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Anxiety in Health
Behaviors and Physical
Illness
Michael J. Zvolensky
University of Vermont
Burlington, Vermont, USA
Jasper A. J. Smits
Southern Methodist University
Dallas, Texas, USA
Michael J. Zvolensky, Ph.D. Jasper A. J. Smits, Ph.D.
Department of Psychology Department of Psychology
University of Vermont Southern Methodist University
John Dewey Hall 6424 Hilltop Lane
2 Colchester Avenue Dallas, TX 75205
Burlington, VT 05405-0134 USA
USA jsmits@smu.edu
Michael.Zvolensky@uvm.edu
9 8 7 6 5 4 3 2 1
springer.com
Preface
Research has been accumulating on the prevalence and nature of the co-
occurrence between various forms of anxiety disorders and problematic health
behaviors as well as physical illness. This research has significant implications
for both those interested and affected by anxiety as well as physical health
factors. Yet, it is striking that there has been little systematic integration of this
health-oriented research in contemporary science and practice on anxiety and
its disorders. This relative neglect is unfortunate given that the co-occurrence of
anxiety and health problems is a major public health priority when measured
both in human and financial terms.
The overarching aim of this book is to provide a single resource that offers
current theoretical perspectives and cutting eZdge reviews of scientific research
on health behaviors and physical illness in relation to anxiety and its disorders.
A critical analysis of this emerging literature is needed to help move this field
forward, making this proposed volume timely. The specific objectives of this
edited book are to (1) provide a review of the literature on the link between
anxiety and certain health behaviors and processes as well as physical illness;
(2) present contemporary theories of their co-occurrence and interplay (e.g.,
onset, maintenance, and relapse); and (3) provide an analysis of recent research
in regard to therapeutic models for targeting these problems.
The book is organized into two general sections. In the first part of the book,
prototypical health behaviors – smoking, alcohol, illicit substance use, exercise,
and sleep – are discussed in relation to anxiety and its disorders. In the second
part of the book, the association between anxiety psychopathology and physi-
cal health conditions – chronic pain, cardiovascular disease, asthma, HIV/
AIDS – and their treatment are covered. In this same section, the potential
role of puberty and the menstrual cycle in the onset and maintenance of anxiety
psychopathology are discussed.
Inspection of the excellent and comprehensive works has yielded a number of
broad-based conclusions relevant to informing research and practice for anxi-
ety disorders. First, there is consistent empirical evidence that medical problems
and poor health behaviors are overrepresented among persons with anxiety
disorders, and vice versa. Thus, there is a pressing need to marshal information
on anxiety-health processes to better serve this population. Second, as each
v
vi Preface
contribution makes clear, there is uniform evidence that both health behaviors
and physical illness can, and do, affect the nature of anxiety psychopathology.
Yet, the exact nature of these associations depends on the specific disorder and
health factor in question. And finally, a variety of the chapters make clear that
persons suffering from anxiety psychopathology and poor health behaviors or
medical illnesses may need specialized interventions to prompt clinical change.
That is, traditional interventions may not be ideally suited or maximize clinical
benefit for this population.
For us, the present book offers the opportunity to appreciate the importance
and complexity involved with the study of anxiety disorders. For many years,
health behaviors and medical illnesses have been a neglected facet of anxiety
disorder research and practice. The contributions in this book help drive home
the message that such neglect is unwarranted, and that by working to better
understand the enigmas between health status and functioning and anxiety
psychopathology, significant clinically-relevant strides can likely be achieved.
We hope the present book helps move such work forward and bring a better
quality of life and reduced morbidity to persons with anxiety disorders in the
future.
We owe gratitude to many people who have helped us complete this project.
First among these are the experts who authored the chapters. We would like to
thank them for their hard work and dedication. We also appreciate the com-
ments and suggestions of Dr. Martin Antony, the editor of the Series in Anxiety
and Related Disorders, and the assistance of Anna Tobias of Spinger with the
publishing of this book. Lastly, we continue to be appreciative of our respective
family members, Heidi and Jack Zvolensky and Jill and Stella Smits, for their
love and support.
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
vii
viii Contents
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
Contributors
ix
x Contributors
Recently, there has been increased effort to better understand linkages between
tobacco use and the anxiety disorders (Feldner, Babson, & Zvolensky, 2007;
Morissette, Tull, Gulliver, Kamholz, & Zimering, 2007; Morrell & Cohen,
2006; Zvolensky, Bernstein, Marshall, & Feldner, 2006; Zvolensky, Feldner,
Leen-Feldner, & McLeish, 2005; Zvolensky, Schmidt, & Stewart, 2003). These
efforts are theoretically and clinically important because substance use pro-
blems frequently co-occur with anxiety psychopathology, and anxiety-related
factors often play a role in tobacco use and dependence (Morissette et al.,
2007; Morrell & Cohen, 2006; Zvolensky, Bernstein et al., 2006). However, our
understanding of the explanatory nature of these comorbid relations is only
beginning to emerge. The purpose of the present chapter is to provide a current
review of extant empirical work pertaining to the inter-relations between
tobacco use and panic psychopathology. We expressly and specifically focus
on panic psychopathology, rather than anxiety disorders more broadly, as
most of the work on tobacco and anxiety relations to date has focused on
panic.
This chapter is organized into four sections. First, we briefly describe panic
psychopathology. Second, we review risk factor terminology developed by
Kraemer, Kazdin, and Offord (1997), in order to establish a nomenclature for
conceptualizing interrelations between tobacco and panic psychopathology.
Third, we describe tobacco use and common patterns of use. Fourth, we discuss
the nature of comorbidity between tobacco use and panic psychopathology and
review and evaluate the related empirical evidence. We focus both on the role of
tobacco use in the onset and maintenance of panic psychopathology, and the
role of panic factors and processes in the onset and maintenance of smoking.
Within each of these sections, we identify gaps in the existing literature and
highlight formative questions for future research.
Michael J. Zvolensky
University of Vermont, John Dewey Hall, Burlington, VT 05405-0134, Tel: 802-656-8994,
Fax: 802-656-8783
Michael.Zvolensky@uvm.edu
Panic Psychopathology
Vulnerability Nomenclature
users in the U.S. and other regions of the world (e.g., India; ACS, 1999).
Epidemiological data in the U.S., for example, suggest that approximately
3% of individuals have used some form of smokeless tobacco – either snuff
(finely ground, shredded tobacco) or chewing tobacco – in the past month
(ACS, 1999). These rates of use are elevated among young Caucasian males
compared to females, and among those in southeastern and north central states
compared to other regions, as well as rural compared to urban settings
(Hatsukami & Severson, 1999). For example, past work suggests that the
highest rates of current use (16.6%) are among Caucasian males 18–25 years
of age (CDC, 1994).
In general, rates of smokeless tobacco use are noteworthy because smokeless
tobacco contains carcinogens (e.g., tobacco-specific nitrosamines [TSNAs];
National Cancer Institute and National Institute of Health (NCI/NIH), 2006)
known to be causal agents in lung, oral, esophageal, liver, and pancreatic
cancer (About: Smoking Cessation, 2006b). In addition, smokeless tobacco
use is associated with greater nicotine absorption and for longer periods of
time (e.g., stays in the bloodstream for greater durations of time) than cigarette
smoking (ACS, 2006; NCI/NIH 2006b). Similar to cigarettes, smokeless
tobacco use can lead to increased rates of physical disease (e.g., oral cancer,
gum disease) and nicotine addiction (ACS, 1999). Whereas the risks associated
with cigarette use have become well-publicized in the U.S., public awareness
about the dangers of smokeless tobacco remains limited. Indeed, many perceive
smokeless tobacco as a ‘‘risk-free alternative’’ to cigarette smoking (CDC,
1994). Although as many as 50% of smokeless tobacco users report wanting
to quit (ACS, 2006a), as with cigarettes, rates of relapse remain high (Hatsu-
kami, Jensen, Allen, Grillo, & Bliss, 1996). In a recent review of smokeless
tobacco treatment programs, Hatsukami and Severson (1999) estimated a 3–6
month abstinent rate of 12%–30% with intensive behavioral treatments fairing
better than other intervention options. Thus, similar to cigarette use, smokeless
tobacco use is an addictive behavior that is difficult to quit and more intensive
care appears to yield relatively better outcomes.
Kandel, Huang, & Davies, 2001; Kandel et al., 1997; Merikangas et al., 1998;
Tilley, 1987). Although such work has importantly directed scientific attention
to tobacco-anxiety relations at the broadest level, it is limited in demarcating
specific rates of co-occurrence for (particular) disorders of interest, such as
panic. Thus, for the sake of explanatory specificity, we focus our summary on
investigations that expressly distinguished panic psychopathology from other
anxiety disorders.
Comorbidity prevalence. The majority of studies have focused on document-
ing rates of smoking among persons with panic psychopathology. The criteria
for smoking behavior has varied across investigations. Moreover, treatment-
based recruitment strategies have been most commonly employed, perhaps
making these data somewhat less generalizable to the overall smoking popula-
tion. Nonetheless, among treatment-seeking adults, several studies have
reported that current daily smoking among patients with panic psychopathology
(either panic disorder or agoraphobia or both) ranged from 19% Panic
(Baker-Morissette, Gulliver, Wiegel, & Barlow, 2004) to 57% (Himle, Thyer, &
Fischer, 1988), with the vast majority of investigations falling between 30% to
50% (Amering et al., 1999; Lopes et al., 2002; McCabe et al., 2004; Pohl,
Yeragani, Balon, Lycaki, & McBride, 1992). These rates of daily smoking are
typically higher than comparison groups involving persons without psychiatric
problems and typically higher, or as high as, rates among persons with other
anxiety or mood disorders (McCabe et al., 2004). Thus, these data collectively
suggest that smoking is a relatively common unhealthy behavior among treat-
ment-seeking individuals with panic psychopathology.
Studies focused on non-treatment seekers are currently limited. Of the
available work, one study focused on youth (Hayward, Killen, & Taylor,
1989; 95 9th graders in public schools) and the other on college students
(Valentiner, Mounts, & Deacon, 2004, n = 337). In both investigations, indi-
viduals with panic attacks, but not necessarily panic disorder or agoraphobia,
had higher rates of cigarette use on a ‘‘regular basis’’ (Hayward et al., 1989;
Valentiner et al., 2004). For example, Hayward et al. (1989) reported that of
those with a lifetime history of panic attacks, 77% had engaged in ‘‘experi-
mental’’ or ‘‘regular’’ cigarette use compared with 48% of adolescents without a
lifetime history of panic attacks. These results, albeit highly limited in overall
scope, generally parallel those of the treatment-oriented investigations noted
earlier in terms of documenting elevated use prevalence among individuals with
panic problems.
Another set of investigations has utilized representative sampling methods to
explore the nature of tobacco use among those with panic psychopathology
(Covey, Hughes, Glassman, Blazer, & George, 1994; Farrell et al., 2001; Lasser
et al., 2000). In perhaps the most comprehensive and well-known of these
investigations, Lasser et al. (2000) examined smoking status according to
psychiatric diagnoses using data from the National Comorbidity Survey (NCS),
a nationally representative study that used structured clinical interviews to docu-
ment mental illness (Kessler et al., 1994). Participants were 4,411 individuals aged
Panic and Tobacco 9
In the only study to focus on cigarette and smokeless tobacco use, Goodwin
and colleagues (2007) found that among a representative sample from the U.S.,
rates of past-year panic attacks (with or without agoraphobia) were greatest
among smokers with nicotine dependence (6.7%), followed by cigarette use
with no dependence (2.2%), both of which were greater than among those with
no past year cigarette or smokeless tobacco use (1.5%). Being dependent on
smokeless tobacco (1.9%) was largely comparable to no past year tobacco use,
both of which were greater than smokeless tobacco use without nicotine
dependence (0.6%).
Overall, the extant literature suggests that heavier rates of cigarette use
(greater degrees of dependence) are associated with a greater rate of comorbid-
ity with panic psychopathology. Although limited, this pattern of findings does
not yet seem to be apparent for smokeless tobacco use, suggesting that factors
related to the ‘‘mode of administration’’ may be an important domain to further
understand in tobacco-panic linkages.
Future directions. Though there are many avenues for future inquiry into the
nature of tobacco-panic comorbidity, here we highlight a few domains of
primary importance based upon the gaps in the existing literature. Before
specific recommendations are made, it is striking to point out that, to the best
of our knowledge, none of the past work focused on comorbidity issues has
been a priori oriented on tobacco-panic relations. Thus, it is, perhaps, not
surprising that some of the assessment approaches used in past work may not
be fully comprehensive or geared towards maximizing information about the
nature of the co-occurrence of these specific behavioral problems. As such, a
first-step in improving research in this domain would be to design evaluations
specifically focused on better understanding tobacco-panic comorbidity.
Beyond this general issue, there are at least three specific points within this
domain that would be particularly useful to address.
First, only one study has provided data on smokeless tobacco and panic
comorbidity. Thus, to foster further empirical knowledge in this domain, it is
necessary to complete investigations wherein multiple forms of tobacco use are
assessed to provide information on both cigarette use and smokeless tobacco.
Aside from providing much needed data on smokeless tobacco and
psychopathology, this type of work would help to define the parameters of
tobacco-panic relations more generally. In this same context, it would be
advisable to clarify the extent to which the observed co-occurrence rates
between tobacco use and panic psychopathology are similar to, or different
from, other health behaviors (e.g., alcohol use, physical exercise). In general,
research suggests smoking is strongly positively related to alcohol and other
substance use and negatively related to exercise (Zvolensky & Bernstein, 2005).
This work is necessary because it would further explicate the degree to which
tobacco use is or is not unique to the co-occurrence of panic psychopathology.
As the present book illustrates, research in the health-anxiety linkage is only
now emerging.
Panic and Tobacco 11
Studies examining the typical age of onset for panic attacks also suggest that
such problems often first occur in adolescence. For example, Goodwin and
Gotlib (2004) reported that the mean age of panic attack onset was 13.4 years
(n = 1,285; age range 9–17). Other studies based on community or school
samples have found similar results, with the modal age of onset of panic attacks
being 12 years old (Hayward et al., 1992; Warren & Zgourides, 1988), and
clinical samples report a slightly younger age of panic attack onset (Alessi &
Magen, 1988; Black & Robbins, 1990). These data suggest that, across studies,
panic attack onset tends to first occur between the ages of 12–13 years. One
important interpretative caveat to these investigations is that they focus
exclusively on youth and expressly do not sample from a larger age range.
Thus, it is possible that the ‘‘average’’ age of onset of panic attacks may be
different if the sampling strategy incorporated adults.
Based on available indirect data from smoking and panic attack age of onset
studies, it appears that in many instances the typical age of onset of panic
attacks precedes the typical age of onset of smoking. However, retrospective
reports of smokers with ‘‘active panic problems’’ are not entirely consistent with
this perspective. For example, Amering and colleagues (1999) examined 102
consecutive panic disorder patients with or without agoraphobia attending an
academic treatment clinic in Austria. Participants were diagnosed using the
SCID-III-R (First, Spitzer, Gibbon, & Williams, 1995) and interviewed about
their smoking status. Individuals presenting with ‘‘severe somatic illness’’
and comorbid depression and other psychiatric illnesses were excluded
from the study. Amering and colleagues (1999) reported that the onset of
smoking preceded the onset of panic disorder (cf. panic attacks) by 12.3 years
(SD = 9.4) in a community sample of individuals with the condition (n = 102).
Bernstein, Zvolensky, Schmidt, and Sachs-Ericsson (2007) directly evaluated
onset patterns among 4,409 adults (Mage = 33.1, SD = 10.7, females = 2,221)
from the NCS (Kessler et al., 1997). Results indicated that among cases with a
lifetime history of comorbid daily smoking and panic attacks (n = 167), the
onset of daily smoking (M = 16.0 years, SD = 3.0) preceded the onset of panic
attacks (M = 27.8 years, SD = 7.6) in the majority, but not among all, of the
comorbid cases (63.7%, n = 106). A relatively large minority of comorbid cases
(33%; n = 55) reported that panic attacks (M = 11.4 years, SD = 5.2) preceded
the onset of daily smoking (M = 18.2 years, SD = 4.7). The concurrent (same
year) onset of these two problems appeared rarely (3.3%, n = 6). Also, as the
pattern of ages of onset above illustrate, daily smoking demonstrated a rela-
tively consistent mean age of onset (mid to late adolescence) across comorbid
sub-samples and the uni-morbid sub-sample of smokers (age 18.5 years). In
contrast, the mean ages of onset of panic attacks differed markedly between the
comorbid sub-samples and the uni-morbid sub-sample of nonsmokers with
panic attacks (age 20.3 years). Overall, while data focused expressly on devel-
opmental course and smoking-panic psychopathology is limited, extant studies
suggest that the majority of cases may involve smoking preceding panic attacks.
Panic and Tobacco 13
panic-relevant cues even among those with panic disorder. Less attention has
been focused on determining the relation between smoking rate and level of
affective distress or impairment. Yet, a number of studies, some involving
prospective measurement (discussed in greater detail below), have found that
smoking rate is related to greater degrees of panic-specific emotional symptoms
(e.g., panic-relevant avoidance; Breslau & Klein, 1999; Goodwin, Lewinsohn, &
Seeley, 2005; Johnson et al., 2000; McLeish, Zvolensky, & Bucossi, 2007;
Zvolensky, Kotov, Antipova, & Schmidt, 2003). Thus, there is empirical
evidence that both smoking status and rate are related to increased risk for
panic-relevant emotional vulnerability.
Cross-sectional tests also have helped to clarify factors that may affect the
smoking-panic relation. In one study of epidemiologically-defined (i.e., repre-
sentative) adult residents of Moscow (n = 95 daily smokers from a larger
sample of about 400 persons; Zvolensky, Kotov et al., 2003), anxiety sensitivity
moderated the effects of cigarettes smoked per day (m = 15) on level of
agoraphobic avoidance. This significant interaction accounted for approxi-
mately 10% of unique variance after controlling for their respective main effects
and the theoretically-relevant factors of problematic alcohol use and negative
affectivity. No interaction, however, was found for panic attacks, potentially
due to the fact that assessment of this factor was restricted to the past (most
recent) week to enhance the validity of panic reports (but probably truncating
variability). Similar moderating effects have been evident for perceived health
among young adult daily smokers (McLeish, Zvolensky, Bonn-Miller, &
Bernstein, 2006), and for neuroticism among a representative sample of adult
smokers (Zvolensky, Sachs-Ericsson, Feldner, Schmidt, & Bowman, 2006).
Overall, these findings suggest smokers are not a homogeneous group in regard
to their risk for panic problems and that individual differences in anxiety
sensitivity (or other cognitive-affective factors like perceived health or neuroti-
cism) may be key factors in accounting for such differences.
Moderating effects for anxiety sensitivity also have been evident in
between-group tests involving smokers and nonsmokers. For example, the
combination of high levels of anxiety sensitivity and a positive current smoking
status predicted panic symptoms and somatic complaints, but not depressive
symptoms in a biological challenge test (Leen-Feldner et al., 2007). Again, such
findings suggest that anxiety sensitivity (and possibly other factors) may mod-
erate the relation between smoking and prototypical panic psychopathology
variables (panic attacks and somatic complaints) even after controlling for
gender and negative affectivity. Moreover, these associations are specific to
panic-relevant processes. In a re-analysis of the Russian epidemiological study
reported earlier, Zvolensky and colleagues extended this smoking and anxiety
sensitivity effect (Zvolensky, Kotov, Bonn-Miller, Schmidt, & Antipova, in
press). Here, anxiety sensitivity, again, moderated the association of smoking
status with indices of anxiety symptoms; effects were evident after controlling
for the variance accounted for by alcohol use problems, environmental stress
(past month), and gender.
Panic and Tobacco 15
later in the chapter. More recently, Goodwin and colleagues (2005) replicated
the results of Breslau and Klein (1999), Johnson et al. (2000), and Isensee et al.
(2003) by finding that daily smoking during adolescence was associated with an
increased risk for panic attacks and panic disorder in young adulthood.
Moreover, the observed effects were no longer evident after controlling for
parental smoking and anxiety disorder status, suggesting that these family
history characteristics may be formative in the linkages between smoking and
panic psychopathology.
Prospective tests examining moderating factors in the tobacco use-panic
relation are very limited. In the only study to date on this topic, McLeish
and colleagues (2007) evaluated the moderating role of anxiety sensitivity in
the relation between smoking rate and panic vulnerability variables among a
community-based sample of 125 daily smokers (60 females; Mage =
26.02 years). Findings indicate that the interaction between anxiety sensitiv-
ity and smoking rate significantly predicted concurrent agoraphobic avoid-
ance (3.2% of unique variance) and change in levels of anticipatory anxiety
about bodily sensations during the 3-month follow-up period (4.7% unique
variance). Smokers high in anxiety sensitivity who also smoked at greater
rates reported the highest levels of avoidance and greatest increase in antici-
patory anxiety. These data, in accord with cross-sectional findings (Leen-
Feldner et al., 2007; Zvolensky, Kotov et al., 2003), once again suggest that
anxiety sensitivity is an important individual difference factor that, when
coupled with higher rates of smoking, is associated with greater levels of
avoidance and anticipatory anxiety among daily smokers, both of which
contribute to the development of panic psychopathology.
Overall, research co-addressing smoking and panic psychopathology
suggests that smoking can be considered a variable risk factor for panic
problems. Indeed, existing work provides evidence regarding relations with
panic problems based on cross-sectional and prospective studies, but it is
noteworthy that this work is rarely multi-method in its approach. To have
more confidence in smoking-panic psychopathology relations, the incorpora-
tion of multi-method assessment protocols would be an important next
research step. Additionally, evidence from cross-sectional, and to a lesser
extent, prospective studies indicates that fears of internal sensations (anxiety
sensitivity) and perhaps other ‘‘affect-amplifiers’’ (e.g., perceived health,
neuroticism) may moderate smoking-panic processes.
Future directions. There is a rapidly developing empirical literature on
tobacco-use and panic psychopathology relations. Such scientific interest in
this work underscores its public health relevance and potential clinical implica-
tions (see Zvolensky, Bernstein, Yartz, McLeish, & Feldner, in press, for an
expanded discussion of treatment implications of tobacco-panic relations). At
the same time, this literature remains relatively under-developed and there are a
number of key areas in need of future study.
First, as in the area of comorbidity prevalence studies reviewed earlier, there
is a dearth of data on smokeless tobacco-panic relations. Virtually no scientific
Panic and Tobacco 17
data exists on this important topic, making it a fertile area for future explora-
tion. Second, available data suggest daily smoking tends to precede the onset of
panic attacks in the majority of cases, although direct evaluations with panic
disorder and agoraphobia have not been completed. Given that smoking can be
changed via intervention (Abrams et al., 2003), there is evidence of its potential
malleability, and hence, possible application to prevention programs for panic
psychopathology. Overall, then, evidence that changing cigarette smoking rate
or smoking cessation will alter the future risk of panic psychopathology from a
preventative standpoint is lacking. Thus, it is currently not clear if smoking
represents a variable marker or a variable causal risk factor for panic psycho-
pathology. To clarify this issue, it is important for future research to examine
changes in smoking prospectively following experimental manipulation
(e.g., smoking cessation intervention; Zvolensky, Schmidt, Bernstein, &
Keough, 2006). Third, research has yet to examine the possibility that shared
or common risk factors may further explain the development of comorbid
tobacco use and panic. It is theoretically possible that certain biological,
psychological, and social factors may partially underlie the etiology and
maintenance of these behavior problems. And finally, while there is a growing
literature on moderating factors, there has been little scientific attention to
mediators of smoking-panic associations and therefore almost no empirical
knowledge exists pertaining to the putative causal mechanisms of interest.
Intensifying the focus on mediators of smoking-panic relations is a clinically-
relevant and timely task. Specifically, clarification of key mechanisms through
which smoking achieves its panicogenic effects will stimulate the development
of targeted interventions focused on therapeutic processes, and help to establish
such processes (e.g., emotional reactivity) as important in the etiology and/or
maintenance of panic-related problems. Only Breslau and Klein (1999)
conducted exploratory analyses of possible mediators by evaluating the
role of lung disease. Although medical illness is one useful process to better
understand, other factors such as perceived health, affect tolerance, various
trajectories of emotional distress (e.g., delayed recovery), withdrawal
symptoms, and avoidance-oriented smoking patterns are all examples of
theoretically-relevant factors deserving of future study (see Zvolensky &
Bernstein, 2005, for an expanded discussion).
Current knowledge regarding the relation between panic psychopathology.
pre-morbid panic risk variables, and tobacco use. Although much of the most
highly publicized work on smoking and panic psychopathology pertains to the
potential role of smoking in the onset or maintenance of panic problems, panic
vulnerability characteristics, broadly encompassing both pre-morbid variables
and full-blown panic problems, may conversely impact smoking behavior
(Zvolensky & Bernstein, 2005). Work in this domain has focused on empirical
evidence related to smoking cessation outcome, expression of withdrawal
symptoms, and motivational and cognitive processes related to smoking
behavior (e.g., outcome expectancies). A major strength of work in this domain
is that study of smoking has involved measurement of various facets of
18 M. J. Zvolensky et al.
among high anxiety sensitive compared with low anxiety sensitive youth. Using a
sample of panic disorder patients, Zvolensky and colleagues (2005) also found
that smokers with panic disorder reported higher levels of smoking to reduce
negative affect than their counterparts without such a history. These
cross-sectional studies are not capable of elucidating the direction of the effects.
Theoretically, coping-oriented smoking motives may have bi-directional effects,
influencing, and being influenced by, affective vulnerability. An initial investiga-
tion exploring this possibility was consistent with such an account (Gregor,
Zvolensky, Bernstein, Marshall, & Yartz, 2007), reporting that coping-oriented
motives were incrementally related to a variety of negative affective and cognitive
factors.
Overall, there are a variety of separate, but related, lines of inquiry indicating
panic psychopathology and a select number of pre-morbid risk factors are
meaningfully related to smoking behavior. These lines of work differ in their
focus, but broadly indicate that panic factors (full blown disorders and certain
pre-morbid risk factors) are related to abstinence duration during smoking
cessation outcome expectancies related to smoking, perceived barriers and
reasons for quitting, nicotine withdrawal symptom severity, and motivational
bases for smoking. Thus, it is most appropriate to conceptualize many of the
studied variables (e.g., anxiety sensitivity) as variable risk factors. Although
definitive prospective work has not been conducted to firmly establish temporal
precedence in many, if not most, of the investigations, theoretically, panic
variables would precede the smoking factors. It also is theoretically possible
that panic and panic-relevant risk factors may not necessarily developmentally
precede smoking, but nevertheless meaningfully influence the course and nature
of smoking behavior over time via many of the processes described throughout
this chapter. Further prospective work will delineate the possibility that these
panic-smoking relations may be transactional over development.
Future directions. As in the earlier sections of this chapter, a first observation
and recommendation for future research is to better understand the relations
between panic psychopathology and smokeless tobacco use. There is no empiri-
cal work completed in this domain to the best of our knowledge, leaving this
facet of the tobacco-panic linkage undocumented. Second, essentially all of the
existing work on panic psychopathology (and related factors) and smoking
behavior is focused on main effects. This approach seems appropriate given
the currently limited knowledge in the area, but represents only a ‘‘first step’’ in a
larger scientific effort. Future work is needed to increase understanding about
linkages among these factors beyond main effects by including moderational
and mediational tests of theoretically relevant variables. Similarly, the possibi-
lity that shared or common risk factors may underlie panic problems,
panic-relevant risk factors, and these smoking-related problems and processes
has received little theoretical or empirical evaluation. Third, the generalizability
of panic psychopathology and smoking research is limited in that it has focused
largely on adults from the U.S. Furthermore, there is very little information on
the nature of these relations among youth. Given the early age of onset of these
22 M. J. Zvolensky et al.
behaviors and their health relevance, as well as the international scope of this
public health problem, research development in these domains is needed.
Finally, little research has directly targeted panic vulnerability factors in smok-
ing cessation interventions. Similarly, there is little work addressing smoking in
the context of panic-related treatments. Given the consistent empirical evidence
of bi-directional associations between these often comorbid behavioral pro-
blems, it is important to develop specialized treatments, as generic interventions
may not target the affective vulnerability processes functioning to maintain
smoking in this population. For example, it may be useful to integrate inter-
oceptive exposure, cognitive restructuring, and psychoeducation exercises
developed for panic prevention and treatment programs with standard smoking
cessation strategies and nicotine replacement therapy. These therapeutic tactics
may be most effective when they target theoretically-relevant panic risk factors
like anxiety sensitivity in order to facilitate cessation. As a second illustration, it
may be useful to target smoking cessation as part of evidence-based panic-
problem treatment strategies. While there have been some inroads made in this
domain, with successful case reports and pilot studies now being reported
(Zvolensky, Bernstein et al., in press; Zvolensky, Lejuez, Kahler, & Brown,
2003; Zvolensky, Schmidt et al., 2006), much work is yet to be addressed in this
domain.
Summary
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Alcohol Use and Anxiety Disorders
The relationship between anxiety and alcohol use is a topic of great theoretical
and practical interest for both scientists interested in the nature and causes of
psychopathology and practitioners working with anxious and/or alcohol abus-
ing clients. Although it has been clearly established that anxiety disorders and
alcohol use disorders are highly ‘‘comorbid’’ or co-occurring conditions (e.g., see
Kushner, Abrams & Borchardt, 2000a for a review), the relationship between the
symptoms or behaviors involved in each disorder (e.g., feelings of anxiety and
levels of alcohol use) has not been as extensively reviewed. This chapter will
review recent empirical evidence linking anxiety and alcohol at both the beha-
vioral and disorder level to determine if similar conclusions can be derived
regarding their relationship from data at both of these levels of enquiry. We
will first briefly describe epidemiological studies linking anxiety disorders and
alcohol use disorders. Then we will examine some of the etiological theories of
the relationship between anxiety and alcohol use and their disorders, with a
review of the empirical evidence supporting each theory. Next, some specific
factors moderating and mediating the relationship between anxiety and alcohol
use will be explored, with an emphasis on individual differences and specific
processes involved in the relationship. A brief discussion of the differences
between factors affecting onset, maintenance, and relapse in the anxiety and
alcohol relationship will follow. The latest empirical evidence and thoughts
about treating both alcohol use and anxiety related problems will also be
reviewed. Finally, we conclude the chapter with some remarks about where the
field stands and directions that future research in this area might profitably take.
Brigitte C. Sabourin
Department of Psychology, Life Sciences Center, Dalhousie University, Halifax, Nova
Scotia, Canada, B3H 4J1, Tel: +902 494 3793, Fax: +902 494 6585
brigitte.sabourin@dal.ca
Anxiety and alcohol use can both be characterized at two different levels: sympto-
matic and syndromal. An association at the former level would entail a clear
relationship, for example, between feelings of anxiety and drinking behavior.
That is, one would expect that higher levels of anxiety would be related to higher
quantities and/or frequency of drinking behavior. In a classic paper, Persons
(1986) describes the advantages of studying psychological phenomena at the
symptomatic level rather than at the diagnostic category (or syndromal) level.
The symptom approach allows for study of important phenomena that may be
ignored by examining only the diagnostic category in question. For example, level
of alcohol consumption is not considered in the diagnosis of alcohol abuse or
dependence according to the fourth edition of the Diagnostic and Statistical
Manual of Mental Disorders (DSM-IV; American Psychiatric Association
[APA], 1994), although there have been some recommendations for incorporating
heavy drinking behaviors in the diagnostic definitions in future editions (Helzer,
Bucholz, & Bierut, 2006). Nonetheless, level of consumption may be an important
risk factor for alcohol problems (Dawson & Archer, 1993) and thus may be of
interest as a ‘‘symptom’’ when considering the anxiety – alcohol relation from the
symptom perspective. Also, the symptom approach recognizes the continuity of
clinical phenomena and behaviors with normal phenomena and behaviors. This is
a crucial point in the study of both drinking behavior and anxiety. For example,
some argue that drinking problems are best viewed as lying on a continuum
ranging from normal, non-problematic social drinking on one end to severe and
pathological alcohol dependence on the other extreme (Sobell et al., 1996).
In addition to the arguments presented above in favor of focusing on symptoms
rather than diagnostic categories, Chilcoat and Breslau’s (1998) discussion of
criteria for establishing causation between anxiety and alcohol abuse also demands
a symptom-focused approach rather than a syndromal- focused approach.
According to Chilcoat and Breslau, one of the criteria for causation includes a
‘‘gradient of effect’’, or dose response relationship between the two phenomena of
interest. That is, as the level of exposure to the causal agent increases, a resulting
increase in the level of the causal outcome should be expected. The gradient of
effect relationship can be studied as it pertains to the relation of any anxiety-related
symptom (e.g., number of panic attacks; severity of cognitive re-experiencing) with
any alcohol-related symptom (e.g., severity of negative consequences resulting
from alcohol use; usual number of alcohol beverages consumed per week).
The relationship between anxiety and alcohol can also be considered at the
syndromal level. At this level, a relationship between alcohol and anxiety would
be demonstrated if a diagnosis of one of the two disorders (i.e., anxiety disorder
or alcohol use disorder) was associated with an increased likelihood of a diag-
nosis of the other disorder. The DSM IV (APA, 1994) distinguishes between two
distinct types of alcohol use disorders: alcohol abuse and alcohol dependence.
Alcohol and Anxiety 31
The relationship between anxiety and alcohol can be described using the concept
of comorbidity, which can be defined as diagnosable, problematic alcohol use and
anxiety symptoms that are both present at some point in a person’s lifetime, but
not necessarily at the same time (Kushner et al., 2000a). Comorbidity rates can be
estimated using either clinical or community samples. Because individuals with
more than one disorder are more likely to seek treatment, clinical samples may in
fact inflate comorbidity estimates (Berkson, 1949). It is believed that community
surveys provide more accurate reflections of the anxiety disorder – alcohol use
disorder relationship. We will review the two most recent large-scale community
surveys, which are representative of the results of these types of surveys.
In this chapter, we will present odds ratios (ORs) to quantify the comorbid
relationship between anxiety disorders and alcohol use disorders. An OR
reflects the odds that individuals will display a second disorder if a first disorder
is present versus if it is not present. An OR of 1.0 reflects a lack of relationship,
with higher ORs reflecting more significant relationships between two disor-
ders. ORs of less than 1.0 reflect a decreased probability of having the second
disorder given the presence of the first disorder.
The National Comorbidity Survey (NCS: e.g., Kessler et al., 1996) reported
12-month ORs for individuals with alcohol dependence and alcohol abuse of
also having suffered from panic disorder (1.7 and 0.5 respectively), social
phobia (2.8 and 2.3), generalized anxiety disorder (4.6 and 0.4), posttraumatic
stress disorder (2.2 and 1.5), and specific phobias (2.2 and 1.2). The 12-month
ORs associated with alcohol dependence are significant for all anxiety disorders
with the exception of panic disorder (although the lifetime OR of alcohol
dependence is significant for panic disorder). On the other hand, although
having any anxiety disorder leads to a significant OR of developing alcohol
abuse, the only specific anxiety disorder with a significant OR is social phobia.
More recently, the National Epidemiologic Survey on Alcohol and Related
Conditions (NESARC; e.g., Grant et al., 2004) reported 12-month ORs for
individuals with alcohol dependence and abuse to also display any anxiety
32 B. C. Sabourin, S. H. Stewart
disorder (2.6 and 1.1, respectively), panic disorder with agoraphobia (3.6 and
1.4) and without agoraphobia (3.4 and 0.8), social phobia (2.5 and 0.9), a
specific phobia (2.2 and 1.1), and generalized anxiety disorder (3.1 and 0.9).1
The NCS (Kessler et al., 1997) also examined sex differences in comorbidity
between alcohol use disorders and anxiety disorders. Anxiety disordered women
and men do not differ significantly in their risk of developing alcohol dependence;
however, women with social phobia, simple phobias or post traumatic stress disorder
hive higher ORs of abusing alcohol than men with these anxiety disorders. Similarly,
the NESARC (Smith et al., 2006) reported ORs of alcohol use disorders and anxiety
disorders by race/ethnicity. Across all races/ethnic groups, there were significant ORs
of any anxiety disorder with alcohol dependence but not with alcohol abuse. How-
ever, the pattern of comorbidity across specific anxiety disorders reveals significant
racial/ethnic effects. For Whites and Blacks, the ORs for alcohol dependence and
anxiety disorders were significant across almost all anxiety disorders. The only
exception was that the OR for panic disorder with agoraphobia was significant for
alcohol abuse but not for alcohol dependence among Blacks. On the other hand, for
Native Americans and Hispanics, only a few of the anxiety disorders were signifi-
cantly associated with alcohol dependence and none with alcohol abuse.
Two general conclusions can be made from the data reported across these
large-scale community surveys. First, the relationship between anxiety disorders
and alcohol dependence appears to be much stronger than between anxiety
disorders and alcohol abuse, with the ORs for dependence much more likely to
be significant than those for abuse. In other words, having a comorbid anxiety
disorder increases the chances of displaying the more severe type of alcohol use
disorder (dependence) moreso than the less severe type (abuse), suggesting a
gradient of effect relationship. . Second, the relationship between alcohol use
disorders and anxiety disorders differs between sexes and racial/ethnic groups.
Although alcohol use is generally more common among men than women (Paa-
vola, Vartiainen, & Haukkala, 2004), alcohol abuse and anxiety disorders are
more closely related for women than for men. Furthermore, it appears that for
Whites and Blacks, anxiety and alcohol dependence are more closely associated
than for Native Americans and Hispanics. The following sections cover etiologi-
cal models of the relationship between alcohol and anxiety, their maintenance,
and their relapse, in an attempt to explicate the high level of comorbidity between
anxiety disorders and alcohol use disorders observed in the epidemiologic surveys.
1
The NESARC did not specify significance of reported 12-month ORs.
Alcohol and Anxiety 33
are three main hypotheses that have been put forward, with some evidence
supporting each hypothesis. First, there is some evidence that the associations
between anxiety and alcohol arise from common underlying variables, such as
common genetic or environmental factors, that cause both anxiety symptoms
and problematic alcohol use. Second, some believe that certain aspects of
problematic alcohol use, such as repeated experiences with alcohol withdrawal,
cause anxiety symptoms and ultimately an anxiety disorder. Finally, others
argue that anxiety symptoms cause alcohol misuse, culminating in an alcohol
use disorder. Evidence examining these three hypotheses is presented below.
