505532

research-article2013
CPXXXX10.1177/2167702613505532Barlow et [Link] Nature, Diagnosis, and Treatment of Neuroticism

Theoretical/Methodological/Review Article

Clinical Psychological Science

The Nature, Diagnosis, and Treatment of 2014, Vol. 2(3) 344­–365

© The Author(s) 2013
Reprints and permissions:
Neuroticism: Back to the Future [Link]/[Link]
DOI: 10.1177/2167702613505532
[Link]

David H. Barlow1, Shannon Sauer-Zavala1, Jenna R. Carl1,

Jacqueline R. Bullis1, and Kristen K. Ellard2,3
1
Department of Psychology, Boston University; 2Massachusetts General Hospital, Boston,
Massachusetts; and 3Harvard Medical School

Abstract
We highlight the role of neuroticism in the development and course of emotional disorders and make a case for shifting
the focus of intervention to this higher-order dimension of personality. Recent decades have seen great emphasis
placed on differentiating disorders into Diagnostic and Statistical Manual of Mental Disorders diagnoses; however,
evidence has suggested that splitting disorders into such fine categories may be highlighting relatively trivial differences.
Emerging research on the latent structure of anxiety and mood disorders has indicated that trait neuroticism, cultivated
through genetic, neurobiological, and psychological factors, underscores the development of these disorders. We raise
the possibility of a new approach for conceptualizing these disorders—as emotional disorders. From a service-delivery
point of view, we explore the possibility that neuroticism may be more malleable than previously thought and may
possibly be amenable to direct intervention. The public-health implications of directly treating and even preventing
the development of neuroticism would be substantial.

Keywords
anxiety disorders, temperament/personality and psychopathology, comorbidity

Received 7/8/13; Revision accepted 8/13/13

Throughout history, philosophers and researchers have as defined in the Diagnostic and Statistical Manual of
attempted to understand the nature of anxiety and its Mental Disorders (5th ed.; DSM-5; American Psychiatric
disorders. As early as 450 BC, the relationship between Association, APA, 2013) to a broader understanding of
an individual’s discrete emotions in response to stressors emotional or internalizing disorders. In particular, we
and his or her enduring proclivity for such experiences seek to call attention to higher-order temperamental fac-
was of interest. For example, the Roman philosopher tors that may be a more appropriate target for assessment
Cicero proposed a theory of emotion that distinguished and intervention than may symptom-level manifestations
between the temporary emotional state of anxiety (angor) of these traits. Although relevant higher-order tempera-
and the enduring tendency to experience anxiety (anxi- mental dimensions associated with the experience of fre-
etas; Lewis, 1970). Furthermore, in perhaps one of the quent and intense negative emotions have acquired a
best-known historical conceptualizations of anxiety, number of labels, we focus on the construct of “neuroti-
Freud (1924) distinguished between objective anxiety cism” as the first (Eysenck, 1947) and still most popular
signaling the presence of an immediate threat (e.g., a (Lahey, 2009) conception of this trait.
loaded gun pressed to the temple) and neurotic anxiety Neuroticism is typically defined as the tendency to
generated when an individual’s defense mechanisms are experience frequent and intense negative emotions in
no longer able to successfully repress an early traumatic
experience, which results in a persistent state of distress
Corresponding Author:
(Reiss, 1997). In this article, we review a variety of David H. Barlow, Department of Psychology, Boston University, 648
research areas with the purpose of shifting focus from Beacon St., 6th Floor, Boston, MA 02215
the study of discrete anxiety, mood, and related disorders E-mail: dhbarlow@[Link]
The Nature, Diagnosis, and Treatment of Neuroticism 345

