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6
Comorbid Psychiatric Illnesses
Einar Thorsteinsson and Rhonda Brown
6.1 Comorbidity Between Anxiety
and Depressive Disorder
Feinstein [1] defined comorbidity as referring to any additional disor-
der that coexists with the first disorder; for example, a client with Major
Depressive Disorder (MDD) and Generalised Anxiety Disorder (GAD)
has comorbid disorders, and their symptoms will be experienced concur-
rently. As outlined in Chapter 1, comorbidity is common across a variety
of disorders [2–4] including anxiety disorders, depressive disorders, and
post-traumatic stress disorder (PTSD). Asdetailed in Chapters 1, 2,and8,
the high comorbidity between anxietyand depressive disorders is expected
E. Thorsteinsson (
B
)
University of New England, Armidale, NSW, Australia
e-mail: ethorste@une.edu.au
R. Brown
Australian National University, Canberra, ACT, Australia
e-mail: rhonda.brown@anu.edu.au
© The Author(s) 2020
R. Brown and E. Thorsteinsson (eds.), Comorbidity,
https://doi.org/10.1007/978-3-030-32545-9_6
139
140 E. Thorsteinsson and R. Brown
given the substantial degree of overlap in their definitions, diagnostic cri-
teria, and symptoms. Each disorder is defined below.
MDD is defined as the loss of interest/pleasure in all activities lasting
for at least 2-weeks, which is associated with five or more other symp-
toms. These symptoms can include vegetative or somatic symptoms (e.g.
changes in appetite, sleep, fatigue), neuropsychological changes (e.g. diffi-
culty thinking, concentrating, making decisions), and affective/cognitive
changes (e.g. feelings of worthlessness/guilt, suicidal ideation) [5]. Anxiety
disorders are characterised by excessive worry that is difficult to control,
lasts more than 6-months, and manifests as a specific disorder such as
panic disorder or GAD. For an anxiety disorder diagnosis to be made, the
anxiety needs to be accompanied by additional symptoms such as somatic
symptoms (e.g. restlessness, muscle tension, disturbed sleep, feeling eas-
ily fatigued), neuropsychological symptoms (e.g. difficulty concentrat-
ing), or affective/cognitive symptoms (e.g. irritability, catastrophising) [5].
Thus, the diagnostic criteria for depressive and anxiety disorders include
somatic symptoms (e.g. change in appetite, sleep, fatigue), neuropsycho-
logical changes (e.g. difficulty thinking and concentrating), and affec-
tive/cognitive changes, but only in the latter case (i.e. affective/cognitive
changes) are the symptoms of the disorders substantially different. Some-
what differently, PTSD is a type of anxiety disorder that is caused by expo-
sure to a specific traumatic event/s (e.g. rape, physical violence, emotional
abuse) that is diagnosed on the basis of eight criteria (A–H), including
symptoms such as intrusive thoughts, flashbacks, and nightmares [5].
In Australia, about 45% of the adult population (16–85 years of age)
have experienced one or more mental health issues (e.g. anxiety disorders,
depressive episodes, bipolar affective disorder, harmful alcohol use, drug
use disorder) in their lifetime [6]. Further, at any given time, about 20%
of the adult Australian population will be dealing with a mental health
disorder [6]. Similarly, 43.4% of the adult UK population are reported
to have experienced a mental health condition at some point in their life,
including 51.2% of females and 35.2% of males (OR = 1.45) [7]. Among
younger adults,females havea much higherprevalence estimatethan males
(26% vs. 9%, OR = 2.89) for a mental health problem [7].That is, nearly
one-half of adults will tend to develop a mental health problem in their
lifetime, including at least one-half of women and one-third of men.
6 Comorbid Psychiatric Illnesses 141
Additionally, anxiety, depressive, and trauma-related distress symptoms
have been observed to be highly concurrent in prospective longitudinal
studies ofwar veterans, whichlikely increased theburden of illnesson indi-
vidual patients [8]. Bidirectional relationships are also typically reported
between depression and anxiety disorders (i.e. ICD-10). For example, a
WHO study of psychological disorders in the primary care setting across
several different countries (e.g. UK, India, Germany, Brazil, USA, China,
and Italy) estimated that comorbidity between anxiety and depressive dis-
orders was about 50%; that is, about one-half of patients with anxiety or
depression had both disorders at the same time [9]. Further, a review of
studies that included children and adolescents estimated that the comor-
bidity rate between anxiety and depression was between 15.9 and 61.9%
[10]. However, not all studies have reported a bidirectional relationship
between the disorders. For example, one longitudinal study showed that
anxiety predicted later depression levels at other time points (r = .29 −
.61) but not vice versa [11]. Thus, the result suggests that bidirectionality
is typically but not always observed.