There is some evidence, provided by two main lines of research, to support the
hypothesis that certain common, underlying factors are causing both anxiety
symptoms and problematic alcohol use (Kushner et al., 2000a). First, family
and twin studies have provided some evidence of possible common genetic
contributions to the correlation between anxiety symptoms and alcohol con-
sumption (e.g., Tambs, Harris, & Magnus, 1997). Family and twin studies have
also examined the heritability of common underlying personality traits asso-
ciated with both anxiety and alcohol use disorders. For example, several cross-
sectional and longitudinal studies have linked the highly heritable personality
trait of neuroticism (Jang, Livesley, & Vernon, 1996) with anxiety and its
disorders (e.g., Jorm et al., 2000; Weinstock & Whisman, 2006). Neuroticism
has also been linked to alcohol use disorders (Cox, 1987). Another personality
dimension that is closely related to neuroticism, negative emotionality, has been
associated with alcohol use disorders (Swendsen, Conway, Rounsaville, &
Merikangas, 2002). In a study by Swendsen et al. (2002) examining heritability
of negative emotionality, non-alcoholic individuals with alcoholic relatives did
not differ significantly on scores of negative emotionality than those without
alcoholic relatives. If negative emotionality were a heritable risk factor, non-
alcoholic individuals with alcoholic relatives would score higher on this trait
than those without alcoholic relatives. These findings suggest that negative
emotionality may indeed be an individual risk factor rather than a heritable
risk factor for alcohol use disorders. The inconsistent results between these two
related personality traits (i.e. both associated with negative emotional states)
demonstrates that common heritability for some of the personality traits rele-
vant to the anxiety – alcohol relationship is still in need of further investigation.
Conversely, another personality risk factor for both anxiety disorders and
alcohol use disorders, anxiety sensitivity (i.e. fear of anxiety; Stewart & Kushner,
2001), does have a strong heritable component that accounts for nearly half of
the variance in scores on anxiety sensitivity measures (Stein, Lang, & Livesley,
1999). Therefore, it appears that some, but not necessarily all, underlying
personality risk factors associated with both alcohol use disorders and anxiety
disorders have a shared heritable component.
34 B. C. Sabourin, S. H. Stewart
Second, results from some prospective studies suggest a possible common ‘‘third
variable’’ contribution to the alcohol – anxiety relationship. For example, Zimmer-
man et al. (2003) found that remitted panic disorder and social phobia were as
important as current panic/social phobia diagnoses in predicting future alcohol
outcomes. That is, even individuals who were not currently experiencing sufficient
symptoms to receive any anxiety disorder diagnosis were at higher risk of developing
alcohol problems if they had ever been diagnosed with either panic or social phobia in
the past. These findings can be interpreted to suggest that a third underlying factor
(such as a common personality vulnerability or genetic predisposition) was driving
both the alcohol problem and the past or current anxiety disorder.
A 21-year longitudinal study (Goodwin, Fergusson, & Horwood, 2004)
found that once other factors were controlled (i.e., prior substance dependence,
concurrent major depression, and affiliations with deviant peers), the ability of
anxiety disorders to predict the development of alcohol dependence was no
longer significant. The study points to a number of possible third variables
including prior substance dependence which could contribute both to the
development of anxiety disorder (see Norton, Norton, Cox, & Belik, in press)
and of alcohol dependence (e.g., alcohol is consumed in larger quantities when
combined with other substances; Barrett, Darredeau, & Pihl, 2006). Unfortu-
nately the study did not test which of these factors was most important in
explaining the link between anxiety and alcohol dependence.
Some factors that have emerged as possible contributors to the increased
vulnerability of developing comorbid anxiety and alcohol use problems include
either common genetic pre-dispositions (e.g., anxiety sensitivity), biological envir-
onment risk factors (e.g., fetal alcohol syndrome), or non-biological environmental
risk factors (e.g., disruptive familial environment; Merikangas, Stevens, & Fenton,
1996). Unfortunately, no research has yet confirmed one or more of these candidate
factors. More research needs to be conducted exploring these additional underlying
mechanisms before one can make conclusions about their influence.
The second hypothesis dealing with the relationship between anxiety and
alcohol use posits that prolonged drinking is actually a causal factor in anxiety
symptoms and disorders. This alcohol-induced anxiety can occur through
either psychosocial or physiological mechanisms. Psychosocially, it is hypothe-
sized that alcohol may interfere with normal adaptation to stressful stimuli
or that negative consequences produced by problematic drinking (e.g., loss
of job or relational problems) can lead to anxiety symptoms and increased
vulnerability of developing anxiety disorders (Kushner et al., 2000a).
Physiologically, alcohol withdrawal can often produce anxiety symptoms
such as shakiness (see Kushner et al., 2000a) or increased startle, a common
symptom of PTSD (Stewart et al., 1998). In addition, neural adaptation occurs
Alcohol and Anxiety 35
with frequent and excessive alcohol use over time such that repeated alcohol
withdrawals actually sensitize this withdrawal-induced anxiety (Breese, Over-
street, & Knapp, 2005). This has often been referred to as the ‘‘kindling-stress
hypothesis’’; that is, repeated withdrawals from chronic heavy drinking are
thought to worsen, or ‘‘kindle’’ withdrawal-induced anxiety.
A number of studies have also demonstrated increased norepinephrine
activity as well as hyperexcitability of the central nervous system, especially of
limbic structures, during alcohol withdrawal (Kushner et al., 2000a; Marshall,
1997). These are the same neural systems that have been implicated in panic
attacks and panic disorder, providing a possible physiological explanation for
the link between panic disorder and alcohol use disorders (Marshall, 1997).
A final area of research supporting the hypothesis that alcohol problems
cause anxiety involves prospective studies. One such study by Kushner, Sher,
and Erickson (1999), for example, found that a diagnosis of alcohol dependence
at baseline quadrupled the risk of developing an anxiety disorder three to six
years later. Prospective studies have also examined the relationship between
PTSD and alcohol abuse to ascertain whether heavy alcohol use can be a risk
factor for developing PTSD. It has been hypothesized that physiological and
neurochemical changes due to prolonged heavy alcohol use and/or past reliance
on alcohol to deal with life stressors at the expense of developing other coping
mechanisms may increase an individual’s susceptibility of developing PTSD
after a traumatic experience (Brown & Wolfe, 1994; Stewart et al., 1998).
A prospective study by Acierno, Resnick, Kilpatrick, Saunders, and Best
(1999) found that a history of alcohol abuse increased the risk of developing
PTSD in rape victims almost three-fold (OR = 2.65) when compared to the
absence of this factor.
It has been hypothesized that anxiety symptoms and anxiety disorders promote
alcohol use, as individuals drink to self-medicate their anxiety. The ‘‘self-med-
ication hypothesis’’ (and the related tension reduction hypothesis) as applied to
the understanding of the relationship between anxiety and alcohol posits that
the pharmacological and/or psychological effects of alcohol lead to decreases in
aversive anxiety symptoms, thereby motivating anxious individuals to increase
their quantity and/or frequency of alcohol use via the process of negative
reinforcement (Kushner et al., 2000a). Although the self-medication and ten-
sion reduction hypotheses clearly do not account for all drinking behavior
(Greeley & Oei, 1999), there has been a good deal of empirical evidence to
support these hypotheses as they apply to the understanding of comorbid
anxiety and alcohol use disorders (Kushner et al., 2000a).
Anxiety disordered individuals do in fact self-report using alcohol to manage
their anxiety (Kushner, Abrams, Thuras, & Hanson, 2000b; Thomas, Randall,
36 B. C. Sabourin, S. H. Stewart
& Carrigan, 2003; see also Kushner, et al., 2000a for a review). In addition,
Thomas and colleagues (2003) found that socially anxious individuals not only
reported that they drank to feel more comfortable in social situations, but that
they would actually avoid social situations if alcohol were unavailable.
As introduced earlier in this chapter, one possible criterion for establishing
causation (Chilcoat & Breslau, 1998) is a dose response, or gradient of effect
relationship: if anxiety causes alcohol use, one would expect that higher levels of
anxiety would be associated with higher levels of alcohol use. Studies have
found positive correlations between severity of PTSD arousal symptoms and
severity of alcohol use disorder symptoms (McFall, Mackay, & Donovan, 1992;
Stewart et al., 1998). Because correlation does not determine causation, one
must rely on laboratory-based studies, such as a study by Abrams, Kushner,
Medina, and Voight (2002), for evidence that induction of anxiety symptoms
causes heavier drinking. The study found that participants with social phobia
consumed more alcohol following an anxiety provoking activity (speaking in
front of a group) than a control activity (reading a book), presumably in an
effort to dampen the anxious feelings caused by the anxiety provoking activity.
Prospective research on non-clinical populations also supports a dose-
response relationship between anxiety and alcohol use. In a diary-based study
by Swendsen and colleagues (2000), moderate drinkers documented their daily
drinking and mood states for a one-month period. The study revealed that only
anxious feelings and not sadness or other negative affective states preceded and
predicted increased alcohol consumption. As can be observed above, findings
from correlational, laboratory-based experimental, and diary-based prospec-
tive research conducted with both clinical and non-clinical populations
converge to provide some evidence for a relationship between anxiety sym-
ptoms and alcohol use where anxiety precedes and contributes to increased
alcohol use.
Social anxiety appears to have a more complicated relationship with alcohol
use than do other types of anxiety, however. Specifically, some studies examin-
ing the relationship between social anxiety and alcohol consumption show a
positive relationship, whereas other studies show either no linear relationship or
even a negative relationship (Ham & Hope, 2005; Stewart, Morris, Mellings, &
Komar, 2006; Tran, Haaga, & Chambless, 1997). The negative relationship
between social anxiety and alcohol consumption may exist because socially
anxious individuals actually avoid the types of social situations that involve
drinking because of their social anxiety, thus leading to lower levels of alcohol
consumption (Stewart et al., 2006). Nonetheless, social anxiety has been found
to predict alcohol dependence, as well as problems caused by alcohol (Gilles,
Turk, & Fresco, 2006; Stewart et al., 2006). Thus, social anxiety does appear
related to alcohol-related consequences, even if it does not always predict
increased alcohol use.
Another criterion discussed by Chilcoat and Breslau (1998) as necessary for
causation is temporality. If anxiety causes increased or problematic alcohol use,
then anxiety symptoms should predate alcohol-related problems, and anxiety
Alcohol and Anxiety 37
More recent work has focused on finding specific variables that either moderate
or mediate the causal relationship between anxiety and alcohol use. A mod-
erator variable is a qualitative (e.g., sex) or quantitative (e.g., anxiety level)
variable that affects the direction and/or strength of the relation between two
38 B. C. Sabourin, S. H. Stewart
other variables (Baron & Kenny, 1986). A mediator variable, on the other hand,
explains how or why the relationship between a predictor and given criterion
(e.g., between anxiety and alcohol use) exists. That is, the mediator actually
accounts for the relationship between the two variables (Baron & Kenny).
Alcohol expectancies. A potential moderator variable between anxiety and
problematic alcohol use includes certain ‘‘alcohol outcome expectancies’’ (i.e.,
beliefs about the consequences of drinking alcohol). For anxious individuals
who self-medicate to avoid anxiety, an important aspect of the self-medication
hypothesis involves the notion that self-medicators anticipate anxiety, and that
they expect that alcohol will actually decrease their feelings of anxiety (e.g.,
Kushner, Sher, Wood, & Wood, 1994; Tran et al., 1997). Studies have shown
that tension reduction expectancies predict drinking frequency and quantity in
non-alcoholic drinkers with panic disorder (Kushner et al., 2000b) and comor-
bid problem drinking in women with PTSD (Ullman, Filipas, & Townswend,
2005). These results support the role of tension reduction alcohol expectancies
as a moderator: increased or problematic drinking occurs among anxiety dis-
order patients only when tension reduction alcohol expectancies are present.
Another methodology that has been employed to investigate the role of
alcohol outcome expectancies in the anxiety – alcohol relationship is the experi-
mental manipulation of expectancies via the placebo-controlled design. If
expecting alcohol were to induce a cognitive or placebo-induced anxiety redu-
cing effect among anxious individuals, such an effect would provide additional
evidence for the contribution of alcohol expectancies in explaining the anxiety –
alcohol relationship. The empirical evidence provided thus far has found mixed
results for this placebo anxiolytic effect. Some studies have found that the belief
that one was consuming alcohol, even when one was actually consuming a
placebo, was enough to lower feelings of anxiety among anxiety-disordered
patients (Abrams, Kushner, Lisdahl, Medina, & Voight, 2001; Lehman, Brown,
Palfai, & Barlow 2002). On the other hand, research by MacDonald, Stewart,
Hutson, Rhyno, and Loughlin (2001) conducted with participants high in
anxiety sensitivity did not support a cognitively-mediated tension reduction
effect of alcohol. The researchers actually found a ‘‘reverse placebo’’ effect,
where high AS participants in a placebo condition, who had expectations of
alcohol-induced tension reduction, but did not benefit from alcohol’s physio-
logical tension-reduction properties, appeared to have even higher levels of
anxiety than participants in a control condition where they neither received
nor expected alcohol. Regardless of the direction of the placebo effect, all of
these findings do suggest a role for cognitive expectancy variables in accounting
for the effects of alcohol among anxious individuals.
A number of studies have examined specific aspects of alcohol expectancies
in individuals with social anxiety. For people high in social anxiety, expecting
that alcohol would decrease social anxiety or increase social assertiveness was
associated with both higher self-reported drinking quantities (Tran et al., 1997)
and higher alcohol consumption in a laboratory setting (Kidorf & Lang, 1999).
More general tension reduction expectancies, on the other hand, had no effect
Alcohol and Anxiety 39
increase the rate of anxiety disorders above the rate associated with alcohol use
only (Kandel, Huang, & Davies, 2001).
A diagnosis of an anxiety disorder combined with a drug use disorder
constitutes a significant risk factor for developing alcohol dependence (lifetime
OR =5.81; Kessler et al., 1997). This increased risk appears to be even higher
than the risk associated with being diagnosed with an anxiety disorder alone
(i.e. without a drug use disorder; lifetime OR = 1.85). Unfortunately, like many
epidemiological surveys, the National Comorbidity Survey does not break drug
use disorders down by drug type/class, which could further elucidate the drug –
anxiety – alcohol relationship. One possible explanation for this elevated risk
for alcohol dependence among those with comorbid anxiety – drug use disor-
ders is that problematic drug use, through the drugs’ potentially anxiogenic
effects, exacerbates the need to self-medicate with alcohol, resulting in increased
risk for alcohol dependence relative to those with non-comorbid anxiety
disorders.
Empirical findings supporting all three causal hypotheses suggest the possibility
of multiple causal pathways involved in the etiology of comorbid alcohol use
disorders and anxiety disorders. The specific causal pathway involved may vary
across people or across anxiety sub-types. Regardless of the etiology of the
comorbid anxiety symptoms and problematic alcohol use, there have been
countless studies confirming that, once comorbid, anxiety and alcohol use do,
in fact, exert important influences on each other (see Kushner et al., 2000a).
Furthermore, processes involved in the initiation of the comorbidity may differ
from those involved in the maintenance of problematic alcohol use and anxiety.
A feed-forward model has been proposed (Kushner et al., 2000a) in which once
both alcohol use and anxiety are present, each promotes the maintenance or
exacerbation of the other. For example, anxious individuals may resort to
alcohol to decrease feelings of anxiety, which might be an effective strategy in
the short term, providing reinforcement for this pattern. However, alcohol, and
especially withdrawal from alcohol, increases anxiety-like symptoms in the
longer run via physiological mechanisms such as kindling. Alcohol may also
worsen anxiety levels because of the negative familial, social or occupational
consequences of heavy drinking. Individuals will then increase their drinking
behavior in an attempt to alleviate these worsening feelings of anxiety because
drinking has become a learned strategy for dealing with these symptoms,
especially if there is a failure to recognize that the alcohol may actually be
promoting the anxiety in the medium to long term.
Finally, in individuals with PTSD, alcohol that is used to cope with anxiety
may prevent normal ‘‘habituation’’ of the anxiety symptoms following trauma
exposure. On the other hand, for individuals who are not drinking, anxious
Alcohol and Anxiety 43
feelings caused by PTSD may naturally remit with time. Thus, when individuals
drink in an attempt to numb or avoid these feelings, they may be preventing this
natural recovery from taking place, leading to maintenance of the anxiety
symptoms in the long run (Stewart et al., 1998).
When individuals who suffer from both anxiety disorders and alcohol use dis-
orders enter treatment for either disorder, their treatment outcome is often nega-
tively affected by their comorbidity. Alcohol use disorders have been found to
predict poorer anxiety disorder treatment outcomes for patients with both PTSD
(Forbes, Creamer, Hawthorne, Allen, & McHugh, 2003), panic disorder with
agoraphobia, social phobia, and generalized anxiety disorder (Bruce et al., 2005).
Comorbid anxiety problems also increase the likelihood of relapse in
treated or abstinent alcoholics (e.g., Driessen et al., 2001; Kushner et al.,
2005; Willinger et al., 2002). For example, if a comorbid PTSD – alcoholic
individual does not know how to cope with flashbacks and nightmares of the
traumatic event in ways other than through drinking, then continued re-
experiencing symptoms can serve as a major risk factor for return to problem
alcohol use following initially effective alcohol abuse treatment. Not all
studies have shown this relationship, however. In one study (LaBounty,
Hatsukami, Morgan, & Nelson, 1992), alcoholics with comorbid panic dis-
order did not differ in their rates of relapse to drinking problems from non
comorbid alcoholics. However, in a recent review, Bradizza et al. (2006) noted
some methodological issues with this paper, including the absence of a valid
and reliable diagnostic measure and the failure to define relapse, limiting the
conclusions that could be drawn from the study. Moreover, despite the
similar relapse rates, the study did find that more comorbid alcoholic and
panic disordered patients reported relapsing to cope with negative emotions
than non comorbid alcoholics. Thus, these observed differences in the relapse
process might be useful for improving treatments for this group.
Another study compared relapse rates for alcoholic individuals with comor-
bid social phobia, or panic disorder with agoraphobia, or agoraphobia without
a history of panic attacks to relapse rates for alcoholics without any comorbid
anxiety disorder (individuals with other anxiety disorders were excluded) fol-
lowing treatment for alcoholism (Marquenie et al., 2006). The results suggested
that the comorbid anxiety disorders did not have a significant impact on either
relapse rates or days to relapse. Nonetheless, some methodological problems
may account for this study’s failure to support higher alcoholism relapse among
treated alcoholic patients with comorbid anxiety disorders. First, the study used
a retrospective design. Participants were contacted for the study an average of
20.3 months (and up to 42 months) after baseline assessment, even though the
majority of participants who relapsed did so within the first few months post
44 B. C. Sabourin, S. H. Stewart
Individuals who suffer from both anxiety problems and alcohol use problems
present a special and challenging population with regards to treatment. As was
shown above, this population often suffers worse anxiety and alcohol treatment
Alcohol and Anxiety 45
Conclusion
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Illicit Drug Use Across the Anxiety Disorders
Prevalence, Underlying Mechanisms, and Treatment
Illicit Drugs
The term illicit drug is used here in reference to any substance that is illegal,
with the distinction of illegal being specific to the United States.1 Such drugs,
as recognized by the Diagnostic and Statistical Manual of Mental Disorders,
Matthew T. Tull
Department of Psychology, University of Maryland, College Park, MD 20742, Tel: 301-405-
3281, FAX: 310-405-3223
MTull@psyc.umd.edu
1
Due to space limitations we do not consider legal drugs used in an illegal manner (e.g., pain
medications used without a prescription).
Reiger et al. (1990), in analyzing data from the ECA study, found that
individuals with any anxiety disorder (as determined by DSM-III criteria)
were 2.5 times as likely to also exhibit a comorbid drug use disorder (Odds
Ratio [OR] = 2.4 for drug dependence and OR = 2.3 for drug abuse).
Specifically, 11.9% of participants with any anxiety disorder diagnosis also
met criteria for a drug use disorder, and this rate was significantly greater than
that found among participants without an anxiety disorder diagnosis. Grant
et al. (2004) found slightly higher ORs in examining data from the NESARC.
Individuals with any anxiety disorder were 4.58 times as likely to also exhibit a
comorbid drug use disorder (OR = 2.15 for drug abuse and OR = 2.43 for drug
dependence).
In another large scale study of comorbidity, Merikangas et al. (1998) ana-
lyzed data from six international epidemiological study sites (Germany,
Mexico, Netherlands, Ontario, and two sites in the United States). They
found that, across all sites, approximately 24.9% of individuals with any life-
time DSM-III-R anxiety disorder diagnosis also exhibited lifetime drug use
(e.g., marijuana, opioids, stimulants, sedatives, or inhalants, but not alcohol),
35.8% exhibited lifetime drug problems (met at least one DSM-III-R abuse
criteria for any drug), and 45.8% met criteria for lifetime DSM-III-R drug
dependence.
Lopez, Turner, and Saavedra (2005) analyzed data from 1,747 young adults
(92% aged 19–21) from Miami-Dade county (Florida) public schools, and
examined drug dependence among individuals with pure anxiety disorder diag-
noses (i.e., the occurrence of one or more anxiety disorders that is not accom-
panied by any additional psychiatric disorder) or an anxiety disorder that
Drug Use and the Anxiety Disorders 59
2
Due to space limitations, only data pertaining to drug use disorders in general will be
presented. Readers interested in data pertaining to rates of drug abuse or dependence
separately across the anxiety disorder diagnoses are referred to Conway et al. (2006).
Drug Use and the Anxiety Disorders 61
prevalence rates pertaining to specific illicit drug use disorders were not exam-
ined. Among respondents who met 12-month criteria for a DSM-IV anxiety
disorder of PD with agoraphobia, 10.58% also exhibited a 12-month drug use
disorder (4.65% drug abuse and 5.94% drug dependence). Rates of 12-month
drug use disorders for other anxiety disorders were: 6.32% (2.17% drug abuse
and 4.16% drug dependence) for PD without agoraphobia, 5.52% (2.59% drug
abuse and 2.94% drug dependence) for SAD, 4.08% (2.13% drug abuse, 1.95%
drug dependence) for specific phobia, and 8.06% (2.82% drug abuse, 5.24%
drug dependence) for GAD.
Finally, data from the NESARC has been used to examine differences in
racial/ethnic background across comorbid anxiety and drug use disorders.
Specific to abuse, Smith et al. (2006) found significant 12-month associations
between drug abuse and all anxiety disorders (with the exception of PD without
agoraphobia). No other significant 12-month associations between drug abuse
and anxiety disorders were found for any other racial/ethnic group, with the one
exception of a significant 12-month association between drug abuse and specific
phobia among Native American respondents. A greater number of significant
associations were found when examining the relationship between drug depen-
dence and specific anxiety disorders across racial/ethnic groups. Significant
associations were found for drug dependence and all anxiety disorders exam-
ined (PD with and without agoraphobia, SAD, specific phobia, GAD) among
White respondents. Significant associations were found for drug dependence
and all anxiety disorders with the exception of specific phobia for Black/African
American respondents. Among Native American respondents, significant asso-
ciations were found for PD without agoraphobia and SAD. Asian/Asian-
American respondents demonstrated significant associations between drug
dependence and PD without agoraphobia, SAD, and GAD, and Latino respon-
dents exhibited significant associations between drug dependence and PD with
agoraphobia, SAD, specific phobia, and GAD.
As mentioned previously, the NESARC is the first to provide comprehensive
data on the co-occurrence of specific anxiety disorders and illicit drug use
disorders. In general, though, limited data is available that examines drug use
within specific anxiety disorders. The one exception, however, may be PTSD, as
a number of studies have examined the co-occurrence of PTSD and illicit drug
use (for a review, see Chilcoat & Menard, 2003). We now move to a review of
this literature, followed by a review of the literature pertaining to drug use
within other anxiety disorders besides PTSD.
Posttraumatic stress disorder. Data from the ECA found that compared to
men and women without a diagnosis of PTSD, men with PTSD were 5 times
more likely to also exhibit a drug use disorder and women with PTSD were
1.4 times as likely to exhibit a drug use disorder (overall odds ratio of 2.2; Helzer
et al., 1987). In the NCS, Kessler, Sonnega, Bromet, Hughes, and Nelson (1995)
found that compared to men and women without a diagnosis of PTSD, men
with PTSD were approximately 2.97 times as likely and women 4.46 times as
likely to exhibit a drug use disorder. Giaconia and colleagues (1995, 2000)
62 M. T. Tull et al.
collected data from 384 18-year-olds as part of The Early Adulthood Research
Project (EARP) and found that compared to individuals without a history
of traumatic exposure, individuals with a lifetime diagnosis of PTSD were
8.8 times as likely to also meet criteria for a lifetime drug dependence diagnosis
and 14.14 times as likely to meet criteria for past year drug dependence.
Calhoun et al. (2000) assessed drug use among a sample of 341 veterans with
PTSD seeking treatment for PTSD. Opiate and marijuana use was reported by
the largest number of patients (23% and 20% respectively). Benzodiazepine use
was reported by 11% of patients, cocaine use by 8% of the patients, barbitu-
rates by 5% of the patients, amphetamines by 3% of the patients, psilocybin by
3% of the patients, LSD by 1% of the patients, and PCP by 1% of the patients.
Other studies have produced similar findings in regard to the use of specific
drugs. For example, Saxon et al. (2001) found that incarcerated veterans with
PTSD were more likely to report a greater degree of cocaine and heroin use as
compared to individuals without a PTSD diagnosis. Tarrier and Sommerfield
(2003) assessed 120 civilians seeking treatment for chronic PTSD on their drug
use histories. Of the 120 participants, 17 used marijuana, 6 used sedatives, 4
used stimulants, 2 used a psychedelic, and 1 used cocaine. Further, in regard to
rates of drug use disorders among younger individuals with PTSD, Kilpatrick,
et al. (2000) collected data from a national sample of 4,023 adolescents (between
the ages of 12 and 17). They found that PTSD was significantly associated with
illicit drug use, including marijuana abuse and dependence and ‘‘harder’’ drug
abuse and dependence (e.g., stimulants).
Panic disorder and panic disorder-related symptoms. Moving beyond PTSD, a
number of studies have examined illicit drug use among individuals with PD or
PD-related symptoms, such as the experience of non-clinical panic attacks.
Biederman et al. (2005) examined the rates of comorbid disorders among 23
individuals with PD and found that 8% exhibited a comorbid psychoactive
substance use disorder. Among individuals with PD and major depression, 21%
exhibited a comorbid psychoactive substance use disorder. Further, Zvolensky,
Bernstein et al. (2006) examined lifetime associations between marijuana use,
abuse, and dependence and panic attacks in a representative sample of 4,745
individuals. They found a positive association between lifetime panic attack
occurrence and marijuana use, even when controlling for the effect of polysub-
stance use, alcohol abuse, and demographic variables (e.g., age, gender, etc.).
Bonn-Miller, Bernstein, Sachs-Ericsson, Schmidt, and Zvolensky (2007) also
examined the relationship between psychedelic (e.g., PCP, LSD, mescaline,
peyote, psilocybin, DMT) use, abuse, and dependence and lifetime panic attack
history within this same sample. Psychedelic abuse and dependence (although
not use) were significantly associated with a heightened risk for the experience
of lifetime panic attacks, controlling for demographic variables, polysubstance
use, alcohol abuse, and a history of major depressive disorder.
Deacon and Valentiner (2000) examined the relationship between panic
attacks and substance use within a sample of 279 college students. Students
with non-clinical panic attacks (n = 25) were significantly more likely than
Drug Use and the Anxiety Disorders 63
students without panic (n = 222) to report the use of drugs, such as sedatives
(not alcohol), cocaine, and stimulants. Further, among non-clinical panickers,
sedative use was not found to be related to distress about panic attacks, panic
attack frequency, the occurrence of unexpected attacks, or general anxiety or
depression symptoms. Valentiner, Mounts, and Deacon (2004) also investi-
gated the relationship between panic attacks and illicit drug use in a sample of
399 incoming college freshman. Similar to Deacon and Valentiner (2000), they
found that non-clinical panickers (n = 47), compared to non-panickers
(n = 290), were significantly more likely to report lifetime use of sedatives,
stimulants, and opioids, but not tobacco, alcohol, cocaine, or hallucinogens. In
regard to specific rates of drug use among panickers, 12.8% reported lifetime
use of sedatives (not alcohol), 6.4% reported lifetime use of cocaine, 55.3%
reported lifetime use of marijuana, 34% reported lifetime use of stimulants,
21.3% reported lifetime use of opioids, and 23.4% reported lifetime use of
hallucinogens. Additional analyses were conducted by Valentiner et al. (2004)
to determine whether the relationships between panic and substance use dif-
fered as a function of gender or racial/ethnic background. Gender only served
as a moderator in the relationship between panic and cocaine use. In particular,
male panickers were significantly more likely to use cocaine than males without
panic. In addition, among non-clinical panickers, substance use was not due to
the number of panic attacks in the past year, panic attack symptom severity,
and the experience of unexpected panic attacks.
Other anxiety disorders. There is a dearth of studies on the relationship
between specific drug use disorders with SAD, GAD, OCD, and specific
phobia. More research is needed, especially given extant evidence that these
anxiety disorder diagnoses may be associated with heightened risk for the
development of illicit drug use disorders. For example, using data from the
ECA Study, Reiger et al. (1990) found that 18.4% of respondents with lifetime
OCD also exhibited a lifetime drug use disorder (11% for drug dependence and
7.4% for drug abuse). Further, this rate was significantly greater than what was
found among individuals without a diagnosis of OCD.
In regard to SAD, Kessler et al. (1996), in examining data from the NCS,
found that respondents with SAD were significantly at greater risk to exhibit a
12-month co-occurrence of drug dependence (OR = 3.2) and lifetime drug
dependence (OR = 2.6). Kessler et al. (1996) also provide data on GAD and
specific phobia. Respondents with GAD were at significantly greater risk to
exhibit lifetime drug dependence (OR = 3.8). Respondents with specific phobia
were at significantly greater risk to exhibit co-occurring 12-month (OR = 1.8)
or lifetime (OR = 2.5) drug dependence. Fewer studies have specifically exam-
ined the relationship between specific drug use and SAD; however, of note,
several studies have also found evidence of an association between SAD and
marijuana use (Buckner, Mallott, Schmidt, & Taylor, 2006; Buckner, Schmidt,
Bobadilla, & Taylor, 2006; Lindquist, Lindsay, & White, 1979; Lynskey et al.,
2002).
64 M. T. Tull et al.
Anxiety and illicit drug use disorder comorbidity in the context of a mood
disorder. It is important to recognize that anxiety disorders are also likely to co-
occur with other disorders, especially mood disorders. Therefore, it will be
important for future studies to begin to examine the impact of mood-anxiety
disorder comorbidity on drug use behavior. Speaking to this potential impact of
mood-anxiety disorder comorbidity on drug use, Goodwin et al. (2002) exam-
ined the relationship between anxiety and drug use disorders among a sample of
130 individuals with a severe affective disorder (recurrent major depression,
bipolar disorder) to examine whether the presence of a comorbid anxiety
disorder diagnoses increases risk for the presence of a drug use disorder. They
found that, in general, among individuals with a severe affective disorder,
having an anxiety disorder was associated with a significantly increased risk
of a cocaine, sedative, stimulant, or opioid use disorder. In examining specific
anxiety disorders, they found that a) the experience of panic attacks increased
the likelihood of having a cocaine, sedative, stimulant, or opioid use disorder; b)
the presence of an OCD diagnosis increase the likelihood of stimulant use
disorder; c) a diagnosis of SAD increased risk for a sedative use disorder; and
d) and a specific phobia diagnosis was associated with increased risk for a
cocaine, sedative, stimulant, and opioid use disorder.
3
It is of note that a fourth possibility also exists. Specifically, anxiety disorder and drug use
disorder diagnoses may develop through a completely independent process. Goldenberg et al.
(1995) examined 181 participants in the Harvard Anxiety Research Project who had a history
of substance use disorders and anxiety disorders in order to test hypotheses pertaining to the
chronology of substance use-anxiety disorder comorbidity. They found, among individuals
with a primary anxiety disorder diagnosis, the anxiety disorder diagnosis was present for, on
average, 11.6 years before the onset of the substance use disorder. Further, substance use
tended to occur a mean of 9.6 years before the onset of a secondary anxiety disorder diagnosis.
Given the amount of time between the onset of the diagnoses, the authors concluded that there
is not an etiological connection between the disorders, but instead, the onset of these disorders
are guided by independent processes.
Drug Use and the Anxiety Disorders 65
In regard to the first hypothesis, Zvolensky, Bernstein et al. (2006) found that a
lifetime history of marijuana dependence was significantly associated with an
increased risk for panic attacks, even when controlling for polysubstance use,
alcohol abuse, and relevant demographic variables. Further, Cottler, Compton,
Mager, Spitznagel and Janca (1992) found evidence for the high-risk hypothesis
of comorbid PTSD-substance use disorder development. This hypothesis essen-
tially states that drug use increases the likelihood of traumatic exposure (due to
the high risk behaviors drug use is often associated with), thereby increasing
risk for PTSD. Using data from the St. Louis Epidemiologic Catchment Area
study, Cottler et al. (1992) examined the order of onset of PTSD and drug use
within the 2,663 respondents. Cottler et al. (1992) found that drug use tended to
precede the development of PTSD. However, it is important to note, that rates
of PTSD in this sample were low (1.35% overall).
In another study, Compton, Cottler, Phelps, Abdallah, and Spitznagel
(2000) examined the temporal relationship of drug dependence and DSM-III-
R psychiatric diagnoses among 425 individuals in drug treatment. In the major-
ity of cases (90%), drug dependence was found to follow the onset of a phobic
disorder (the authors did not indicate whether this referred to SAD, specific
phobia, or both). However, among individuals with a diagnosis of GAD, in
65% of the cases, the onset of the anxiety disorder followed the onset of the drug
dependence, suggesting that, at least with GAD, the diagnosis may be second-
ary to drug dependence.
Studies have also provided support for the hypothesis that illicit drug use
follows an anxiety disorder diagnosis. This hypothesis has most extensively
been studied in PTSD. For example, Chilcoat and Breslau (1998) found that a
PTSD diagnosis greatly increased the risk for the subsequent development of a
SUD; however, traumatic exposure not resulting in PTSD did not have this
effect, suggesting that the relationship between traumatic exposure and sub-
stance use is unique to those individuals who develop PTSD. They also found
that substance abuse/dependence did not increase risk for traumatic exposure
or PTSD (thus not providing support for the high-risk hypothesis). Consistent
with a self-medication model of illicit drug use where drug use develops in an
attempt to alleviate anxiety disorder symptoms, it has been demonstrated that
exposure to trauma cues among PTSD-SUD patients is associated with sub-
stance craving, suggesting that the experience of PTSD-related symptoms may
increase motivation to use substances in an attempt to relieve those symptoms
(Coffey et al., 2002; Saladin et al., 2003).
66 M. T. Tull et al.
Additional support for the hypothesis that the presence of an anxiety dis-
order increases risk for illicit drug use comes from findings of Lopez et al. (2005)
who found that, within their sample of 1747 young adults, the mean age of onset
for an anxiety disorder diagnosis was consistently lower than that for substance
dependence. In addition, an anxiety disorder diagnosis tended to occur before
the onset of substance dependence 80% of the time.
Common Third Variables that may Underlie Both Illicit Drug Use
and Anxiety Disorders
Much less research has examined the third hypothesis of third variables that
may function as a common underlying mechanism for both anxiety disorders
and illicit drug use, especially in regard to the identification of common neuro-
biological and psychological mechanisms for the relationship between anxiety
and drug use disorders. Two variables that are worthy of strong consideration
are neurobiology and individual difference variables, which we will review
below. First, however, it is also important to note that another important
third variable for future consideration is gene by environment interactions.
Although no current research has directly examined shared genetic transmis-
sion of anxiety and illicit drug use disorders, this is likely an important area for
further pursuit. Specifically, the interaction between life stress and a poly-
morphism in the regulatory region of the serotonin transporter gene may be a
particularly promising area of study. Indeed, although the preponderance of the
work in this area has focused on the development of depression, some emerging
research has separately identified the role of this interaction in the development
of anxiety (Kendler, 1996) and illicit drug use (see Kreek, Nielsen, Butelman, &
LaForge, 2005).
Neurobiology. One aspect of neurobiology that may be potentially relevant
to the development and maintenance of both anxiety disorders and illicit drug
use involves the hypothalamic-pituitary-adrenal (HPA) axis, which controls the
secretion of hormones for the pituitary and adrenal cortex. The HPA axis plays
a central role in mediating the body’s response to stress and anxiety and is
extremely sensitive to inputs from the limbic system and prefrontal cortex, two
brain areas that are important in modulating reinforcement and motivational
processes. The activity of the HPA axis is reflected in changes in serum or
salivary cortisol levels (de Kloet & Reul, 1987), and has been found to account
for differences in stress reactivity to physical and psychological laboratory
challenges (Kaye et al., 2004; Wetherell et al., 2006). Neurobiological models
of drug addiction hypothesize that dysregulated HPA axis functioning contri-
butes to a state of chronic deviation of the regulatory system from its normal
operating level, resulting in increased reinforcing effects of illicit drugs (Koob &
Le Moal, 2001). More specifically, the HPA and brain stem stress circuits are
hypothesized to be recruited in feed forward loops during response to stress,
Drug Use and the Anxiety Disorders 67
such that the corticotrophin releasing factor (CRF) in the extended amygdala
drives norepinephrine systems in the pons-medulla of the brain stem, which in
turn drives CRF in the extended amygdala. The extended amygdala is thus
hypothesized to play a key role in regulating the HPA axis (i.e., stress response)
and subsequent recruitment of negative reinforcement behavior (Koob &
Le Moal, 2006), which may be especially relevant if substances are used for
self-medication of anxiety symptoms. As much of this work is focused more on
the relationship between stress and illicit drug use, as opposed to anxiety
disorders specifically, it will be important for additional work to target the
relationship between anxiety disorders and illicit drug use specifically. It is
important to note, though, that dysregulation of the HPA axis has been
found to play a role in the anxiety disorders (for a review, see Risbrough &
Stein, 2006) and especially in PD (e.g., Erhardt et al., 2006) and PTSD (e.g., de
Kloet et al., 2006; Yehuda, 2001) – two anxiety disorders that have been found
to frequently co-occur with illicit drug use, suggesting that dysregulated func-
tioning of the HPA axis may be common pathway at least for PD or PTSD and
illicit drug use. However, further research is needed to test this hypothesis.