response to various sources of stress. These negative “splitting” approach to nosology ensured high rates
emotions are usually broadly construed to include anxi- of diagnostic reliability, there is evidence that it may
ety, fear, irritability, anger, sadness, and so forth, but the have come at the expense of validity; in other words,
greatest focus has been on the experience of anxious or the current diagnostic system may be overemphasizing
depressive mood. Accompanying this exaggerated nega- categories that are minor variations of a broader underly-
tive emotionality is the pervasive perception that the ing syndrome (T. A. Brown & Barlow, 2005, 2009).
world is a dangerous and threatening place, along with Neuroticism, combined with other temperamental vari-
beliefs about one’s inability to manage or cope with chal- ables, likely represents this syndrome.
lenging events. These beliefs often are manifested in Despite the marked emphasis during the past 30 years
terms of heightened focus on criticism, either self-gener- on discrete DSM-based categories of emotional disorders
ated or from others, as confirming a general sense of and their treatment, a few investigators have continued to
inadequacy and perceptions of lack of control over focus attention on the existence and salience of broader
salient events (Barlow, 2002; L. A. Clark & Watson, 2008; underlying syndromes. For example, Andrews (1990) and
Eysenck, 1947; Goldberg, 1993). Tyrer (1989) each argued for the existence of a “general
The label neuroticism was first used by Eysenck neurotic syndrome” as a more parsimonious and heuris-
(1947) to describe this statistically derived personality tic account of emotional disorders. In addition, Lahey
trait; Eysenck coined the term after the commonly used (2009), summarizing the growing evidence for the pub-
clinical label at that time: neurosis—the early DSM cate- lic-health significance of neuroticism, documented that
gory comprising people with anxiety, depression, and neuroticism is strongly associated with and predicts many
related disorders. Building on earlier work by Slater different mental and physical disorders, as well as treat-
(1943), who used the term neurotic constitution, Eysenck, ment seeking for not only mental disorders but also gen-
no fan of things Freudian even in the 1940s, regretted eral health services. Indeed, he underscored evidence
employing this term and noted that “it would no doubt that neuroticism may act as a salient predictor of the
be preferable in some ways to use a more neutral kind of quality and longevity of our lives. Lahey called for a more
label” (p. 49). Nevertheless, he made it clear that indi- substantial focus on the nature and origins of neuroticism
viduals with the diagnosis of neurosis occupied the path- and the mechanisms through which this trait is linked to
ological extreme of the personality trait of neuroticism. both mental and physical disorders. Moreover, Cuijpers et
Eysenck also noted, in a prescient bit of writing, that al. (2010) examined the economic cost of the trait of neu-
these two constructs could be relatively independent and roticism and found, in a large representative sample of
that “some so called ‘neurotic’ inmates (of a hospital) the Dutch population, that these economic costs were
show very little evidence of the ‘neurotic constitution’ enormous and exceeded costs of common mental disor-
and would likely be situated rather towards the normal ders. Cuijpers et al. noted that “we should start thinking
end of the distribution” (p. 48). He went on to theorize about interventions that focus not on each of the specific
that these individuals would have been subjected to negative outcomes of neuroticism but rather on the start-
extreme life stress, whereas individuals high on the trait ing point itself” (p. 1086).
of neuroticism would require relatively little life stress to The current review begins with a section highlighting
trigger neurosis, thereby clearly presaging the stress-dia- commonalities among the emotional disorders, including
thesis model of psychopathology. high rates of comorbidity, broad rather than narrow treat-
Although the study of trait or temperament models of ment responsiveness among comorbid disorders, and
anxiety and related negative emotions has continued for shared neurobiological mechanisms. Next, we present
decades, this literature has had decreasing influence on the emerging research on the latent structure of emo-
nosological schemes. DSM-III (3rd ed.; APA, 1980) repre- tional disorders that may underlie these observed com-
sented the advent of an objective, empirically based clas- monalities followed by a brief description of theoretical
sification system for mental disorders; patients previously accounts of the origins of neuroticism or trait anxiety.
receiving a diagnosis of neurosis were now classified The following section describes common functional rela-
more narrowly into specific anxiety, depressive, and tionships in emotional disorders, particularly among
related disorders. These new discrete diagnostic catego- emotional expression, negative appraisals under stress,
ries indeed had a meaningful impact on the development and avoidance, as well as new approaches to conceptual-
of pharmacological and individual psychological treat- izing these disorders and suggests the possibility of more
ments, particularly for anxiety and mood disorders (e.g., satisfying dimensional nosological and assessment
Barlow et al., 1984). This approach allowed for the devel- schemes. Finally, a review of diverse research on the mal-
opment of interventions targeting specific forms of psy- leability of neuroticism in both normal and pathological
chopathology and the ability to evaluate treatment expressions sets the stage for a discussion of possible
response on the basis of discrete outcomes. Although this new strategies for treatment and prevention that focus
346 Barlow et al.

not on individual negative outcomes of neuroticism the T. A. Brown et al. (2001) study was 5%. However,
in the form of the DSM-defined emotional disorders when the hierarchical rule that generalized anxiety disor-
but, rather, on neuroticism itself as well as related der should not be assigned when occurring exclusively
temperaments. during a course of a mood disorder was suspended, the
comorbidity estimate increased to 90%. These data also
Commonalities and Dimensions Among ignore the presence of subthreshold symptoms that did
not meet diagnostic thresholds for one disorder or
Anxiety and Related Disorders another.
Empirical conceptions of the anxiety and major emo- Second, psychological treatments for a given anxiety
tional disorders are emerging that underscore their com- disorder often produce improvement in additional
monalities (Barlow, 2002; T. A. Brown, 2007; T. A. Brown comorbid anxiety or mood disorders that are not specifi-
& Barlow, 2009). Major developments in at least three cally addressed in treatment (Allen et al., 2010; Borkovec,
areas—high rates of comorbidity, broad treatment Abel, & Newman, 1995; T. A. Brown, Antony, & Barlow,
response across comorbid disorders, and shared neuro- 1995; Tsao, Lewin, & Craske, 1998; Tsao, Mystkowski, &
biological mechanisms—support this conception. First, Zucker, 2002). For example, we examined the course of
studies of phenomenology and nosology with a particu- additional diagnoses in a sample of 126 patients who
lar focus on comorbidity have suggested considerable were being treated at CARD for panic disorder with or
overlap among disorders. At the diagnostic level, this without agoraphobia (T. A. Brown et al., 1995). A signifi-
overlap is most evident in high rates of current and life- cant pre- to posttreatment decline in overall comorbidity
time comorbidity (e.g., Allen et al., 2010; T. A. Brown, was noted (40% to 17%, respectively). This effect could
Campbell, Lehman, Grisham, & Mancill, 2001; Kessler, represent the generalization of elements of treatment to
Berglund, & Demler, 2003; Kessler et al., 1996; Kessler independent facets of both disorders or the effective tar-
et al., 1998; Kessler et al., 2008). In a study of 1,127 geting of “core” features of emotional disorders. The fact
patients presenting at the Center for Anxiety and Related that a wide range of emotional disorders (e.g., major
Disorders (CARD) at Boston University, 55% of patients depressive disorder, obsessive-compulsive disorder,
with a principal anxiety disorder had at least one addi- panic disorder) respond approximately equivalently to
tional anxiety or depressive disorder at the time of assess- antidepressant medications has also been interpreted by
ment, and this rate increased to 76% when lifetime some researchers as indicating shared features among
diagnoses were considered (T. A. Brown et al., 2001). To these disorders (e.g., Hudson & Pope, 1990).
take one example, of 324 patients diagnosed with DSM- There are several possible explanations for high rates
IV-TR (4th ed., text rev.; APA, 2000) panic disorder with of comorbidity and overlapping treatment response that
or without agoraphobia, 60% met criteria for an addi- we have reviewed extensively elsewhere (T. A. Brown &
tional anxiety or mood disorder, breaking down to 47% Barlow, 2002, 2009), including overlapping definitional
with an additional anxiety disorder and 33% with an criteria, artifactual reasons (e.g., differential base rates of
additional mood disorder. When lifetime diagnoses were occurrence in our setting), and the possibility that disor-
considered, the percentages rose to 77% of the patients ders are sequentially related such that the features of one
experiencing any comorbid anxiety or mood disorder, disorder act as risk factors for another disorder. Another
breaking down to 56% for an additional anxiety disorder more intriguing explanation, noted earlier, is that this pat-
and 60% for a mood disorder. The principal diagnostic tern of comorbidity argues for the existence of what has
categories of posttraumatic stress disorder and general- been called a general neurotic syndrome (Andrews, 1990,
ized anxiety disorder were associated with the highest 1996; Tyrer, 1989). Under this conceptualization, hetero-
comorbidity rates. Similarly, Merikangas, Zhang, and geneity in the expression of emotional disorder symp-
Aveneoli (2003) followed approximately 500 individuals toms (e.g., individual differences in the prominence of
for 15 years and found that relatively few people suffered social anxiety, panic attacks, anhedonia) is regarded as
from anxiety or depression alone; when patients did trivial variation in the manifestation of a broader syn-
meet criteria for a single disorder at one point in time, an drome. We return to this argument later.
additional anxiety or depressive episode disorder almost Third, recent research from affective neuroscience has
certainly emerged at a later time. suggested the existence of a biological syndrome that is
These summaries are most likely conservative as a common across emotional disorders. For example,
result of artifactual constraints in DSM-IV-TR (which were research among individuals with anxiety and related dis-
continued in DSM-5), such as the nature of inclusion- orders has suggested that hyperexcitability of limbic
exclusion criteria used. For instance, when adhering structures, along with limited inhibitory control by corti-
strictly to DSM-IV-TR diagnostic rules, the comorbidity cal structures, may be one explanation for the increased
between dysthymia and generalized anxiety disorder in negative emotionality among individuals with such
The Nature, Diagnosis, and Treatment of Neuroticism 347