As discussed in Chapter 1, a considerable proportion of patients with a
mental health condition will also have another physical or mental health
condition. For example, nearly one-half (46%) of UK participants who
had a mental health problemalso had a chronic physical health problem/s,
whereas fewer (30%) of them who had a chronic physical condition also
had a mental health problem [12], suggesting that mental ill-health is
a common comorbid health problem that has implications for physical
health. Additionally, comorbidity can substantially increase illness bur-
den in individual patients, as indicated in the Global Burden of Disease
Study [13] that evaluated acute and chronic illness and injury burden in
patients across 188 countries (1990–2013) using Years Lived with Dis-
ability (YLD). In particular, depression is known to be a leading cause of
global burden of disease (GBD) based on YLD and disability-adjusted-
life-years (DALY), especially as it is related to suicide and cardiovascular
disease [14]. Furthermore, anxiety and depression are associated with an
increased risk of mortality. For example, people with anxiety/depression
have been reported to die 7.9 years earlier than people without the symp-
toms (HR = 1.6; US National Health Interview Survey, 1999–2011) [15]
and have shown an increased mortality risk and/or hospital readmission
142 E. Thorsteinsson and R. Brown
rate (OR = 2.0) [15].Inastudy[16] of more than 5 million US veter-
ans of whom 850,000 were depressed, baseline depression was linked to
a 17% increased risk of all-causes mortality and increased specific mor-
tality risks from heart disease, respiratory illness, cerebrovascular disease,
accidents, diabetes, nephritis, influenza, Alzheimer’s disease, septicaemia,
suicide, Parkinson’s disease, and hypertension. However, there was a lower
risk of death from cancer and liver disease, after controlling for baseline
demographics and clinical characteristics. Thus, it is clear that anxiety
and depression are associated with an increased mortality risk, although
few studies have examined anxiety/depression comorbidity in relation to
mortality risk, so it is unclear how the effects interact in this case.
Anxiety, depression, and related symptoms (e.g. fatigue) are also com-
mon in non-clinical populations. It is therefore important to study the
concurrence ofthese symptoms in non-clinicalpopulations as wellas those
with severe mental health disorders [17]. Adding further tothe complexity
of the topic, comorbidity can potentially lead to misdiagnosis. For exam-
ple, individuals with an autism spectrum disorder (ASD) are more likely
to be diagnosed with a mental health condition than people without ASD
as characteristics of the disorder tend to overlap with the characteristics
of some mental health disorders. In particular, people with ASD are more
likely to be diagnosed with an anxiety disorder, including panic disorder,
specific phobia, andsocial anxiety disorder, anddual diagnosis of ASD and
an anxiety disorder is common practice [18], although it might be prob-
lematic. For instance, it is possible that a common mechanism underpins
the development of ASD and anxiety disorders. Impaired interoception
(perceptionof bodily sensations and physiological feedback from the body)
that results in alexithymia (inability to identify and describe one’s emo-
tions) has been suggested to underpin the core characteristics of ASD as
well as the affective symptoms/disorders (e.g. anxiety disorders) which are
commonly associated with it. In light of this, Hatfield and colleagues [19]
have recently presented a new integrated theory which posits that people
with ASD will experience a reduced capacity to interpret interoceptive
information, and this could result in a narrowed attentional bodily focus
as well as reduced motivational and behavioural drives.
Finally, as detailed in Chapter 9, comorbidity is likely to complicate the
treatment of each disorder, as the therapies are likely to involve different
6 Comorbid Psychiatric Illnesses 143
treatment approaches and employ different health practitioners or health-
care teams. A recent meta-analysis, for example [20], suggested that the
strong relationship between drug or alcohol use and MDD and anxiety
disorders is likely to complicate the treatment of each disorder. However,
if the comorbid conditions have shared putative risk factors/causes, then
it may be prudent to target these shared risk factors in the treatment
of different-but-related conditions at the same time. For example, prior
research has suggested that comorbidity between attention deficit hyper-
activity disorder (ADHD) and anxiety disorders may partly be caused by
sleep problems [21], suggesting that the targeting of sleep problems in
therapy may result in both reduced ADHD and anxiety symptoms.