Anxiety sensitivity. Anxiety sensitivity (AS) is an individual difference vari-
able representing the tendency to fear anxiety-related sensations (e.g., increased
heart rate, shortness of breath) due to beliefs that they will have negative
somatic, cognitive, or social consequences (Reiss, 1991). Reiss (1991) originally
proposed AS as a predisposing personality factor for the pathogenesis of the
anxiety disorders, and research supports this, as demonstrated through the
finding of elevated levels of AS across the anxiety disorders, with the exception
of specific phobia (see Cox, Borger, & Enns, 1999). Although AS was originally
proposed as a vulnerability factor for the anxiety disorders in general, its role as
a specific vulnerability factor for PD has been examined most extensively.
Studies consistently find higher levels of AS among individuals with PD,
compared to individuals with other anxiety disorders (with the exception of
PTSD) and healthy controls (see Cox et al., 1999). Further, AS has been
predictive of the later development of spontaneous panic attacks (e.g., Schmidt,
Lerew, & Jackson, 1997, 1999), as well as fearful responding to biological
challenge tasks, such as hyperventilation and CO2 inhalation (Donnell &
McNally, 1990; Harrington, Schmidt, & Telch, 1996; Rapee & Medoro, 1994;
Schmidt & Telch, 1994; Telch, Silverman, & Schmidt, 1996; see also Zvolensky
& Eifert, 2001, for a review). Similarly, successful treatment of PD has been
found to be associated with corresponding reductions in AS following a
cognitive behavioral group for PD (Telch et al., 1993) and individual cognitive
behavior therapy (CBT) for anxiety medication discontinuation (Bruce,
Spiegel, Gregg, & Nuzzarello, 1995).
Research exploring AS as an underlying vulnerability for psychopathology
in general has also been conducted, producing evidence that AS may underlie
other psychiatric conditions as well, including depression (e.g., Otto, Pollack,
Fava, Uccello, & Rosenbaum, 1995; Taylor, Koch, Woody, & McLean, 1996;
Tull & Gratz, in press; Tull, Gratz, & Lacroce, 2006), borderline personality
68 M. T. Tull et al.
disorder (Gratz, Tull, & Gunderson, in press), and certain types of drug use
patterns (see Lejuez, Paulson, Daughters, Bornovalova, & Zvolensky, 2006;
Otto, Safren, & Pollack, 2004; Stewart & Kushner, 2001; Zvolensky & Schmidt,
2004). In regard to AS and drug use in particular, across the substance use
disorders, McNally (1996) predicted that those individuals high in AS should
specifically be at risk for drugs that include anxiolytic or depressive psycho-
pharmacological effects as opposed to those with arousal properties (i.e.,
stimulants). However, research examining the role of AS in drug use is in its
infancy, and across substances, alcohol and tobacco use have been most exten-
sively studied (see chapters in this book; for reviews, see also Stewart, Samoluk,
& MacDonald, 1999; Zvolensky et al., 2003). Few studies have been conducted
that specifically examine the relationship between AS and other drug use.
However, there is some evidence to suggest that elevated levels of AS may be
associated with certain drug classes (besides tobacco and alcohol).
Consistent with the relationship between arousal dampening drugs and AS,
individuals reporting both chronic back pain and high AS report greater use of
analgesic medications (Asmundson & Norton, 1995), and heightened AS has
been found to be associated with elevated use of anxiety medications in general
(Telch, Lucas, & Nelson, 1989). Bruce et al. (1995) examined successful benzo-
diazepine (Alprazolam) medication discontinuation in individuals receiving
treatment as usual or the same procedure together with CBT treatment.
While CBT significantly decreased anxiety and depression compared to control
at 6-month follow-up, across both groups successful drug discontinuation was
predicted by AS reduction from baseline to post-treatment. While McNally’s
prediction has been generally supported regarding arousal dampening effects
(but see Forsyth, Parker, & Finlay, 2003), the prediction that individuals with
high AS should avoid arousal related drugs have not been confirmed to date.
No differences have been found in preferences for illicit stimulants (e.g., cocaine
or amphetamines) between high and low AS individuals (Norton et al., 1997;
DeHaas, Calamari, Bair, & Martin, 2001; Forsyth et al., 2003) or for other
stimulants such as caffeine (Stewart, Karp, Pihl, & Peterson, 1997). These
findings suggest that while AS may act as a risk factor for drugs with arousal
dampening effects, it does not act as a prophylactic against arousal producing
self-medication.
Research investigating the role of AS in marijuana use has provided mixed
results. Whereas marijuana use has been reported to correlate with high AS in
adolescents (Comeau, Stewart, & Loba, 2001), the opposite was found among
adults in which low AS correlated with marijuana use (Norton et al., 1997;
Stewart et al., 1997). In a recent investigation into adult tobacco users, mar-
ijuana users high in AS were at increased risk for more severe anxiety-related
symptoms (Zvolensky, Bonn-Miller et al., 2006), controlling for the effects of
cigarettes per day, alcohol use, and negative affectivity. In addition, AS has
been found to predict the severity of marijuana withdrawal symptoms among
young adult marijuana smokers, controlling for frequency of past 30-day
marijuana use, number of cigarettes smoked per day, alcohol consumption,
Drug Use and the Anxiety Disorders 69
Given the high rates of comorbidity between anxiety disorders and substance
use disorders, as well as suggestions that comorbid anxiety and substance use
disorders may be better characterized as a single unique disorder (Hien, Cohen,
Miele, Litt, & Capstick, 2004; Morissette et al., 2007), specialized treatments
designed to specifically target this comorbidity are beginning to be developed.
Of those treatments that are available, the majority are focused on the comor-
bidity between PTSD and substance use disorders.
Seeking Safety. Najavits (2002) developed Seeking Safety to specifically
target comorbid PTSD and substance use disorders. Seeking Safety is a
24-session cognitive behavioral group therapy protocol treatment that teaches
individuals with this comorbid symptom presentation a variety of cognitive,
behavioral, and interpersonal skills particularly applicable to individuals with
both PTSD and substance use difficulties, all of which are designed with the
idea that safety is the top priority in recovery from each disorder (Najavits,
Weiss, & Liese, 1996). That is, coping skills are focused on maintaining absti-
nence, reducing self-destructive and high-risk behavior, and establishing sup-
port. Seeking Safety has been found to be effective, with patients exhibiting
significant reductions in substance use behavior, trauma-related symptoms,
suicide risk, suicidal thoughts, depression, and thoughts about substance use,
and improvements in social adjustment, family functioning, and problem
72 M. T. Tull et al.
solving (e.g., Hien et al., 2004; Najavits et al., 1996; Zlotnick, Najavits, Rohse-
now, & Johnson, 2003).
Concurrent Treatment of PTSD and Cocaine Dependence. Another treatment
specifically designed for individuals with comorbid PTSD and substance use
disorders is Back, Dansky, Carroll, Foa, and Brady’s (2001) Concurrent Treat-
ment of PTSD and Cocaine Dependence (CTPCD). This treatment consists of
16 individual 90-minute sessions. The treatment was designed by integrating
previously validated cognitive behavioral treatments for substance dependence
(Carroll, 1998) and PTSD (Foa, Rothbaum, Riggs, & Murdock, 1991; Foa &
Rothbaum, 1998). CTPCD involves psychoeducation on the link between
PTSD and cocaine dependence, coping skills training, relapse prevention skills,
and cognitive restructuring. Further, patients undergo in-vivo and imaginal
exposure in order to address their PTSD symptoms. In an initial examination of
CTPCD, Brady, Dansky, Back, Foa, and Carroll (2001) found that individuals
who completed treatment evidenced significant reductions in depressive symp-
toms, PTSD symptoms, and cocaine use severity.
Anxiety Sensitivity Treatment for Heroin Users. Targeting AS, as opposed to
any specific disorder, we (Tull, Schulzinger, Schmidt, Zvolensky, & Lejuez, 2007)
recently developed an acceptance-based behavioral treatment (the Anxiety Sensi-
tivity Treatment for Heroin Users; AST-H) meant to be used in conjunction with
standard substance abuse treatment. Our treatment was designed to have specific
relevance for heightened heroin users with heightened AS. Previous research
(Lejuez et al., 2006) has demonstrated that heightened AS may increase risk for
substance use treatment drop-out among heroin users. In particular, a tendency to
fear of and unwillingness to have anxiety-related sensations may prompt indivi-
duals to attempt to avoid these sensations through the use of heroin. Therefore, we
developed a six session adjunctive treatment where individuals engage in inter-
ceptive exposure exercises in order to facilitate acceptance of, and tolerance for,
aversive internal sensations, with the goal of preventing the use of heroin for self-
medication of these sensations. In an initial examination of this treatment’s
effectiveness, the AST-H was found to result in reductions in AS, heroin cravings,
avoidance behavior, and emotion dysregulation (Tull et al., 2007). Improvements
were maintained when measured over one month post-treatment. Current efforts
are underway to replicate this finding within a randomized controlled trial.
Conclusion
Recent years have seen a rise in studies examining the co-occurrence of illicit
drug use and anxiety disorder diagnoses, and these studies provide convincing
evidence that illicit drug use is prevalent among individuals with anxiety dis-
order diagnoses. Further, the impact of this co-occurrence on psychological
functioning and physical health is clear. Yet, although studies have begun to
address the mechanisms underlying this co-occurrence, all anxiety disorders
Drug Use and the Anxiety Disorders 73
and forms of illicit drug use have not been examined equally. Therefore, future
research is needed to better understand the functional relationship between all
anxiety disorders and forms of illicit drug use, with the goal of informing the
development of novel and targeted interventions for this comorbidity, as well as
prevention efforts.
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The Promise of Exercise Interventions
for the Anxiety Disorders
Introduction
There is consistent evidence for the role of exercise in increasing longevity (Lee &
Paffenbarger, 2000; Lee, Hsieh, & Paffenbarger, 1995) and reducing risk for
coronary disease (Berlin & Colditz, 1990; Kohl, 2001), stroke (Wannamethee &
Shaper, 1992), diabetes (Chipkin, Klugh, & Chasan-Taber, 2001), obesity (Ross &
Janssen, 2001) and various cancers (Lee et al., 1995; Lee, Paffenbarger, & Hsieh,
1991; Lee, Paffenbarger, & Hsieh, 1992; Lee, Sesso, & Paffenbarger, 1999).
Evidence from a variety of sources also suggests that physical activity benefits
mental health (see for review Biddle, 2000; Stathopoulou, Powers, Berry, Smits, &
Otto, 2006). Several large cross-sectional population studies have demonstrated
that physical activity is associated with fewer symptoms of anxiety and depression
(Stephens, 1988), lower levels of stress, anger, and cynical distrust (Hassmen,
Koivula, & Uutela, 2000) as well as better social functioning and vitality among
persons with anxiety and substance use disorders (Schmitz, Kruse, & Kugler,
2004). Prospective studies have further shown that physical activity is associated
with a decreased risk of developing depression (Camacho, Roberts, Lazarus,
Kaplan, & Cohen, 1991; Paffenbarger, Lee, & Leung, 1994) even after controlling
for age, social economic status and educational level (Farmer, Locke, Mosciki,
Larson, & Radloff, 1998). Lastly, there is a growing body of research demonstrat-
ing the efficacy of exercise interventions for mental health (Stathopoulou et al.,
2006).
If effective for the prevention and treatment of anxiety disorders, physical
activity interventions would have a significant public health impact. In this
chapter, we review the literature on the relationship between physical activity
and anxiety. Specifically, we discuss findings from epidemiological, basic and
clinical studies, and consider potential mechanisms by which physical activity
Jasper A. J. Smits
Southern Methodist University, Department of Psychology, 6424 Hilltop Lane, Dallas, TX.
Tel: 214-768-4125, Fax: 214-768-0821
jsmits@smu.edu
anchored to VO2R (i.e., the difference between resting VO2 and maximal VO2)
values. As can be seen in Table 1, intensity of exercise prescriptions can also be
guided by a person’s heart rate reserve, maximal heart rate, or subjective ratings
of perceived exertion (i.e., RPE; Borg, 1998).
Data from the 2002–2004 National Health Interview Survey (NHIS), which
included a representative sample of 93,222 U.S. adults, indicated that 62% of
adults engaged in at least in some leisure-time physical activity over the past year
(i.e., light, moderate or vigorous activity episodes that last at least 10 minutes;
Adams & Schoenborn, 2006). Physical activity status further varies as a function
of several demographic factors. For example, physical activity is significantly
more prevalent among men compared to women (64% versus 60.2%) and among
White and Asian adults (63.7% and 62.1%) compared to Black and Hispanic
adults (51.3% and 47.6%). Likewise, physical activity decreases with age and
increases with education and family income (Adams & Schoenborn, 2006).
There have been several large-scale studies providing evidence for the negative
association between physical activity and anxiety. For example, Stephens
(1988) collapsed data from four national health surveys conducted in the
United States and Canada between 1971 and 1981 (e.g., the National Health
and Nutrition Examination Study, Canada Health Survey, National Survey of
Personal Health Practices and Consequences, and the Canada Fitness Survey).
This procedure yielded a total sample size of approximately 55,000 persons
between ages 10 and 74. Both mental health and level of leisure time exercise
were assessed by self-report. The findings supported the hypothesis that physi-
cal activity is associated with good mental health, including fewer symptoms of
depression and anxiety, even after controlling for education and physical health
status. Interestingly, the strength of this relationship varied as a function of age
and sex, where a stronger link was observed among women and among those
over age 40. Recently, Schmitz and colleagues (Schmitz et al., 2004)
extended these findings by showing a link between physical activity and
enhanced psychological and health-related well-being among persons suffering
from DSM-IV anxiety disorders. They used data from the German National
Health Interview and Examination Survey (GHS) which comprised a represen-
tative sample of approximately 7,000 persons between ages 18 and 79.
Diagnoses (12-month prevalence) were determined by a combination of
86 J. A. Smits et al.
self-report and interviewer measures, while physical activity level and emotional
well-being were assessed by self-report. Of those suffering from anxiety
disorders (n = 573), 63% indicated that they were inactive. These inactive
individuals reported significantly lower quality of life across a number of health
and mental health domains relative to anxiety disorder sufferers who reported
regular exercise. Further, the associations remained significant after controlling
for theoretically-relevant variables, but they did not depend on age or gender.
In addition to evidence for the association between physical activity and general
emotional well-being, there is also survey data indicating that physical inactivity is
related to clinical levels of anxiety. Using data from the National Comorbidity
Survey (NCS), which comprised a probability sample of approximately 6,000
individuals between ages 15 and 54, Goodwin (2003) estimated the 12-month
prevalence of DSM diagnoses among persons who indicated that they exercised
‘‘regularly’’ (60.3%) and compared the rate to those exercised occasionally, rarely
or never. Findings revealed a dose-response relationship between physical activity
and the likelihood of having an anxiety disorder. Specifically, physical activity was
associated with a significantly decreased likelihood of agoraphobia, panic attacks,
generalized anxiety disorder (GAD), specific phobia, and social phobia, even after
controlling for comorbid physical illness and demographic variables. Interestingly,
the relationship between physical activity and GAD was no longer significant after
additionally adjusting for comorbid mental disorders, suggesting that physical
inactivity may not be directly linked with GAD.
The linkage between phobic anxiety and cardiovascular disease and mortality
(Coryell, Noyes, & House, 1986; Coryell, Noyes, & Clancy, 1982; Gomez-
Caminero, Blumentals, Russo, Brown, & Castilla-Puentes, 2005; Kawachi
et al., 1994; Kawachi, Sparrow, Vokonas, & Weiss, 1994; Kawachi, Sparrow,
Vokonas, & Weiss, 1995; Weissman et al., 1990; see also White et al. in Chapter
11 in this volume) has prompted research on physical fitness among individuals
suffering from pathological anxiety, and particularly panic disorder. There
have been several studies that have employed standardized exercise testing
protocols to determine cardiorespiratory fitness among individuals with panic
disorder (Broocks et al., 1997; Gaffney, Fenton, Lane, & Lake, 1988; Martinsen,
Raglin, Hoffart, & Friis, 1998; Meyer, Broocks, Bandelow, Hillmer-Vogel, &
Ruther, 1998; Schmidt, Lerew, Santiago, Trakowski, & Staab, 2000; Taylor et
al., 1987). For example, Martinsen and colleagues (1998) subjected 35 patients to
a submaximal bicycle ergometer test and found that their VO2max was on
average at 82% (1.9 liters/min) of the expected value. Similarly, Brooks and
colleagues (1997) reported that, relative to a group of non-psychiatric partici-
pants (n = 24), individuals with panic disorder (n = 38) showed significantly
Promise of Exercise Interventions for the Anxiety Disorders 87
reduced VO2max. Specifically, the mean relative VO2max values for panic
disorder patients was 31.0 ml/kg/min (SD = 9.1) versus 37.6 ml/kg/min
(SD = 6.3) for non-psychiatric controls. In a follow-up study, the authors
(Meyer et al., 1998) showed that a 10-session exercise training program was
associated with significant improvements in VO2max values.
To clarify the link between panic disorder and fitness, Schmidt and colleagues
(Schmidt et al., 2000) designed a study to determine whether the relatively poor
cardiorespiratory fitness estimates among individuals with panic disorder may
be biased by elevated levels of anxiety symptoms. To this end, they randomly
assigned 27 panic disorder and 27 matched healthy control participants to a
submaximal bicycle ergometer test with or without heart rate feedback. This
study yielded several important findings. First, panic disorder participants
showed reduced cardiorespiratory fitness relative to non-psychiatric partici-
pants even after controlling for anxiety responses during the testing protocol
(26.4 ml/kg/min (SD = 11.4) versus 34.11 ml/kg/min (SD = 9.8), respectively).
Second, although anxiety sensitivity (i.e., fear of anxiety-related sensations), a
cognitive disposition that has been implicated in the onset and maintenance of
panic disorder (McNally, 2002), was not directly associated with poorer fitness,
it appeared to moderate the effects of diagnostic status and heart rate feedback
on cardiorespiratory fitness. Specifically, cardiorespiratory fitness was particu-
larly poor among panic disorder suffers with elevated levels of anxiety sensitiv-
ity. Similarly, heart rate feedback during testing was only associated with poorer
fitness among individuals who reported elevated levels of anxiety sensitivity.
Collectively, these findings suggest that cardiovascular conditioning is impaired
among individuals with panic disorder, and emphasize the importance of consid-
ering anxiety sensitivity in investigations of the relationship between physical
activity and anxiety. Indeed, support for the linkage between anxiety sensitivity
and physical activity is growing. Recently, McWilliams and Asmundson (2001)
observed an inverse relationship between exercise frequency and anxiety sensitivity
in a non-clinical sample. Likewise, Smits and Zvolensky (2006) reported that
anxiety sensitivity mediated the relationship between physical inactivity and mea-
sures of panic severity in a community sample of individuals with panic disorder.
Further research regarding the linkage between exercise and anxiety sensitivity will
be discussed in the next section on the effects of exercise interventions on anxiety.
Although the studies discussed above support the hypothesis that physical
activity plays a role in the etiology, maintenance and treatment of anxiety
pathology, the cross-sectional nature of many of these investigations leave
open several alternative explanations for the observed relationships. In this
section, we will discuss a number of studies that have experimentally manipu-
lated physical activity, providing some evidence for the causal effects of physical
activity on anxiety.
88 J. A. Smits et al.
(e.g., 12–30 minutes) intense exercise session (e.g., 70% of max HR; 60–70%
VO2max, >6mm of blood lactate). Together, these findings suggest that single
exercise sessions result in anxiolysis in non-clinical participants.
maintenance of the disorder (McNally, 2002; Smits, Powers, Cho, & Telch,
2004). Cognitive-behavioral treatments for panic disorder target anxiety sensi-
tivity by prescribing exposure to these feared sensations (i.e., interoceptive
exposure) in conjunction with cognitive interventions to help patients eliminate
catastrophic interpretations of these symptoms (Margraf, Barlow, Clark, &
Telch, 1993). Accordingly, in addition to the general benefits of exercise on
anxiety reduction, as documented for nonclinical samples, exercise also has the
potential to provide patients with exposure to feared sensations of bodily
arousal. Indeed, aerobic exercise induces many of the somatic sensations
(e.g., heart racing, rapid breathing, and sweating) that have shown to elicit
increased anxiety reactions in panic disorder patients (Rief & Hermanutz,
1996). The notion that exercise can serve as an interoceptive exposure proce-
dure is also consistent with early reports that exercise can be anxiogenic for
these patients. For example, Cameron and Hudson (1986) observed significant
increases in subjective anxiety during submaximal exercise testing in 31% of
patients with panic disorder, but only in 7% of patient and non-patient con-
trols. Similarly, two more recent studies reported that panic disorder patients
are more likely to prematurely terminate submaximal exercise testing compared
to non-clinical controls (Schmidt et al., 2000; Stein, Tancer, & Uhde, 1992).
Consistent with previous evidence that repeated exposure to biological pro-
vocation procedures is associated with clinical benefits for panic disorder
sufferers (van den Hout, van der Molen, Griez, Lousberg, & Nansen, 1987),
Broman-Fulks, Berman, Rabian and Webster (2004) developed a brief
exercise intervention to target anxiety sensitivity. The intervention consisted
of six 20-minute high-intensity (60–90% maximal heart rate) sessions on a
treadmill. This intervention was compared to a similar protocol low-intensity
(below 60% of maximal heart rate) level aerobic exercise program. Neither
group received a specific treatment rationale or cognitive interventions. Results
revealed that the high intensity intervention was associated with significantly
greater reductions in anxiety sensitivity compared to the low intensity interven-
tion (pre- to posttreatment raw score mean reductions of 9.14 and 2.88, respec-
tively). Preliminary results from our own laboratories suggest that preceding
the interventions with a rationale emphasizing the importance of exposure to
reducing anxiety sensitivity coupled with coaching participants during and
following exercise sessions (i.e., ‘‘what are you learning from this?’’)
may enhance the effect of this exercise intervention on anxiety sensitivity
(Smits et al., 2007).
In addition to the direct application of exercise as an interoceptive exposure
procedure to reduce anxiety sensitivity, exercise may also have general anxio-
lytic properties for patients with panic disorder. Using a counterbalanced
design, O’Connor (2005) asked 10 women with panic disorder to complete a
maximal treadmill exercise test, 25 minutes of submaximal treadmill walking
(i.e., 65% of VO2 max), and 25 minutes of seated rest during three consecutive
sessions. Self-report of state anxiety was assessed 5 and 15 minutes before and
after each session. Consistent with hypothesis, patients reported significant
Promise of Exercise Interventions for the Anxiety Disorders 91
There is little research on the mechanism by which exercise exerts its ameliora-
tive effects on anxiety. In this section, we will discuss several proposed
physiological and psychological mechanisms of exercise anxiolysis for which
there is some preliminary supporting evidence.
receptors, and specifically the 5-HT2C receptors. In a first study to test this
hypothesis, they compared marathon runners to sedentary controls on their
responses to meta-chlorophenylpiperazine (m-CPP), a 5-HT agonist that pro-
duces anxiogenic symptoms via 5-HT2C receptors (Broocks et al., 1999).
Marathon runners showed a diminished cortisol response to m-CPP, providing
evidence consistent with the idea that chronic exercise results in a reduced
hormonal reaction to m-CPP mediated by postsynaptic 5-HT2C receptors. In
a second study, the authors (Broocks et al., 2001) found that untrained
participants show a similar blunted cortisol response to m-CPP following a
10-week aerobic exercise program of moderate intensity. The authors
concluded that these data collectively suggest that the anxiolytic effects of
exercise may be mediated by the downregulation of 5-HT2C receptors.
The efficacy of benzodiazepines for reducing anxiety forms the basis of
research examining the potential of exercise on -aminobutyric acid (GABA)
function. Studies suggest that measuring the amount of time a rat spends in an
open field (open field locomotion) with or without treadmill exercise is a useful
animal model for studying the anxiolytic effects of exercise (Dishman,
Armstrong, Delp, Graham, & Dunn, 1988; Morgan, Olson, & Pedersen, 1982;
Royce, 1977). Injections of GABA into the nucleus accumbens septi (NAS)
reduces open field locomotion and injections of a GABA antagonist into
the NAS increases locomotion in rats (Jones & Mogenson, 1980a; Jones &
Mogenson, 1980b; Jones, Mogenson, & Wu, 1981). Since exercise also increases
open field locomotion in rats (Tharp & Carson, 1975); (Weber & Lee, 1968),
Dishman and colleagues (1996) have posited that exercise may reduce anxiety
by the downregulation of GABAa receptor density in the corpus striatum.
Consistent with this hypothesis, they found that voluntary exercise in rats
increased open field locomotion with a corresponding GABAa downregulation
(Dishman et al., 1996). Human studies are needed to test the hypothesis that
exercise anxiolysis in humans can be accounted for by GABAa downregulation
or other changes in central neurotransmitter function.
Sleep Restoration
findings converge to suggest that changes in slow wave sleep (SWS), which
occurs during restorative stages 3 and 4 of the sleep cycle, may be particularly
relevant to the anxiolysis following exercise. Specifically, reduced SWS is ubi-
quitous among anxiety disorder sufferers (Arriaga & Paiva, 1990; Arriaga et al.,
1996; Bourdet & Goldenberg, 1994; Fuller, Waters, Binks, & Anderson, 1997)
and exercise appears to enhance SWS (Horne, 1981; Shapiro, Griesel, Bartel, &
Jooste, 1975). There is some controversy with respect to the mechanism under-
lying the effects of exercise on SWS. Some studies suggest that it may be the
elevation in body temperature created by exercise that may be responsible for
sleep effects (Atkinson & Davenne, 2006; Horne & Moore, 1985; Horne &
Shackell, 1987; Horne & Staff, 1983). However, other studies show that low
intensity activity without a corresponding increase in body temperature can
also increase SWS (Naylor et al., 2000). Also, well-controlled studies show that
the anxiolytic effects of acute exercise are not solely due to body temperature
(Youngstedt, Dishman, Cureton, & Peacock, 1993).
There is some evidence suggesting that exercise may exerts its effect on anxiety
by enhancing perceived coping ability. Steptoe and colleagues (Moses, Steptoe,
Mathews, & Edwards, 1989) observed parallel decreases in perceived coping
and anxiety in anxious individuals who initiated an exercise program. Similarly,
Bodin and Martinsen (2004) found that exercise that targeted self-efficacy
(e.g., 45 minutes of martial arts) corresponded with significantly greater
improvements in positive affect and state anxiety compared to exercise that
did not target self-efficacy (e.g., 45 minutes of stationary bike exercise). As an
alternative to enhanced self-efficacy, some have suggested that physical exercise
may only serve as distraction from ruminations, worries, and anxiety (Bahrke &
Morgan, 1978; Leith, 1994). Interestingly, Goode and Roth (1993) found that it
is not distraction per se but the content of the distraction techniques in which
people engage that is associated with changes in emotional well-being. They
found that that runners who focused on nonassociative thoughts (those not
related to exercising) showed less fatigue and in some cases decreases in tension
and anxiety, compared to runners who focused on associative thoughts
(monitoring the body and the exercise itself).
Exposure
2006b). Other elements of exercise dose that warrant further study are intensity
and duration.
In addition to exercise dose, it is important to determine the relative impor-
tance of exercise type. There is currently a paucity of available data on the
effects of anaerobic exercise (resistance training) for anxiety. Findings
from the depression literature indicate that resistance training may be equally
effective compared to aerobic activity in reducing symptoms of depression
(e.g., Doyne et al., 1987; Martinsen et al., 1989). Support for the use of
anaerobic exercise for depression was further strengthened by a recent study
completed by Singh and colleagues (Singh et al., 2005). They demonstrated that
high intensity progressive resistance training (PRT) (80% maximum load) was
more effective in treating depression than lower intensity PRT (20% maximum
load). Perhaps more important was the finding that the effects of PRT on
depression reduction were accounted for by expectancy in the low intensity
condition but not in the high intensity condition, suggesting that anaerobic
exercise, when prescribed at the higher doses, offers more than a placebo effect.
An important implication of these findings is that resistance training may be an
alternative for patients for whom aerobic activity may be inappropriate or for
those who do not have the initial motivation for aerobic activity.
When examining the utility of new interventions, it is important consider
issues related to effectiveness in addition to efficacy. It remains to be seen how
exercise is best integrated within provider networks. Within specialty care,
exercise interventions may emerge as another adjunctive clinical tool that has
the advantage of providing a broad spectrum of health benefits in addition to its
benefits on mental health (Stathopoulou et al., 2006). In primary care, exercise
may emerge as a more fundamental intervention that can be prescribed by the
primary care physician or provider team. Specifically, exercise has a potential
for targeting many mental and physical health problems simultaneously. In this
application, exercise is likely to bring with it all the challenges of any health
promotion intervention. Adherence to exercise recommendations has been low
in the United States (Schoenborn, Adams, Barnes, Vickerie, & Schiller, 2004);
although there is some evidence suggesting that exercise for mental health
benefits may fare better than when prescribed for improving physical health.
The use of exercise interventions for anxiety disorders has one clear advantage
over exercise for general health promotion. Unlike exercise interventions that
are prescribed for the prevention of health problems, exercise interventions for
treating anxiety disorders are linked with immediate benefits (i.e., acute bouts
of exercise are associated with significant changes in anxiety). As reported by
Christensen-Szalanski and Northcraft (1985), adherence to recommended
health behavior changes is greater when there is direct symptom reduction
that is linked with the behavior change. There also appears to be wide
acceptance of nontraditional treatment strategies for mental health among
individuals suffering from mood and anxiety disorders (Kessler et al., 2001).
Indeed, exercise interventions have the potential of avoiding the social stigma
associated with other mental health interventions (Sirey et al., 2001). Although
Promise of Exercise Interventions for the Anxiety Disorders 97
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Anxiety and Insomnia
Theoretical Relationship and Future Research
Introduction
The major focus of this chapter is to identify future research directions for
advancing knowledge about two phenomena, anxiety and insomnia, which
are highly prevalent, co-existent problems in humans. Despite this universal
observation across different cultures, the medical field has a poor under-
standing of the pathophysiology and causal relationships between anxiety
and insomnia. The physiological and neurobiological relationships between
anxiety and insomnia remain one of medicine’s mysteries. Given the promi-
nence and relevance of these co-occurring complaints among individuals
seeking medical care, the lack of research is somewhat surprising and may
be a by-product of conceptualizing anxiety and insomnia as simply non-
specific manifestations of most systemic diseases. Such attributions impede
the development of new treatments that can improve appreciably the health
and well-being of not only patients with primary insomnia and anxiety dis-
orders but also individuals with cancer, metabolic, and other multi-system
medical diseases.
The goal of this chapter is to encourage clinicians and investigators to think
about anxiety-insomnia from different theoretical, even highly speculative
perspectives, with the hope that new areas of research will be undertaken by
the research community. We understand that some ideas regarding future
research directions are not necessarily logical ‘‘next step’’ studies, but rather,
areas of high-risk investigation that in their own right (and in the opinion of the
authors) may lead to an improved, understanding of the anxiety-insomnia
coupling.
Thomas W. Uhde
Department of Psychiatry and Behavioral Sciences, Medical University of South
Carolina (MUSC), 67 President Street, 5 South, Charleston, SC
M. J. Zvolensky, J. A. Smits (eds.), Anxiety in Health Behaviors and Physical Illness. 105
Ó Springer 2008
106 T. W. Uhde, B. M. Cortese
Definitions
Theoretical Models
Fig. 1 In the single spectrum disorder model, anxiety (or a diagnostic subtype) and insomnia
represent the same disorder with a common diathesis and predictable evolution of symptoms.
In this model, the common underlying pathological process (i.e., neurobiological abnorm-
ality) leads to different symptoms or components (e.g. anxiety or insomnia) of the illness
Fig. 2 In the different disorders with secondary complications model, anxiety and insomnia are
separate and distinct pathological conditions with different underlying neurobiological
abnormalities. Early stages of the disorder may reflect this distinction, while later stages
show increasingly similar symptoms (e.g. anxiety and insomnia) due to the downstream
development of secondary complications
108 T. W. Uhde, B. M. Cortese
of these theoretical models might explain high co-morbid rates of insomnia and
anxiety observed in patients seeking treatment for an anxiety disorder or
primary insomnia.
A. Age: Age of onset could help to distinguish anxiety and insomnia as separate
and distinct disorders if it was found to be considerably different for these
two disorders. Recent data from the World Mental Health Survey (WMH)
describes an early age of onset for some anxiety disorders, with a later onset
for others. For example, phobias and separation anxiety disorder was found
to have a median age of onset in the range of 7–14 years (interquartile range
[IQR] = 4–20 years). The age of onset distributions for panic, generalized
anxiety, and posttraumatic disorders, on the other hand, ranged from 25 to
53 years (IQR = 15–75 years; Kessler et al., 2007). The NCS-R median age
of 11 for the onset for anxiety reported by Kessler et al. (2005) and a 7 year
(IQR = 7 years) median age of onset for a first anxiety disorder reported by
Johnson, Roth, and Breslau (2006) are consistent with the WMH results and
further demonstrate the early age of onset for anxiety.
With respect to insomnia, the evidence supports the view that older
individuals are most at risk (Morphy, Dunn, Lewis, Boardman, & Croft,
2007). In fact, several studies reveal that nearly half of individuals over the
age of 65 report sleeping difficulties and insomnia-like symptoms (Monane,
1992; Foley et al., 1995; Ganguli, Reynolds, & Gilby, 1996).
Anxiety and Insomnia 111
Fewer studies have specifically assessed the age of onset for insomnia. In
one retrospective analysis of adolescents from the ages 13 to 15 years,
Johnson et al. (2006) reported a median age of onset for insomnia at age 11
(IQR = 5 years). Although this study found a relatively young age of onset
for children identified specifically with insomnia, most other studies with
children assess individuals with unspecified sleep problems that includes
insomnia, but could also include numerous other difficulties surrounding
sleep (Paavonen, Solantaus, Almqvist, & Aronen, 2003; Gregory &
O’Connor, 2002; Johnson, Chilcoat, & Breslau, 2000), making it difficult
to draw clear conclusions about age of onset for insomnia.
B. Gender: A second factor that could distinguish anxiety and insomnia as a
single spectrum disorder versus two separate disorders is gender distribution.
With respect to both insomnia and anxiety, data suggest a similar gender
distribution for these two disorders. Anxiety, for example, is nearly twice as
prevalent in women as in men (Kessler et al., 1994, 2005). Although not as
consistent as the anxiety data, most studies report higher prevalence rates for
females than males, with female gender as a strong risk factor for insomnia
(Ford & Kamerow, 1989; Mellinger, Balter, & Uhlenhuth, 1985; Bixler,
Vgontzas, Lin, Vela-Bueno, & Kales, 2002; Zhang & Wing, 2006).
C. Symptoms and Sleep EEG: Insomnia, as a subjective sleep complaint, is
reported by many patients with anxiety disorders. The report of insomnia
is so prevalent among patients with anxiety disorders that it is widely
assumed among clinicians, and even by most anxiety disorder specialists,
that the treatment of core anxiety symptoms in anxiety disorder patients will
be associated with parallel improvement in sleep quality (see discussion).
Some anxiety disorders, however, appear to be more commonly associated
with insomnia and two specific anxiety disorders, panic disorder and gen-
eralized anxiety disorder, deserve special mention insofar as they appear to
share important but different symptom characteristics compared with
patients with primary insomnia.
Patients with generalized anxiety disorder often have subjective com-
plaints that are nearly identical to those reported by patients with primary
insomnia. These include worrying about obtaining good quality or sufficient
amounts of sleep and problems falling or maintaining sleep. Patients with
primary insomnia, essentially by operational criteria, report almost identical
sleep complaints, but, for reasons that remain unclear, experience their
complaints within the context of a sleep problem, rather than within the
context of a mental health problem. Patients with GAD and primary insom-
nia typically report symptoms of physiological hyperarousal and increased
vigilance (‘‘feeling keyed up’’) with intermittent fatigue and disturbances in
concentration and memory. There are also nearly identical polysomno-
graphic findings; sleep architecture and REM measures are normal whereas
both syndromes have EEG evidence of increased sleep latency and distur-
bances in maintaining sleep (for reviews, see Papadimitriou & Linikowski,
2005; Uhde, 2000).
112 T. W. Uhde, B. M. Cortese
1997). Breslau, Roth, Rosenthal, and Andreski (1996) also found that a
history of insomnia increased the risk for developing anxiety compared to
individuals with no history of insomnia (OR=1.97, 95% CI 1.08–3.60).
2. Anxiety, with secondary insomnia.
Other evidence supports the course of illness progression from primary
anxiety to secondary insomnia. Ohayon and Roth (2003) retrospectively
assessed the temporal relationship between insomnia and anxiety in a
large, multinational European, general population study. In this study,
current severe insomnia was the strongest predictor of a past psychiatric
history (OR=5.8, 95% CI 2.4–14.0). Further evidence demonstrating an
illness progression from anxiety to insomnia included the finding that the
onset of insomnia preceded the development of anxiety in only 18% of the
cases, while the onset of anxiety preceded the insomnia in more than 43%
of the cases. In another retrospective analysis of a community-based
sample of adolescents from the ages 13 to 15 years, Johnson et al. (2006)
sought to assess the directionality of association between insomnia
and psychiatric disorders including anxiety and depression. This study
reported a high prevalence rate of insomnia in individuals with a
history of anxiety that varied between 24% and 43% depending on the
specific anxiety disorder. Additionally in 73% of the individuals that
were co-morbid for anxiety and insomnia, the anxiety disorder preceded
the onset of the insomnia. Risk associated with either anxiety or insomnia
by the prior onset of the other disorder was also assessed to evaluate
directionality. This analysis revealed that a prior anxiety disorder increased
the risk of subsequent insomnia more than 3 fold, but that prior insomnia
was unrelated to the later development of an anxiety disorder.