diagnoses (Etkin & Wager, 2007; Mayberg et al., 1999; on nosological schemes. It is interesting that almost every
Porto et al., 2009; Shin & Liberzon, 2010). Specifically, theory of personality structure references neuroticism-
increased “bottom-up” processing through amygdala and extraversionlike traits, which suggests the fundamen-
overactivation, coupled with inefficient or deregulated tal importance of these dimensions for functioning ( John
cortical inhibition of amygdala responses, has been & Srivastava, 1999). Current well-accepted personality
shown in studies of social anxiety disorder (Lorberbaum conceptualizations, such as the Big Three (Eysenck &
et al., 2004; Phan, Fitzgerald, Nathan, & Tancer, 2006; Eysenck, 1975; Tellegen, 1985; Watson & Clark, 1993) and
Tillfors, Furmark, Marteinsdottir, & Fredrikson, 2002), the Big Five (Digman, 1990; John, 1990; McCrae & Costa,
posttraumatic stress disorder (Shin et al., 2005), general- 1987), prominently feature these dimensions of personal-
ized anxiety disorder (Etkin, Prater, Hoeft, Menon, & ity despite disagreement on additional traits (e.g., con-
Schatzberg, 2010; Hoehn-Saric, Schlund, & Wong, 2004; straint in the Big Three and agreeableness, openness,
Paulesu et al., 2010), specific phobia (Paquette et al., and conscientiousness in the Big Five) and different
2003; Straube, Mentzel, & Miltner, 2006), and depression methods of formulation.
(Holmes et al., 2012). This same amygdala overactivation In addition to understanding the structure of personal-
has also been found in individuals high in the personality ity, researchers have been interested in the neurobiologi-
dimension of neuroticism (Keightley et al., 2003). Of cal basis for such traits. Eysenck’s (1961, 1981) influential
course, a few unique and idiosyncratic neurobiological theory led to the development of the Big Three, and he
factors have also been associated with discrete DSM-IV- was the first to implicate neuroticism and extraversion.
TR diagnoses (Blair et al., 2008; Chorpita, Albano, & He based his trait theory on variations in levels of cortical
Barlow, 1998), but it seems likely that the broader based activation and autonomic nervous system reactivity and
genetic and neurobiological commonalities reviewed suggested that extraversion/positive emotion is associ-
earlier may better account for the nature of emotional ated with moderate levels of arousal, whereas neuroti-
disorders. Although these three commonalities among cism/negative emotion is associated with under- or
emotional disorders have garnered attention, a recent overarousal. A number of researchers have examined the
focus on the hierarchical structure of emotional disorders relationship of neuroticism (and extraversion) in the
may be more heuristic. development of anxiety and other negative emotions. For
example, Gershuny and Sher (1998) found, in a sample
Latent Temperamental Structure of composed of 466 young adults, that the combination of
high neuroticism and low extraversion at Time 1 seemed
Emotional Disorders to play an important and predisposing role in the emer-
Emerging research on the latent dimensional features of gence of anxiety assessed 4 years later.
emotional disorders has revealed a hierarchical structure Further bolstering the importance of neuroticism and
that places emphasis on two genetically based core extraversion in the experience of negative emotion, Gray
dimensions of temperament: neuroticism and, to a lesser (1982; Gray & McNaughton, 1996) described a similar
degree, extraversion (Barlow, 2002). Extraversion, com- trait theory and its neurobiological correlates that map
monly associated with social qualities, broadly refers to onto Eysenck’s (1961, 1981) traits, namely, the behavioral
an energetic approach to the world, including activity inhibition system, behavioral approach system, and fight-
and positive emotionality in addition to sociability. flight system. In Gray’s theory, the biological basis for
Although these traits have received various labels, includ- anxiety is the behavioral inhibition system’s (over)reac-
ing negative affect, behavioral inhibition, trait anxiety, tion to novel signals or punishment with exaggerated
and harm avoidance as alternate terms for neuroticism inhibition. High levels on Gray’s behavioral inhibition
and positive affect or behavioral activation as alternate system roughly relate to high levels of neuroticism and
terms for extraversion, substantial existing literature has low levels of extraversion in Eysenck’s model, and the
underscored the roles of these constructs in accounting behavioral approach system roughly corresponds to high
for the onset, overlap, and maintenance of anxiety, extraversion and low neuroticism (Barlow, 2002). The
depressive, and related disorders (T. A. Brown, 2007; fight-flight system involves unconditioned escape behav-
T. A. Brown & Barlow, 2009; T. A. Brown, Chorpita, & ior (i.e., flight) and defensive aggression (i.e., fight) in
Barlow, 1998; Gershuny & Sher, 1998; Griffith et al., 2010; response to unconditioned punishment, such as pain,
Kasch, Rottenberg, Arnow, & Gotlib, 2002; Kessler et al., and unconditioned frustrative nonrewards (Gray, 1991;
2011; Krueger, 1999; Watson, Clark, & Carey, 1988). Gray & McNaughton, 1996). As such, the fight-flight sys-
The study of trait or temperament models of anxiety tem may represent a biological vulnerability specifically
and related negative emotions has been ongoing for to the distinct emotion of fear/panic, as opposed to anxi-
decades in spite of the decreasing influence of this work ety more generally.
348 Barlow et al.

