is proposed to explain comorbidities between the aforementioned

2.2 Sleep, Body Temperature, and Circadian

Fig. 2.2 Original caption reads: “Diagrammatic representation of normally

In zijn eigen vertrekken teruggekeerd, deed hij moeite om te slapen,

Wat zou dat den volgenden ochtend een genoeglijke ontmoeting

Tegen den ochtend sluimerde hij in van vermoeidheid en toen zijn

De tafel in de achtergalerij stond voor het ontbijt gedekt. Louise was

Daar kwam ze aan!

„Ben je gisteravond nog uit geweest?”

„Ik geloof dat we elkaar gepasseerd zijn.”

„’t Is wel mogelijk.”

„Ik meen het zeker te weten. ’t Was in gang.…”

„Och kom! Daar behoefde ik anders volstrekt niet te wezen.”

„Ben je bij den ouden heer geweest?”

„Ja. Ik heb hem eens opgezocht.”