E. Neuroanatomy & Pharmacology: Any attempt to examine the relationship
between anxiety and insomnia should consider the neuroanatomical sub-
strates and related neurotransmitter-neuromodulatory receptor systems that
mediate wake versus sleep states, keeping in mind that ‘‘alarm’’ mechanisms
are likely to influence both wakefulness and sleep. This is based on observa-
tions that states of fear (Uhde 2000) can take place during sleep and wakeful-
ness. Neither insomnia nor anxiety, therefore, necessarily reflect
disturbances in those neurobiological systems that mediate either wakeful-
ness or sleep per se. In fact, neuroreceptor-neurotransmitters that mediate
alarm functions might represent a third factor that contributes to the high
co-morbidity of chronic insomnia in many anxiety disorders (see Fig. 3).
Keeping these theoretical constructs in mind, we briefly review the neuro-
anatomy of wakefulness-promotion and sleep-promotion in relation to those
neurotransmitter and neuropharmacological systems most commonly impli-
cated in anxiety and insomnia.
1. Wakefulness-Promotion versus Sleep-Promotion
Wakefulness is mediated in part by midbrain and pontine-acetyl choli-
nergic, pontine locus ceruleus-noradrenergic, reticular formation system
114 T. W. Uhde, B. M. Cortese
al., 1998), and open field (Parks, Robinson, Sibille, Shenk, & Toth, 1998)
tests. In humans, fenfluramine, a 5-HT releasing agent, induces both
anxiety and increases in blood cortisol. Of interest, over-activity of the
hypothalamic-pituitary-adrenal (HPA) axis is associated with some types
of severe insomnia (for review, see Roth, Roehrs, & Pies, 2007).
Drug Action: Similar to benzodiazepines, selective serotonin reup-
take inhibitors (SSRI) are widely used by clinicians to treat most of the
anxiety disorders. And, trazodone, a tetracylic SSRI with 5-HT2
antagonist effects, may be the most frequently prescribed medication
for the treatment of insomnia by psychiatrists and primary care phy-
sicians. There are limited data regarding the secondary improvement
in insomnia following the targeted treatment of anxiety (or vice versa).
It is known that older patients with anxiety disorders (60 years of age
with mainly GAD) show decreased change scores on the Pittsburgh
Sleep Quality Index (PSQI), suggesting that quality of sleep improves
after the targeted treatment of anxiety in elderly patients (Blank et al.,
2006). Not all anxiety disorders (e.g. PTSD), however, show conver-
gent and parallel improvements in anxiety symptoms and insomnia (or
sleep efficiency on polysomnography) when treated with SSRI’s;
moreover, responses to some SSRI’s may be either ineffective or
actually induce insomnia in PTSD, people with primary insomnia or
healthy subjects (Davis, Frazier, Williford, & Newell, 2006; Winokur
et al., 2001). Thus, while the SSRI’s play a crucial role in the treatment
of many anxiety disorders, including those wherein sleep problems are
a core feature, the effects of these same agents on the treatment of
insomnia appear to be less predictable.
F. Other ‘‘Third’’ Factors: An important question that remains to be answered is
whether sleep deprivation is a contributing factor to insomnia and/or anxiety.
Contrary to popular belief, there is a lack of good evidence for significant sleep
loss in insomnia. Despite the fact that insufficient sleep is a hallmark feature of
insomnia, there is little data demonstrating actual sleep loss or sleep restriction
in individuals reporting insomnia. Sleep polysomnography (PSG) documents
this lack of relationship between subjective reports of insomnia and objective
measures of poor sleep including reduced sleep time. In general, individuals
with insomnia underestimate sleep time compared to actual sleep time recorded
by PSG. For example, Rosa and Bonnet (2000) reported no relationship
between the subjective experience of insomnia and poor EEG sleep, defined
by increased sleep latency or decreased efficiency. Specifically, chronic insom-
niacs reported significantly worse laboratory sleep compared to controls, while
objective EEG-assessed sleep revealed little difference between the groups.
Means, Edinger, Glenn, and Fins (2003) who also assessed individuals with
insomnia and compared them to normal sleepers corroborate the findings of
Rosa and Bonnet (2000) and go further to describe that insomniacs show a
wide range of sleep misperception, from considerable underestimation to both
118 T. W. Uhde, B. M. Cortese
accurate and overestimation of sleep time. In all, these studies suggest that
insomnia is a complex condition associated with factors that extend beyond
reduced sleep time.
Recent findings from our anxiety, stress and trauma laboratory also
suggest a difference between subjective reports of sleep duration (i.e., sleep
quantity) and subjective experience of sleep quality. We administered the
Pittsburgh Sleep Quality Index (PSQI) to a small group of individuals with
motor vehicle accident-related PTSD. The PSQI is a widely used, valid and
reliable instrument designed to measure sleep disturbance through seven
components including sleep quality, sleep latency, sleep duration, habitual
sleep efficiency, sleep disturbances, use of sleeping medications, and daytime
dysfunction (Buysse, Reynolds, Monk, Berman, & Kupfer, 1989). To
achieve a pure score for sleep quality (i.e., score that excludes sleep quantity)
we eliminated the two components of the sleep efficiency domain (i.e., sleep
duration and habitual sleep efficiency) from the overall PSQI score (Cole et
al., 2006). We then correlated this modified score (i.e., sleep quality) with
subjective reports of average sleep duration (i.e., amount of sleep in minutes)
and found no relationship between these two variables (r = 0.20;
F1,26=1.04, p=0.32). Our findings in this small group of anxious individuals
demonstrate an apparent distinction between sleep quantity and quality and
suggest that individuals suffering from anxiety who report poor sleep may
not have a reduction in sleep duration (i.e., restriction/deprivation).
Although limited data exists concerning the effects of sleep deprivation on
insomnia and anxiety, the available evidence suggests that sleep deprivation or
restriction could have opposing effects on insomnia or anxiety, findings that
support a clear distinction between these 2 disorders. On one hand, sleep
deprivation/restriction has shown positive results in people with insomnia,
while no consistent benefits have been shown for sleep deprivation in indivi-
duals diagnosed with anxiety. Specifically, sleep deprivation is associated with
an increase in anxiety symptoms in healthy individuals and has been shown to
worsen anxiety in patients with some but not all anxiety disorders. Roy-Byrne,
Uhde, and Post (1986) assessed depression and anxiety levels after one night of
total sleep deprivation in patients with panic disorder who were not currently
depressed. Individual responses of panic patients to sleep deprivation varied,
with a subset of panic patients (7/12 [58%]) demonstrating a worsening of
anxiety and 4 of the 12 panic patients (33%) experiencing a spontaneous panic
attack the day following the sleep deprivation procedure. Labbate et al. (1997)
also assessed the effects of sleep deprivation on anxiety and reported a
worsening of anxiety symptoms after sleep deprivation in a small sample of
panic (n=5) patients. In this study, 3 of the 5 panic patients experienced at
least one panic attack the morning after sleep deprivation, while none of the
control subjects experienced sleep deprivation-induced panic. With respect to
other anxiety subtypes, one night of sleep deprivation revealed inconsistent,
and for some negative, effects in patients with primary OCD (Joffe & Swinson,
Anxiety and Insomnia 119
1988; Labbate et al., 1997), social phobia (SP) and generalized anxiety dis-
order (GAD; Labbate et al., 1998).
Several studies describe the positive effects of sleep deprivation/
restriction on insomnia and suggest its potential utility in treating this dis-
order. In one study (Stepanski, Zorick, Roehrs, & Roth, 2000), sleepiness
and total sleep time for primary insomniacs was significantly increased,
compared to baseline, during the recovery night following one night of
total sleep deprivation. In addition, post-deprivation sleep measures in the
insomniacs were comparable to the age- and sex-matched normal sleeper
controls.
Discussion
Future Research
institution(s), which have research expertise in both sleep and anxiety disorder
research in order to minimize internal and external sources of variation. To
investigate the convergent, co-morbid relationship between anxiety and insom-
nia, priority might be given to the study of patients who a) meet DSM-IV criteria
for GAD plus seek treatment at anxiety disorder clinics versus b) patients meet-
ing ICD-10 criteria for insomnia plus seek treatment from sleep clinics. Other
than these entry criteria, we recommend that there be few, if any, exclusion
criteria in designing such comparator studies. Specifically, we would not include
or exclude on the basis of sleep misperception or, perhaps, even the degree or
duration of subjective insomnia. Such differences or similarities across groups
seeking treatment for anxiety versus insomnia might themselves be markers that
distinguish group differences.
A particular problem for clinicians is the lack of information on the impact
of long-term pharmacological treatments or the comparative efficacy of drug
versus cognitive behavioral interventions. Such studies are time-intensive but
necessary to advance knowledge about the validity of any of the proposed three
theoretical models but also to develop evidence-based treatment packages for
the long-term treatment of anxiety-insomnia syndromes. Even more proble-
matic is the lack of information on the course of anxiety and insomnia after
treatment discontinuation.
It is beyond the scope of this chapter to review and recommend the beha-
vioral, physiological, and neuroimaging studies, which might be conducted to
best characterize the relationship between insomnia and anxiety. Clearly, neu-
roimaging strategies would be useful, although current MRI, MRS and fMRI
imaging strategies have resolution limitations that make it difficult to define with
precision the neuroanatomical substrates and functional circuits underlying
anxiety, insomnia, and mixed anxiety-insomnia syndromes. Nonetheless, the
emerging field of sleep neuroimaging (Nofzinger, 2004) may ultimately provide
tools for understanding fundamental constructs such as ‘‘time perception’’ or
‘‘sleep consciousness’’ (Uhde et al., 2006). Such hypothesized third factors
(Fig. 3) might be amenable to investigation with imaging strategies, which are
not conducive to examination with traditional polysomnography or even
spectral analysis methods (Nofzinger et al., 1999, 2002, 2004). An examination
of the comparator effects of sleep deprivation under laboratory-controlled
conditions would be of interest to better differentiate the behavioral, cognitive,
MSLT and neuroendocrine effects of sleep restriction. Likewise, caffeine is an
ideal chemical model of anxiety (Lin, Uhde, Slate, & McCann, 1997; Uhde,
1995) and has been recently proposed as a tool to study primary insomnia
(Drake, Jefferson, Roehrs, & Roth, 2006). Studying the behavioral (including
sleep perception and polysomnographic measures), neuroendocrine, and phy-
siological effects of caffeine in primary insomnia and GAD would provide useful
information. Disturbances in hypothalamic-pituitary-adrenal axis function
remain a focus of much anxiety (Uhde & Singareddy, 2002) and insomnia
research (Drake, Roehrs, & Roth, 2003; Vgontzas & Chrousos, 2002); yet, the
122 T. W. Uhde, B. M. Cortese
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Part II
Physical Conditions and Anxiety Disorders
Anxiety Disorders and Physical Illness
Comorbidity: An Overview
Introduction
Tanya Sala
Department of Psychiatry, University of Manitoba. PsycHealth Centre, PZ430-771
Bannatyne Avenue, Winnipeg, MB, Canada, R3E 3N4, Tel: 204-787-7078, Fax: 204-787-4879
tsala@hsc.mb.ca
M. J. Zvolensky, J. A. Smits (eds.), Anxiety in Health Behaviors and Physical Illness. 131
Ó Springer 2008
132 T. Sala et al.
focus on large epidemiologic and clinical studies where available in the existing
literature. However, the relative lack of such studies mandates some considera-
tion of research that falls outside these parameters. The majority of currently
available studies in this area are cross-sectional in nature. To avoid unnecessary
repetition, unless otherwise specified, all studies referred to are cross-sectional.
The chapter is organized into sections for each anxiety disorder, with subsections
by system of disease where warranted by available literature.
For the purposes of this literature review, searches of PubMed and PsycInfo
were performed using the general term anxiety disorder as well as each specific
anxiety disorder (e.g. panic disorder), in combination with the general terms
medical condition, physical illness, and medical illness as well as terms for
individual systems of disease (e.g. cardiovascular). Searches included studies
published from 1985 to 2007. For a discussion of associations between pain and
anxiety disorders, please refer to the chapter by Asmundson et al.
Sareen et al. (2005) examined the relationship between anxiety disorders and a
range of physical disorders in the US National Comorbidity Survey (NCS), a
large nationally representative dataset. This study found that among respon-
dents with one or more physical disorders, a comorbid anxiety disorder diag-
nosis was associated with an increased likelihood of disability even after
adjusting for severity of pain, comorbid mood, and substance use disorders.
Interestingly, adjusting for smoking did not affect these associations. Using
German Health Survey data, Sareen et al. (2006) again examined these associa-
tions. Advantages of this study included both a large sample size and the fact
that the presence of physical illness was based on physician assessment and not
individual self-report, thus increasing reliability. Unfortunately, this study did
not include PTSD. After adjusting for sociodemographic factors and other
common mental disorders, the presence of an anxiety disorder was significantly
associated with thyroid disease, respiratory disease, gastrointestinal disease,
arthritis, migraine headaches, and allergic conditions. The presence of a comor-
bid anxiety disorder with one or more physical disorders was significantly
134 T. Sala et al.
associated with poor quality of life and disability in this study. Important
clinical implications of these associations exist, including the possibility that
the co-occurrence of physical disorders and anxiety disorders may confer a
more disabling condition.
Method of assessment of anxiety and physical illness varies considerably
between studies. Some have assessed anxiety as a unified entity, rather than
distinguishing amongst anxiety disorders (Anderson et al., 2002; Engum, 2007;
Engum, Bjoro, Mykletun, & Dahl, 2002; Hermanns, Kulzer, Krichbaum,
Kubiak, & Haak, 2005; Kruse, Schmitz, & Thefeld, 2003; Shaban, Fosbury,
Kerr, & Cavan, 2006), adding to the challenge of interpretation and clinical
application.
Cardiovascular Disease
A link between PTSD or trauma and cardiovascular disease has been suggested
by a number of studies. A recent prospective study of community-dwelling US
military veterans found a significant association between PTSD symptoms at
baseline and subsequent development of coronary heart disease, even after
controlling for depressive symptoms (Kubzansky et al., 2007). A study of
Korean War and World War II veterans reported increased rates of physi-
cian-diagnosed cardiovascular disease among veterans with PTSD (Schnurr,
Spiro, & Paris, 2000). Studies demonstrating increases in basal cardiovascular
activity in PTSD sufferers offer a potential biological pathway (Buckley &
Kaloupek, 2001).
One important possible consequence of PTSD secondary to a medical con-
dition or medical treatment is the potential for lower levels of adherence to
medical treatment. Shemesh et al. (2001, 2004, 2006) examined the hypothesis
that symptoms of MI-related PTSD were linked to nonadherence to medical
follow-up. The authors hypothesized that patients who experience myocardial
infarction as a traumatic event may not take medications as prescribed, with
nonadherence representing part of the avoidance dimension of PTSD. In these
studies, PTSD symptoms were significantly associated with nonadherence to
medical treatment. In support of these findings, others have reported that
alleviation of PTSD symptoms in a series of burn patients could improve
adherence to treatment (Countermanche & Robinow, 1989).
Neurological Disease
prevalence of traumatic events and/or PTSD in patients with PNES. Among the
17 studies included in this review, ten analyzed the PTSD diagnosis in PNES
patients. Although the prevalence rates reported in these ten studies varied
considerably, rates of PTSD were consistently higher than those found in the
general population. However, when compared with control groups who had
epilepsy, only two studies found a significant difference in rates of PTSD.
Limitations acknowledged by the authors include the fact that all 17 studies
were hospital-based, and many had small sample sizes. The authors speculate
that PNES, which has been traditionally thought of as a dissociative phenom-
enon, might be understood as a severe form of PTSD that includes prominent
dissociative features. There is currently too little information to warrant con-
clusions on this premise.
Endocrine/Metabolic/Autoimmune Disease
Among the significant associations with PTSD in the study by Sareen et al.
(2005), metabolic/autoimmune conditions showed the most robust association
(AOR 3.32, CI 1.96-5.62). A number of studies have supported an alteration
in thyroid function in individuals with PTSD, both in chronic combat-related
PTSD (Mason et al., 2004; Wang & Mason, 1999; Wang et al., 1995) and in
survivors of childhood sexual abuse (Friedman, Wang, Jalowiec, McHugo, &
McDonagh-Coyle, 2005). In both studies by Wang et al., alterations in
thyroid function were specifically associated with increased hyperarousal
symptoms. Through promotion of ongoing noradrenergic transmission,
elevations in triiodothyronine (T3) have been proposed by some authors as
a possible underlying biological mechanism perpetuating arousal features in
PTSD (Prange, 1999), although this hypothesis remains speculative at this
stage.
Using data from a large national sample of Vietnam veterans, Boscarino
(2004) tested the hypothesis that chronic sufferers of PTSD may be at increased
risk for certain autoimmune diseases, including rheumatoid arthritis, thyroid
disease, insulin-dependent diabetes, and psoriasis. After adjusting for a variety
of factors, including age, alcohol and drug abuse, and history of cigarette
smoking, the authors noted significant associations between chronic PTSD
and all the above-mentioned illnesses. In a large study of US male veterans
with diabetes, Trief, Ouimette, Wade, Shanahan, and Weinstock (2006) noted
significantly higher cholesterol, LDL, weight, and BMI in subjects with PTSD
and depression, compared to depression alone, PTSD alone, or neither.
Goodwin and Davidson (2005), using the NCS dataset, examined the asso-
ciation between self-reported diabetes and PTSD in a community sample of
adults. In this study, self-reported diabetes was found to be significantly asso-
ciated with an increased likelihood of PTSD, but not with an increased like-
lihood of any other mental disorder. This study not only provides evidence for
Anxiety Disorders and Physical Illness Comorbidity: An Overview 137
Cancer
Cardiovascular Disease
Given the high level of symptom overlap, it is not surprising that an association
between panic disorder and cardiac disease has been relatively well studied. Of
the 13 symptoms of a panic attack listed in DSM-IV, many could also represent
cardiovascular disease. Many patients with panic disorder present first to the
emergency room requesting medical assessment (Huffman & Pollack, 2003).
Data from the NIMH ECA study suggested that individuals who present with
numerous medically unexplained symptoms have 200 times increased odds of
having panic disorder, compared with 17 for major depression (Simon & Von
Korff, 1991). A strong relationship has been reported between panic attacks and
hypertension diagnosed by physical exam in a primary care sample (Davies et al.,
1999). Similarly, myocardial infarction has been associated in at least two studies
with increased likelihood of new-onset panic attacks. Physiological mechanisms
such as decreased heart rate variability, increased platelet activity, and increased
sympathetic tone have been implicated in the relationship between anxiety and
cardiac disease (Kawachi, Sparrow, Vokonas, & Weiss, 1995).
In a retrospective study of a large random community sample, Weissman,
Markowitz, Ouellette, Greenwald, and Kahn (1990) examined the association
between PD and cardiovascular/cerebrovascular disorders. After adjusting for
a number of demographic factors, participants with PD were at higher risk of
reporting high blood pressure, heart attack, and stroke than a group of respon-
dents with no psychiatric disorder, but when compared with other psychiatric
disorders, only stroke remained significant. One limitation of this study is that
existence of cardiovascular or cerebrovascular disease was based on self-report.
Anxiety Disorders and Physical Illness Comorbidity: An Overview 139
Respiratory Disease
Chronic obstructive pulmonary disease (COPD) and asthma are featured most
prominently in the literature, although a smaller number of studies examine an
association between panic disorder and allergic reactions in both children and
adults (Goodwin, 2002; Kovalenko et al., 2001). As with cardiovascular disease,
the high level of symptom overlap presents unique challenges in understanding
repeatedly observed associations. Given the early age of onset of asthma, many
have speculated that it could be a contributor to the development of panic
disorder, although there is evidence supporting a bidirectional influence of the
disorders (Hasler et al., 2005), as well as studies questioning whether both may
be due to a third variable (Goodwin, Fergusson, & Horwood, 2004).
Lifetime rates of respiratory disease have been reported to be as high as 47%
in individuals with panic disorder (Zandbergen et al., 1991). Rates of panic
disorder in individuals with respiratory illness have also been found to be
increased above those reported in general population studies, not only within
clinical samples of adults, but also in community samples and within child and
adolescent populations (Goodwin & Eaton, 2003; Goodwin, Jacobi, et al.,
2003; Goodwin, Olfson, et al., 2003; Goodwin, Pine, & Hoven, 2003). In a
community sample of more than 4000 individuals with current severe asthma,
10% also had panic disorder (Goodwin, Jacobi, et al., 2003).
Using the NCS dataset, Sareen et al. (2005) did not find a relationship
between panic attacks and respiratory disease, as previous studies have reported
(Goodwin & Eaton, 2003; Goodwin, Jacobi, et al., 2003; Goodwin et al., 2003;
Goodwin, Pine, et al., 2003; Ortega, McQuaid, Canino, Goodwin, & Fritz,
2004). A possible explanation suggested by the authors is that the discrepancy
140 T. Sala et al.
may be related to severity. The NCS did not distinguish severity of physical
disorders, but in a German community sample, severe asthma diagnosed by a
physician was associated with panic attacks while non-severe asthma was not
(Goodwin, Jacobi, et al., 2003).
Special considerations arise in the treatment of comorbid asthma and panic
disorder. Treatments for asthma, in particular short-acting b2 agonists, may
exacerbate anxiety symptoms as a side effect of their use, presenting a dilemma
both for the individual and health care provider. If symptoms are attributed to
asthma and a short-acting b2 agonist is used, symptoms may worsen if related to
panic rather than respiratory causes. Some evidence exists that patients with
comorbid panic disorder and asthma may make greater use of short-acting b2
agonists than asthma-only patients, independent of pulmonary function,
asthma medication class, and sociodemographic status (Feldman, Lehrer,
Borson, Hallstrand, & Siddique, 2005).
Several studies have reported an increased risk of panic disorder in indivi-
duals with COPD (e.g. Karajgi, Rifkin, Doddi, & Kolli, 1990). A recent review
by Brenes (2003) noted consistently increased rates of panic disorder and GAD
across studies, but commented on the lack of evidence to guide treatment
decisions in this population.
Neurological Disease
Heinz, & Strohle, 2006) reported that although fear arising on the first day
of an acute vestibular episode did not predict the development of panic,
fear of vertigo one week after the dysfunction was a significant predictor.
After six weeks, persistent fear of vertigo remained a significant predictor.
Results of a small clinical study suggested that subclinical vestibular dys-
function might contribute to symptoms of panic disorder, (Jacob, Furman,
Durrant, & Turner, 1996). Although the majority of studies assessing
vestibular function in individuals with panic disorder report a high pre-
valence of abnormal results of vestibular testing, no consistent pattern of
vestibular dysfunction has been observed across studies. Similarly, although
results of studies examining psychiatric symptoms in patients with vestibu-
lar dysfunction in general show increased levels of anxiety symptoms,
especially panic, no consistent pattern of association has yet been
described.
The majority of studies within this system of disease have focused on associa-
tions of anxiety disorders with ‘‘Functional’’ GI symptoms. Functional refers
to symptoms reported by an individual that do not correlate to any tissue
pathology detectable by medical testing. In a nationally representative survey
of over 13,000 individuals in the United States, Lydiard et al. (1994) found
that individuals with panic disorder had the highest rate of unexplained GI
symptoms (7.2%) compared with other diagnostic categories. Respondents
who reported two gastrointestinal symptoms had significantly higher lifetime
prevalence rates for panic disorder and agoraphobia than those who reported
no GI symptoms. In patients with severe irritable bowel syndrome (IBS),
panic disorder has been associated with impaired functioning (Creed et al.,
2005).
In a longitudinal study of a representative cohort of Swiss adults by
Hochstrasser and Angst (1996), subjects were assessed for functional GI
symptoms and anxiety and depressive disorders. Cross-sectionally, a signif-
icant relationship was found between functional GI complaints and panic
disorder, subthreshold panic disorder, agoraphobia, social phobia, simple
phobia, and GAD. However, those who reported functional GI complaints
at younger ages were not at increased risk for subsequent development of
an anxiety disorder. The authors concluded that functional gastrointestinal
complaints reflect a non-specific concomitant vegetative disturbance asso-
ciated with anxiety disorders, not a risk factor for the development of a
specific anxiety disorder. Data from a large-scale, nationally representative
sample of Japanese subjects was analyzed for comorbidity of IBS with
panic disorder and agoraphobia (Kumano et al., 2004). Significantly higher
rates of PD and agoraphobia were observed in subjects with IBS than in
142 T. Sala et al.
Endocrine/Metabolic Disease
Within this category, thyroid disease and diabetes have received the most
attention from researchers. A recent review of studies examining associations
between thyroid dysfunction and anxiety disorders found significantly elevated
rates for panic disorder in patients with a history of thyroid disease, and
concluded that inquiring about thyroid symptoms and screening for thyroid
disease is warranted in patients with panic disorder (Simon et al., 2002). How-
ever, of the 12 studies included in this review, only six were controlled, and the
findings of studies varied considerably.
Results from larger studies have been mixed. Analyzing a community
sample, Sareen et al. (2005) did not find an association between panic attacks
and self-reported diagnosis of metabolic/endocrine disease. Analysis of a
different community sample also did not find a significant association
between panic disorder/agoraphobia and self-reported thyroid disease
(Patten, Williams, Esposito, & Beck, 2006). However, analysis of a large
clinical sample showed an association between panic disorder and thyroid
disease (Rogers et al., 1994).
Cancer
Cardiovascular Disease
Barger and Sydeman (2005), using data from a large US community sample of
adults aged 25–74, found that independently of depression, subjects with GAD
were more likely to have coronary artery disease risk factors, as measured by
self-reported smoking status, body mass index, and recent medication use for
hypertension, hypercholesterolemia, and diabetes.
Gastrointestinal Disease
Goodwin and Stein (2002) examined a possible link between GAD and peptic ulcer
disease (PUD) among adults in a community sample. After controlling for differ-
ences in sociodemographic characteristics, psychiatric comorbidity, and physical
comorbidity, the authors found a significantly increased risk of self-reported PUD
in subjects with GAD. A dose-response relationship was also found between
number of GAD symptoms and higher likelihood of PUD. A review of a number
of smaller studies (Lydiard, 2001) reported a consistent link between irritable
bowel syndrome and GAD. In the NCS sample, Sareen et al. (2005) found GAD
to be associated exclusively with gastrointestinal disease after adjusting for socio-
demographic factors, other anxiety disorders, and depression. See the section on
Panic Disorder and gastrointestinal disease for discussion of a relevant study by
Hochstrasser and Angst (1996).
Endocrine/Metabolic/Autoimmune Disease
Studies of this body system have primarily examined associations with either
thyroid disease or diabetes mellitus. In a small study of a clinical sample, Carta
et al. (2005) found that subjects with Hashimoto disease showed higher fre-
quencies of GAD compared to subjects with euthyroid goiter and controls. See
the section on Panic Disorder and endocrine/metabolic disease for discussion of
a relevant review by Simon et al. (2002).
Studies in clinical samples have also supported an association between GAD
and diabetes (Kovacs, Goldston, Obrosky, & Bonar, 1997). However, both studies
of diabetes and studies of thyroid disease typically involve smaller numbers of
individuals and are subject to the sampling bias that accompanies studies of
treatment-seeking populations. In a recent review of anxiety in adults with diabetes
(Grigsby, Anderson, Freedland, Clouse, & Lustman, 2002), the authors concluded
that 14% of diabetic subjects in the included studies also had GAD, well in excess
of the prevalence reported in community surveys (Kessler, Chui, Demler,
144 T. Sala et al.
Merikangas, & Walters 2005). However, of the 18 studies included in this review,
only 5 included a non-diabetic control group, and most of the subjects were drawn
from clinical populations. In contrast, an analysis of general population data
(Sareen et al., 2005) found no significant association between metabolic/endocrine
or autoimmune diseases and GAD.
Gastrointestinal Disease
See the section on Panic Disorder and gastrointestinal disease for discussion of
a relevant study by Hochstrasser and Angst (1996).
Endocrine/Metabolic Disease
Autoimmune Disease
Respiratory Disease
Gastrointestinal Disease
See the section on Panic Disorder and gastrointestinal disease for discussion of
a relevant study by Hochstrasser and Angst (1996).
Endocrine/Metabolic Disease
Cancer
See the section on Panic Disorder and cancer for discussion of relevant studies
by van’t Spijker et al. (1997) and Honda and Goodwin (2004).
Concluding Comments
Conclusions
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The Relation Between Puberty and Adolescent
Anxiety: Theory and Evidence
Ellen W. Leen-Feldner
University of Arkansas, Department of Psychology, 216 Memorial Hall, Fayetteville, AR
72701, Tel: 479-575-5329, Fax: 479-575-3219
eleenfe@uark.edu
M. J. Zvolensky, J. A. Smits (eds.), Anxiety in Health Behaviors and Physical Illness. 155
Ó Springer 2008
156 E. W. Leen-Feldner et al.
(Angold, Costello, & Worthman, 1998), eating disorders (Killen, et al., 1992),
and substance use problems (Patton et al., 2004).
With this backdrop, researchers have begun to consider the potential role
that puberty and its associated parameters (e.g., timing) may play in the
development and maintenance of anxiety problems among adolescents. Indeed,
a number of empirical articles have been published on this topic in the past
decade; nonetheless, the literature is still in its relative infancy. Accordingly, the
overarching objective of the current chapter is to stimulate additional research
in this important domain; our specific goals are to 1) discuss methodological
and conceptual issues pertinent to the study of puberty, 2) present an overview
of the empirical literature focused on the association between puberty and
anxiety, and 3) provide some conceptually-driven suggestions for future work
in the area.
Dick, Rose, Viken, & Kaprio, 2000). Although the timing of puberty has
changed in the past two decades (earlier onset), given the current state of our
knowledge, altering the timing of puberty is not currently conceptualized as a
reasonable target of intervention. Therefore, pubertal timing is considered
non-malleable and classified as a fixed marker. Importantly, pubertal timing
is non-specific in nature as it has been linked to an array of clinical sequelae,
including problematic health behaviors (e.g., excessive dieting and
exercise [McCabe & Ricciardelli, 2004]; alcohol, cigarette, and marijuana use
[Lanza & Collins, 2002; Wichstrom, 2001; Weisner & Ittel, 2002]) as well as
elevated risk of clinical symptomatology and diagnoses (e.g., depressive-type
problems [Graber, Seeley, Brooks-Gunn, & Lewinsohn, 2004; Kaltiala-Heino,
Kosunen, & Rimpela, 2003); eating-related pathology [Kaltiala-Heino,
Rimpela, Rissanen, & Rantanen, 2001]).
As highlighted by the current volume, the important link between health
behaviors and anxiety is just beginning to be fully appreciated. As these two
outcomes, anxiety and unhealthy behaviors, both increase at puberty, it will
become increasingly important to untangle both pubertal status and pubertal
timing effects associated with health behaviors in addition to unraveling the
potential interaction between onset of anxiety and initiation of unhealthy
behaviors in the peripubertal period.
association such that, compared to on-time and late developers, early maturing
females who also were associated with mixed (as opposed to same-sex) peer
groups in the 7th through 9th grades were more likely to evidence psychological
distress in the 10th grade. This study highlights the complex inter-relations that
characterize the association between pubertal timing and anxiety, and further-
more suggests that negative effects of off-time maturation may not be transient,
but rather persist over time.
Overall, pubertal timing appears to be an important fixed marker in the
development and maintenance of anxiety-type symptoms, particularly among
females. Interestingly, not only does the timing of puberty alter psychiatric risk
but psychological factors may alter the timing of puberty (reviewed in more
detail below). Thus, in theory, pubertal timing is malleable. However, from an
intervention standpoint, understanding how pubertal timing affects outcomes
may be a more feasible goal than attempting to alter the timing of puberty itself.
Therefore, at this stage of research development, we consider pubertal timing to
be non-malleable (i.e., fixed marker). In addition, as noted earlier, the associa-
tion between pubertal timing and psychiatric outcomes is non-specific in
nature. For both these reasons (non-malleability; non-specificity) identification
of mediators and moderators of the pubertal timing-anxiety association
is critical. In particular, it will be important for researchers to consider
gender-specific characteristics that may mediate or moderate the timing-anxiety
association, as the link between timing and anxiety appears to differ across
males and females. For instance, sexual assault exposure (Hayward & Sanborn,
2002) and body image and weight concerns (Richards, Boxer, Petersen, &
Albrecht, 1990) may be particularly important among females, whereas
risk-taking activities (e.g., substance use; Andersson & Magnusson, 1990)
may be important to consider among males.
Temporal Dimensions of the Pubertal Timing-Anxiety Association. As
mentioned above, a complicating facet of the putative link between pubertal
timing and anxiety pertains to the chicken-and-the-egg issue. Specifically, two
pathways are viable. First, the timing of maturation may potentiate anxiety for
some youth (e.g., early maturing females develop anxiety-related problems;
Graber et al., 2004). However, it has also been posited that the direction of
the association may be from contextual ‘‘stress’’ in the early environment to
pubertal timing. Both neurobiological (e.g., changes to the HPA-axis secondary
to childhood stress; Meschke, Johnson, Barber, & Eccles, 2003) and
sociobiological (Belsky, Steinberg, & Draper, 1991) mechanisms have been
theorized. For instance, Belsky and colleagues highlight the utility, from an
evolutionary perspective, of commencing reproductive activities as soon as
possible if an organism is reared in a stressful environment where the viability
of progeny is questionable. Therefore, children reared in a stressful environ-
ment are predicted to experience the hormonal and physical changes of puberty
earlier than youth from stable home environments. There is a relatively large
body of work examining the role of early stress in relation to pubertal timing.
For instance, among females, dysfunctional family background (e.g., parental
166 E. W. Leen-Feldner et al.
We have three specific suggestions for future research, aimed at increasing the
methodological and conceptual sophistication of the literature. First, there is a
general need for more comprehensive and integrated assessments of puberty.
For instance, it will be important to replicate and extend findings from the
hormone literature suggesting a main effect of specific hormones on anxious
symptomatology (Granger et al., 2003). Here, methodologically innovative
approaches that involve multiple assessments across the course of puberty
will be critical for addressing questions related to the short-term (e.g., rapidly
escalating hormones; Apter, 1980) and long-term effects of hormonal changes
during puberty. In addition, because hormones affect each other in complex
ways (Johnson & Everitt, 2000) it will be important for researchers to obtain
indices of several different hormones and examine their independent and com-
bined effects on anxiety. Although expansion of the hormone-anxiety literature
would fill an important empirical gap, perhaps a more pressing challenge is to
evaluate the combined (additive and interactive) effects of pubertal status,
timing, and hormones on anxiety, as well as the impact of childhood anxiety
on pubertal maturation. An integrated approach to pubertal assessment is
critical here, as these aspects of puberty are fundamentally inter-related
(Brooks-Gunn et al., 1994). As an illustrative example, consider breast devel-
opment among females. This process is driven by gonadal hormones, which
may have an independent effect on anxious reactivity (Susman et al., 1991).
However, personal and social (e.g., parents; peers) reactions to a female’s
status on this relatively visible pubertal event may also contribute to anxiety
(Brooks-Gunn, 1984), particularly if she is ‘‘off-time’’ with respect to her
contemporaries (Brooks-Gunn & Warren, 1985). Of course, some of the
168 E. W. Leen-Feldner et al.
Time
Mediators
(e.g., fear-relevant
learning; gonadal
steroids)
Time
Moderator
(e. g., youth HIGH in
anxiety sensitivity)
Presence of Panic-
Puberty Related Problems
Absence of Panic-
Related Problems
Moderator
(e. g., youth LOW in
anxiety sensitivity)
Conclusions
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Anxiety, Anxiety Disorders,
and the Menstrual Cycle
Phases of the normal menstrual cycle are typically based on a 28-day timeline
that corresponds to changing hormone levels in a woman’s body (e.g., Hillard &
Deitch, 2005). The normal range of women’s cycles varies from 24–35 days. The
Sandra T. Sigmon
University of Maine, 5742 Little Hall, Orono, ME 04469-5742, Tel: 207-581-2049,
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sandra.sigmon@umit.maine.edu
M. J. Zvolensky, J. A. Smits (eds.), Anxiety in Health Behaviors and Physical Illness. 181
Ó Springer 2008
182 S. T. Sigmon, J. G. Schartel
uterus, ovary, and pituitary play a large role in menstrual cycle functioning with
the hypothalamus playing a central control function. Research in the menstrual
literature has typically delineated 3 distinctive phases: follicular (days 1–13),
ovulation (days 13–14), and luteal (days 15–28). Days 1–7 represent menses and
days 21–28 are generally considered the premenstrual or late luteal phase of the
cycle.
Table 1 Sample of measures used in assessing symptoms across the menstrual cycle
Retrospective
Measure Purpose (PMS/PMDD) or Prospective
Premenstrual Tension Rating Scale, self Diagnostic and Treatment Both
and observer forms (Steiner et al., 1980) Response – PMS
Daily Rating Form (Endicott et al., 1986) Assess Symptoms – PMS P
Premenstrual Symptom Diary Diagnostic – PMS P
(Thys-Jacobs et al., 1995)
Calendar of Premenstrual Experiences Diagnostic – PMS P
(Mortola et al., 1990)
Menstrual Distress Questionnaire (Moos, Assess Symptoms – Both R
1968)
Menstrual Distress Diagnostic – PMS; P
Questionnaire – Today version (Blake et al., Treatment response
1998)
Premenstrual Assessment Form (Halbreich Assess Symptoms – Both R
et al., 1982)
Daily Record of Severity of Problems Diagnostic – PMDD P
(Endicott et al., 2006)
Daily Symptom Rating Scale (Taylor, 1979) Assess Symptoms – Both P
Anxiety and the Menstrual Cycle 185
depression or anxiety. Hartlage and Gehlert (2001) suggest the problem is that
symptoms of PMDD overlap significantly with other affective disorders and
argue for phase specificity in diagnosing PMDD (i.e., symptoms occur solely
during the premenstrum). They propose that PME can be distinguished from
PMDD if clinicians consider one symptom at a time. This leaves unresolved the
possibility of some symptoms of an anxiety disorder occurring across the entire
cycle while others do not. How many of the symptoms of PMDD must be
distinct from the symptoms of the ongoing anxiety disorder remains unclear.