In another trait theory, Kagan (1989, 1994) examined a hierarchical structure. In this structure, neuroticism and
children’s approach-and-withdrawal behavior and cre- extraversion emerged as higher-order factors to the DSM-
ated profiles characterizing their levels of behavioral inhi- IV-TR disorder factors, with significant paths from neu-
bition. Kagan’s (1989) definition of behavioral inhibition roticism to each of the five DSM-IV-TR factors. In accord
is similar to Gray’s (1982) in that it involves a low thresh- with a reformulated hierarchical model of anxiety and
old for limbic arousal and uncertainty regarding unfamil- depression (Mineka, Watson, & Clark, 1998), results
iar events. Kagan considered these stable profiles as showed that extraversion was predictive of unipolar
representing temperaments; physiological (increased depression and social anxiety disorder only (see also
salivary cortisol levels and muscle tension, greater pupil T. A. Brown & McNiff, 2009). In addition, Rosellini,
dilation, and elevated urinary catecholamine levels) and Lawrence, Meyer, and Brown (2010) found recently that
external (subsequent development of anxiety disorders) agoraphobia (but not panic disorder) was associated
correlates of behavioral inhibition have also been found with low extraversion, which provided support for the
(Biederman et al., 1993; Hirshfeld-Becker et al., 1992). change in DSM-5 that separates agoraphobia from panic
Robinson, Kagan, Reznick, and Corley (1992) suggested disorder as a distinct, new, diagnosis. In this model, auto-
that temperament is clearly heritable; however, only 30% nomic arousal, which we consider to reflect largely the
of individuals who clearly met criteria for behavioral inhi- phenomenon of panic, emerges as a lower-order factor
bition as young children went on to develop anxiety dis- with significant paths from panic disorder and general-
orders (Biederman, Rosenbaum, Hirshfeld, & Faraone, ized anxiety disorder, which demonstrated a negative
1990). Moreover, temperament (as described in Kagan relationship with autonomic surges.
& Snidman, 1991) appears to be somewhat malleable, These findings on latent structure have recently been
which suggests that environmental factors are also impor- extended both by our research team (T. A. Brown, 2007;
tant determinants in temperament and anxiety vulnera- T. A. Brown & Barlow, 2009) and by other researchers
bility. These findings support the notion of a “constraining” (e.g., Griffith et al., 2010; Kessler et al., 2011). For exam-
biological vulnerability (in contrast to a “determining” ple, Griffith et al. (2010), studying a large sample of eth-
role of temperament) in the development of anxiety in nically diverse adolescents and including both self-report
adolescence and adulthood, a theme to which we return and peer-report measures of neuroticism, found that a
in our later discussion of treatment. single internalizing factor was common to lifetime diag-
Finally, in one of the best known modern conceptual- noses of mood and anxiety disorders and that this inter-
izations of temperaments related to anxiety and depres- nalizing factor was all but isomorphic with neuroticism.
sion, L. A. Clark and Watson (1991) proposed two Noting the replication of earlier findings (e.g., T. A.
genetically based core dimensions, neuroticism/negative Brown et al., 1998), Griffith et al. suggested that these
emotionality and extraversion/positive emotionality, as results provided further evidence that neuroticism may
part of their tripartite theory (L. A. Clark, 2005; L. A. Clark, be the core of “internalizing” disorders. Using factor anal-
Watson, & Mineka, 1994; Watson, 2005). These concepts, ysis, Krueger (1999) similarly found that the variance in
originally based on Eysenck’s (1961, 1981) model, are seven anxiety and mood disorders can be accounted for
also closely related to Gray’s (1982) constructs of behav- by the higher-order dimension of internalizing/neuroti-
ioral inhibition and behavioral activation both conceptu- cism. Although the key features of the DSM anxiety and
ally and empirically. Although the traits reviewed earlier mood disorders (i.e., the specific symptoms used to dis-
may turn out to be distinct in some way, current evidence criminate between diagnoses) cannot be collapsed indis-
in this area from CARD and elsewhere (L. A. Clark, 2005; criminately into higher-order temperamental dimensions,
Watson, 2005) lump these concepts together in a partially it seems safe to conclude, on the basis of these studies,
heritable temperament that we have labeled neuroticism/ that what is common outweighs what is not. Thus, virtu-
behavioral inhibition (or just neuroticism1) and behav- ally all of the considerable covariance among latent vari-
ioral activation/positive affect (T. A. Brown, 2007; T. A. ables corresponding to the DSM-IV-TR constructs of
Brown & Barlow, 2009; T. A. Brown et al., 1998; Campbell- depression, social anxiety disorder, generalized anxiety
Sills, Liverant, & Brown, 2004). disorder, obsessive-compulsive disorder, and panic disor-
We have been studying the latent structure of emo- der was explained by the higher-order dimension of neu-
tional disorders for the past 20 years (e.g., T. A. Brown roticism (and extraversion); bipolar disorder was not
et al., 1998; Zinbarg & Barlow, 1996) and have confirmed, included in these studies.
with some modifications, the tripartite model of emo- Our own framework for understanding the origins of
tional disorders first proposed by L. A. Clark and Watson neuroticism as well as emotional disorders describes
(1991). For example, the findings from T. A. Brown et al. three separate but interacting diatheses or vulnerabilities
(1998), which used a sample composed of 350 patients (i.e., triple vulnerability theory; Barlow, 1988, 2000;
with DSM-IV-TR anxiety and mood disorders, confirmed Barlow, Ellard, Sauer-Zavala, Bullis, & Carl, 2013). We
The Nature, Diagnosis, and Treatment of Neuroticism 349