6.2 Relationships Between Stress,
Depression, Anxiety, and Impaired Sleep
Similar to findings in the clinical literature, stress, including stressful life-
events (e.g. loss of a loved one), chronic stressors (e.g. poverty, disability,
work-stress), and perceived (or psychological) stress is theorised to be a
potential contributor to the development of mental health disorders and
symptoms including anxiety and depression. Stress may contribute to
mental ill-health via one or more biological processes. For example, pro-
longed and repeated stress and MDD are associated with marked changes
in cerebral metabolism and cerebral blood flow, and structural abnormal-
ities in a number of brain regions (e.g. hippocampus) [22, 23]. Stress may
also contribute to impaired sleep [24], and together, it and the effects
of stress may contribute to the development of mental health problems
[24]. For instance, a persistent difficulty falling asleep may lead to a sleep
disorder diagnosis (e.g. insomnia disorder), which in turn contributes to
the development of stress and anxiety symptoms [25]. In a study of more
than 2000 young adults, stress-induced sleep problems were shown to be
linked to an increasedepression symptoms [26], and in other studies, poor
sleep quality has been related to mental health indicators such as depres-
sion, anxiety, and stress symptoms [24]. Further, sleep problems do not
only increase the risk of depressive symptoms, but they may also interfere
with depression treatment, with one study reporting that sleep problems
144 E. Thorsteinsson and R. Brown
at the end of depression treatment tend to increase the risk of depression
relapse [27]. To complete a potential ‘vicious circle’, depression may also
contribute to sleep problems by reducing sleep quality [28].
Thus, there is strong evidence for a bidirectional relationship between
anxiety, depression, and impaired sleep, which could be interpreted as
bidirectional causal pathways involving anxiety and depression as causes
of impaired sleep as well as sleep problems potentially resulting in later
anxiety and depression [25]. It is also likely that stress or anxiety-related
rumination interferes with the onset of sleep [29], and over time, this leads
to a sleep disorder diagnosis. The sleep problem might then contribute
to specific sleep-related anxieties and rumination, which further interfere
with sleep, and might later result in an anxiety disorder.
The likely causal mechanisms underpinning these bidirectional path-
ways arenot always clear, with multiple mechanisms havingbeen proposed
to account for these relationships. Adding further complexity, as detailed
in Chapter 3, it is possible that obesity (or one or more risk factors for
obesity, e.g. late-night eating or stress or anxiety-related eating) can con-
tribute to impaired sleep. A recent review supports this notion, reporting
that both epidemiological and laboratory studies indicate a relationship
between obesity and impaired sleep (i.e. shorter sleep duration, less sleep
quality).
Traumatic stressful events may cause individuals to develop PTSD.
A review by Olff and colleagues [30] suggests that about one-half of the
population will experience a traumatic event in their lifetime, and as a
result, one in twenty men (5%) and one in ten women (10%) will end
up developing PTSD in their lifetime. PTSD typically presents after a
person has experienced a traumatic event, including adverse childhood
experiences (e.g. abuse). It is characterised by symptoms such as cognitive
intrusions, avoidance, and changes in cognition and mood, which last for
more than 1-month. It is unclear why some people will develop PTSD
after trauma whereas others will not. However, it is thought that different
styles of cognitive appraisal and coping may h elp to explain this [30]. The
central nervous system (CNS) and peripheral sympathetic nervous sys-
tem (SNS) are both activated when an individual experiences a traumatic
event, thus enabling fight or flight if it is necessary, whereas the hypothala-
mus–pituitary–adrenocortical (HPA) system will typically affect the body
6 Comorbid Psychiatric Illnesses 145
within minutes after the traumatic event [30]. Dysregulation of the two
systems has been reported to underpin the PTSD; for example, low- or
high-cortisol levels and high or low sensitivity to cortisol responses [30].