The criteria of five symptoms has also been challenged as being arbitrary and
too restrictive to accurately assess the impact of symptoms on women’s
functioning (Smith et al., 2003; Freeman, 2003). Yonkers (1997) suggests that
premenstrual complaints can vary in severity, degree of comorbidity with other
psychological disorders and level of impairment. For example, a woman may
only demonstrate two out of five symptoms, but they may be severe enough to
cause significant interference with her day to day functioning.
Researchers have also questioned the validity of defining and measuring the
‘‘absence’’ of a symptom. The requirement of symptom absence is unique to
PMS/PMDD, and there are currently no good assessment measures that
reliably measure this criterion. Furthermore, most criteria require symptoms
be absent for the duration of the follicular phase. This requirement has been
challenged as being unrealistic due to the natural fluctuations in mood and
occurrence of life events over the course of the cycle (Freeman, 2003; Smith
et al., 2003). For example, Bailey and Cohen (1999) assessed the number of
women seeking treatment for premenstrual symptoms who experienced symp-
toms across the menstrual cycle. Over 60% of their sample met criteria for either
a mood or anxiety disorder or both, indicating they experienced symptoms
diagnostic of PMS across all phases of the cycle. Instead, researchers like
Freeman (2003) suggest we would be better served to look at changes in
symptom severity or overall frequency (i.e., degree of change). Although
suggestions have been made (e.g., Smith et al., 2003), no conclusion has yet
been reached regarding what would represent a clinically significant change
from one menstrual cycle phase to the next phase.
There is a significant amount of variability both between and within indivi-
dual women’s symptoms from cycle to cycle. Bloch, Schmidt, and Rubinow
(1997) looked at the stability of premenstrual symptoms in 16 women with PMS
(defined as 30% increase in symptom frequency during the luteal phase) for 3 or
more cycles. Results indicated that symptom presentation from cycle to cycle
varied considerably, with anxiety (83%), irritability (85%), and mood lability
(77%) exhibiting the most stability across the 3 cycles. Freeman (2003) also
notes that the timing of symptom appearance/remission varies between women.
Some women experience PME for only a few days of the premenstrual phase at
either the beginning or end and some symptoms are experienced on nonconse-
cutive days. Thus, the literature suggests that in well-defined PMS samples,
symptoms persist across time and can cause significant impairment in women’s
Anxiety and the Menstrual Cycle 187
lives even if two consecutive symptomatic cycles are not established during the
diagnostic period.
could not distinguish between women with PMS alone or women with PMS who
also met criteria for an anxiety disorder.
Cross-cultural research in Western societies seems to parallel the results
obtained in the United States. A study on women in the United States, United
Kingdom, and France (N = 1045) revealed considerable impairment at home,
in social relationships, and work. Across countries, more than 60% of women
reported increases in anxiety, fears and tension premenstrually, and less than
25% had sought treatment for their symptoms (Hylan et al., 1999).
Premenstrual Dysphoric Disorder. Researchers have estimated that the impact
and burden associated with PMDD to be similar to that of other affective
disorders (e.g., Halbreich et al., 2003). Wittchen, Becker, Lieb, and Krause
(2002) contend that PMDD can persist for the duration of a woman’s reproduc-
tive years. In their research, depression was the first ranked symptom (91%) and
anxiety was noted by 67% of the sample, with 47% of women with PMDD
meeting criteria for a comorbid anxiety disorder. Several studies have found
that comorbid anxiety disorders may be found in as many as 59% of women
diagnosed with PMDD (Fava et al., 1992; Pearlstein, Frank, Rivera-Tovar,
Thoft, et al., 1990). Research has also indicated that women with PMDD report
more stressors and experience more distress premenstrually than intermenstrually
compared to controls (e.g., Fontana & Badawy, 1997) and also report more state
anxiety than controls (e.g., Christensen & Oei, 1989).
and intermenstrual phases of their cycles. Results indicated that half of the
women reported PME of OCD symptoms.
Generalized Anxiety Disorder. Only one study has investigated menstrual cycle
relationships with GAD (McLeod, Hoehn-Saric, Foster, & Hipsley, 1993) and
PTSD (Perkonigg, Yonkers, Pfister, Lieb, & Wittchen, 2004). McLeod and
colleagues (1993) recruited women with GAD with and without comorbid PMS.
Results indicated that women who had both GAD and PMS reported significant
PME of anxiety symptoms during the luteal phase. Unfortunately, assessment
points were not consistent between groups, making comparisons difficult.
PTSD. Perkonigg and colleagues (2004) followed women with PTSD over a
span of 42 months, assessing for predictors of PMDD at three time points. The
best predictor of PMDD diagnosis was subthreshold PMDD symptoms at the
initial interview. However, the experience of traumatic events and anxiety
disorder presence both significantly predicted subsequently meeting diagnostic
criteria for PMDD. PMDD symptoms were only assessed retrospectively and
interviews were conducted without respect to menstrual cycle phase; however
their results do suggest that trauma and anxiety may impact women’s experi-
ence of symptoms across the menstrual cycle.
Although results across different disorders, populations, and methods of
reporting have been inconsistent, there is nonetheless some evidence to suggest
that for some women, menstrual cycle phase may have a significant impact on
their experience, or at least the reporting of symptoms. Symptom patterns may
also vary from cycle to cycle and may be related to life events, stress, fatigue,
interpersonal or relationship problems. Many authors have suggested that this
heterogeneity both between and among women may interfere with accurate
diagnosis and interpretation of effect sizes in treatment studies (Vulink et al.,
2006). Given recent advances in statistical methods for prospective data and in
general understanding of anxiety disorders, more research investigating
menstrual cycle effects on women’s experience of anxiety is warranted.
to humans. To study any aspect of the menstrual cycle without the contexts of
stress and lifestyle will result in incomplete assumptions (e.g., Koeske, 1983).
Thus, feminist views about the menstrual cycle mirror similar concerns that
have been raised in other approaches.
Biological Explanations. Reproductive hormones play a significant role in
mood symptom fluctuation across the menstrual cycle; however, the exact
mechanisms involved are not well understood (e.g., Hendrick, Altshuler, &
Burt, 1996). Progesterone metabolites and estrogen levels typically decrease
during the premenstrual phase and remain low through the early follicular
phase. These hormones modulate neurotransmitter levels (e.g., serotonin,
GABA, dopamine, norepinephrine) that are hypothesized to play an important
role in the development and maintenance of psychological disorders, in
particular anxiety and depression (e.g., Dubrovsky, 2006; Le Mellédo &
Baker, 2002). This area of research is relatively new and is hampered by the
use of small samples, retrospective methodology, and lack of precision in
determining menstrual cycle phase.
Biological explanations of PMS typically begin with a discussion of hormonal
control of the menstrual cycle. The development of premenstrual symptoms is
purported to be linked to the rapid decrease in progesterone during the late luteal
phase (e.g., Poromaa, Smith, & Gulinello, 2003). However women with and
without PMS often do not show differences in absolute levels of progesterone
across the menstrual cycle (e.g., Rubinow et al., 1988; Hammarbäck, Damber, &
Bäckström, 1989). Thus, researchers have proposed that there may be differ-
ences in sensitivity to the changing hormone levels (e.g., Poromaa et al., 2003;
Halbreich, 2003). In addition, because progesterone metabolites enhance GABA
(i.e., gamma-aminobutyric acid) activity (e.g., Olsen & Sapp, 1995) and GABA
has been implicated in anxiety symptoms (e.g., Ninan et al. 1982), researchers
have proposed models of complex hormonal interactions that may link
premenstrual symptoms and anxiety disorders (e.g., Facchinetti, Tarabusi, &
Nappi, 1998). However, more research is needed to determine the mechanisms
affecting sensitivity to these interactions (Roy-Byrne, Cowley, Greenblatt,
Shader, & Hommer, 1990).
Research has also demonstrated several biological links between menstrual
disorders and anxiety disorders. Women diagnosed with PMS and LLPDD
(i.e., Late Luteal Phase Dysphoric Disorder) report increased in panic
symptoms, negative interpretations of sensations, and state anxiety in response
to a lactate challenge (e.g., Facchinetti et al., 1998; Kent et al., 2001). Further,
approximately 60–70% of women with panic disorder and with LLPDD experi-
ence panic attack in response to lactate infusion and inhaled carbon dioxide.
Panicogenic responding to challenge tasks was previously thought to be specific
to panic disorder, and the similar rates of responding may suggest a shared
biological vulnerability and account for the high levels of anxiety reported by
LLPDD patients (for a review see Vickers & McNally, 2004). Other evidence to
support a link between PMS and anxiety disorders comes from the responsive-
ness to alprazolam in women with PMS (e.g., Facchinetti et al., 1998). Although
194 S. T. Sigmon, J. G. Schartel
these findings are preliminary, they do suggest intriguing links between anxiety
symptoms and PMS. Biological links between PMDD and anxiety have also
been explored. For example, symptoms disappear or decrease in women diag-
nosed with PMDD when they do not ovulate, when ovaries are removed, or
when they take medications that inhibits ovulation (e.g., Steiner, 2000).
Biopsychosocial Models. More complex models of menstrual distress incor-
porating social and psychological processes are surfacing as it has become clear
that biological explanations alone cannot suffice (e.g., Anson, 1999). A woman’s
experience of premenstrual symptoms is influenced by socialization practices and
environmental contextual factors (e.g., Anson, 1999). Menstrual attitudes and
beliefs that develop from interactions with peers, family, and the media (e.g.,
Aubuchon & Calhoun, 1985; Woods, Mitchell, & Lentz, 1995) may play a
significant role in the reporting and experience of premenstrual symptoms.
Reports of premenstrual complaints vary depending on retrospective reports
(e.g., Marván & Cortés-Imiestra, 2001; Rapkin, Chang, & Reading, 1988),
number and severity of daily and life stressors (e.g., Fontana & Palfai, 1994),
use of maladaptive coping strategies (Sigmon, Whitcomb-Smith, Rohan, &
Kendrew, 2004), complex role conflicts (e.g., Ross & Steiner, 2003), and history
of sexual abuse (e.g., Ross & Steiner, 2003). These represent but a few of the
factors proposed to play a contributory role in the experience and reporting of
premenstrual difficulties.
Researchers have also examined the role that the perception of stress and
interference with functioning might play in the reporting of increases in anxiety
during the premenstrual phase. Davydov and colleagues (2004) assessed anxiety
symptoms during the luteal and follicular phases in nurses, who reported higher
levels of anxiety on working days during the luteal phase than during days off
during the luteal phase or during the follicular phase. Studies examining
menstrual interference in college samples (e.g., Brooks-Gunn & Ruble, 1986)
have found that perceived interference, menstrual pain, and premenstrual pain
were the best predictors of emotional distress. The menstrual cycle itself has
been conceptualized as a stressor (e.g., Logue & Moos, 1986). Elliott and
Harkins (1992) found that for normal women menstrual and premenstrual
pain and perception of interference were the strongest predictors of emotional
distress. According to the authors, results provided support that how
individuals appraise or perceive interference from a particular condition or
stressor (e.g., menstrual cycle) may represent an important component in stress
and coping processes.
There are several treatment options available for women who experience
significant levels of anxiety either as a result of PME or as a core symptom of
PMS or PMDD. Efficacious treatments include lifestyle changes, medications,
Anxiety and the Menstrual Cycle 195
a wait-list control condition (Blake et al., 1998). However, CBT may be more
effective for managing depressive symptoms than anxiety symptoms, as some
studies have found no reduction in anxiety scores following treatment (Blake
et al., 1998). CBT has demonstrated equal efficacy to medication (i.e., fluoxetine)
in treating PMDD with better maintenance after one year (Hunter et al., 2002 ).
A combination of medication and psychotherapy did not demonstrate any
additional benefits to each alone. It is interesting to note, that women treated
with fluoxetine reported greater improvement in anxiety than those who received
CBT. The authors attributed this to either the known anxiolytic effects of the
medication or the tendency for CBT to focus on depressive symptoms and not
anxiety.
Selective serotonin reuptake inhibitor (SSRI) anti-depressants have been
found to be effective for alleviating symptoms of PMS and PMDD (see
Kornstein & Smith, 2004). Only two controlled trials have demonstrated
efficacy for intermittent dosing of anxiolytic medication for treating PMS
(e.g., Freeman, Rickels, Sondheimer, & Polansky, 1995). However, treatment
with SSRIs can result in decreases in both anxiety and depression symptoms,
with the option to add anxiolytics if residual anxiety symptoms remain
(Rapkin, 2003). Several reviews of the existing literature on antidepressant
treatment of PMS and PMDD are available (e.g., Kornstein & Smith, 2004;
Dimmock, Wyatt, Jones, & O’Brien, 2000). Clearly, more research is needed
on what components of psychological and biological treatments are effective
for anxiety symptoms across the menstrual cycle.
number of normal women and those suffering from menstrual or clinical anxiety
disorders may experience increased anxiety symptoms during the premenstrual
phase. Prospective assessment of at least 2 months is necessary to determine if
the anxiety symptoms only increase during the premenstrual phase. Such a
determination is crucial given that different treatment options may be
warranted. If anxiety symptoms persist across all phases of the menstrual
cycle, then treatment may be focused more on anxiety than phase-specific
effects. Thus, assessment and treatment decisions are crucial given the possible
complex relationships between anxiety and the premenstrual phase.
In this review, several issues have been delineated that make the literature on
anxiety, its disorders and menstrual cycle phases difficult to summarize.
Retrospective and prospective methods of reporting anxiety symptoms across
the menstrual cycle reveal many inconsistent findings. Researchers are often
unclear about whether they are discussing anxiety as a symptom caused by the
premenstrual phase of the menstrual cycle or the exacerbation of a
pre-existing anxiety disorder. The menstrual literature is replete with differing
definitions of premenstrual complaints, menstrual cycle timing, and
premenstrual exacerbation of existing pathologies. Conceptually, researchers
need to reach consensus on diagnostic criteria for premenstrual difficulties
and premenstrual exacerbation of psychological disorders. In addition,
researchers need to be more consistent in definitions and lengths of menstrual
cycle phases. It may be time for researchers to conduct more translational
research in which both camps agree on these matters.
Future Research
cycle phases and anxiety interact. More information is also needed to increase
our understanding of how beliefs, expectations, cultural ‘‘knowledge’’, and
personal experiences influence the experience, reporting, and attribution of
symptoms as well as the perception of control over them. A taxometric
approach may also be helpful in investigating emotional vulnerability factors
in the prediction of premenstrual anxiety. Finally, measurement issues need to
be addressed. The use of prospective monitoring over longer periods of time
coupled with agreement over definitions of premenstrual concepts needs to
standardized. In general, the relationship between menstrual cycle effects and
anxiety symptomatology needs further refinement.
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Pain and Anxiety Disorders
Introduction
There is growing evidence that chronic pain, typically that which is associated
with the musculoskeletal system (e.g., arthritis, low back pain, fibromyalgia),
frequently co-occurs with the anxiety disorders. This co-occurrence is often
overlooked in practice because it is neither standard protocol nor obvious that
clinicians consider pain experiences in the context of screening or assessment of
anxiety disorders. Yet, people with both an anxiety disorder and chronic
musculoskeletal pain typically present with greater distress and functional
impairment compared to those with only one of these conditions. As a result,
both assessment and treatment can be complicated. The goals of this chapter
are several. First, we review the core characteristics of acute and chronic pain,
and present data regarding the extent of its co-occurrence with the anxiety
disorders. Second, we summarize models that have been offered to explain the
co-occurrence of these conditions. Third, we review evidence supporting the
postulates of these models. Fourth, we discuss practical issues that are intended
to improve assessment, treatment, and outcomes for people who present with
an anxiety disorder accompanied by clinically significant pain. Much of the
discussion focuses on the relationship between chronic musculoskeletal pain
and posttraumatic stress disorder (PTSD), as it is the anxiety disorder that has
received the most empirical attention in this context. We conclude with a brief
outline of issues that warrant future research attention.
Gordon J. G. Asmundson
Anxiety and Illness Behaviours Laboratory, University of Regina, Regina, Saskatchewan,
S4S 0A2, Tel: (306) 347-2415, Fax: (306) 585-4854
gordon.asmundson@uregina.ca
M. J. Zvolensky, J. A. Smits (eds.), Anxiety in Health Behaviors and Physical Illness. 207
Ó Springer 2008
208 G. J. G. Asmundson et al.
Understanding Pain
received the vast majority of theoretical and empirical attention with regard to
co-occurrence with the anxiety disorders; thus, unless otherwise indicated, it
will be the focus of much of the discussion that follows.
Epidemiology
Investigators have consistently observed that rates of some anxiety disorders are
elevated in people with chronic musculoskeletal pain. Table 1 and Table 2 show
the 12-month prevalence of various anxiety disorders in people reporting
primarily chronic musculoskeletal or migraine headache pain in community
and treatment seeking samples, respectively. In community samples, the most
prevalent past 12-month anxiety disorders were specific phobia (formerly
simple phobia; ranging from 12.5% to 15.7%), social anxiety disorder (SAD;
ranging from 8.3% to 11.8%), and PTSD (ranging from 7.3% to 10.7%). This
pattern of findings is consistent with, but higher than, the general US popula-
tion 12-month prevalence rates (i.e., specific phobia, 8.7%; SAD, 6.8%; PTSD,
3.5%; Kessler, Chiu, Demler, & Walters, 2005). In a large (N=85,088) survey
of community dwelling adults from 17 countries, Demyttenaere et al. (2007)
most recently reported pooled results indicating that those with back or neck
pain, compared to those without, were approximately two times more likely to
have had past 12-month panic disorder (PD)/agoraphobia and SAD, and
almost three times more likely to have had generalized anxiety disorder
(GAD) or PTSD. Raphael, Janal, Nayak, Schwartz, and Gallagher (2006)
have likewise reported that community-dwelling women with fibromyalgia
were five times more likely than others to have had a lifetime diagnosis of
obsessive-compulsive disorder (OCD), four times more likely to have had
PTSD, and more than four times as likely to have had GAD.
In treatment seeking samples the most prevalent past 12-month anxiety
disorders were phobic disorders (including SAD; ranging from 9% to 13%),
followed generally by GAD (ranging from 0% to 13.4%) and PD (ranging from
1% to 7.2 %). Twelve-month prevalence of any anxiety disorder was 26.5% to
35.1% in community samples with chronic pain, and 8 to 28.8% in treatment
seeking samples with chronic pain, both elevated relative to the general popula-
tion (18.1%; Kessler, Chiu, et al., 2005). Lifetime prevalence of various anxiety
disorders reported by patients with chronic musculoskeletal pain, as illustrated
in Table 2, have been elevated relative to the general population (Kessler,
Berglund, Demler, Jin, & Walters, 2005) in some (Atkinson, Slater, Patterson,
Grant, & Garfin, 1991), but not all (Kinney, Gatchel, Polatin, Fogarty, &
Mayer, 1993; Polatin, Kinney, Gatchel, Lilio, & Mayer, 1993), studies.
It is noteworthy that the 12-month and lifetime prevalence rates for PTSD in
the treatment seeking chronic pain samples described in Table 2 were neither
Table 1 Prevalence of anxiety disorders among persons with pain (community samples)
210
Study Participants Data set Diagnostic criteria % Meeting criteria for an anxiety disorder
McWilliams et Nationally National DSM-III-R Chronic pain (arthritis; n = 382) General population (n = 5495)
al. (2003) representative Comorbidity Any anxiety disorder 35.1 Any anxiety disorder 18.1
sample of the Survey Part II PD 6.5 PD 1.9
U. S. (NCS) AWHPD 8.4 AWHPD 3.3
population (n SP 11.8 SP 7.8
= 5877)
SiP 15.7 SiP 8.3
PTSD 10.7 PTSD 3.3
GAD 7.3 GAD 2.6
McWilliams et Nationally Midlife DSM-III-R Arthritis (n = 588) No arthritis
al. (2004) representative Development in Panic attacks 11.2 Panic attacks 5.8
sample of the the United States GAD 5.6 GAD 2.7
U. S. Survey (MIDUS) Migraine (n = 340) No migraine
population (n Panic attacks 17.4 Panic attacks 5.5
= 3032)
GAD 9.1 GAD 2.5
Back pain (n = 614) No back pain
Panic attacks 13.0 Panic attacks 5.3
GAD 6.2 GAD 2.5
Von Korff et al. Nationally National DSM-IV Chronic spinal pain (n = 2397) -
(2005) representative Comorbidity Any anxiety disorder 26.5
sample of the Survey PD 4.8
U. S. Replication AWHPD 1.3
population (n (NCS-R) SP 8.3
= 5692)
SiP 12.5
PTSD 7.3
GAD 6.4
Note: PD = Panic Disorder; AWHPD = Agoraphobia Without History of Panic Disorder; SP = Social Phobia (also called social anxiety disorder);
SiP = Simple Phobia; PTSD = Posttraumatic Stress Disorder; GAD = Generalized Anxiety Disorder; Not all studies evaluated all anxiety disorders;
G. J. G. Asmundson et al.
Reich et al. (1983) Mixed chronic pain patients (n = 43) DSM-III - Any anxiety disorder 7.0
(PTSD only)
Katon et al. (1985) Mixed chronic pain patients (n = 37) DSM-III - Any anxiety disorder 16.2
(PD only)
Large (1986) Mixed chronic pain patients (n = 50) DSM-III - Any anxiety disorder 8.0
GAD 4.0
PD 2.0
PTSD 2.0
Fishbain et al. Mixed chronic pain patients (n = 283) DSM-III - Any anxiety disorder 19.4
(1986)
Atkinson et al. Chronic low back pain patients (n = 97) DSM-III Any anxiety 37.9 Any anxiety disorder 28.8
(1991) disorder
Generalized 22.7 Generalized disorder 13.4
disorder
PD 8.2 PD 7.2
OCD 13.4 OCD 8.2
Kinney et al. (1993) Chronic back pain patients (n = 90) DSM-III-R Any anxiety 29.0 Any anxiety disorder 25.0
disorder
PD 3.0 PD 3.0
Phobic disorders 17.0 Phobic disorders 13.0
OCD 3.0 OCD 3.0
PTSD 2.0 PTSD 2.0
GAD 4.0 GAD 4.0
211
212
Table 2 (continued)
Diagnostic
Study Participants Criteria Lifetime prevalence (%) Current prevalence (%)
Polatin et al. (1993) Chronic low back pain patients (n = DSM-III-R Any anxiety 19.0 Any anxiety disorder 17.0
200) disorder
PD 3.0 PD 3.0
Phobic disorders 11.0 Phobic disorders 9.0
OCD 2.0 OCD 2.0
PTSD 1.0 PTSD 1.0
GAD 2.0 GAD 2.0
Asmundson et al. Chronic musculoskeletal pain patients DSM-IV - Any anxiety disorder 17.0
(1996) (n = 200) PD 2.1
SP 11.0
SiP 2.7
OCD 0.0
PTSD 2.1
GAD 0.0
Note: PD = Panic Disorder; OCD = Obsessive-Compulsive Disorder; PTSD = Posttraumatic Stress Disorder; GAD = Generalized Anxiety
Disorder; SP = Social Phobia (also called social anxiety disorder); SiP = Simple Phobia; Not all studies evaluated all anxiety disorders.
G. J. G. Asmundson et al.
Pain and Anxiety 213
ranging from 50% to 80% (for recent reviews, see Asmundson et al., 2002; Otis
et al., 2003). Recent findings from a sample of female veterans using the
Veterans Administration (VA) Health Care System confirm that these finding
generalize across gender (Asmundson, Wright, & Stein, 2004). Road traffic
collisions, work-related injury, and service in combat and emergency theatres
are the most common events precipitating the development of PTSD accom-
panied by chronic pain (Asmundson, Norton, Allerdings, Norton, & Larsen,
1998; Beckham et al., 1997; Blanchard & Hickling, 2004).
Sareen, Cox, Clara, and Asmundson (2005) recently used data from the US
National Comorbidity Survey Part II to evaluate associations between the
anxiety disorders and diagnoses of general medical conditions, including
those for which pain is often a significant component. After controlling for
socio-demographic variables and other common mental disorders, robust asso-
ciations were found amongst PTSD, panic attacks, and agoraphobia and the
physical disorders. Most strikingly, individuals with PTSD were more than
twice as likely as others to have a past-year neurological disorder (e.g., multiple
sclerosis), roughly twice as likely to have a past-year gastrointestinal disorder
(e.g., ulcer, hernia), more than three times as likely to have a past-year meta-
bolic or immune disorder (e.g., diabetes, lupus), two and one half times as likely
to have a past-year bone or joint conditions (e.g., arthritis, rheumatisms, other
bone/joint disease), and almost twice as likely as others to have one or more
past-year physical disorders.
Overall, it appears that conditions characterized by some degree of persistent
pain are prevalent in people with anxiety disorders, particularly PTSD and
panic-related conditions. This avenue of inquiry is in its infancy; thus, further
investigation geared toward replication of findings in community and treat-
ment-seeking samples, using comprehensive pain assessment batteries, is
warranted.
Course
Few studies have systematically investigated the extent to which anxiety dis-
orders exist prior to the onset of pain, or vice versa. There is some evidence to
suggest that anxiety disorders precede the onset of pain. In a sample of injured
workers with chronic musculoskeletal pain, Asmundson, Jacobson, Allerdings,
and Norton (1996) found that in all but one case, the anxiety disorder preceded
the pain complaint. Kinney et al. (1993) found that among 90 chronic low back
pain patients, 23% had a preexisting anxiety disorder. In the only prospective
study to date, we recently demonstrated that PTSD symptoms measured prior
to surgery made a unique contribution to the prediction of post-surgical pain
disability in chronic pain patients undergoing general surgery (Martin, Dzyuba,
Halket, Asmundson, Katz, 2007); thus, PTSD symptoms may be important in
the development and/or maintenance of pain disability. There is also evidence
Pain and Anxiety 215
that the probability of onset of an anxiety disorder before versus after pain
onset is comparable. In a study of 97 chronic back pain patients, 30 of whom
had a comorbid anxiety disorder, 46.7% reported onset of anxiety before pain,
and 53.3% reported onset after pain (Atkinson et al., 1991). Additional
research, particularly that which uses prospective methods, is needed to deline-
ate the temporal sequence of co-occurring anxiety disorders and chronic pain.
Theoretical Overview
The mutual maintenance model (Sharp & Harvey, 2001) holds that certain
components of PTSD (e.g., physiological arousal, absence of positive emotions,
avoidance of trauma stimuli) maintain or exacerbate symptoms of pain
and, similarly, that certain components of chronic musculoskeletal pain
(e.g., physiological arousal, catastrophizing about pain, avoidance of physical
exertion) maintain or exacerbate symptoms of PTSD. The model predicts, for
216 G. J. G. Asmundson et al.
We (Asmundson et al., 2002; Asmundson, & Taylor, 2006) and others (Otis
et al. 2003; Turk, 2002) have extended the idea of mutual maintenance, suggest-
ing that some maintenance factors may actually denote a shared vulnerability,
or diathesis, for developing both conditions. The shared vulnerability model
(see Fig. 1) holds that there are individual difference factors, possibly geneti-
cally influenced, that predispose people to develop PTSD and chronic muscu-
loskeletal pain when exposed to certain environmental conditions. Specifically,
the model suggests that the interaction of individual difference characteristics –
a psychological vulnerability for feelings of loss of control (and anxiety), and a
lowered physiological threshold for alarm reactions (i.e., activation of physio-
logical processes that prepare one to fight or flee) to stressors – and instigating
Psychological
Vulnerability
(e.g., high injury
sensitivity, high
anxiety sensitivity)
Autonomic Nervous
System and Muscular
Responsivity
Emotional Disabling
Life Event Avoidance
Response Condition
(e.g. traumatic of situations or activities
(e.g. fear, anxiety, (specific or
incident, injury) perceived as negative
worry, agitation) co-occurring)
Hypervigilance and
Cognitive Biases
Summary
Symptom Overlap
Anxiety Sensitivity
AS (i.e., fear of anxiety based on the belief that it may have harmful conse-
quences) is one of several individual difference factors that increase sense of
danger and fearful responding. AS is elevated in patients with PTSD (Taylor
et al., 2001, 2003) and in some patients with chronic musculoskeletal pain (for
review, see Asmundson, Wright, & Hadjistavropoulos, 2000), is positively
correlated with the severity of PTSD symptoms (Fedoroff, Taylor, Asmundson,
& Koch, 2000), increases the risk of pain-related avoidance and disability
following physical injury (for review, see Keogh & Asmundson, 2004), and
is partly influenced by genetic factors (Stein, Jang, & Livesley, 1999). Conse-
quently, it has been postulated that AS is responsible for the extreme emotional
Pain and Anxiety 219
responses to trauma and pain associated with injury, and that it denotes the
specific vulnerability that predisposes people to develop both PTSD and
chronic musculoskeletal pain (Asmundson et al., 2002; Asmundson & Taylor,
2006; Turk, 2002). It has yet to be established that elevated AS precedes the
development of PTSD and chronic musculoskeletal pain; thus, it remains a
possibility that AS becomes elevated as a consequence of PTSD and chronic
musculoskeletal pain and thereafter serves to maintain symptoms (see Sharp &
Harvey, 2001). Longitudinal studies are needed to assess these possibilities.
Additional study of other potential vulnerability factors (e.g., illness/injury
sensitivity, fear of pain) is also warranted.
Pain and anxiety are both associated with physiological arousal (e.g., acceler-
ated heart rate, elevated blood pressure, increased respiration, decreased gas-
trointestinal activity, increased muscular tension, increased blood flow to
skeletal muscles; Hoehn-Saric & McLeod, 1993). The bodily changes stemming
from arousal serve a protective function, promoting escape and withdrawal, but
can have detrimental effects if prolonged. Physical injury and traumatic experi-
ences also initiate other complex neural and hormonal processes (e.g., release
of cytokines, b-endorphin, 5-HT-moduline) that, while designed to promote
tissue healing and reinstate homeostasis, can be destructive to muscle, bone,
Pain and Anxiety 221
and neural tissue when prolonged (e.g., Kiecolt-Glaser, McGuire, Robles, &
Glaser, 2002; Melzack & Katz, 2004). In short, prolonged physiological arousal
and activation of neural and hormonal processes, whether initiated by pain or
anxiety, act as a stressor (i.e., they are perceived as threatening and uncontrol-
lable) that can have detrimental effects on various body systems (McEwen,
1998). Illustrating these effects, and as noted in our discussion of epidemiology
of co-occurrence, Sareen et al. (2005) found strong associations between anxiety
disorders, particularly PTSD, and general medical conditions characterized
by pain.
We have been particularly interested in the role that autonomic nervous
system (ANS) dysregulation may play in anxiety disorders and in chronic
musculoskeletal pain. This interest is predicated on the notion that chronic
arousal is, in part, responsible for the symptoms of both conditions. One of the
most robust findings reported in the PTSD literature over the past two decades
is that sympathetic activity is increased and parasympathetic activity decreased,
both in general and in response to trauma-related stimuli. This pattern of
findings has been observed across a wide variety of measures of cardiovascular
reactivity in both traumatized adults (Keane et al., 1998) and children
(Scheeringa, Zeanah, Myers, & Putnam, 2004). Although ANS dysregulation
in chronic musculoskeletal pain has received little empirical scrutiny, available
findings suggest a pattern similar to that observed in PTSD. Rainville, Bao, and
Chretien (2005), for example, used hypnosis to alter mood, perceived pain
unpleasantness, and severity of pain induced in healthy participants, showing
that increases in negative mood and pain unpleasantness were positively asso-
ciated with changes in heart rate variability. This suggests that pain-related
emotion impacts ANS responsivity. We recently completed an investigation of
patients with chronic musculoskeletal pain (n=33), acute musculoskeletal pain
(n=12), and healthy controls (n = 30) using tasks designed to evoke measur-
able, bi-directional ANS responses. Preliminary analyses indicate no between-
group differences with regard to tasks that augment vagal tone; however, the
chronic pain patients exhibited increased sympathetic activity compared to
controls on tasks designed to induce rapid vagal withdrawal followed by
sympathetic discharge (i.e., dysregulated sympathetic discharge). Collectively,
these data indicate both PTSD and chronic musculoskeletal pain are character-
ized by labile sympathetic responsivity.
The literature regarding pain threshold (i.e., the point at which a stimulus is
detected as being painful) and pain tolerance (i.e., the length of time that a pain
stimulus can be endured) in each of PTSD and chronic musculoskeletal pain
may also provide some clues as to the mechanism of association; however, the
findings are mixed and complex. There is, for example, a body of evidence
indicating that hyperalgesia (i.e., reduced pain threshold and tolerance or, in
other words, exaggerated pain perception) is induced by elevations in state and
trait anxiety (e.g., Carter et al., 2002; James & Hardardottir, 2002). Since
elevations in state and trait anxiety are central features of PTSD and chronic
musculoskeletal pain, it is plausible that PTSD and chronic musculoskeletal
222 G. J. G. Asmundson et al.
pain may induce hyperalgesia. On the other hand, there is a body of literature
indicating that conditioned stress-induced hypoalgesia/analgesia (i.e., increased
pain threshold and tolerance or, in other words, attenuated pain perception)
plays an important and potentially causal role in both chronic musculoskeletal
pain (e.g., Flor, Birbaumer, Schulz, Grüsser, & Mucha, 2002) and PTSD (e.g.,
Foa, Zinbarg, & Rothbaum, 1992). This literature suggests that dysregulation
of the endogenous opioid system – perhaps functioning to deactivate fear
structures in the short term through heightened release of endogenous opioids –
may play a role in blunting pain perception (e.g., higher pain threshold and
tolerance), reducing avoidance behavior, and increasing emotional numbing
associated with chronic musculoskeletal pain and PTSD. It is noteworthy that
pain tolerance, but not threshold, is affected by naloxone (a drug that blocks
opioid receptors) only when pain levels are high, suggesting only partial media-
tion by the endogenous opioid system.
These mixed findings are intriguing when placed in the context of evidence
showing that AS does not impact pain tolerance or threshold, but is associated
with pain intensity (for review, see Keogh & Asmundson, 2004). It is possible
that different mechanisms may be operating at different levels of the stimulus-
response range (i.e., from just noticeable sensation through intolerable pain) and
that their operations are partially regulated by individual difference factors that
influence processing of pain sensation as alarming. Given recent observations
that unpredictable and predictable pain are associated with hyperalgeisa and
hypoalgesia/analgesia, respectively (Ploghaus, Becerra, Borras, & Borsook,
2003), it is equally possible that different mechanisms are operative depending
on whether pain evokes anxiety (i.e., response to unpredictable, future threats)
or fear (i.e., response to an immediate threat).
Chronic dysregulation of the ANS and endogenous opioid system appears to
play important, possibly interactive roles in reducing the threshold for alarm in
PTSD and chronic musculoskeletal pain and, in part, may account for their
substantive co-occurrence. This remains to be evaluated in direct comparisons
between those with PTSD, chronic musculoskeletal pain, both PTSD and
chronic musculoskeletal pain, and healthy as well as clinical control partici-
pants. This, combined with evidence that the serotonergic system – an aminer-
gic neurotransmitter system responsible for maintaining homeostasis via
modulation of the release of 5-HT from serotonergic neuron terminals – may
be dysregulated in both PTSD and chronic musculoskeletal pain (e.g., David-
son & Connor, 2001), provides clues as to the peripheral and central physiolo-
gical mechanisms underlying the suggestion of a lower threshold for alarm.
Summary
There exists a small and growing body of empirical support for postulates of the
mutual maintenance and shared vulnerability models of co-occurring PTSD
Pain and Anxiety 223
As noted above, clinically significant pain often goes unnoticed when assessing
and planning treatment for a patient with an anxiety disorder. When over-
looked, pain can make treatment of the anxiety symptoms complicated at best,
and frustrating and ineffective at worst. There is little information available on
assessment and treatment planning for anxiety disorder patients who present
with co-occurring pain symptoms. In order to facilitate clinical and research
efforts, we provide a brief overview of tactics for assessment and treatment in
this context.
Assessment
Treatment
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Asthma in Anxiety and Its Disorders: Overview
and Synthesis
Lisa S. Elwood
National Crime Victims Research and Treatment Center, Medical University of South
Carolina, 165 Cannon Street, P.O. Box 250852, Charleston, SC 29425, Tel: 843-792-2366,
Fax: 843-792-3388
elwood@musc.edu
M. J. Zvolensky, J. A. Smits (eds.), Anxiety in Health Behaviors and Physical Illness. 237
Ó Springer 2008
238 L. S. Elwood, B. O. Olatunji
consider the specificity of the relation between asthma and anxiety. Finally,
cognitive behavioral models of the asthma and anxiety relation will be provided
and the efficacy of cognitive behavioral treatments for individuals with asthma will
be reviewed.
Asthma
Research examining risk factors for asthma have identified sex, race, weight,
timing of birth, smoking, environmental factors, and atopy (i.e., allergic
responses) as potential risk factors for the development of asthma. The relation-
ship between sex and asthma appears to fluctuate over time. Studies have found
that asthma appears to be more prevalent in males in childhood (van Merode,
Maas, Twellar, Kester, & van Schayck, 2007), but in females in adulthood
(Apter, 2007; Wenzel & Busse, 2007). Members of ethnic minority groups,
with the exception of Mexican Americans, appear to be at an increased risk
for asthma when compared to Caucasians (Apter, 2007, McCoy et al., 2006).
Specifically, within the US, asthma appears to be most prevalent in Puerto
Rican Americans, followed by Native Americans, African Americans, and then
by Caucasians. In addition, members of minority groups and individuals with
low socioeconomic status (SES) appear to be at an increased risk for not
receiving appropriate medical care for asthma, resulting in higher rates of
medical visits and death related to asthma (Apter, 2007; Joseph, Williams,
Ownby, Saltzgaber, & Johnson, 2006). However, one study found support for
chronic stress as a mediator between low SES and decreased immune processes
and asthma symptoms (Chen, Hanson et al., 2006). A meta-analysis examining
the relation between weight and asthma indicated that both high weight at
birth and at middle childhood appear to be related to increased risk for future
asthma (Flaherman & Rutherford, 2006). The article suggests that diet, gastro-
esophageal reflux, mechanical effects of obesity, atopy, and hormonal influ-
ences may serve as links between body weight and asthma symptoms. The link
between overweight status and asthma has also been supported in adolescents
(OR 1.4, 95% confidence interval (CI) 1.1–1.6; Jones, Merkle, Fulton, Wheeler,
& Mannino, 2006). Research suggests that obesity in adulthood is associated
with the presence of asthma symptoms in females, but not males (McLachlan
et al., 2007). A separate meta-analysis revealed that premature birth may also
serve as a risk factor for asthma (Jaakkola et al., 2006). However, the strength
of the association varied across studies, with cross-sectional design, broad
outcome criteria, small sample size, young sample, and more recent publication
displaying the strongest associations between pre-term birth and asthma
symptoms.