have explicated these vulnerabilities in some detail else- toward negative information, but then they tend to
where (Barlow et al., 2013) but included a general bio- quickly turn their attention away from such negative
logical (heritable) vulnerability common across disorders, information (MacLeod & Mathews, 2012; Mathews &
a general psychological vulnerability consisting of a MacLeod, 2005). These individuals also react strongly to
heightened sense of unpredictability and uncontrollabil- negative emotions when they occur with attempts to sup-
ity and associated changes in brain function resulting press or avoid the emotional experience (Aldao, Nolen-
from adverse early experiences, and a more specific psy- Hoeksema, & Schweizer, 2010; Baker et al., 2004; Moore,
chological vulnerability, also largely learned, accounting Zoellner, & Mollenholt, 2008; Tull & Roemer, 2007; Turk,
for why one particular emotional disorder may emerge Heimberg, Luterek, Mennin, & Fresco, 2005). In addition,
instead of another. It seems increasingly evident that the individuals with emotional disorders, compared with
two generalized vulnerabilities identified in the triple vul- healthy individuals, display greater intolerance for uncer-
nerability theory are implicated in the development and tainty, ambiguity, or situations that are perceived as uncon-
expression of neuroticism itself (T. A. Brown, 2007; T. A. trollable, which leads to heightened negative affect. For
Brown & Barlow, 2009). Indeed, we hypothesize that example, intolerance of uncertainty and distress have been
these two generalized vulnerabilities function as direct demonstrated across a range of disorders, including
risk factors for the development of neuroticism, which in depression, generalized anxiety disorder, and social anxi-
turn mediates risk for the development of anxiety and ety disorder (Boelen, Vrinssen, & van Tulder, 2010;
mood disorders. What is notable for our purposes is that Boswell, Thompson-Hollands, Farchione, & Barlow, 2013;
adverse experiences contribute strongly to changes in Lee, Orsillo, Roemer, & Allen, 2010; Tolin, Abramowitz,
brain function and that later experiences may alter result- Brigidi, & Foa, 2003). Increased perceptions of emotions
ing temperamental expression and associated brain cir- as uncontrollable and intolerable as well as increased
cuits (Kagan & Snidman, 1991; Nemeroff, 2013). attempts at emotional control are also evident across dis-
orders. A wide range of research has suggested that these
ways of interpreting and responding to negative emotions
The Nature of Emotional Disorders paradoxically serve to increase and maintain negative
Negative reactivity to emotional experience appears fun- emotions and emotional disorder symptomatology. Thus,
damentally connected to neuroticism and resulting emo- we consider this pathological reaction to emotional expe-
tional disorder pathology. Emotional disorder is a term rience as the phenotypic core of emotional disorders. The
that has been used to group anxiety, unipolar mood, and following section discusses in detail the nature of these
related disorders, such as somatoform and dissociative response tendencies and their sequelae.
disorders (Barlow, 1991; Barlow et al., 2011; T. A. Brown Evidence has suggested that how one interprets or
& Barlow, 2009). These disorders are characterized by a reacts to negative emotions when they occur can affect
number of shared emotional disturbances, which appear the intensity and duration of the emotional experience
to be closely linked to neuroticism. As described earlier, (Sauer & Baer, 2009; Sauer-Zavala et al., 2012). A clear
individuals with emotional disorders, compared with example of how this process unfolds can be seen in early
healthy individuals, have higher levels of negative affect models of panic disorder (Barlow, 1988; D. M. Clark,
(e.g., T. A. Brown & Barlow, 2009) and report experienc- 1986). In these models, physical symptoms associated
ing more frequent and intense negative emotions with initial panic attacks (e.g., increased heart rate) evoke
(Campbell-Sills, Barlow, Brown, & Hofman, 2006; Mennin, anxiety about impending consequences (e.g., heart
Heimberg, Turk, & Fresco, 2005). In addition, individuals attack), which intensifies anxiety and its related physical
with emotional disorders, compared with healthy indi- symptoms and possibly triggers additional panic attacks.
viduals, report less emotional clarity (Baker, Holloway, It is important to note that in individuals without panic
Thomas, Thomas, & Owens, 2004; McLaughlin, Mennin, disorder, occasional panic attacks do not evoke strong
& Farach, 2007; Tull & Roemer, 2007; Weiss et al., 2012) emotional reactions (nonclinical panic; Bouton, Mineka,
and acceptance of emotional experiences (McLaughlin et & Barlow, 2001). Thus, the central issue in panic disorder
al., 2007; Tull & Roemer, 2007; Weiss et al., 2012) and is not the experience of panic attacks but the negative
find the experience of negative emotions more unpleas- emotional reaction to the intense fear (panic) itself.
ant (Roemer, Salters, Raffa, & Orsillo, 2005). Negative reactions or interpretations of emotions that
In view of these reactions to negative emotions, it is intensify the experience are also prominent in other anxi-
not surprising that individuals with emotional disorders ety and depressive disorders. For example, in research on
also display a range of cognitive and behavioral strate- obsessive-compulsive disorder, Rachman and de Silva
gies aimed at reducing encounters with or the impact (1978) found that the content of ego-dystonic intrusive
of negative emotions. Individuals with emotional disor- thoughts under stress are similar in patients diagnosed
ders exhibit early vigilant information-processing biases with obsessive-compulsive disorder and nonclinical
350 Barlow et al.