PTSD is also highly comorbid with other mental health problems (e.g.
anxiety disorder, depressive illness) [31]. Thus, it is likely that PTSD will
need to be co-managed with other mental health condition/s in therapy,
although protocols for the co-treatment of the disorders are not currently
available. Nonetheless, the existing research suggests the need to man-
age a PTSD client’s biological stress systems, potentially by changing the
way in which they appraise or cope with their symptoms (e.g. cogni-
tive intrusions). Alternatively, mindfulness-based interventions (MBI) or
acceptance-based therapy approaches (e.g. Acceptance and Commitment
Therapy [ACT]) might be used to treat the symptoms, by encouraging the
person to accept the symptoms as they arise, without reacting emotion-
ally to them or cognitively labelling them in an unhelpful way. Research
suggests that ACT may help in treating PTSD [32]whileMBImaynot
[33]. A systematic review [34] of ACT suggests some promising find-
ings but notes the lack of randomised control studies. Another systematic
review into MBI [35] suggested MBI may improve mental health espe-
cially depression. ACT may be especially helpful in treating a person’s
symptoms in the case that they are unable to control them, and such an
approach has previously been used in the treatment of chronic pain [36],
tinnitus distress [37], anxiety [38], depression [39], sleep problems [40],
and fatigue (fibromyalgia)[41]. Finally, given that PTSDcan impact upon
family members and carers of people with PTSD, it might also adversely
impact upon the carers’ mental health [42, 43]; thus, any PTSD interven-
tion needs to be extended to cover the needs of carers and family members
of the PTSD sufferer.
6.3 Risk and Protective Factors for Mental
Ill-Health
Many comorbid psychological disorders share not only overlapping symp-
toms, but also common risk factors and protective factors. Some of the
factors (e.g. coping strategy use) are likely to be under our own control, at
146 E. Thorsteinsson and R. Brown
least to some extent, but other factors are uncontrollable and unchange-
able (e.g. disability). Lazarus and Folkman [44] assert that uncontrollable
and unchangeable stressors are the most difficult stressors for people to
deal with, and they typically result in the use of emotion-focused coping
(e.g. avoidancecoping) ratherthan problem-focusedcoping (e.g. problem-
solving coping). A comprehensive assessment ofall known risk andprotec-
tive factors for mental ill-health is beyond the scope of this chapter; thus,
only the most consistently documented factors in chronic illness patients
will be detailed here.
Insomnia/impaired sleep is highly comorbid with depression and other
mental health disorders (e.g. anxiety disorders) [24, 25]. For example,
stress-induced sleep problems are linked to worse depression symptoms
[26]. As noted in Chapter 2, impaired sleep and low mood (e.g. depres-
sion) are thought to be bidirectionally and causally related to each other
such that impaired sleep negatively impacts on mood, and in turn, low
mood contributes to impaired sleep [25]; although as detailed below, the
relationship is likely to be indirect, for example, mediated by ruminative
thinking [29, 45] or HPA axis hyperactivity [46, 47]. In contrast, good
quality sleep may help to buffer against the potential impact of stress on
mental health [29], and if a person’s sleep can be improved this might also
improve mental health. The results from a pilot nightmare intervention
for PTSD sufferers supports this hypthesis [48].
Overweight/obesity has been found to be positively associated with anxi-
ety [49, 50] and depression [51, 52], with BMI being positively associated
with night-eating [53]. A review of the literature shows that night-eating
has extensive associations with psychiatric conditions, including anorexia,
sleep problems, anxiety, depression, and substance use [54]. Among uni-
versity students, night-eating seems t o be caused by stress and maladap-
tive coping strategies [55]. Other eating disorders such as anorexia and
bulimia nervosa also have multiple comorbid conditions. One study [56]
reported that 55% of anorexia sufferers and 68% of bulimia sufferers had
at least one anxiety disorder. Binge eating has been associated with dia-
betes mellitus type-II. Night-eating in combination with diabetes mellitus
type-II—controlling for age, sex, race, and MDD—has been associated
with increased risk of obesity (OR = 2.6), haemoglobin A1c >7% (OR
6 Comorbid Psychiatric Illnesses 147
= 2.2), and diabetes complications (OR = 2.6) [57]. Furthermore, dia-
betes mellitus type-II is associated with increased risk of depression (OR
= 2.0) irrespective of sex [58], and it is also associated with increased risk
of anxiety [59]. See further discussions in Chapters 3–5.