240 L. S. Elwood, B. O. Olatunji
Atopy has consistently been supported as a risk factor for asthma (Shapiro,
2006). Atopy describes an allergic response which frequently affects parts of the
body that are not in contact with the allergen. Atopic responses include eczema,
allergic rhinitis, and allergic conjunctivitis. Both the presence of atopy in the
child and parental atopy or asthma appear to serve as risk factors for the
development or maintenance of asthma symptoms in children (Shapiro,
2006). Studies have consistently shown a high comorbidity between asthma
and rhinitis (i.e., irritation and inflammation of the nose) and have posited that
rhinitis serves as a risk factor for asthma (Bousquet, van Cauwenberge, &
Khaltaev, 2001). It has been proposed that rhinitis and asthma may be two
expressions of a common mucosal susceptibility and may affect and amplify
each other (Jani & Hamilos, 2005). For individuals with both rhinitis and
asthma, there is some evidence that treatment of rhinitis may improve co-
existing asthma symptoms (Bousquet et al., 2001). Other medical conditions
that have been associated with asthma include heartburn and acid regurgitation
(Hancox et al., 2006).
Studies suggest that smoking or being exposed to second hand smoke serves
as a strong risk factor for the development of asthma (McCoy et al., 2006;
Shapiro, 2006). In fact, a recent study found that the risk of developing asthma
was significantly higher among current smokers with an adjusted odds ratio
(OR) of 1.33 (95% CI 1.00–1.77) and among ex-smokers with an adjusted
OR 1.49 (CI 1.12–1.97) compared with never-smokers (Piipari, Jaakkola,
Jaakkola, & Jaakkola, 2004). Similarly, a prospective cohort study among
2,609 children with no lifetime history of asthma or wheezing found that regular
smoking was associated with increased risk of new-onset asthma and the
increased risk from regular smoking was greater in nonallergic than in allergic
children (Gilliand et al., 2006). A third study which assessed individuals over a
eight year period reported that smokers reported a higher frequency of new
onset asthma than non-smokers, OR 2.14 (95% CI 1.30–3.00; Frank, Hazell,
Morris, Linehan, & Frank, 2007). A study examining poor asthma control,
based on patient diaries over a 4 week period, in individuals being treated for
asthma revealed that smoking, along with lung function and ethnicity, was
associated with the presence of asthma episodes (McCoy et al., 2006). Smoking
has been shown to be a unique and independent predictor of the development of
asthma. The smoking-asthma relation may be largely attributable to airway
narrowing and hyperresponsiveness secondary to emphysema and chronic
bronchitis.
Many studies have outlined how immunological and physiological factors mod-
erate asthma outcomes (e.g., Grupp-Phelan, Lozano, & Fishman, 2001; Watson,
Becker, & Simons, 1993). However, the potential influence of psychological
Asthma and Anxiety 241
factors on asthma has received relatively less attention (Katon et al., 2004). The
available literature does suggest that approximately 40% of individuals with
asthma present with clinically elevated levels of psychological distress (Mullins,
Chaney, Pace, & Hartman, 1997) with 21% to 25% reporting depressive symp-
toms (Badoux & Levy, 1994; Chaney et al., 1999). Furthermore, it has been
shown that asthma is longitudinally associated with a significant increase
in suicidal ideation and suicide attempt, independent of major depression
(Goodwin & Eaton, 2005). These findings highlight the importance of psycho-
logical distress in the conceptualization of the etiology, maintenance, and treat-
ment of asthma.
Recent research has shown that a wide range of mental health problems
are common among patients with asthma (Goodwin, Messineo, Bregante,
Hoven, & Kairam, 2005). However, data from epidemiologic samples suggest
that anxiety disorders, relative to other mental health problems, are especially
prevalent among patients with asthma (e.g., Ortega, McQuaid, Canino,
Ramirez, Fritz, & Klein, 2003).
Anxiety disorders have the highest overall prevalence rate among psychiatric
disorders, with a 12-month rate of 18.1% and a lifetime rate of 28.8% (Kessler,
Berglund, Demler, Jin, Merikangas, & Walters, 2005; Kessler, Chiu, Demler, &
Walters, 2005). The estimated costs associated with anxiety disorders has been
reported to be over $45 billion, accounting for over 30% of total expenditures in
mental health (DuPont et al., 1996). Anxiety disorders also have a substantial
negative impact on quality of life (Mendlowicz & Stein, 2000; Olatunji, Cisler, &
Tolin, 2007).
Asthma is the most common medical disorder among adolescents and is asso-
ciated with increased functional impairment and lost days at school (Weitzman,
Gortmaker, Sobol, & Perrin,1992). There is also evidence that the presence of
asthma increases the risk for the development of an anxiety disorder. As outlined
in Table 1, the presence of asthma in children and adolescents has been linked with
anxious disorders and symptoms in clinical (Butz & Alexander, 1993; Gupta,
Mitchell, Giuffre, & Crawford, 2001; Vila, Nollet-Clemencon, de Blic, Mouren-
Simeoni, & Scheinmann, 2000) and non-clinical samples (Goodwin, Pine, &
Hoven, 2003; Goodwin, Fergusson, & Horwood, 2004; Ortega et al., 2003; Ortega,
Table 1 Findings of studies examining the relation between asthma and anxiety in children and adolescents
242
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Main Findings
Butz and Children 7–12, Recruited Self-reported number and State-Trait Inventory for None 65% reported feeling
Alexander from pediatric ER, type of symptoms, Children, reported ‘‘panic’’ at the
(1993) Diagnosis of acute number of hospital and emotion at the beginning of an asthma
asthma ER visits, limitation of beginning of an asthma attack, feeling panic at
activity, medication attack the beginning of an
attack significantly
predicted trait, but not
state, anxiety
Goodwin Data drawn from an Parents report of child DISC; Child global Asthma to no Asthma was associated
et al. (2003) epidemiology study asthma symptoms and assessment scale asthma with an increased
hospitalization for likelihood of panic
asthma attacks; severe asthma
was associated with an
increased likelihood of
panic attacks and
disorder; Number of
panic symptoms was
associated with an
increased likelihood of
asthma and severe
asthma
Goodwin, Data collected during the Classified as presence of Items from CIDI; asked None Asthma was related to
Fergusson, course of a longitudinal absence of asthma for the previous two anxiety prior to
& study of an unselected during age 16–18 and years; Assessed GAD, (OR=1.6 (CI
Horwood birth cohort; at ages 18 18–21. Presence was social phobia, specific 1.2–2.2)), but not after
(2004) and 21 participants determined by reported phobia, and controlling for adverse
were asked about diagnosis and agoraphobia; assessed childhood experiences
asthma symptoms during the panic attacks and (e.g., SES, abuse,
L. S. Elwood, B. O. Olatunji
Table 1 (Continued)
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Main Findings
time period; also symptoms but not parental conflict) OR
obtained self-report of disorder = 1.2 (CI .5–2.9);
number of asthma suggested a third
Asthma and Anxiety
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Main Findings
Ortega et al. Community sample, Parent report of asthma DISC, used diagnostic Asthma to no After controlling for
(2003) sample based on symptoms, diagnosis, categories of anxiety, asthma maternal mental
island-wide probability or asthma related affective, and health, income, and
household sample of hospitalization disruptive disorders; education asthma
children diagnoses of separation diagnosis was
anxiety, social phobia, associated with having
major depression, any psychiatric
conduct disorder, disorder, any affective
oppositional defiant disorder, having more
disorder, and ADHD than one disorder, and
ADHD; Asthma
attack associated with
most disorders, but not
social phobia or
conduct disorder;
hospitalization was
associated with
separation anxiety
disorder.
Ortega et al. Community sample, Parental reports of an DISC; anxiety disorders Children with Children with a history of
(2004) sample based on asthma diagnosis and included: panic and without asthma attacks had
island-wide probability parental reports of the disorder, separation reported higher prevalence of
household sample of child ever having an anxiety disorder, social histories of any anxiety disorder;
children asthma attack phobia, PTSD, and asthma however, separation
GAD anxiety disorder was
the only individual
anxiety disorder that
was significantly
different between
L. S. Elwood, B. O. Olatunji
groups
Table 1 (Continued)
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Main Findings
Rietveld Adolescents with and Severity of asthma STAI With asthma to No sig differences in state
(2000) without asthma; with classified from one to healthy or trait anxiety
asthma recruited from five; class 1 (if needed controls
Asthma and Anxiety
Table 1 (Continued)
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Main Findings
Wamboldt Children aged 7–19 were Severity was determined RCMAS; CBCL (parent None Neither child-reported
et al. (1998) recruited from asthma by a pediatric report) anxiety nor parent-
related summer camps pulmonologist and reported internalizing
and an inpatient unit; allergist/immunologist symptoms were
both children and a by reviewing medical significantly elevated
parent participated records. Asthma rated
as mild, moderate, or
severe. Parent report of
number of days missed
from school, number of
hospitalizations,
number of days
hospitalized, and
number of emergency
visits for asthma.
Note. ADHD = Attention Deficit Hyperactivity Disorder, CBCL= Child Behavior Checklist, CIDI = Composite International Diagnostic Inter-
view, DISC = Diagnostic Interview Schedule for Children; GAD = Generalized Anxiety Disorder PTSD = Posttraumatic Stress Disorder, RCMAS
= Revised Children’s Manifest Anxiety Scale, STAI = State-Trait Anxiety Interview, Sig. = p < 0.05.
L. S. Elwood, B. O. Olatunji
Asthma and Anxiety 247
McQuaid, Canino, Goodwin, & Fritz, 2004) samples. The association between
asthma and anxiety in children has been reported by studies using a variety of
methodologies, including cross-sectional (Butz & Alexander, 1993; Gupta et al.,
2001; Vila et al., 2000), epidemiological (Goodwin et al., 2003; Ortega et al., 2003;
Ortega et al., 2004), and longitudinal (Goodwin et al., 2004). However, it should
be noted that some studies have failed to find a relation between asthma and
anxiety in children (e.g., Wamboldt, Fritz, Mansell, McQuaid, & Klein, 1998).
While one study reported that children suffering from asthma report higher levels
of general anxious symptoms than healthy controls (Gupta et al., 2001), two
studies failed to find significant differences between children with asthma and
healthy controls on trait anxiety (Rietveld, 2000; Rietveld, Everaerd, & van Beest,
2000). A detailed review of the literature suggests that the discrepancy between
studies may partially be accounted for by methodological differences. When
relations between asthma and specific anxiety disorders are examined, asthma
has been linked specifically to panic disorder (Goodwin, Pine, et al., 2003),
separation anxiety disorder (Ortega et al., 2003; Ortega et al., 2004; Vila et al.,
2000), and generalized anxiety disorder (Vila et al., 2000) in children.
The inconsistent findings regarding the relationship between asthma and
anxiety in children highlights the importance of considering sampling
approaches as well as the source of data. For example, Wamboldt and collea-
gues (1998) found that child and parent ratings of the child’s psychological
symptoms displayed inconsistent patterns. While the child’s reported level of
anxiety failed to be significantly related to asthma severity, asthma severity was
significantly related to parent’s ratings of the child’s internalizing symptoms. In
addition, parental ratings of the child’s internalizing symptoms were signifi-
cantly related to the parent’s personal level of physical symptoms, suggesting
that parental reports of child symptoms may be biased by their own distress
(Wamboldt et al., 1998).
Table 2 Findings of studies examining the relation between asthma and anxiety in adults
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Findings
Afari et al. Adult patients with Completed a DIS-III-R Compared to Participants endorsed PD,
(2001) diagnosis of mild to methacholine prevalence agoraphobia, and social
moderate asthma inhalation challenge rates phobia at higher rates than
recruited from an test to confirm general population
asthma clinic airway reactivity; prevalence rates
FEV1/ FVC
Brown et al. Recruited participants FEV1 SCID-IV None 59% met criteria for at least
(2000) using medication one anxiety disorder; 28%
regularly scheduled to specific phobia, 19%
receive prednisone at an PTSD, 15% PD, 13%
asthma clinic, social phobia
Davis et al. Evidence of asthma, ‘‘objective evidence of ASI, Sheehan Patient None 37% received an anxiety
(2002) recruited from an asthma based on the Rated Anxiety Scale disorder; 11% PD, 6%
asthma clinic Canadian Consensus (SPRAS), ADIS PTSD, 16% GAD, 3%
Guidelines’’ social phobia, 2% specific
phobia
Di Marco COPD patients were diagnosis of COPD; Italian version of the COPD a greater percentage of
et al. (2006) recruited from a FEV1 values; Italian STAI patients asthma participants
respiratory unit and versions of the compared endorsed high levels of
controls were recruited modified Medical to healthy anxiety (28%) than the
from annual check-ups Resource Council controls control participants (6%).
dyspnea scale and the
St. George’s
Respiratory
Questionnaire
L. S. Elwood, B. O. Olatunji
Table 2 (Continued)
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Findings
Erhabor & Respiratory unit clinic Diagnosis of asthma, General Health Orthopedic Asthma patients reported a
Mosaku Questionnaire, and healthy significantly higher level of
(2004) STAI 1 and 2 controls state anxiety than
Asthma and Anxiety
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Findings
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Findings
Goodwin, Adult primary care Asthma diagnoses PRIME-MD; Patient Compared Participants with asthma were
Olfson, et al. patients at an internal obtained from billing Health patients sig more likely to report PA
(2003) medicine clinic encounter data Questionnaire; with and and GAD than those
Asthma and Anxiety
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Findings
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Findings
FEV1, 65%, or no
best trial. absence of early asthma
Respiratory symptoms, similar pattern
symptoms were for no early symptom non-
coded as present or smokers.
absent: 1) a cough in
morning or winter or,
2) in the summer,
3) any phlegm from
chest in the morning
in the winter, or 4)
the summer, 5) a
period of increased
cough and phlegm
lasting for 3 weeks þ
during the past 3
years,
6) shortness of
breath, and 7)
wheezy or whistling
sounds in chest
Lavoie et al. Adult patients presenting Primary diagnosis of PRIME-MD Compared 25% met criteria for one or
(2005) to asthma clinic asthma; Asthma asthma more anxiety disorder, PD
Control patients most common (12%); 36%
Questionnaire and with and reported a lifetime history
Asthma Quality of without of PAs
253
Table 2 (Continued)
254
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Findings
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Findings
Nascimento Outpatients from an asthma defined by MINI None 52% met criteria for at least
et al. (2002) asthma unit (age range recurrent episodes of one current anxiety
13–80, mean 50.2) dyspnea with diffuse disorder; PD 14%,
Asthma and Anxiety
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Findings
Pollack et al. Patients presenting for Used a computerized SCID None 41% reported PAs and 11%
(1996) pulmonary function grading system reported PD. 67% of
testing developed by the participants with COPD
hospital met criteria for PD.
Participants with PAs or
disorder were significantly
more likely to complain of
dyspnea at rest and irritable
bowel syndrome. No sig.
differences in pulmonary
functioning abnormalities
or severity
Shavitt et al. Recruited from asthma Screening None 13% indicated agoraphobia
(1992) outpatient clinic (age questionnaire without panic, 6.5%
range from 14–58, mean asking about the indicated PD; 6% simple
26.8) presence of panic/ phobias, 5% social phobia;
anxiety symptoms concluded found greater
in association with than expected prevalence
troubled breathing rates of agoraphobia and
or subjective panic when compared to
anxiety, previous general population
experience of panic,
agoraphobic fears,
and a question
about whether or
not they considered
themselves to be
anxious; SCID
L. S. Elwood, B. O. Olatunji
Table 2 (Continued)
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Findings
Sreedhar Adult patients recruited Diagnosis at clinic Manifest Anxiety General Females experienced higher
(1989) from an asthma out- Scale hospital levels of anxiety than males,
patient clinic, a hospital, out- but the sexes demonstrated
Asthma and Anxiety
Comparison
Study Sample Asthma Measurement Anxiety Measurement group Findings
van Peski- Adult patients recruited to Physician diagnosis ADIS-R, STAI, Participants In individuals with asthma,
Oosterbaan a lung function based on chart Agoraphobic given 9% met criteria for current
et al. (1996) laboratory for a review; International Cognitions Scale, diagnosis PD and 12.8% in past year,
histamine challenge test Union Against Body Sensations of asthma In non-asthma
for clinical diagnosis Tuberculosis and Questionnaire, compared participants, 9% current
Lung Disease Panic Attack to those and 11% in past 12 mos. No
Questionnaire; Borg Questionnaire not given sig. differences in PD. Also
scale to assess diagnosis no sig. differences in
breathlessness; of asthma pulmonary functioning.
spirometry; FEV1
Yellowlees Adult patients recruited Pulmonary function Interview assessing None 36% met criteria for an
et al. (1987) from a respiratory unit, tests- FEV1, PaO2, DSM-III criteria anxiety disorder; 24% PD,
patients were required to PaCO2 10% GAD, 2% PTSD
have chronic airflow
obstruction from due to
bronchitis, emphysema,
or asthma
Note: ASI = ADIS = Anxiety Disorders Interview Schedule, Anxiety Sensitivity Inventory, COPD = Chronic Obstructive Pulmonary Disorder, DIS-
R = Diagnostic Interview Schedule- Revised, FEV1 = Forced Expiratory Volume in the first second of exhalation, FVC = Full Vital Capacity, GAD
= Generalized Anxiety Disorder, HADS = Hospital Anxiety and Depression Scale, MINI = Mini International Neuropsychiatric Interview, PAs =
Panic attacks, PD = Panic Disorder, PTSD = Posttraumatic Stress Disorder, SCID = Structured Clinical Interview for DSM-III-R, SCL-90-R =
Symptom Checklist 90-R, STAI = State Trait Anxiety Inventory. Sig. = p < 0.05.
L. S. Elwood, B. O. Olatunji
Asthma and Anxiety 259
Kelly, & Gamble, 2005; Nascimento et al., 2002; Yellowlees et al., 1987),
posttraumatic stress disorder (Brown et al., 2000), specific phobia (Brown et al.,
2000; Goodwin, Olfson, et al., 2003), and anxiety not otherwise specified
(Goodwin, Jacobi et al., 2003). The association between anxiety and asthma in
adults has been supported in clinical (Afari et al., 2001; Brown et al., 2000; Davis,
Ross, & MacDonald, 2002; Di Marco et al., 2006; Erhabor & Mosaku, 2004;
Goodwin, Olfson, et al., 2003; Heaney et al., 2005; Lavoie et al., 2005; Nascimento
et al., 2002; Perna et al., 1997; Pollack et al., 1996; Shavitt et al., 1992; Sreedhar,
1989; Yellowlees et al., 1987) and non-clinical samples (Goodwin & Eaton, 2003;
Goodwin, Jacobi et al., 2003; Goodwin & Pine, 2002; Halser et al., 2005; Jonas et
al., 1999). The relation has been reported by cross-sectional (Afari et al., 2001;
Brown et al., 2000; Davis et al., 2002; Di Marco et al., 2006; Erhabor & Mosaku,
2004; Goodwin & Pine, 2002; Goodwin, Olfson, et al., 2003; Heaney et al., 2005;
Lavoie et al., 2005; Meuret, White, Ritz, Roth, Hofmann, & Brown, 2005;
Nascimento et al., 2002; Perna et al., 1997; Pollack et al., 1996; Shavitt et al.,
1992; Sreedhar, 1989; Yellowlees et al., 1987), epidemiological (Goodwin & Eaton,
2003; Goodwin, Jacobi, et al., 2003; Halser, et al., 2005), and longitudinal (Halser
et al., 2005; Jonas, Wagener, Lando, & Feldman, 1999) studies. Recently, the
World Mental Health Survey examined the relation between psychopathology
and asthma (Scott et al., 2007). Participants from 17 different countries provided
information about whether or not they had ever been diagnosed with asthma and
completed a structured interview to assess for the presence of selected psychologi-
cal disorders (GAD, panic disorder, PTSD, social phobia, dysthymia, major
depressive disorder, and alcohol use and dependence) in the past year. The pooled
estimate of the OR for the anxiety disorders fell within the 1.3–1.8 (all anxiety
disorders exhibited an OR greater than 1) and the pooled estimate of the OR for
any anxiety disorder was 1.5 (95% CI 1.4–1.7, Scott et al., 2007). When the
individual surveys were examined, all but one survey fell within the 95%
confidence interval. Both depressive disorders and alcohol use disorders were
also significantly associated with asthma and similar strengths of association
were evidenced across the mental disorders (Scott et al., 2007).
Although it is clear that the experience of asthma and anxiety share many
overlapping features, research attempting to highlight the specific nature of this
overlap in adults has yielded inconsistent findings. For example, some studies
have found that individuals with asthma display higher levels of general anxious
symptoms than healthy controls (Di Marco et al., 2006; Sreedhar, 1989). How-
ever, another study found significant differences in state, but not trait, anxiety
(Erhabor & Mosaku, 2004). One study differentiating between airway obstruc-
tion specific anxiety and trait-like anxiety also failed to find a significant
relation between levels of airway obstruction anxiety and baseline measures
of anxiety (Spinhoven, van Peski-Oosterbaan, Van der Does, Willems, & Sterk,
1997). However, a recent longitudinal study found that the onset of anxiety
was significantly associated with the development of asthma nine years later,
OR = 3.53 (CI 1.03–12.1; Neuman et al., 2006).
260 L. S. Elwood, B. O. Olatunji
Panic disorder has been suggested to be the anxiety disorder that most fre-
quently co-occurs with asthma and has been more frequently studied in relation
to asthma than other anxiety disorders. Indeed, studies have consistently shown
that individuals with asthma report higher levels of both panic attacks and
panic disorder than found in the general population (Goodwin & Eaton, 2003;
Goodwin, Jacobi et al., 2003; Perna et al., 1997; Pollack et al., 1996). Butz and
Alexander (1993) reported that 65% of their sample of children diagnosed with
acute asthma reported feeling ‘‘panic’’ at the beginning of an asthma attack, and
the presence of panic feelings accompanying asthma attacks significantly pre-
dicted trait anxiety. The relation between asthma and anxiety is supported when
individuals with anxiety are examined as well. Meuret and colleagues (2005)
found that 13% of participants seeking treatment for panic disorder reported
current asthma. Those with co-occurring asthma and panic also reported higher
cardio-respiratory symptoms than participants with panic alone but did not
differ in severity on other types of panic symptoms (i.e., autonomic/somatic and
cognitive symptoms; Meuret et al., 2005). In an attempt to examine the associa-
tion between asthma and anxiety in families, van Beek, Schruers, and Griez
(2005) recruited family members of individuals receiving treatment for an
anxiety disorder and obtained information about their pulmonary health.
Results revealed that family members of individuals with panic disorder were
significantly more likely to report a lifetime prevalence of asthma than family
members of individuals diagnosed with other anxiety disorders.
Panic attacks and asthma attacks have similar symptom presentations includ-
ing sensations of being smothered, choking, and hyperventilation (Feldman,
Giardino, & Lehrer, 2000; Perna et al., 1997). However, studies have shown that
asthma and panic can be differentiated by specific processes. For example,
Schmaling and Bell (1997) recruited participants suffering from either panic
disorder or asthma who completed the Asthma Symptom Checklist (ASC;
Kinsman, Luparello, O’Banion, & Spector, 1973) for a relevant attack. The
findings showed that the panic fear, OR = 0.5, and hyperventilation/hypercap-
nia, OR = 0.70, subscales of the ASC significantly predicted panic disorder,
while the airway obstruction scales, OR =1.73 (dyspnea and congestion) pre-
dicted asthma. There is also some evidence suggesting that individuals suffering
from asthma and panic are able to differentiate between the two. Indeed, one
study found that 96% of participants, outpatients receiving treatment for allergy
at a specialized clinic, described their panic attacks as ‘‘completely different’’
than their asthma attacks (Perna et al., 1997). When the temporal nature of the
two conditions is examined, participants typically report experiencing asthma
attacks before panic attacks (Feldman, Lehrer, Borson, Hallstrand, & Siddique,
2005; Perna et al., 1997).
Studies that have compared patients with asthma and panic to those with
asthma alone suggest that individuals with co-occurring asthma and panic
Asthma and Anxiety 261
suffer from additional consequences. For example, individuals with asthma and
panic have been found to endorse increased dyspnea at rest, irritable bowel
syndrome, and global distress (Dorhofer & Sigmon, 2002; Pollack et al., 1996).
Feldman and colleagues (2005) found that individuals with asthma (physician
diagnosed) and panic disorder (based on results of a structured interview)
reported more frequent visits to their primary care providers, lower overall
quality of life, greater restriction of activities, and greater emotional difficulties
than individuals with asthma alone. In addition, women with asthma and panic
exhibited significantly greater skin conductance responses and anxious mood
than individuals with asthma alone after being exposed to both neutral and
asthma related scenes (Dorhofer &, Sigmon 2002). Taken together, these find-
ings suggest that individuals with comorbid asthma and panic disorder display
lower levels of functioning across various domains than individuals with
asthma alone.
Longitudinal examinations may provide valuable information about the
temporal nature of the comorbidity of asthma and panic. In a longitudinal
epidemiological study, Goodwin and Eaton (2003) found that the presence of
asthma was significantly associated with the presence of panic attacks one
year later. A recent 20 year longitudinal epidemiological study found a
bidirectional relationship between panic disorder and asthma (Halser et al.,
2005). Asthma served as a significant predictor of future panic disorder, OR
= 4.5 (CI 1.1–20.1), and panic disorder served as a significant predictor of
future asthma, OR = 6.3 (CI 2.8–14.0). When the criteria were expanded
to include any panic symptoms, panic symptoms predicted future asthma
but asthma failed to predict future panic symptoms. Interestingly, when
demographic variables were controlled for, asthma remained a predictor
of future panic disorder in women, OR = 2.9 (CI 1.1–8.6), and smokers,
OR = 3.5 (CI 1.0–13.4), but not for men, OR = 1.9 (CI .2–19.6), and
nonsmokers, OR = 2.1 (CI .5–8.5). Family history of allergy, OR = 1.8 (CI
1.1–2.9), smoking, OR = 1.6 (CI 1.0–2.5), and childhood anxiety, OR = 0.6
(CI .3–1.3), demonstrated the strongest relations with the development of
panic disorder and appear to be the strongest confounds of the panic-asthma
relation (Halser et al., 2005).
Although more recent research has begun to address processes that underlie
the comorbidity between asthma and panic disorder, the specificity of the
asthma-panic relation remains somewhat unclear. For example, one study
failed to find significant differences in the diagnosis of panic disorder between
the asthma and non-asthma groups among patients referred for a histamine
challenge test (van Peski-Oosterbaan, Spinhoven, van der Does, Willems, &
Sterk, 1996). In addition, no differences in asthma symptom severity were
found between those with and without panic disorder. The authors concluded
that panic disorder was unlikely to be specifically related to asthma, but rather
was likely to be generally related to illness and medical attention seeking
behaviors (van Peski-Oosterbaan et al., 1996).
262 L. S. Elwood, B. O. Olatunji
One explanation of the relation between asthma and anxiety is that individuals
experience anxiety in response to their asthma symptoms (Katon et al., 2004). In
support of this notion, two studies (Hommel, Chaney, Wagner, & McLaughlin,
2002; Hommel, Chaney, Wagner, White, Hoff, & Mullins, 2003) have reported
significant correlations between objective asthma illness severity (peak flow
rates) and self-reported anxiety (using the Beck Anxiety Symptom Inventory;
BAI). However, several studies have also failed to find significant relations
between asthma severity and/or pulmonary functioning and levels of anxiety
(Di Marco et al., 2006; Feldman et al., 2005; Kinsman, Dirks, & Jones, 1980;
Lavoie et al., 2005; Pollack et al., 1996; Rimington, Davies, Lowe, & Pearson,
2001; Rushford, Tiller, & Pain, 1998; Sández, Vázquez, Romero-Frais, Blanco-
Aparicio, Otero, & Verea, 2005). Furthermore, no significant relationship has
been observed between self-reported (both questionnaire and diagnostic inter-
view) baseline anxiety and respiratory symptom severity perception during
histamine induced bronchoconstriction in patients with asthma (Spinhoven
et al., 1997). Individuals with life-threatening asthma also do not appear to
endorse significantly higher levels of anxiety disorders, based on responses to
diagnostic interviews, than those with less severe asthma (Yellowlees, Haynes,
Potts, & Ruffin, 1988). In a study that compared asthmatics with and without
panic disorder, results of a histamine challenge test indicated that patients
did not differ in overall pulmonary functioning as measured by FEV1 (van
Peski-Oosterbaan et al., 1996). However, asthmatic patients with panic dis-
order reported higher levels of perceived breathlessness after completing
the histamine challenge test than asthmatic patients without panic disorder
(van Peski-Oosterbaan et al., 1996).
Although the findings are equivocal, there does not appear to be a strong
relation between asthma severity and anxiety symptoms. An alternative expla-
nation for the relation between anxiety and asthma is that the presence of
anxiety could potentially influence the individual’s interpretation of and reac-
tion to his or her asthma symptoms. In a recent study by Chen and collogues
(Chen, Hermann, Rodgers, Oliver-Welker, & Strunk, 2006), eighty-six children
with mild or moderate asthma had symptom perception and pulmonary func-
tion measured throughout methacholine challenge (to induce bronchoconstric-
tion). Higher trait anxiety was associated with heightened symptom perception
and greater asthma severity was associated with blunted symptom perception
and with a slower rate of increase in symptom perception across the methacho-
line challenge. These results suggest that anxiety may only play a role when
symptoms are mild, whereas medical variables, such as asthma severity, play a
role in perception of changes in asthma symptoms as bronchoconstriction
worsens. Past studies have failed to find a significant relation between anxiety
and subjective severity of symptoms, suggesting that the interpretation of the
symptoms themselves may not be different between those with and without
Asthma and Anxiety 263
anxiety (Hommel et al., 2002, Hommel et al., 2003). Rather, the influence of
anxiety may result in behavioral changes such as increased treatment seeking,
increased avoidance of situations perceived as threatening, and decreased self-
efficacy which may reduce the individual’s quality of life.
Anxiety and asthma share common symptoms and are often comorbid, perhaps
reflecting a shared pathophysiological vulnerability (Smoller & Otto, 1998).
The construct of ‘‘panic-fear’’ (P-F) has been proposed as a potential vulner-
ability that may account for the occurrence of excessive anxiety in patients with
asthma (Kinsman et al., 1973). P-F refers to subjective panic and anxious
feelings associated with asthma episodes and the perception of bronchocon-
striction. Individuals high in P-F react to asthma symptoms by emphasizing
their distress in an anxious, dependent, and ineffective way (Kinsman et al.,
1980). P-F was originally assessed as a subscale of the Asthma Symptom
Checklist (Kinsman et al., 1973), however Dirks and colleagues later developed
a 15-item MMPI subscale to assess the construct (Dirks, Jones, & Kinsman,
1977). The MMPI scale uses original MMPI questions and was created by
selecting items that significantly differentiated between individuals that scored
low, moderate, and high on the ASC’s P-F scale. One study found that while the
ASC P-F scale significantly predicted the diagnosis of panic disorder in parti-
cipants with asthma, the MMPI P-F scale did not (Carr, Lehrer, & Hochron,
1995). This suggests that items that assess physical symptoms specifically (i.e.,
the ASC) may be more strongly related to panic disorder. High levels of P-F
have been linked with poorer asthma-related quality of life (Vázquez, 2000),
particularly in the physical (e.g., limitations in self-care, physical and social role
activities, bodily pain, and poor physical health) domain (Sández et al., 2005).
Individuals with high P-F have also been found to be more pessimistic about
their ability to cope with and master their asthma, feel more stigmatized and
psychologically different from others, feel more anxiety about their asthma
attacks, and feel more frequent irritation, worry, isolation, and hyperventila-
tion (Kinsman et al., 1980). Finally, levels of P-F have differentiated between
individuals with asthma that frequently visit the emergency room and those
without emergency room visits (Nouwen et al., 1999).
Anxiety sensitivity (AS) has also been examined as a potential vulnerability
that may account for the link between asthma and anxiety. AS is the fear of
anxiety and anxiety related sensations based on the belief that the symptoms
have harmful consequences (Reiss, 1991). AS is a stable, trait-like characteristic
that functions as a vulnerability to the development and maintenance of
anxious symptoms, particularly panic disorder (Taylor, Koch, & McNally,
1992). AS also has been found to significantly predict levels of panic fear
among individuals with asthma (Carr et al., 1995). Carr, Lehrer, Rausch, and
Hochron (1994) conducted a study examining the role of AS in individuals with
asthma and found that endorsement of panic symptoms was significantly
related to level of AS. Thirty-six percent of participants that endorsed high
levels of AS met criteria for panic disorder, while none of the individuals that
endorsed low levels of AS met criteria for panic disorder. In addition, the mean
AS scores of the participants with asthma and panic disorder were higher than
Asthma and Anxiety 265
those without panic disorder (Carr et al., 1994). A similar study found that
women with asthma alone, panic alone, and asthma and panic endorsed higher
levels of AS than controls (Dorhofer & Sigmon, 2002). However, one study did
fail to find a significant relation between severity of asthma and level of AS
(Asmudson & Stein, 1994). The precise nature of the relation between AS and
asthma is unclear. However, a review of the available literature did lead to a
tentative conclusion that that there may not be a direct relation between asthma
and AS, but instead that the relation may be mediated by their common
association with panic disorder (Asmundson, Wright, & Hadjistavropoulos,
2000).
There is also evidence that smoking is a risk factor for, and may serve to
maintain, some anxiety conditions, particularly; panic attacks and panic dis-
order (see Zvolenksy & Bernstein, 2005). However, few studies have examined
how smoking and anxiety interact in the context of asthma. In a population-
based cohort study of 5,231 participants (Jonas et al., 1999), non-asthmatic
persons aged 25 to 74 were followed for 13 years. For nonsmokers and persons
without respiratory symptoms, a high level of anxiety was a predictor of
increased asthma incidence rates. For the smokers, the relative risks for high
anxiety were not significantly elevated and there was no clear pattern between
anxiety symptoms and risk for the development of asthma. Although research
has also shown a robust association between anxiety and asthma, preliminary
findings highlight the possibility that the presence of smoking may suppress the
effects of anxiety symptoms on the subsequent development of asthma.
Although the extant research literature suggests that individuals with asthma
are at an increased risk of developing anxiety disorders, and panic disorder in
particular, when compared to healthy controls (Goodwin, Jacobi, et al., 2003;
Goodwin & Eaton, 2003; Goodwin & Pine, 2002), comparing individuals with
asthma to healthy controls does not provide information about the specificity
of the relation between asthma and anxiety. Consequently, some studies have
taken the approach of including an additional non-asthmatic medical group as
a comparison condition. Such studies are particularly helpful in determining if
increased anxiety is related to the presence of a medical condition or a reflection
of an effect that is unique to asthma. In an early study, Sreedhar (1989)
compared participants with asthma to general hospital outpatients, ‘‘neurotic’’
psychiatry patients, and controls (with no physical or mental disorder). Results
revealed that participants with asthma endorsed significantly higher levels of
266 L. S. Elwood, B. O. Olatunji
anxiety than the general outpatients and controls, but were not significantly
different on anxiety than the psychiatric participants (Sreedhar, 1989). Simi-
larly, Erhabor and Mosaku (2004) found that patients with asthma reported
higher levels of state anxiety and other psychiatric symptoms than orthopedic
participants and controls, but failed to find significant group differences for
trait anxiety. However, there is evidence that children with asthma endorse
higher levels of trait anxiety than children with diabetes (Vila et al., 1999).
Asthma patients have also been found to report higher levels of trait anxiety
than patients with peptic ulcers and controls (Shanmugam & Kaliappan, 1982).
Children with asthma and those with congenital heart disease have been found
to score significantly higher than the general population on multiple measures
of anxiety (Gupta et al., 2001). However, asthmatic children were found to
score higher than children with congenital heart disease only on medical fears
(Gupta et al., 2001). These findings generally suggest that individuals with
asthma endorse greater levels of anxiety than individuals with other medical
conditions.
Asthma and symptoms of anxiety share many similar symptoms and often co-
occur, suggesting that perhaps both conditions share a common underlying
vulnerability. It has been suggested that respiratory distress may be the com-
mon pathophysiology between asthma and anxiety symptoms, particularly the
experience of panic and panic disorder (Smoller, Pollack, Otto, Rosenbaum, &
Kradin, 1996). Respiratory distress as a common pathophysiology may also be
observed as exaggerated increases in respiratory drive. There is research evi-
dence that increases in respiratory drive (typically assessed by introducing
occlusion of breathing during inhalation through a tube) can be easily induced
in asthmatics (Kelsen, Fleeger, & Altose, 1979). Respiratory distress may lead
to episodes of hyperventilation, particularly in the absence of increases of a
physiological need for ventilation (Lehrer, 1998). The physical sensations asso-
ciated with episodes of hyperventilation may give rise to panic and anxiety.