control participants, which supports the notion that the just as important in the development of emotional
way these thoughts are interpreted and managed has disorders as is the frequency and intensity of emotional
implications for the development of this emotional disor- experience.
der. In addition, individuals with generalized anxiety dis- Another transdiagnostic construct that has been impli-
order may find unexpected, uncontrolled emotional cated in the development and maintenance of emotional
reactions that result from unplanned or mildly threaten- disorders is experiential avoidance, defined as the unwill-
ing situations particularly aversive and may engage in ingness to remain in contact with uncomfortable internal
worry or checking behavior to regulate this emotional experience (e.g., thoughts, emotions, sensations, memo-
experience (Newman & Llera, 2011). Once again, the ries, urges) through escape or avoidance (Hayes, Wilson,
focus of an emotional disorder (panic attacks, intrusive Gifford, Follette, & Strosahl, 1996). Self-report studies
thoughts, and social evaluation) may be determined by have demonstrated that individuals with anxiety disor-
early learning experiences; however, the negative emo- ders (Begotka, Woods, & Wetterneck, 2004; Hayes,
tional reaction itself and one’s attempts to cope with or Luoma, Bond, Masuda, & Lillis, 2006; Kashdan, Breen,
downregulate this emotional reaction are at the core of Afram, & Terhar, 2010) and depressive disorders (Berking,
the disorder. Neacsiu, Comtois, & Linehan, 2009; Hayes et al., 2006;
Several constructs capturing the problematic reactions Shahar & Herr, 2011; Tull, Gratz, Salters, & Roemer, 2004)
to emotions that may be implicated in the transdiagnostic display high levels of self-reported experiential avoid-
development and maintenance of emotional disorders ance. The existing literature also has suggested that expe-
have been identified; specifically, these constructs mea- riential avoidance both predicts generalized anxiety
sure the tendency of individuals to find emotional experi- disorder symptoms even when the variance associated
ences aversive and, as such, engage in attempts to avoid with frequency of negative affect is parceled out (Lee
them. Anxiety sensitivity, defined as a propensity for et al., 2010) and mediates the relationship between neu-
developing beliefs that anxiety-related symptoms will roticism and posttraumatic stress disorder symptoms
have negative somatic, cognitive, and social conse- (Maack, Tull, & Gratz, 2012; Pickett, Lodis, Parkhill, &
quences (Reiss, 1991), is one such construct. Anxiety sen- Orcutt, 2012). Furthermore, Cheavens and Heiy (2011)
sitivity represents an individual’s characteristic way of recently found that avoidant coping partially mediates
evaluating and responding to an emotional experience the relationship between the experience of negative
(specifically anxiety) when it occurs, distinct from the emotions and major depressive symptoms among indi-
frequency or intensity of anxiety itself (Cox, Taylor, & viduals high in experiential avoidance. Taken together,
Enns, 1999; Lilienfeld, 1999). Although anxiety sensitivity these findings suggest that emotional disorder symptoms
was originally introduced as a risk factor for panic disor- are not simply a product of high levels of negative affect;
der (Reiss, Peterson, Gursky, & McNally, 1986) and has instead, the combination of strong negative emotions and
predominantly been studied in the context of this disor- how one relates to them when they occur appears to be
der (e.g., Maller & Reiss, 1992; Plehn & Peterson, 2002; important for the development of these disorders.
Rassovsky, Kushner, Schwarze, & Wangensteen, 2000), a Individuals with emotional disorders also show defi-
large literature also has implicated anxiety sensitivity in cits in mindfulness (Cheavens et al., 2005; Hayes et al.,
the development of other anxiety disorders and depres- 1996), a related construct that refers to attention and
sion (see Boswell, Farchione, et al., 2013; Naragon- awareness toward the present moment in an accepting
Gainey, 2010; Taylor, 1999). manner regardless of how unpleasant the experience
For example, prospective studies have demonstrated (Kabat-Zinn, 1982). Studies have shown that deficits in
that anxiety sensitivity predicts the onset of anxiety and mindfulness are common across the emotional disorders
depressive disorders (Maller & Reiss, 1992; Schmidt, (Baer, Smith, Hopkins, Kritemeyer, & Toney, 2006;
Keough, Timpano, & Richey, 2008) beyond the contribu- K. Brown & Ryan, 2003; Cash & Whittingham, 2010;
tions of the tendency to experience anxiety (see McNally, Rasmussen & Pidgeon, 2011), which supports the case
1996, for a review) and that reductions in anxiety sensi- for similar underlying constructs in these disorders.
tivity during treatment predict symptom improvement Results of a recent study on the effects of dispositional
(Gallagher et al., 2013). In addition, anxiety sensitivity mindfulness on response to a laboratory stressor sug-
has demonstrated incremental validity above trait neu- gested that individuals reporting higher levels of mindful-
roticism in the prediction of most mood and anxiety dis- ness display lower levels of self-reported anxiety and an
orders (Collimore, McCabe, Carelton, & Asmundson, attenuated cortisol response than do individuals endors-
2008; Cox, Enns, Walker, Kjernisted, & Pidlubny, 2001; ing lower levels of this construct (K. Brown, Weinstein, &
Kotov, Watson, Robles, & Schmidt, 2007; Norton et al., Creswell, 2011). The impact of mindfulness on stress-
1997; Reardon & Williams, 2007). These results support related cortisol secretion has been associated with atten-
the notion that how one relates to negative emotions is uated amygdala activation in response to threat (Creswell,
The Nature, Diagnosis, and Treatment of Neuroticism 351