Physical activity may help to protect against the negative effects of stress
on mental health. For example, findings from a randomised controlled
trial suggest that exercise can improve wellbeing and reduce the experi-
ence of stress, distress, and burnout [60]. Further, a large meta-analysis
has shown that exercise can have large effects in reducing symptoms of
depression (1.11 standardised mean difference [SMD] units) [61], anxiety
(SMD = 0.58) [62], and sleep problems (SMD = 0.50) [63]. In sharp
contrast, a sedentary lifestyle is reported to adversely impact on health,
including sleep [64], and it is weakly correlated with job strain [65]and
bidirectionally associated with depression severity [66]. This suggests that
physical inactivity may contribute to impaired sleep and stress/affective
distress, as well as low mood and impaired sleep contributing to physical
inactivity.
In chronic illness patients, medical illness factors [67]areknowntobe
risk factors for mental ill-health. This has been indicated in relation to
numerous medical health conditions, including physical disability, symp-
tom severity (e.g. pain) [67, 68], disfigurement, loss of vigour, and poor
prognosis illness [69, 70]. Additionally, depression and anxiety have been
shown to predict later pain and pain-related disability, but not the reverse
[71]. Disability can limit a person’s ability to function adequately, either
mentally or physically or both, in their current environment [72], which
may adversely impact on various aspects of their lives including social
interaction and social roles [73]. Compared with physical health condi-
tions, mental health conditions can increase the odds of severe disability
burden toa greater extent[74], and the odds of experiencing severedisabil-
ity are more than additive when patients have both mental and physical
health conditions[74]. Furthermore,the effectsof disabilitytend toextend
beyond the individual to the family unit and broader community; hence,
the effects of disability can be extensive. For example, disabled patients
are more likely to have greater support requirements than non-disabled
patients (e.g. need for a carer), and the disability may interfere with their
148 E. Thorsteinsson and R. Brown
ability to work, potentially causing financial stress, which could further
worsen the patient’s mental health.
Electronic device use is reported to be a risk factor for mental ill-health.
For example, Internet and social media use can bring a person in contact
with online bullies or ‘trolls’, or it can provide a platform to spend too
much money on online shopping or gambling. Problematic (or excessive)
Internet usage is generally linked to negative mental health outcomes, and
in therapy, it is often regarded as a form of addictive behaviour, although
it is not recognised as such in the DSM-5 [5]. Specifically, a study of 449
participants (16–71 years of age) showed that problematic Internet use
was linked to greater emotion-focused and avoidance coping in adults
and greater rumination and less self-care in adolescents [75]. Similarly, a
meta-analysis of 23 independent samples reported a relationship between
problematic Facebook use and distress (r = .34) and wellbeing (r =−.22)
[76]. However,another meta-analysis [77], based on 67 independentsam-
ples, showed the relationship between time spent on social network sites
and mental health indicators (e.g. wellbeing, life satisfaction, depression,
and loneliness)to be generallylow (r < |.12|), suggestingthat time spenton
social networking sites may not sufficiently capture problematic Internet
behaviour. Similarly, a recent 12-month follow-up pilot study surveying
adolescents reported reduced depression levels in relation to instant mes-
saging and social network use [78].Taken together, the results suggest that
Internet usage is not synonymous with mental ill-health, and the mixed
results suggest that researchers have much yet to learn about the effects of
Internet use on mental health. Other types of electronic devices (e.g. elec-
tronic readers, computer use) are examined in more detail in Chapter 7,
in regard to mental health, sleep, and physical health.
Coping strategy use is another known risk factor (or protective factor)
for mental ill-health, depending on whether the strategy is adaptive (e.g.
seeking out social support) [79] or maladaptive (e.g. ‘acting out’ involving
drug/alcohol use) [80, 81]. Thus, adaptive coping facilitates good mental
health while maladaptive coping may contribute to mental ill-health [80,
82, 83]. For example, in a sample of 510 Australian adolescents, greater
social support (i.e. social support satisfaction and number of supports)
was associated with reduced impact of stress on depression, whereas mal-
adaptive coping (i.e. rumination, acting out including drug use) increased