Feldman and colleagues (2000) have suggested that the experience of respira-
tory distress (e.g., dyspnea) in asthma and anxiety-related conditions may also
be mediated by CO2 hypersensitivity. As a consequence of bronchoconstriction
in asthma, medullary chemoreceptors and/or the locus coeruleaus may be
stimulated. Repeated stimulation of the chemoreceptors may result in a low
‘‘suffocation alarm’’ threshold (Klein, 1993). This process may serve as the
developmental context for a vulnerability for anxiety/panic vulnerability in
patients with asthma. Although biological models based on CO2 hypersensitiv-
ity and a low ‘‘suffocation alarm’’ threshold are consistent with the clinical
description of anxiety/panic symptoms observed in patients with asthma, the
Asthma and Anxiety 267
Although asthma may be a fixed marker, specific interventions derived from the
cognitive behavioral model may have clinical utility for the treatment and
prevention of anxiety among patients with asthma (Smoller et al., 1996). Such
interventions directly target catastrophic cognitions and the preoccupation and
fear of bodily sensations that may have specific links with anxiety, as such
symptoms appear to differentiate asthma patients who develop an anxiety
disorder, particularly panic, from asthma patients that do not develop an
anxiety disorder (Carr et al., 1994). However, it should be noted that the
experience of anxiety among patients with asthma is not necessarily
Asthma and Anxiety 269
Dysfunctional Beliefs
Overestimating the likelihood/severity of having an
asthma attack
Respiratory Vigilance
Safety-Seeking Behaviors
Perception of
Uncertainty/Anxiety/Panic Airway Symptoms
misinterpretation of
activate respiratory fear
ambiguous symptoms
Catastrophic Cognitions
About Symptoms
Conclusion
The presence of asthma may induce the clinical expression of anxiety and panic
in those that may already be genetically vulnerable. Indeed, many studies have
shown that asthma and anxiety, specifically panic disorder, are often comorbid
with the onset of anxiety-related conditions occurring after the onset of asthma.
However, there is evidence that the association between asthma and anxiety and
its disorders is not necessarily causal and the high rate of comorbidity may
reflect common factors/diathesis that are related to both conditions (Goodwin
et al., 2004). Indeed, there is little evidence suggesting individuals with comor-
bid asthma and anxiety display more impaired pulmonary functioning than
those with asthma alone. Furthermore, other chronic medical problems that
share symptoms with anxiety presentations (e.g., cardiac problems) display a
Asthma and Anxiety 271
similar pattern of relations with anxiety and its disorders. Thus, the specificity
of the asthma-anxiety relation remains relatively unclear. However, what is
clear is that the comorbidity between asthma and anxiety may influence inter-
pretations of and reactions to respiratory symptoms. The consequences of this
comorbidity appear to be largely observed in poorer asthma related quality of
life, worse asthma control, and increased treatment seeking. Attempts to
address these poor outcomes have appealed to the identification of common
factors/diatheses that are related to both asthma and anxiety conditions. The
tendency to fear physical symptoms due to their perceived harmful conse-
quences (i.e., panic-fear, AS) may function as the underlying vulnerability for
the development of excessive anxiety among patients with asthma.
Previous research has succeeded in identifying a link between asthma and the
experience of anxiety, both generally and with specific disorders. However,
much of the past research has focused on examining the frequency of the
comorbidity of asthma and anxiety, without providing information about the
nature or strength of the relation. Many non-psychological risk factors have
been identified for asthma, some of which (e.g., smoking habits) have also been
previously identified as risk factors for anxiety. Initial research suggests that the
relation between asthma and anxiety remains even when controlling for risk
factors, but that the relation may vary between individuals with and without
prominent risk factors (Halser et al., 2005). Future research should improve
assessment and consideration of non-psychological risk factors. Findings also
suggest that the prevalence of anxiety disorders and symptoms is higher in
individuals with asthma than in individuals with other medical conditions.
However, there is evidence to suggest that additional medical conditions with
similar presentations to anxiety symptoms (e.g., cardiac problems) may be also
be associated with anxiety. Continued use of medical control groups is needed
to determine if general factors related to illness are linked with anxiety, or if the
asthma-anxiety relation is unique.
Future research explicating the relation between asthma and anxiety may
benefit from appeal to a cognitive behavioral model. This model highlights the
importance of dysfunctional beliefs based on misinterpretations of benign
respiratory symptoms and excessive asthma-related safety-seeking. This
model offers components that are amenable to basic laboratory research and
identification of moderators (variables that alter the strength or direction of the
relation between asthma and anxiety) and mediators (mechanism that explains
the association between asthma and anxiety) of the cognitive behavioral model
inform effective treatment and prevention of excessive anxiety among patients
with asthma. Moderators in this context may consist of important individual
difference characteristics (i.e., high AS, chronic stress) that, in the presence of
272 L. S. Elwood, B. O. Olatunji
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Cardiovascular Disease and Anxiety
Kamila S. White
Introduction
A broken heart is a common metaphor used when a human being suffers an emotional
or physical loss, to the extent that it begins to cause them physical or physiological pain.
This condition is known as heartbreak.
– Wikipedia
Despite the age-old and virtually universal idea that emotions stem from the
heart, science has only recently begun to understand why a stressed, sad, or
anxious heart is unhealthy. Speculation about the role of psychological factors
in the etiology of heart problems dates back to the early 19th century (irritable
heart) (Da Costa, 1871). Systematic study of the association between heart and
mind began in the late 1950s with the pioneering work of Meyer Friedman and
Ray Rosenman, two cardiologists who coined the term Type A behavior
pattern. Since that time, increasing clinical attention and empirical research
has been focused on both biomedical and psychosocial influences on coronary
heart disease (CHD).
CHD is the leading cause of death and disability in the United States
(American Heart Association, 2006) and in much of the Western world,
especially among industrialized nations (Zevallos, Chiriboga, & Herbert,
1992). CHD claims more lives each year than the next five causes of death
combined. Psychosocial factors that may be important to the presentation and
clinical course of CHD include: Psychological stress, job strain, vital exhaus-
tion, social isolation and lack of social support, hostility and anger, depression,
and anxiety. Negative emotions exert a harmful influence on CHD outcomes
and quality of life. Relative to the sizeable, persuasive literature linking the
negative emotions of depression and hostility and CHD morbidity and
mortality, less is known about how anxiety may influence CHD. Failure to
Kamila S. White
University of Missouri-Saint Louis, Department of Psychology, One University Boulevard,
212 Stadler Hall, Saint Louis, MO 63121. Tel: 314.516.7122, Fax: 314.516.5392
whiteks@umsl.edu
M. J. Zvolensky, J. A. Smits (eds.), Anxiety in Health Behaviors and Physical Illness. 279
Ó Springer 2008
280 K. S. White
understand and address some of these more upstream psychological risk factors
including anxiety may be one explanation for why CHD morbidity and
mortality remain so high.
Chest pain is one of the most common, frightening medical complaints. And
anxiety is one of the first, most powerful psychological responses to a cardiac
event. Sudden, strong emotion is one of the two most common precipitating
events experienced prior to sudden cardiac death (SCD); exercise is the other
event (Lampert et al., 2005). Considerable epidemiological evidence implicates
the emotion of anxiety in the development of CHD and SCD. This chapter
reviews the empirical literature on the emotion of anxiety and its relation with
cardiovascular illness. First, epidemiological evidence that points to anxiety
(particularly phobic anxiety) as a risk factor for CHD morbidity and mortality
is reviewed. Several prospective studies are described, and a number of
methodological challenges to the interpretation of this research are noted.
Considering the apparent comorbidity of anxiety and depression, studies
encompassing the construct of negative affectivity which includes the
underlying structure of both anxiety and depression are also described. Next,
research on the comorbidity of anxiety disorders and CHD are highlighted.
Included is a discussion of patients with non-cardiac chest pain (NCCP),
a sizable segment of the population referred for cardiological workup and a
group worthy of psychological study. Second, pathophysiological mechanisms
or pathways by which negative emotions (i.e., anxiety, depression, and anger/
hostility) are thought to influence CHD development and progression are
discussed. Several possible mechanisms for the anxiety-CHD link include
connections with behavior, with the atherosclerotic process, and with cardiac
instability. Third, treatment studies designed to reduce negative emotion and its
impact on CHD endpoints are reviewed. Finally, the chapter ends with a
discussion of the limitations of past research and highlights of a number of
exciting future directions in understanding the anxiety-CHD association.
roughly 40 million American adults in a given year (Kessler, Chiu, Demler, &
Walters, 2005). Relative to other negative emotions (i.e., depression, anger/
hostility), far less empirical research has been paid to the impact of anxiety and
its possible cardiotoxic influences in CHD development, progression, and
outcome. Most research to date on the anxiety-CHD link has examined the
role of a construct defined as phobic anxiety. Increasing evidence from several
prospective studies has implicated phobic anxiety as a risk factor for CHD, and
considerable retrospective and correlational research has consistently found a
link between anxiety and CHD. Indeed, the relationship between anxiety
disorders and other forms of subclinical anxiety symptoms and CHD have
not been studied systematically. Correlational and prospective studies with
both healthy and ill populations are reviewed here, and some important
methodological challenges to interpretation of this research are highlighted.
Perhaps the most compelling support for a link between anxiety and CHD has
arisen from longitudinal studies conducted with initially healthy samples that
have controlled for the effects of known cardiovascular risk factors in the
prediction of subsequent disease. In the recent two decades, large-scale
community-based studies have established a significant relationship between
anxiety and subsequent death due to cardiac pathology in men (Haines,
Imeson, & Meade, 1987; Kawachi, Colditz et al., 1994; Kawachi, Sparrow,
Vokonas, & Weiss, 1994) and women (Eaker, Pinsky, & Castelli, 1992). Support
from these studies is bolstered because each study examined the anxiety-CHD
link in samples free of CHD at baseline, controlled for some known cardiovas-
cular risk factors, and predicted follow-up at time periods of up to 20 years.
First, one of the earliest prospective studies to systematically examine the
anxiety-CHD link was the Northwick Park Heart Study. The Northwick study
followed 1,457 initially healthy men across 10 years (Haines et al., 1987). After
controlling for a set of cardiovascular risk factors, elevated phobic anxiety, as
assessed by the Crown-Crisp Index (Crown & Crisp, 1966), was associated with
fatal CHD in this initially healthy sample of men. In a second study also
conducted exclusively with males, the Health Professionals Follow-up Study
(Kawachi, Colditz et al., 1994), Kawachi and colleagues followed a large sample
(N = 33,999) of health professionals free of CHD at baseline. Results revealed
that over the two-year follow-up period, the age-adjusted relative risk of fatal
CHD among men with the highest levels of phobic anxiety was three times that
compared to men in the lowest levels of anxiety. Risk for fatal CHD increased
with mounting phobic anxiety even after controlling for risks conferred by
other major cardiovascular risk factors (e.g., family history of heart disease,
smoking, blood pressure); notably, the excess risk conferred by phobic anxiety
was confined to SCD, defined as death within 1 hour of symptom onset, rather
Cardiovascular Illness 283
not all of this risk was accounted for by CHD risk factors (i.e., hypertension,
diabetes, and elevated cholesterol) associated with phobic anxiety (Albert,
Chae, Rexrode, Manson, & Kawachi, 2005). Similar to results with male-only
samples, findings suggest that phobic anxiety is prospectively associated with
increased risk of fatal CHD among females (Albert et al., 2005).
In sum, these prospective epidemiological studies using initially healthy
samples provide compelling evidence that anxiety contributes to subsequent
CHD. Both the strength and consistency of the claim that anxiety contributes to
CHD risk and outcomes beyond the traditional CHD risk factors are evident
across the studies. Moreover, in each of these studies, varied but valuable efforts
were made to control for the effects of known risk factors, and at least one or
multiple hard endpoints (i.e., documented MI, cardiac mortality) were
investigated.
1998; Martin, Cloninger, Guze, & Clayton, 1985) have not found a significant
prospective anxiety-CHD association. The extent to which publication bias has
influenced the availability of negative findings is also uncertain.
Summary
Although the experiences of anxiety and fear are universal, research examining
the incidence of clinically significant anxiety in CHD has received considerably
less attention. Accumulating data support a high rate of comorbid anxiety
disorders in patients with CHD. Although strictly prospective research
examining anxiety disorders as risk factors for CHD is absent, correlational
and retrospective research supports an anxiety disorder-CHD association.
Incidentally, the prevalence of anxiety disorders in CHD appears to at least
parallel the high rate of depressive disorders in this group (Gonzalez et al., 1996;
Hance, Carney, Freedland, & Skala, 1996).
A high proportion of patients with estabshed CHD suffer from anxiety
disorders (Fleet et al., 2000; Goldberg et al., 1990). One of the first systematic
studies of anxiety disorders in cardiology outpatients was conducted by
288 K. S. White
One diagnostic category of patients that often present to cardiology settings but
whom are less well understood is those experiencing non-cardiac chest pain
(NCCP). In contrast to patients who have a detectible cardiovascular cause for
their chest pain, the majority of patients who experience recurrent chest pain are
found to have normal coronary angiograms and show no other identifiable
medical condition (Fleet & Beitman, 1997). It has been estimated that more
than 6 million people present annually to US emergency departments with chest
pain suggestive of MI (American Heart Association, 2006), however, the
majority of these individuals do not receive an organic explanation for their
chest pain (Kroenke & Mangelsdorff, 1989). Ten to 13 billion dollars is spent
annually to care for patients who are admitted with suspected ischemic
symptoms but who do not sustain acute MI (Roberts & Kleinman, 1994).
Despite their apparently favorable cardiac prognosis, patients with NCCP
show poor outcomes that are comparable to patients who are diagnosed with
CHD (Eifert, Hodson, Tracey, Seville, & Gunawardane, 1996). In fact, when
compared to cardiac patients, surgical patients, and normal controls, indivi-
duals with NCCP (i.e., often accompanied by subjective heart-focused anxiety)
experience more physical symptoms and are as equally fearful of these physical
sensations as cardiac patients (Eifert et al., 1996). This attention to and fear of
heart-related problems (often termed heart-focused or cardiac anxiety) has been
shown to be predictive of the severity of the chest pain as well (Zvolensky,
Eifert, Feldner, & Leen Feldner, 2003). Heart-focused anxiety, as assessed via
the Cardiac Anxiety Questionnaire (Eifert, Thompson et al., 2000), is thought
to be conceptually distinct from trait anxiety, anxiety sensitivity, and other
forms of health anxiety (Eifert, Zvolensky, & Lejuez, 2000) and shares only
moderate zero-order correlations with the ASI. For example, trait anxiety taps
into anxiety-based negative affect generally, heart-focused anxiety relates to
specific fears of cardiac-related events, physical sensations, and functioning.
Research has demonstrated the prevalence and costs associated with NCCP,
however, factors associated with its onset, severity, and persistence are not
290 K. S. White
well-understood (Eifert, Zvolensky et al., 2000; Fleet et al., 1996; White &
Raffa, 2004). Theoretical conceptualizations of NCCP generally assert that
the etiology of the pain is multi-causal and interactive (Eifert, Zvolensky
et al., 2000; Mayou, 1998; White & Raffa, 2004). It has been hypothesized
that the functional syndrome of NCCP may partially result from psychological
vulnerabilities (i.e., greater awareness of internal bodily sensations, somatic
hypervigilance) that focus on circumstances associated with threat or danger
(e.g., heart disease, death) (White & Raffa, 2004).
Although most cases of NCCP are thought to be benign, unrecognized
CAD and microvascular angina (i.e., cardiac syndrome X, a condition char-
acterized by apparent vasospasm of the arteries that nourish the heart but that
are not visible on cardiac catheterization) may explain an unknown portion of
NCCP cases in the general population (Allan & Scheidt, 1999). Recent
reviews have suggested that the clinical prognosis of patients with NCCP
may not be as benign as is commonly thought (Bugiardini & Bairey Merz,
2005). Moreover, identification of heart disease risk factors in this patient
group may help to determine optimal methods for identification and preven-
tion of clinical events through risk factor management (White, Malone, &
Gervino, 2006). In light of the extensive research that has documented the
heritable (e.g., sex, age, race, family history) and modifiable risk factors
(e.g., tobacco use, obesity, hypertension, physical inactivity, diabetes mellitus)
associated with an increased risk for heart disease (American Heart
Association, 2006), a systematic examination of cardiac risk in patients with
NCCP may have important implications for identification, risk stratification,
or intervention. One study conducted by our research group found that
patients with NCCP endorsed on average 4 CHD risk factors (SD = 1.6)
(White, Malone et al., 2006). The most common risk factors endorsed
included a family history of CHD (46%), physical inactivity (42%), and
obesity (34%). This elevated risk was associated with elevated anxiety (both
in general and heart-focused anxiety), and hierarchical regressions showed
that risk factor incidence, general anxiety, and heart-focused anxiety all
predicted significant variance in chest pain interference (45%; large effect
size f 2 = .81). These findings indicated that not only are CHD risk factors
present and appear to exacerbate chest pain in patients with NCCP, but that
the subjective anxiety may be well-founded and perhaps prematurely related
to later CHD. Ongoing longitudinal research by our group and others may
help to disentangle this important question.
Considerable research has investigated the relationship between psychiatric
illness and NCCP. Bass and colleagues conducted a series of studies and
concluded that two-thirds of patients with normal or near-normal coronary
arteries have predominantly psychiatric, as opposed to cardiac disorders; anxi-
ety neurosis was the most common diagnosis in this patient group (Bass &
Wade, 1984; Bass, Wade, Hand, & Jackson, 1983). Indeed, research by our
group has explored the prevalence of anxiety and mood disorders in patients
with NCCP and found that almost half of patients (47%) with NCCP also were
Cardiovascular Illness 291
persuasive and undeniably indicate that anxiety plays a part in CHD; however,
some qualifications need to be considered when interpreting this research.
A number of factors influence how robust these findings are including: 1) factors
associated with study outcome (i.e., type of research design, method of assess-
ment), 2) factors associated with construct definition (i.e., fear, anxiety, the
panic spectrum, anxious arousal, worry) and construct validity (i.e., type of
anxiety or anxiety disorder assessed, construct overlap among negative
emotions), and 3) factors associated with assessment (i.e., diagnostic structured
clinical interviews, self-report symptom rating scales). Relevance to current
conceptualizations of anxiety and their psychometric acceptance, construct
definition overlap (i.e., the co-occurrence, intersection of anxiety and other
negative emotions), and the directionality of anxiety and CHD may be vital.
Conceptualizations of Anxiety
Directionality
First, one possible mechanism that may mediate the anxiety-CHD link is via
health-compromising behaviors. Specifically, it may be that anxiety gives rise to
health-compromising behaviors (e.g., physical inactivity, smoking, caloric
intake, lack of sleep, poor diet, alcohol consumption, drug use, and lack of
compliance with medications). Perhaps initially providing some temporary
relief, these negative health behaviors may grow to become habitual and
mediate the anxiety-CHD relationship. Although a sizable research has
examined and shown positive correlational associations between anxiety and
health-compromising behaviors (Breslau, Kilbey, & Andreski, 1991; Fisher,
Schneider, Pegler, & Napolitano, 1991; Hayward, 1995), truly prospective
296 K. S. White
Another possible mechanism by which anxiety has its effect on CHD is through
the progression of atherosclerosis. Using a broadly-defined condition of anxiety
neurosis, Sims and Prior found a higher death rate from atherosclerotic disease
among those with anxiety neurosis (Sims & Prior, 1982). Several factors are
thought to contribute to atherosclerosis including elevated cholesterol and
triglyceride in the blood (hypercholesterolemia), high blood pressure (hyperten-
sion), and cigarette smoking. Elevated cholesterol levels have been documented
among patients with anxiety disorders (Huang, Wu, Chiang, & Chen, 2003;
Peter, Goebel, Muller, & Hand, 1999; Peter et al., 2002); indeed, Peter and
colleagues found that patients with anxiety disorders have elevated or high
cholesterol levels almost three times as often as control subjects, even after
controlling for anxiety-specific avoidance of physical exercise and special
dietary habits (Peter et al., 1999). With regard to hypertension, one study that
specifically examined predictors of blood pressure changes in middle-aged
women found that women experiencing anxiety showed greater increases of
systolic blood pressure over a 3-year follow-up period (Markowitz, Matthews,
Wing, Kuller, & Meilahn, 1991). Several more studies of anxiety (as assessed by
Cardiovascular Illness 297
Anxiety is one of several psychosocial stressors that may bring about chronic
autonomic imbalance with sympathetic predominance. Altered cardiac auto-
nomic tone is a credible explanation for why anxiety may be associated with
increased CHD risk. This possible mechanism could involve amplified sympa-
thetic stimulation (that is associated with the occurrence of arrhythmias and
SCD) or impaired vagal control (that is also associated with CHD mortality)
(Farrell et al., 1987; Lown, Verrier, & Corbalan, 1973; Rich et al., 1988).
Evidence supporting these hypotheses includes findings that individuals with
anxiety disorders have a reduced HRV (Kawachi et al., 1995), consequently,
indicating an alteration in autonomic tone.
298 K. S. White
1995; Krittayaphong et al., 1997; Stein et al., 2000) and decreased HRV is
generally accepted as one mechanism linking depression to increased cardiac
mortality in post-MI patients (Carney et al., 2001). Failure to consider overlap
and co-occurrence among the negative emotions may have influenced some of
the conclusions that can be drawn from the HRV research to date.
Susceptibility to Ventricular Arrhythmia. A related possible mechanism that
may explain the harmful effects of anxiety on CHD and CHD-related mortality
is through a susceptibility to ventricular arrhythmias. Ventricular arrhythmias
occur when a group of heart cells in the lower two chambers of the heart (i.e., the
ventricles) trigger contractions out of sync with the normal rhythm established
by the sinus node; in short, arrhythmias are abnormal rhythms of the heart that
cause the heart to pump blood less effectively. Blood is pumped through the
heart in a controlled sequence of muscular contractions; these contractions are
controlled by bundles of cells which control the electrical activity of the heart.
When this sequence is disturbed, heart arrhythmias occur. Arrhythmias are
abnormal rhythms of the heart, and many types of heart disease are associated
with ventricular arrhythmias. Some researchers have posited that anxiety may
be related to an increased risk of CHD and CHD-related mortality through the
altered electrical stability of the heart including ventricular arrhythmias.
Evidence of an association between psychological factors and ventricular
arrhythmias is mixed (Follick et al., 1990; Follick et al., 1988; Freeman,
Cohen-Cole, Fleece, Waldo, & Folks, 1984; Orth-Gomer, Edwards, Erhardt,
Sjogren, & Theorell, 1980). Support for anxiety in particular as an arrhythmic
mechanism is demonstrated by the known relationship between anxiety and
increased sympathetic and parasympathetic cardiac control (Kawachi et al.,
1995; Thayer, Friedman, & Borkovec, 1996; Watkins, Blumenthal, & Carney,
2002) and by findings that phobic anxiety increases the risk of SCD (Kawachi,
Colditz et al., 1994). One particularly revealing study lends support to the
premise that the increased risk in SCD observed in individuals with phobic
anxiety may be due to ventricular arrhythmias. Watkins and colleagues directly
examined the relationship between phobic anxiety and ventricular arrhythmias
(Watkins et al., 2006) and found that phobic anxiety (and depression) predicted
subsequent ventricular arrhythmias in 940 patients with CAD during a 3-year
follow-up. The phobic anxiety-arrhythmia association was independent of
comorbid depression; however, the composite (of anxiety and depression)
resulted in a larger effect size than either construct independently.
The most common type of ventricular arrhythmia (in both healthy and
diseased individuals) is the ventricular premature beat (VPB). VPBs increase
with psychological stress (Taggart, Carruthers, & Somerville, 1973; Taggart,
Gibbons, & Somerville, 1969), and VPBs have also been identified as risk factors
for electrical instability of the heart and SCD (Lown & Graboys, 1977; Lown &
Ruberman, 1970). Kubzansky and colleagues summarized much of this research
and theorized that anxiety (characterized as both an intense and acute
psychological state) may be one psychological state which predisposes
individuals to VPBs (Kubzansky et al., 1998). Indeed, one study found that
300 K. S. White
Future Directions
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HIV and Anxiety
Introduction
Conall O’Cleirigh
Massachusetts General Hospital, Psychiatry Department, Department of Psychiatry,
Behavioral Medicine Massachusetts General Hospital, 1 Bowdoin Square BS-07B, Boston,
MA 0211
cocleirigh@partners.org
This research was supported in part by the National Institute of Health, National Institute on
Drug Abuse (NIDA) grant R01-DA018603, PI. Steven Safren, Ph. D.
M. J. Zvolensky, J. A. Smits (eds.), Anxiety in Health Behaviors and Physical Illness. 317
Ó Springer 2008
318 C. O’Cleirigh et al.
An Overview of HIV
proliferative responses are progressively impaired and natural killer cell cyto-
toxicity (NKCC) decreases (Klimas, Baron, & Fletcher, 1991). The average
time between infection and progression to AIDS can vary as a function of
antiretroviral medication regimen (Fischl, 1995) or route of infection and a
range of psychosocial characteristics (see Leserman, 2003).
The clinical care of HIV infected individuals has improved dramatically over
the last decade. In fact, the disease course has changed from a virtual death
sentence via progressive deterioration of the immune system to a manageable
chronic condition. Treatment began with the introduction of the first antiretro-
viral agent, zidovudine (AZT) in 1987. With the advent of combination therapies
that include newer reverse transcriptase inhibitors and HIV-specific protease
inhibitors (PI), referred to as highly active antiretroviral therapy (HAART),
significant further improvement has been made in delaying AIDS and mortality
(Lima, Hogg, Harrigan, et al., 2007). The success of HAART has greatly increased
HIV survival with recent estimates greater than 24 years post HIV diagnosis
(Schackman, Gebo, Walensky, et al., 2006). As life expectancy increases so also
does the cost of HIV-related medical care. The life time cost of HIV medical care
has been estimated at between $385,200 and $618,900 depending primarily of the
discounts available for antiretroviral medication (Schackman, Gebo, Walensky,
et al., 2006) constituting a significant public health expense and identifying pre-
vention of future cases of HIV infection as a continued public health concern.
In the U.S., estimates of lifetime anxiety disorders among HIVþ individuals range
from 3.6% to 19% (e.g., Johnson, Williams, Rabkin, Goetz, & Remien, 1995;
Sewell, Goggin, Rabkin, Ferrando, McElhiney, & Evans, 2000). These estimates
appear to be somewhat lower than in the general population where prevalence of
lifetime anxiety disorders is estimated to be approximately 29% (Kessler, Chiu,
Demler, & Walters, 2005). Estimated rates of current anxiety disorders among
HIVþ individuals range widely from less than 1% to 43% (e.g., Chandra, Ravi,
Desai, & Subbakrishna, 1998; Johnson et al., 1995; Perretta et al., 1996;Perkins
et al., 1994; Savard, Laberge, Gauthier, Ivers & Bergeron, 1998; Sewell et al., 2000).
This wide variability in prevalence estimates is likely due to several factors, one
of which is the variation in measures used to assess anxiety. Higher prevalence
rates (36–43%)have been found in studies using clinical cutoffs on screening
measures such as the Hospital Anxiety and Depression Scale (HADS; Zigmond &
Snaith, 1983) as opposed to a diagnosis based on the Structured Clinical
Interview for the Diagnostic and Statistical Manual (DSM) (under 20%)
(SCID; Spitzer Williams, Gibbon et al., 1995). Additionally, the variability in
prevalence estimates likely results from the small sample sizes that have been used
to assess the prevalence of any anxiety disorder. Among the studies noted above,
the largest sample size was 442 (Brown et al., 1992) with the remainder having
sample sizes below 200 (Chandra et al., 1998; Perretta et al., 1996).
320 C. O’Cleirigh et al.
anxiety disorders between HIVþ and HIV-negative MSM (Perkins, et al., 1994;
Rosenberger et al., 1993; Sewell et al., 2000). For example, a two-year long-
itudinal study of HIVþ and HIV-negative MSM who were non-intravenous
drug users found that the two groups did not differ in their rates of either
lifetime or current anxiety disorders (Sewell et al., 2000).
HIVþ Women and Anxiety Disorders. PTSD appears to be over-represented
in HIV-infected women, likely because of increased exposure to traumatic
stressors such as physical violence and sexual assault (Kimerling et al., 1999).
In a study of 67 inner-city African-American women beyond the initial stages of
HIV infection, it was found that over a third of the sample met DSM-IV criteria
for PTSD. More elevated rates have been reported in higher-risk samples. For
instance, in a sample of 81 HIVþ incarcerated women, Lewis (2005) found that
nearly three quarters of the sample met criteria for lifetime PTSD. Not only do
these rates appear higher than among community samples of women (10.4%;
Kessler, Sonnega, Bromet, Hughes, & Nelson, 1995) but are also higher
than among incarcerated females in general (30–42%; Jordan, Schlenger,
Fairbank, & Caddell, 1996; Teplin, Abram, & McClelland, 1996). Although
high-risk HIVþ women appear to be at greater risk for anxiety disorders,
particularly PTSD, this risk may not apply to HIVþ women in general. A
study comparing HIVþ and –negative women without current substance
abuse found that the two groups did not differ in their rates of anxiety disorders,
although the HIVþ women were more likely to have depression (Morrison
et al., 2002).
Conclusions. Based on the current literature, it is difficult to determine
whether anxiety disorders in general are more prevalent among HIVþ indivi-
duals compared with normative samples. This is due to the fact that no known
large-scale studies have examined the prevalence of overall rates of anxiety
disorders in people living with HIV. Smaller studies have yielded inconsistent
results likely due to subgroup and measurement variation. However, there is
evidence that particular anxiety disorders, (i.e., PTSD and GAD) may be more
prevalent among those with HIV. Higher prevalence of PTSD may be indicative
of traumatic responses to HIV diagnoses and co-occurrence of other traumatic
stressors. Additionally, there is evidence that prevalence of anxiety disorders
may be elevated among groups with higher HIV prevalence rates than the
general population, particularly MSM and high-risk women.
Few studies specifically examine the role of anxiety in risk for contraction or
transmission of HIV. Most research examining the role of psychological dis-
tress in HIV risk investigates other phenomena such as depression or substance
use (e.g., Johnson, Cunningham-Williams, & Cottler, 2003; Stall et al., 2003).
Further, the research is limited by methodological problems regarding the
HIV and Anxiety 323
are limited by the wide range of samples and method for measuring anxiety.
Research studies also vary in choice of dependent variables, such as unprotected
intercourse (e.g., Hart & Heimberg, 2005) and behaviors associated with unpro-
tected intercourse such as number of sexual partners (Rosario, Scrimshaw, &
Hunter, 2006). Measures of emotional stress that incorporate anxiety items and
screening measures of anxiety have demonstrated conflicting associations with
HIV risk behavior. Future research examining when anxiety exerts risky versus
protective effects, and for whom it exerts these effects, is therefore warranted.
Lastly, it would be beneficial to examine the effects of more specific types of
anxiety, as some appear to be associated with less risk (e.g., trait anxiety;
Bancroft et al., 2003) and some with more risk (e.g., social performance anxiety;
Hart & Heimberg, 2005)
The results of these studies provide some evidence that anxiety, generally
assessed, is associated in with sub-optimal medication adherence in diverse
samples of patients with HIV. The results of these studies suggest also that
symptoms of social phobia, panic, and GAD are associated with medication
non-adherence. The largest effects were observed for GAD and panic symp-
toms. PTSD symptoms of avoidance and intrusion specifically related to HIV
were significantly associated with multiple measures of adherence but measures
based on diagnostic criteria of PTSD produced only weak associations. All but
one of the studies reviewed here used cross-sectional designs creating difficulties
specifying the direction of the significant effects. It is possible that the severity
of anxious symptoms interferes with adherence but it is also plausible that
adherence violations (typically assessed with in the past week) contribute to
anxious affect and other symptoms of anxiety.
Anxiety and Substance Use in HIV. Substance use in patients with HIV
confers multiple disadvantages. Substance use has been associated with both
accelerated disease progression and with poorer adherence to antiretroviral
medication (e.g., Arnsten et al., 2001; Lucas et al., 2002), with delayed response
to ART (Palepu, Tyndall, Yip, et al., 2003) and with failure to achieve HIV viral
suppression for those initiating HAART (Lucas, Cheever, Chaisson, et al.,
2001). Injection drug use in HIV has also been associated with poorer immune
(Wood, Montaner, Yip, et al., 2004) and clinical disease (Moore, Keruly, &
Chiasson, 2004) outcomes.
Although the co-occurrence of substance use and anxiety disorders has been
widely studied in the general population (e.g., Kessler et al., 2005) there is a
paucity of research examining this co-morbidity in people with HIV (Chander,
Himehoch & Moore, 2006). A recent study estimates the 1 year prevalence rates
of comorbid substance use and anxiety/mood disorder in HIV is greater than
8% (Pence, Miller, Whetten, Eron, & Gaynes 2006). Most dramatically, alcohol
and substance use disorders were 2.5 and 7.5 time more prevalent than in the
general population. These findings are broadly consistent with earlier estimates
(Bing et al., 2001) although rates of GAD (15.8%) and panic (10.5%) were
higher and drug dependence and heavy alcohol use predicted the presence of
mood or anxiety disorders.
In a large sample (n = 1168) of HIVþ MSM, Ibnanez, Purcell, Stall, Parsons
and Gomez (2005) reported higher rates of anxiety, childhood sexual abuse, and
hostility among injection drug users (IDUs) compared to non-IDUs and higher
rates of sexual transmission risk behavior than those reporting no drug use.
Among 355 African-American crack abusing women, general measures of
anxiety and PTSD symptom severity were significantly associated with multiple
sexual partners (Roberts, Wechsberg, Zule, & Burroughs, 2003). More recently,
among a group of 198 HAART naı̈ve HIVþ patients, the probability of mood/
anxiety and substance use disorders predicted a slower rate of viral suppression
and a faster rate of overall virologic failure after suppression. Alcohol and
substance abuse/dependence also predicted faster overall virologic failure
(Pence, Miller, Gaynes, & Eron, 2007).
HIV and Anxiety 329
and with increased utilization of health care services in the previous 9 months.
In fact, PTSD symptom severity, trauma history and stressful life events
accounted for 27% of the variance in health related functioning controlling
for CD4 cell count and HIV-viral load. Smith et al. (2002) reported that PTSD
was significantly associated with greater pain intensity and impairment. Also
within a cross-sectional design, Holmes et al. (1997) reported that the presence
of Axis 1 disorder was significantly associated with lower HRQOL domain
scores for health perceptions and mental health. General measures of anxiety
have also been related to physical functioning in HIV controlling for HIV
disease severity among men (McDaniel, Fowlie, Summerivlle, Farber, and
Cohen-Cole, 1995), women (Tostes, Chalub, & Botega, 2004), and intravenous
drug users (Lipsitz, et al., 1994).
The results of the research reviewed above provide good evidence for a
relationship between symptoms of anxiety and HRQOL and other measures
of physical functioning. Measures of anxiety based upon diagnostic criteria
appear to provide the most consistent evidence for a relationship with
health-related functioning and the strongest evidence (replication in a large
representative sample) appears to exist for the relationship between PTSD
and health-related physical functioning. The relative paucity of longitudinal
research in this area makes it difficult to specify the directionality of these
relationships. It is possible that HIV disease related decrements in physical
functioning might lead to the onset of anxiety symptoms and disorders or
exacerbate existing symptoms as the results reported by Orlando et al. (2005)
may suggest. It is also plausible that the presence of anxiety disorders may either
contribute to decrements in physical functioning (as Leserman et al., 2005
suggest) or at least incline people living with HIV to lower their estimates of
their own physical health. In any event there is sufficient evidence reported here
to conclude that diagnostic assessment of anxiety may well help inform patients’
HIV symptom reports and reports of physical functioning. The application of
randomized trials of cognitive-behavioral therapy to treat anxiety disorders in
people with HIV would allow for an examination of treatment related changes
in physical functioning and HIV-symptom burden. The results of these
studies would help characterize the relationship between anxiety and HRQOL
more fully.
Behaviors
Medication Adherence
Substance Use
Transmission Risk
Behavior (STIs,
superinfection)
Health-Related Quality
of Life (HQOL)
Fig. 1 A Depiction of the direct and mediated relationships between anxiety and health and
disease outcomes in HIV
Note: The above model describes some of the pathways by which anxiety and its disorders
may impact the disease process and health outcomes in HIV. This model is not intended to
describe all possible relationships but to suggest potential mechanisms for which there is some
initial evidence in the literature reviewed. In the model, anxiety has two main pathways by
which it exerts its impact on HIV. In the behavioral pathway the presence of anxiety disorders
negatively influence behaviors (adherence, substance use, transmission risk behavior) which
in turn can negatively impact immune control of the HIV virus and lead to poor survival and
accelerated clinical progression of the disease. In the second pathway the presence of anxiety
disorders directly impacts underlying physiology through higher levels of stress hormones
which down regulate the immune system leading to poorer immune control of HIV and less
favorable disease course.
HIV and Anxiety 333
The most conspicuous gap in the research on HIV and anxiety is the
absence of psychosocial or psychopharmacological clinical intervention
research designed to treat anxiety disorders in people with HIV. There is
some evidence of the efficacy of broad based coping and stress management
group interventions that have been associated with reductions in intrusion
and avoidance symptoms of anxiety in HIVþ patients with CSA histories
(Sikkema Hansen, Kochman et al., 2007), and with reductions in anxious
mood in MSM (Antoni, et al., 2000; Chesney, Chambers, Taylor, Johnson, &
Folkman, 2003). Most critically, there is an unmet need for efficacious and
effective interventions to treat the full range of anxiety disorders in people
with HIV. The success of adapted CBT interventions in the treatment of
depression in HIV (for review see Olatunji, Mimiaga, O’Cleirigh, & Safren
2006) augurs well for the generalizability of CBT procedures to treat anxiety
in HIV. It seems from this review that the development of efficacious treat-
ments for PTSD is a priority. In particular, the development of psychosocial
interventions, or the adaptation of existing technologies, with specific appli-
cation in HIV for women and MSM with CSA histories is warranted. PTSD
and related symptoms are over represented in these groups, and are associated
with increased risk for transmission risk behavior, accelerated disease pro-
gression, increased symptom burden, poorer medication adherence, and cor-
tisol dysregulation.
There is some evidence that psychosocial intervention related changes in
anxiety have been associated with changes in norepinephrine in patients with
HIV (Antoni et al., 2000) and with reductions in HPA dysregulation in
patients with GAD (Tiller, Biddle, Maguire, & Davies 1988). The incorpora-
tion of biological measures of disease progression (CD4þ cell and HIV viral
load) and stress hormones as secondary outcomes into randomized clinical
trials to treat anxiety disorders could help to specify the physiological
pathways by which anxiety exerts its influence on disease and health outcomes
in HIV.