Way, Eisenberger, & Leiberman, 2007). Consistent with and intensity (Rassin, Muris, Schmidt, & Merkelbach,
data on experiential avoidance, results from studies have 2000; Wegner, Schneider, Carter, & White, 1987). High
suggested that the degree to which one responds to neg- levels of emotion suppression have been demonstrated
ative emotions in a mindful manner predicts psychologi- across emotional disorders, including depression, gener-
cal symptoms over and above the contributions of a alized anxiety disorder, obsessive-compulsive disorder,
traitlike tendency to experience negative emotions (Sauer and posttraumatic stress disorder (Purdon, 1999), and
& Baer, 2009; Segal, Williams, & Teasdale, 2002). have also been shown to exacerbate symptoms
Evidence has suggested that many of the maladaptive (Abramowitz, Tolin, & Street, 2001). In particular, emo-
behaviors associated with emotional disorders serve a tional suppression has been associated with increased
function of facilitating escape or avoidance of intense physiological arousal (Hofmann, Heering, Sawyer, &
emotions. Such behaviors include overt situational avoid- Asnaani, 2009). It is hypothesized that emotion suppres-
ance as well as more subtle forms of avoidance and safety sion, like other forms of avoidance, is a negatively rein-
behaviors. For example, situational avoidance is a hall- forced behavior that produces short-term reductions in
mark feature of social anxiety disorder, specific phobias, negative affect, despite then spawning increased negative
posttraumatic stress disorder, depression, agoraphobia, emotions in the longer term.
and panic disorder (APA, 2013). Subtle forms of avoid- Rumination refers to repetitively and passively focus-
ance are also typical across most emotional disorders. In ing on negative mood and its possible causes, meanings,
generalized anxiety disorder and obsessive-compulsive and consequences (Nolen-Hoeksema, 1991). Like sup-
disorder, engaging in worry or compulsions (Newman & pression, rumination can be conceptualized as an avoid-
Llera, 2011), respectively, are subtle ways of avoiding the ant strategy because passive focus on surface matters
distress associated with experiencing anxiety. In social may serve to protect individuals from more distressing
anxiety, subtle avoidance can include behaviors such as concerns (Lyubomirsky & Nolen-Hoeksema, 1995;
decreased eye contact or standing farther away from peo- Lyubomirsky, Tucker, Caldwell, & Berg, 1999). Rumination
ple during conversations or safety behaviors, such as has been shown to intensify negative affect (Nolen-
engaging in social interactions only with a close friend Hoeksema, Wisco, & Lyubomirsky, 2008), which leads to
present. In panic disorder, subtle avoidance includes more rumination, in what Selby, Anestis, and Joiner
avoiding activities that produce anxietylike sensations, (2008) described as an emotional cascade; this process
such as exercise or drinking coffee (i.e., interoceptive continues until a maladaptive behavior (reassurance
avoidance). Safety behaviors across disorders include car- seeking, substance use, binge eating, etc.) interrupts the
rying around medications or even empty medication bot- cycle. Rumination appears to be prominent across emo-
tles, making sure to always have a cell phone or water on tional disorders (see Aldao et al., 2010) and prospectively
hand, or engaging in certain activities only with a “safe” predicts increases in anxiety and depressive symptoms
person. (Butler & Nolen-Hoeksema, 1994; Calmes & Roberts,
Addressing such behavioral avoidance is an important 2007; Hong, 2007; Nolen-Hoeksema, 2000; Nolen-
element of most cognitive-behavioral treatments for emo- Hoeksema, Larson, & Grayson, 1999; O’Connor,
tional disorders, such as through use of fear and avoid- O’Connor, & Marshall, 2007; Sarin, Abela, & Auerbach,
ance hierarchies in anxiety disorder protocols or activity 2005; Segerstrom, Tsao, Alden, & Craske, 2000).
scheduling in depression treatments. Some treatment It seems clear that negative reactions to strong emo-
protocols posit behavioral avoidance as comprising the tions lead to similar forms of avoidant cognitive coping
core of the dysfunction, as in the example of behavioral (e.g., emotion suppression and rumination) common to
activation, a well-supported treatment for depression, all emotional disorders. These strategies that intensify
which is based on the notion that depressive symptoms already strong negative emotions appear to lead to
are maintained by chronic avoidance of engagement or greater use of disorder-specific behavioral coping.
activity (Manos, Kanter, & Busch, 2010). Overall, the literature has suggested that individuals with
In addition to engaging in problematic avoidant emotional disorders experience strong negative emotions
behaviors, individuals with emotional disorders engage with frequency and evaluate these experiences as aver-
in cognitive coping motivated by avoidance. Such pro- sive. As a result of these negative reactions to their emo-
cesses include emotion suppression and rumination. tions, such individuals are more likely to engage in
Emotion suppression is a strategy in which individuals avoidant coping strategies to manage emotional experi-
deliberately attempt to push unpleasant, emotion-induc- ences, and these strategies, in turn, paradoxically increase
ing cognitions out of awareness; paradoxically, this strat- the frequency/intensity of negative emotions. Once
egy has been shown to produce rebound effects in which again, we suggest that this functional relationship, driven
the suppressed thoughts return with greater frequency by neuroticism, is at the core of disorders of emotion.
352 Barlow et al.