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Physical Illness and Treatment of Anxiety
Disorders: A Review
Norman B. Schmidt, Meghan E. Keough, Lora Rose Hunter, and Ann P. Funk
Norman B. Schmidt
Department of Psychology, Florida State University, Tallahassee, FL 32306-1270, Tel: (850)
644-1707, Fax: (850) 644-7739
schmidt@psy.fsu.edu
M. J. Zvolensky, J. A. Smits (eds.), Anxiety in Health Behaviors and Physical Illness. 341
Ó Springer 2008
Table 1 Summary of cited studies
342
Primary
Primary Primary Diagnostic Tools Primary Diagnostic
Diagnosis Medical Design Sample used to Assess Tools used to Assess
Study Evaluated Comorbidity Treatment (groups) Size Psychopathology Physical Illness
CCAP Panic Medical CBT plus Randomized 232 -CIDI -RxRisk-V score
Roy-Byrne, Disorder Illness Medication Control
Stein et al., burden Management
2005 vs. Usual
Care
CCAP Panic Medical CBT plus Randomized 232 -CIDI -WHO Disability Scale
Roy-Byrne, Disroder Disability Medication Control -Fear
Craske Management Questionnaire
et al., 2005 vs. Usual -Anxiety
Care Sensitivity
Index
CCAP Panic Medical CBT plus Combined 111 -CIDI -WHO Disability Scale
Craske Disorder Disability Medication Analysis (sub- -Fear
et al., 2005 vs. from sample Questionnaire
Medication Control and of -Anxiety
Treatment study Sensitivity
Groups total) Index
Schmidt & Panic Health CBT-G No Control 71 -SCID-NP -General Health
Telch, 1997 Disorder Perceptions Survey
Chronic
Health
Condition
Schmidt et al., Panic Health CBT-G Randomized 46 -SCID-NP -General Health
2003 Disorder Perceptions Waitlist Survey
Control -Physical Health
Rating Form
Klein et al., Panic Health CBT (delivered Randomized 55 -ADIS-IV -Self-reported number
N. B. Schmidt et al.
PTSD Scale
Shemesh PTSD Myocardial CBT plus Non- 14 -Impact Event -Physician Diagnosis
et al., 2006 Infarction Education vs. Randomized Scale confirmed by study
Education -PTSD Cardiologist
Diagnostic
Scale
-SCID-P
Kennedy Anxiety Spinal Cord Cognitive Non- 85 -STAI -Physician Diagnosis
et al., 2003 Depression Injury Effectiveness Randomized -BDI
Training Matched
343
Historic
Control
Table 1 (continued)
Primary
344
l Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime Version (K-SADS-PL)
Physical Illness and Treatment of Anxiety Disorders: A Review
section is organized by the strength of the research design. In the second section
we focus on comorbidity in the context of pharmacological treatments. This
section is organized according to the issues explored in the limited relevant
literature. For each study, our goal is to give a sense of the nature of both the
anxiety condition and the physical illness including how adequately each was
assessed. In addition, we clarify the nature of the intervention that was used in the
trial. Finally, we give a sense of the level of effect in terms of the outcomes that
were assessed (e.g., changes on anxiety symptoms, changes in physical illness). As
the reader will note, there are relatively few studies that have utilized strong
methodologies (e.g., large samples randomized to active treatment and control
conditions for psychological treatments, double-blind placebo controlled trials
for pharmacological interventions). As a result, we felt that we should include
weaker designs that could be informative since the state of knowledge in this area
is so nascent.
The Collaborative Care for Anxiety and Panic study (CCAP) (Craske et al.,
2005; Roy-Byrne, Craske et al., 2005; Roy-Byrne, Stein et al., 2005) sought to
investigate the effectiveness of CBT and medication combined versus usual care
in the treatment of patients with panic disorder in primary care settings. This was
a multi-site study involving six clinics from three different cities. Participants
were recruited through brief screenings in the clinic waiting room or referrals
from medical providers. Eligibility was determined over the telephone using the
Composite International Diagnostic Interview (CIDI; World Health Organiza-
tion, 1997). Patients met DSM-IV criteria for panic disorder and were randomly
assigned to care as usual or to the combined CBT and medication treatment
condition. In the treatment condition, participants were assigned to a health care
specialist who delivered six in-person sessions of CBT along with six brief
booster sessions via the telephone. The CBT techniques employed were relaxa-
tion, exposure to feared situations, homework, provision of information about
panic attacks, identification of cognitive errors, challenge of cognitive errors and
modification of behavioral response to feared bodily sensations. The health care
specialist also coordinated the medication management for each participant.
Published reports from CCAP study have indicated that the combination of
CBT plus medication outperformed usual care in terms of number of remitters
and responders as well as greater improvement in functional status and health
related quality of life (Roy-Byrne, Craske et al., 2005). Further comparison of
individuals who received CBT plus medication versus medication alone, regard-
less of randomized condition, also revealed an advantage to the combined
treatment (Craske et al., 2005). Of particular interest to the current review,
Physical Illness and Treatment of Anxiety Disorders: A Review 349
a medical illness burden score was calculated based on the number and type of
prescription medications participants reported taking along with their self-
reports of chronic disease (Roy-Byrne, Stein et al., 2005). Based on this calcula-
tion, the participants were split into those below and above the median score for
burden of medical illness. Individuals above the median reported more anxiety
symptomatology, psychiatric comorbidity and disability than their counter-
parts. However, CBT and pharmacotherapy produced comparable response
rates in both groups. The authors cautioned that although both groups
responded at a similar rate, the medically burdened group continued to exhibit
more symptomatology at follow-up due to their higher baseline symptoms.
Thus, the medically burdened group might require a longer intervention to
reach the same level of symptomatology as the less medically burdened group.
In another report relevant to health ratings, number of medical visits, and
anxiety symptoms, Klein, Richards, and Austin (2006) assessed the effectiveness
of different CBT delivery methods for individuals with panic disorder (Klein
et al., 2006). Participants’ diagnoses were established via the clinician adminis-
tered anxiety disorders interview schedule (ADIS-IV; Brown, DiNardo, &
Barlow, 1994). Participants were randomly assigned to one of three conditions;
internet based CBT, CBT manual, or information only control group. The
internet condition was composed of one introductory module, four learning
modules, and a relapse prevention module. Techniques included controlled
breathing instruction, cognitive restructuring, and interoceptive and situational
exposure. Each participant was instructed to complete one module a week for six
weeks and received support and feedback from a therapist via e-mail. Individuals
in the manual condition were mailed a copy of Mastery of Your Anxiety and
Panic: MAP-3 (Barlow & Craske, 2000). This manual included the same CBT
information as the internet modules but differed in presentation and organiza-
tion. In addition, the manual group received support and guidance from a
counselor who contacted them weekly via the telephone. The information only
group was given psychoeducation regarding the nature, causes, effects and
treatment options for panic disorder. They were also contacted weekly via the
telephone by a study therapist who provided minimal support, checked their
symptoms, and encouraged them to reread the informational material. A num-
ber of standardized anxiety measures were conducted at each assessment point
(pretreatment, post-treatment and follow-up). Participants’ health ratings were
established during each assessment point by asking patients how many times
they had seen their general practitioner in the past month and also asking them
to rate their physical health on a scale from 0 (extremely poor) to 10 (extremely
good). The two CBT groups showed greater improvement than the control
group on all dependent variables including panic disorder symptomatology,
panic related cognitions, negative affect, number of general practitioner visits,
and physical health ratings. The gains on all of these variables were maintained
or further improved at the 3-month follow-up screening. The internet group
outperformed the manual group on health ratings at follow-up and general
350 N. B. Schmidt et al.
practitioner visits at both post and follow-up. Analyses were not conducted to
determine whether health status moderated treatment outcome.
Kissane et al., (2003) investigated whether cognitive-existential group psy-
chotherapy (CEGT) among women with breast cancer improved their mood
and mental attitude toward cancer. Previous investigations have reported that
anxiety and depression are quite common among women recently diagnosed
with breast cancer (Burgess et al., 2005). Participants were recruited from nine
metropolitan hospital oncology departments and all had been diagnosed with
early stage breast cancer confirmed through histology reports. The 303 partici-
pants were randomly assigned to receive relaxation classes or CEGT plus
relaxation. During three relaxation sessions, participants were taught progres-
sive muscle relaxation with guided imagery. CEGT was manualized and had six
goals: promoting a supportive environment, facilitating grief over losses,
reframing negative thoughts, enhancing problem solving and coping, fostering
hope, and examining priorities for the future. The CEGT was conducted in
small groups by two therapists over 20 weekly 90-minute sessions. The thera-
pists were trained in this therapy through a series of workshops and came from
the professional fields of psychology, psychiatry, social work, occupational
therapy, and oncology nursing. Participants were assessed at baseline and
follow-up using the Hospital Anxiety Depression Scale (Zigmond & Snaith,
1983) and the Affects Balance Scale (Derogatis, 1992), a self-report measure
designed to assess a range of positive and negative affective states. CEGT group
therapy exhibited a trend toward reducing anxiety (d = 0.217) yet failed to
significantly impact negative mood (d = 0.254). Psychologists were more
successful at decreasing both negative mood and anxiety, with a moderate effect
size of d = 0.515. Analyses were not conducted to determine whether pretreat-
ment anxiety moderated treatment effects.
Bryant, Moulds, Guthrie, and Nixon (2003) evaluated whether PTSD could
be prevented among mild traumatic brain injury patients experiencing acute
stress disorder. All patients were injured through a motor vehicle accident or a
nonsexual assault within the two weeks prior to study enrollment. Mild brain
injury was operationalized as posttraumatic anterograde amnesia of less than
24 hours and a Glasgow Coma Scale score between 13 and 15. Participants also
met criteria for Acute Stress Disorder as assessed by the Acute Stress Disorder
Interview (Bryant, Harvey, Dang, & Sackville, 1998). Patients were randomly
assigned to receive CBT or supportive therapy. Both therapies were adminis-
tered individually in five weekly 90-minute sessions. CBT techniques included:
education about traumatic reactions, progressive muscle relaxation training,
imaginal exposure to traumatic memories, cognitive restructuring, and graded
in vivo exposures to avoided situations. Supportive therapy provided education
about trauma and problem-solving skills. At post-treatment and 6-month
follow-up, participants were assessed for PTSD using the clinician administered
PTSD Scale (Blake et al., 1995). Individuals in the CBT group exhibited sub-
stantially lower rates of PTSD development at both post-treatment (d = 1.16)
and at 6-month follow-up (d =0.87).
Physical Illness and Treatment of Anxiety Disorders: A Review 351
Shemesh et al. (2006) reported on individuals who met PTSD threshold on the
Impact Event Scale (IES; Horowitz, Wilner, & Alvarez, 1979) following a
myocardial infarction (MI). Original MI diagnoses based on symptoms, electro-
cardiogram changes and enzymes changes were confirmed by a study cardiolo-
gist. All participants received an informational session regarding the importance
of following medical advice after an MI. Additionally, a self-selected subset also
participated in four to five sessions of CBT focused on their traumatic symptoms.
All self-selected participants also met criteria for PTSD on the Structured Clinical
Interview for DSM-IV (First, Spitzer, Gibbon, & Williams, 2001). The abbre-
viated CBT administered in this study was manualized, provided by a psychiatrist
and focused on relaxation, exposure and cognitive reprocessing. The psycholo-
gical measures were the IES, the Posttraumatic Stress Disorder Diagnostic Scale
(PDS; Foa, Cashman, Jaycox, & Perry, 1997), the Beck Depression Inventory
(BDI; Beck, Ward, Mendelson, Mock, & Erbough, 1967), and the SCID-IV.
Participants in the information only group showed significant improvement only
in adherence to aspirin treatment. Those in the CBT group exhibited significant
improvement in aspirin adherence, several medical risk factors (reduced high
blood pressure, smoking and cholesterol) and anxiety symptoms (reduced PDS
scores by 57% and IES scores by 22%).
Kennedy, Duff, Evans, and Beedie (2003) evaluated inpatients from a
rehabilitation unit who had suffered a recent traumatic spinal cord injury
(SCI). This group was of particular interest because of their previously reported
increased risk for developing psychopathology, particularly anxiety and depres-
sion. Anxiety and depression were assessed using the state portion of the State
Trait Anxiety Inventory (Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, 1983)
and the BDI (Beck et al., 1967). Patients were invited to participate in coping
effectiveness training, which was based on Lazarus and Folkman’s cognitive
theory of stress and coping (1984) as well as CBT techniques. Sessions were
devoted to normalizing stress reactions; assessing typical appraisal and coping
techniques; developing appraisal and coping skills; examining the connections
and distinctions between thoughts, feelings and behaviors; increasing pleasant
activities and relaxation; and challenging negative thoughts. The intervention
consisted of seven 60- to 75-minute small group sessions. For analyses, partici-
pants were matched with an archival sample of SCI patients. When compared to
the control group, the intervention group showed a significant reduction in
anxiety and depression symptoms but no improvement in coping strategies as
assessed by the COPE (Carver, Scheier, & Weintraub, 1989).
Another study among spinal cord injury patients was designed to immunize
participants against depression and anxiety (Craig, Hancock, Chang, &
Dickson, 1998). Previous work indicates that approximately 30% of individuals
with an SCI exhibit elevated levels of depression and anxiety up to two years
following the injury (Craig, Hancock, & Dickson, 1994). Participants were
Physical Illness and Treatment of Anxiety Disorders: A Review 353
No Comparison Group
Schmidt and Telch (1997) directly examined whether health status and health
perception affected participants’ response to CBT for panic disorder. Patients
(N = 71) diagnosed with panic disorder through a diagnostic interview (SCID-
NP; First et al., 1994) received 12 sessions of CBT over eight weeks. The CBT
protocol included four main components: education regarding the etiology and
maintenance of panic disorder, cognitive therapy, respiratory control techni-
ques and interoceptive exposure. Medical comorbidity and physical health
perceptions were assessed with the General Health Survey. Both were related
to poorer outcomes post treatment, though participants’ perceptions proved to
be a better indicator of treatment outcome than medical status. Participants
were considered to have met PD recovery criteria if they fell within normal
range on measures of anxiety and phobic avoidance, and were no longer
experiencing panic attacks. Following treatment, 35% of participants who
viewed their health as poor met recovery criteria, whereas 71% of those who
perceived their health as good met recovery criteria.
As noted in the introduction, we generally excluded articles involving treat-
ment of comorbid physical illness and anxiety when the latter was assessed
secondarily. Typically, they did not contribute to our understanding of the
treatment of Axis I anxiety problems. Yet we briefly summarize a few such
studies that highlight some relevant points. Holmberg, Karlberg, Harlacher,
Rivano-Fischer, and Magnusson (2006) evaluated the effects of CBT for indi-
viduals with phobic postural vertigo (PPV) which is characterized by dizziness,
avoidance and anxiety often caused by a vestibular disorder (Holmberg et al.,
2006). All study participants received education regarding the disorder and
were shown how to perform self-administered vestibular exercises, which they
354 N. B. Schmidt et al.
were encouraged to perform twice daily for fifteen minutes. Half of the parti-
cipants also received CBT. Participants in the CBT group reported significantly
greater gains on anxiety as measured by the Hospital Anxiety and Depression
Scale (Zigmond & Snaith, 1983). This study illustrates the application of CBT in
a patient population typically not considered in collaborative health efforts.
Psychotherapy also yielded gains when Speca, Carlson, Goodey, and Angen
(2000) investigated the effects of a mindfulness meditation-based stress reduc-
tion group program on a variety of psychological symptoms among cancer
patients. Individuals in the treatment condition exhibited large to medium
reductions in anxiety, depression, anger, confusion, and stress subscales of the
Profiles of Mood States (McNair, Lorr, & Droppelman, 1971). Yet results were
mixed in another severe patient population. Anson and Ponsford (2006) studied
CBT’s effectiveness in improving traumatic brain injury patients’ coping stra-
tegies and emotional adjustment. PParticipants reported improved competency
and understanding of emotional issues and adaptive coping strategies; however,
there were no significant changes in depression, anxiety, self-esteem or psycho-
social functioning. Together these studies illustrate the issue that less specific
anxiety assessment may make it hard to distinguish the clinical significance of
any improvements.
Suh, Jung, Kim, Park, and Yang (2002) evaluated individuals with end stage
renal failure being maintained on hemodialysis, to determine if regular exercise
would affect their level of anxiety, depression and quality of life. Participants
exhibited a significant improvement in anxiety symptomatology and quality of
life but not depression following the exercise program. Exercise is one of several
typical components in behavioral health therapy. This study raises the issue that
improvements–even in more impaired populations–may accrue from fewer
components, shorter durations, or smaller doses.
Although much research remains to be conducted, this review provides a
promising look at the effects of psychotherapy, particularly CBT, on comorbid
physical illness and anxiety. CBT was shown to improve health perceptions,
decrease anxiety symptoms, and reduce doctor visits among individuals with
panic disorder (Klein et al., 2006; Roy-Byrne et al., 2005; Schmidt et al., 2003).
CBT also significantly reduced both medical and anxiety symptoms for asth-
matics who had panic disorder (Ross et al., 2005). Patients with PTSD as a
result of a myocardial infarction reported both decreased medical risk factors
and anxiety symptomatology following CBT (Shemesh et al., 2006). Individuals
with comorbid traumatic brain injury and acute stress disorder were less likely
to develop PTSD when they received CBT (Bryant et al., 2003). Similarly, a
trend toward decreased anxiety symptoms for spinal cord injury and breast
cancer patients existed following cognitive therapy, particularly when anxiety
was higher at baseline or treatment was delivered by psychologists (Craig et al.,
1998; Kissane et al., 2003).
While improvements in physical and mental health status have been demon-
strated, the potential mechanisms for change are largely unclear. Very few
studies investigated the moderating effect of health status on the relationship
Physical Illness and Treatment of Anxiety Disorders: A Review 355
between treatment and anxiety outcome. Schmidt and Telch (1997) reported
that poor health perception had a clearly negative impact on response to CBT
among panic disorder patients. Roy-Byrne et al. (2005) indicated the medical
burden did not affect rate of response to CBT among panic disorder patients but
that due to their more severe symptomatology they would require longer treat-
ment duration to be considered remitted. Further investigation into the modera-
tional role of health status on treatment response is warranted to determine what
impact it has on the different medical-anxiety illness comorbidities.
The nature of each child’s illness and treatment was well documented. Most
were inpatients at the start of the study (9 out of 15), most were receiving
chemotherapy (14 out of 15), and most had a poor prognosis, which was defined
as a less than 30% chance of survival. Patients did not alter the other medica-
tions they were receiving during the trial.
The safety, tolerability, and benefits of fluvoxamine were assessed using
biological assays, self-report measures, and clinician ratings. Measures were
taken at baseline, four weeks, and eight weeks. Blood levels of liver enzymes,
blood urea nitrogen, and creatinine were taken to assess organ response to
fluvoxamine. Patients completed the Children’s Depression Rating Scale-
Revised (CDRS-R; Pozananski & Mokros, 1995) and the Pediatric Anxiety
Rating Scale (PARS; Research Unit on Pediatric Psychopharmacology Anxiety
Study Group, 2001). Additionally, the child and adolescent psychiatrist rated
Clinical Global Impressions (CGI; National Institute of Mental Health, 1985)
of severity at baseline and improvement at four and eight weeks.
Response to treatment for individuals with anxiety disorders was assessed by
PARS scores changes. Four out of five patients diagnosed with an anxiety
disorder showed over 50% improvement in total PARS scores. Decreases in
the scores were significant at four weeks, but there was no further decrease by
eight weeks. Moreover, none of the patients experienced adverse physical
consequences. While three patients reported fleeting side effects including
abdominal pain and dry mouth, none of them were lasting or required dose
reduction.
The Gothelf et al. (2005) study provided preliminary evidence that anxiety
disorders can be safely treated with psychotropic medications in children with
chronic physical illnesses. The thorough assessments of anxiety psychopathol-
ogy as well as physical condition were particular strengths. However, as a
preliminary investigation there was no placebo control group with which to
compare results. Moreover, patients were only receiving active treatment for
eight weeks. The long-term effects of fluvoxamine on children with cancer could
not be determined.
In addition to the safety of using psychotropic medications in severely ill
populations, another consideration when treating individuals with comorbid
physical illness and anxiety disorders is whether the medical illness adversely
affects responses to treatment. The CCAP conducted by Roy-Byrne et al. (2005)
and mentioned in the previous section was a randomized effectiveness trial
investigating responses to combined CBT and medication treatment versus
medication alone. One goal was to investigate treatment collaborations by
community behavioral health specialists and primary care physicians. Conse-
quently, the specific pharmacological intervention was less restricted than other
studies reviewed in this chapter. The physicians were given a one-hour didactic
about recognizing panic disorder in their patients, as well as information about
options and delivery of psychotropic medication. In both groups, the interven-
tion consisted of six weeks of SSRIs with dose titration. However, if a partici-
pant had already had two unsuccessful trials of treatment with SSRIs, other
Physical Illness and Treatment of Anxiety Disorders: A Review 357
CGI (National Institutes of Mental Health, 1985), and specific symptoms of IBS
including the frequency and severity of abdominal pain, constipation, diarrhea,
incomplete emptying, and bloating.
In general, both groups responded well to paroxetine. Symptoms decreased in
frequency and severity across the domains of IBS physical symptoms. Indivi-
duals with anxiety disorders experienced somewhat greater alleviation of symp-
toms than the group without anxiety, however the differences were not
statistically significant. For example, the criteria for full remission, greater
than 70% improvement of symptoms, was met by 7 of 10 patients with anxiety
disorders as opposed to 2 of 10 patients without anxiety disorders (p=.07).
While the small number of participants limited the power of analyses, these
tentative findings suggested a fairly dramatic difference across comorbidity
groups. This potentially underscores a significant relationship between anxiety
disorders and IBS, perhaps suggesting not only shared etiology, but that IBS can
sometimes be a physical symptom of anxiety. On the other hand, several
researchers have demonstrated that in the absence of anxiety conditions,
SSRIs are still relatively effective in treating IBS (Creed et al., 2003; Creed
et al., 2005; Masand et al., 2002).
In an initial effectiveness study, Creed and colleagues (2003) compared
psychotherapy, antidepressants, and routine gastroenterologist care for
patients with severe IBS. They found patients with severe IBS responded sig-
nificantly better to either psychotherapy or pharmacotherapy. In a follow-up
study designed to target anxiety, Creed et al. (2005) compared responses of
severe IBS patients with and without psychological comorbidity on psychody-
namic interpersonal therapy, paroxetine, or routine IBS care from a gastro-
enterologist and a general practitioner. Anxiety disorders were diagnosed using
the Schedules for Clinical Assessment in Neuropsychiatry (SCAN; World
Health Organization, 1994), a clinical interview that was administered by a
psychiatrist. In general, patients in both treatment groups experienced signifi-
cant improvement in their IBS symptoms; whereas, those in the treatment as
usual condition did not. For those in the active treatment conditions, there were
no differences between patients with and without psychological comorbidity in
improvements in physical symptoms. Despite a moderate correlation between
improvement in physical symptoms and improvement in psychological symp-
toms, the researchers concluded that the health-related outcomes in IBS result-
ing from paroxetine or psychotherapy were better accounted for by factors
beyond just improvements in psychological functioning.
Similar to IBS, serotonin is believed to play a role in migraine disorders.
5-HT agonists have been found to be effective in reducing the occurrence of
migraines, called migraine prophylaxis (Pascual & Berciano, 1991). In order to
investigate the primary prophylactic effects of buspirone, Lee, Park, and Kim
(2005) conducted a randomized, double-blind, placebo-controlled study.
Seventy-four individuals were diagnosed with both GAD and migraine disor-
der. Anxiety disorders were diagnosed according to the Diagnostic and Statis-
tical Manual, fourth edition (DSM-IV) criteria for GAD, in combination with a
Physical Illness and Treatment of Anxiety Disorders: A Review 359
Future Directions
Given the limited research in this area, our conclusions must certainly be
tempered. Much research remains to be conducted to fully examine the treat-
ment implications of the various comorbidities between medical illnesses and the
anxiety disorders. However, it appears that we can make some preliminary
statements about the treatment of patients presenting with both physical ill-
nesses and anxiety. First, people with a wide range of physical illnesses (cardi-
opulmonary, brain injury, cancer) that are treated for their anxiety problems
appear to benefit from empirically supported treatments like CBT or certain
classes of psychotropic medications. Moreover, these patients appear to benefit
in terms of their anxiety and to an extent, their physical health as well. Some
limited data hint that this physical improvement may occur directly (i.e., as a
result of the intervention) as well as indirectly (i.e., through changes in anxiety
symptoms). Although some data suggest that comorbid patients may not benefit
quite as much as those without physical illness, these patients do show some
gains. Unfortunately, there are few studies or even speculation about how to
handle comorbid patients differently to improve responsiveness. One idea is to
simply provide them with more treatment, though ‘‘dose response’’ studies in the
anxiety literature are not clear that more is always better. We would suggest that
clinicians consider incorporating interventions within existing CBT protocols
that are specific to the comorbid physical illness. For example, treating asth-
matics with panic disorder could involve specific discussions of the respiratory
physiology of asthma and how anxiety affects asthma symptoms, specialized
interoceptive techniques designed to assess and tease apart asthma and panic
symptoms, and evaluation and discussion of potential medical safety aids such
as carrying inhalers.
Stanley et al. (2005) created such a protocol by designing CBT-RADAR, an
integrated cognitive behavioral treatment for reducing anxiety and depression
among patients with Chronic Obstructive Pulmonary Disease (COPD). They
noted that differential assessment and treatment is complicated by symptom over-
lap between medical and mental health symptoms, such as shortness of breath,
chest pain, weakness, sleep disturbance, decreased energy, fatigue,. As a result, they
integrated two intervention models with documented efficacy and potential utility
for medical patients. The first model is CBT-GAD/PC: an approach targeting
treatment of generalized anxiety in later life consisting of education/awareness,
Physical Illness and Treatment of Anxiety Disorders: A Review 361
One method of considering these studies is to put them into the context of what
might be considered ideal designs for the evaluation of treatment outcome in
comorbid physical illnesses and anxiety. The first criterion that should be
considered involves standardized, clinical assessments of both conditions. An
ideal study should have comprehensive medical determination of illness con-
ducted by physicians. Many of the studies reviewed relied on patient self-reports
of physical illness. Although there are data suggesting that people can validly
report physical conditions, medical evaluation should be considered the gold
standard for future work. Similarly, the assessment of anxiety psychopathology
should be determined by a structured diagnostic interview and conducted by
trained clinicians. It may be fruitful to simply assess anxiety symptoms, as was
done in a number of the reports reviewed. Certainly self-report assessments of
symptoms can complement diagnostic assessments. However, the evaluation of
clinical syndromes is compelling not only in terms of public health significance,
but because Axis I conditions may yield different treatment results if they are
discontinuous from subclinical or nonclinical expressions of anxiety (Kotov,
Schmidt, Lerew, Joiner, & Ialongo, 2005; Schmidt et al., 2007). Moreover, the
symptom overlap between certain physical illnesses and anxiety problems is
considerable. These comprehensive assessments are needed to ensure accuracy
of differential diagnoses (i.e., between physical and psychiatric diagnoses). In
addition, standardized medical and psychiatric interviews should be repeated at
posttreatment and follow-up. This will allow researchers to ascertain whether
the intervention yielded any changes in terms of the medical as well as the
psychiatric problems. In this review, very few reports implemented this standard.
A second criterion needed for clarification of the effects of comorbidity
on outcomes involves the implementation of standardized, empirically
supported treatments. In this regard, our review suggests that the literature has
done a fairly good job of utilizing empirically supported treatments. However,
362 N. B. Schmidt et al.
these studies have largely focused on treatments aimed at the psychiatric condi-
tion. As we noted in the introduction, very few studies using empirically sup-
ported medical treatments that are designed to intervene on a physical illness
appear to be concerned with the co-occurrence of Axis I anxiety psychopathol-
ogy. This is certainly a fertile ground for future work.
The final consideration is analytic. We suggest that researchers should
consider: (1) treatment effects on both physical illness and anxiety, (2) modera-
tor effects, and (3) mediator effects. Our review found that often studies failed to
measure changes in both physical illness and anxiety domains, which is certainly
unfortunate since changes in both arenas are of considerable interest. A few
studies assessed for moderator effects, for example, whether having a certain
physical illness influenced how anxious patients responded to the treatment.
Evaluation of such effects is very important for the identification of individuals
who may not respond well to standard treatment protocols. Mediator effects are
useful in determining whether changes in one domain (e.g., anxiety) are respon-
sible for changes in the other domain (e.g., physical illness). Such analyses have
been conducted in only a small minority of the studies evaluated but could be
very important in beginning to identify mechanisms that are critical to change
among patients with comorbidity.
We hope that this review will inspire additional work in this area. Despite
highly efficacious treatments for anxiety, there is room for improvement and
there are some suggestions that patients respond less optimally because of
comorbid physical illnesses. In sum, much can be done to improve our under-
standing of the interplay between physical illnesses and anxiety and how this
impacts treatment interventions.
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Index
367
368 Index
PD, see Panic disorder (PD) asthma with, diagnoses of, 259
Peak expiratory flow (PEF), 238 in CAD patients, prevalence of, 288
Pediatric anxiety rating scale (PARS), for CBT for, 350
anxiety disorder, 356 and childhood sexual abuse, prevalence
Pediatric autoimmune neuropsychiatric of, 325
disorders associated with childhood sexual abuse and, 325
streptococcus infection and chronic musculoskeletal pain
(PANDAS), 142, 143 patients, 207–216
Peptic ulcer disease (PUD), 141 assessment methods, 223–225
Peripheral neuropathy, 318 hypoalgesia/analgesia in, 222
Pharmacotherapy, in PTSD and pain physiological arousal, 220, 221
treatment, 227 symptom overlap and anxiety
Phobias, 110 sensitivity, 218, 219
social phobia, 328 treatments and therapies, 225–227
Phobic anxiety, 293 concurrent treatment of, 72
anxiety-CHD for construct of, 293 depression, substance abuse and anxiety
CHD risk factors associated with, disorders, 321
284, 291 diagnostic criteria for, 59
as risk of SCD, 282, 299 drug use disorder, 61
Phobic disorders, prevalence of, 283 and health-related physical functioning,
Phobic postural vertigo (PPV), effects of relationship between, 330
CBT for, 353 in HIV-infected women, 322
Physical functioning, health-related, in HIV patients, prevalence of, 320
relationship between PTSD and HIV risk, 324
and, 330 in menstrual cycle, 192
Physical illness and anxiety NE in patients with, levels of, 331
future directions for, 360–361 prevalence rate in HIVþ individuals, 320
future methodological considerations for, symptoms of, 283
361–362 treatments for, 333
pharmacological treatment of, 355–360 PPV, see Phobic postural vertigo (PPV),
psychosocial treatment of, 348 effects of CBT for
no comparison group, 353–355 Premenstrual anxiety
nonrandomized with control group, health behaviors, 196, 197
352–353 research
randomized with treatment in normal women, 187–188
comparison group, 348–350 in women with PMDD, 189
randomized with waitlist, 351 in women with PMS, 188–189
Physiological arousal, in pain and anxiety treatments and therapies, 194–196
disorders, 220, 221 Premenstrual Dysphoric Disorder
Pittsburgh Sleep Quality Index (PSQI), (PMDD), 182
117, 118 assessment measures, 183–186
Polymorphous light eruption (PLE), 110 cognitive-behavior therapy, 195, 196
Pontine nucleus locus ceruleus, 114 diagnosis of, 183
Poor sleep, 117, 118 research on, 189
Postsynaptic serotonin receptors, down- selective serotonin reuptake inhibitor,
regulation of, 93 196
Posttraumatic stress disorder (PTSD), 283 Premenstrual exacerbation (PME), and
association with comorbidity, 185, 186
cancer, 135–136 Premenstrual symptoms, and anxiety
cardiovascular disease, 133 disorders
endocrine/metabolic/autoimmune assessment measures, 182–186
disease, 134–135 interaction models, 192–194
neurologic disease, 133–134 OCDs and GADs, 191, 192
Index 377
panic disorder, and symptoms, 190, 191 role in adolescent anxiety: theory and
PTSD, 192 evidence, 155
Premenstrual syndrome (PMS), 182 conceptually-driven suggestions,
and biological factors, 193 167–172
cognitive-behavior therapy, 195, 196 future perspectives, 167
research on women, 188, 189 operationalization and assessment,
selective serotonin reuptake 156–160
inhibitor, 196 psychological problems, 155, 156
Present pain index (PPI), in SF-MPQ, 224 pubertal status and timing effects
Primary anxiety disorder, observations, 106 puberty assessment, 156–160
Primary insomnia, 106 research, 166, 167
Progressive resistance training (PRT), 96 undesirable bodily events, 156
Prototypical panic psychopathology, 14 Puberty-anxiety association, researches,
Pseudoseizure, and psychogenic seizure, 133 166–169
Psychedelic abuse, and dependence, 62
Psychiatric comorbidity, 349 QT interval variability (QTV), 298
obesity, PD and MDD for, 296 Quality of life (QOL)
Psychiatric illness, and NCCP, relationship anxiety disorders for negative impact
between, 290 on, 241
Psychocardiology, 280 asthma related, effect of anxiety on, 263
Psychoeducation, in anxiety and pain and HIV, 329–330
treatment, 225
Psychogenic nonepileptic seizure (PNES), Reduced heart-rate variability (HRV),
133, 134 298–299
Psychological distress Reductions, in anxiety with exercise, 87
in asthma, importance of, 241 Relaxation training in anxiety and pain
in HIV risk, role of, 322 treatment, 226
Psychopathology Renal failure, 354
of anxiety Rhinitis, treatment of, 240
assessment of, 361 Rutgers Alcohol Problem Index (RAPI), 47
physical illness and, 341
treatment of, 346–348 SAM systems, see Sympathetic adrenal
and asthma, relation between, 259 medullary systems,
Psychosocial clinical intervention research, dysregulation of
importance of, 333 Schedules for clinical assessment in
Psychosocial treatment, for physical illness neuropsychiatry (SCAN), for
and anxiety, 348 anxiety disorders, 358
Psychotherapy Schizophrenia, 355
effects of, 354 Screen for Child Anxiety Related Emotional
in premenstrual anxiety, 195 Disorders (SCARED), 355
PTSD, see Posttraumatic stress disorder Seizure, 138
(PTSD) Selective serotonin reuptake inhibitors
Pubertal hormones (SSRI), 117
and anxiety, 162, 163 in PMS and PMDD treatment, 196
in puberty assessment, 158, 159 Serotonergic receptor system, 114, 116
Pubertal status Serotonin, role in migraine disorders, 358
and anxiety, 160–162 Serotonin selective reuptake inhibitors
in puberty assessment, 157 (SSRIs), 346
Pubertal timing for treatment of IBS, 357, 358
and anxiety, 163–166 Sertraline, for depression, 303
in puberty assessment, 157–159 Sexual activity, among HIV-infected
Puberty adolescents, 324
and risk factor, 159, 160 Sexually transmitted disease (STD), 323
378 Index
Shared vulnerability/stress models for pain Spinal cord injury (SCI), 354
and anxiety disorders, 216, 217 with depression and anxiety, 352
Shingles, 318 Spirometry role, in FEV1 measurement, 238
Short Form McGill Pain Questionnaire SSRIs, see Serotonin selective reuptake
(SF-MPQ), in anxiety disorder inhibitors (SSRIs)
assessment, 224 State trait anxiety inventory (STAI), for
Simple phobia (SP) in premenstrual anxiety and depression, 352, 353
anxiety, 185 Stress
Single spectrum disorder model, anxiety and cardiomyopathy, 300
insomnia, 107, 108 for low SES and asthma symptoms, 239
Sleep deprivation, 110, 117, 118, 156 Stress hormones in anxiety
panic induced by, 118 HIV and pathophysiology of, 330–331
Sleeping difficulties, and insomnia-like HPA and SAM systems, dysregulation
symptoms, 111 of, 330–331
Sleep polysomnography (PSG), 117 Structured clinical interview diagnostic
Sleep restoration, mechanism of, 93–94 (SCID)
Sleep restriction, 118 for assessment of anxiety disorders, 329
Slow wave sleep (SWS), 94 for DSM, 293
Smokeless tobacco, developmental course Subacute cutaneous lupus erythematosus
for, 13 (SCLE), 109
Smoking, 287, 304 Substance use, 317, 322, 325, 326
for development of asthma, 240 in HIV, anxiety and, 328
Smoking behavior, conceptualization and Substance use disorders (SUD), 71, 328
measurement of, 18 anxiety and medication adherence,
Smoking cessation, 291 relationships with, 326–327
Smoking-panic relations and anxiety-related HIV sexual risk, 325
cross-sectional tests to clarify factors in asthma, prevalence of, 237
affecting, 14 comorbidity of, 329
psychopathology of, 12 in HIV patients, 328
study of, 15 Sudden cardiac death (SCD), 280
tests for examining moderating factors anxiety for, 295
affecting, 16 emotion of anxiety in development
Social anxiety of, 280
and HIV risk occurrence of, 297
gay and bisexual youth, 323 due to phobic anxiety, 282, 299
unprotected sex, 324 predictor of, 298
impact on drinking behavior of Suicidal ideation, in asthma, 241
undergraduate student, 40 Suicidality, 325
Social anxiety disorder Sympathetic adrenal medullary systems,
autoimmune disease, 144 dysregulation of, 331
endocrine/metabolic disease, 143–144
gastrointestinal disease, 143 Tachycardia, ventricular, 298
in pain patients, 209–212 Tanner staging system, in pubertal status
Social phobia (SP), 118 assessment, 157
asthma with, 259 T-helper cells, and HIV infection, 318
diagnoses of, 247 Third factor model, anxiety and insomnia,
Specific anxiety disorders, relationships with 108, 109
illicit drug use, 59 apolipoprotein E gene polymorphism, 110
Specific or simple phobia cardiovascular disease, 110
cancer, 145 Threat-related stimuli, attention, 219, 220
endocrine/metabolic disease, 144–145 Thyroid disease, 341
gastrointestinal disease, 144 Tobacco-panic comorbidity, nature of, 10
respiratory disease, 144 Tobacco-panic psychopathology linkages, 11
Index 379