Neuroticism/Trait Anxiety, Nosology, that emerge as “blips” on a general background of tem-

and Dimensional Diagnosis of perament. The conceptualization of emotional disorders
in a more dimensional fashion should result in a more
Emotional Disorders
satisfactory representation of salient aspects of these dis-
It was long thought that DSM-IV-TR represented the orders that would eliminate vexing issues of comorbidity.
zenith of a splitting approach to nosology we described But moving from this conceptualization to a dimensional
earlier and that began in the 1980s with the publication system of diagnostic assessment with implications for
of DSM-III, an approach basically unchanged in DSM-5. treatment has proven an exceedingly difficult task even
The advent of an objective empirically based system of in areas such as personality disorders in which there is
classification of mental disorders was an enormous widespread agreement that this would be the preferred
advance over previous systems based on unsupported approach (Widiger & Crego, 2013). The recent failure to
etiological theories best exemplified by the term neuro- accomplish this goal in DSM-5 underscores these
sis. Beginning in the 1980s, with the splitting of neuroses difficulties.
into anxiety, depressive, somatoform, and related disor- In a preliminary attempt to conceptualize how this
ders, meaningful research on outcomes of pharmacologi- effort might work for emotional disorders, we proposed
cal and individual psychological treatments, particularly a dimensional classification scheme to reflect the research
cognitive-behavioral therapy, targeting these disorders described earlier (T. A. Brown & Barlow, 2009). The pur-
appeared (e.g., Barlow et al., 1984). It also became clear pose would be to create a profile that may provide a
at that time, on the basis of the pioneering work of Strupp more complete portrayal of a patient’s clinical presenta-
(1973), that clinical trials require the generation of tion than would a more categorical approach that often
detailed individual therapeutic protocols to specify an consists of several individual comorbid diagnoses. The
independent variable. As a result, these psychotherapeu- profile would highlight levels of constructs thought to be
tic treatments were increasingly characterized by well- important in forming a useful case conceptualization,
articulated individual protocols targeted to specific forms including neuroticism, extraversion (referred to as behav-
of psychopathology as articulated in DSM-III and its suc- ioral activation/positive affectivity in this model), avoid-
cessors, particularly anxiety and depressive disorders. ance, mood, and specific foci of anxiety (e.g., panic and
These treatments were then evaluated empirically and other autonomic surges, somatic symptoms, intrusive
found efficacious in a variety of formats, uses, and set- cognitions, social evaluation, and trauma). Scores on the
tings (Barlow, 1996, 2004, 2008; Barlow, Gorman, Shear, dimension of trait neuroticism, arguably the most impor-
& Woods, 2000; Heimberg, Liebowitz, & Hope, 1998; tant construct in this model, reflect the frequency, inten-
Nathan & Gorman, 2007). sity, and distress associated with negative emotions, as
It is fair to say that these findings have had a substan- well as perceptions of uncontrollability regarding future
tial impact in that public-health authorities have allocated challenges and low self-efficacy regarding one’s ability to
billions of dollars for training and dissemination of these cope. The higher-order dimension of extraversion/posi-
treatments (McHugh & Barlow, 2010). This approach to tive affect is also represented because low levels of this
nosology also has ensured high rates of diagnostic reli- trait are specifically associated with major depressive dis-
ability; however, as mentioned earlier, there was growing order, social anxiety disorder, and agoraphobia, whereas
suspicion both that advances in classification and treat- high levels are associated with euthymic states of bipolar
ment development represented by this approach came at and cyclothymic disorders. As highlighted earlier, indi-
the expense of diagnostic validity and that the current viduals with high levels of neuroticism are likely to dis-
system may be overemphasizing categories that are minor play avoidance behaviors. In this dimensional system,
variations of broader underlying syndromes. The careful avoidance is broken into two types: behavioral/intero-
consideration of these broader underlying syndromes as ceptive and cognitive/emotional.
a conceptual approach to nosology would not imply a Specific examples of disorder profiles highlight the
return to a nonempirical system of classification based on heuristic clinical value associated with dimensional clas-
theories of etiology. Rather, this thinking points to a sification of emotional disorders. For example, individu-
quantitative approach using structural equation modeling als with a principal diagnosis of panic disorder would
to examine the full range of anxiety and mood disorders likely display profiles with high levels of neuroticism,
without the constraints of artificial categories, given their avoidance, and preoccupation with panic/autonomic
strong relationship and potential overlap. Thus, our arousal and other somatic symptoms. In contrast, patients
evolving view is that DSM-5 emotional disorder catego- presenting with posttraumatic stress disorder might dis-
ries do not qualify in any sense as real entities (Kendell, play high neuroticism and preoccupation with panic/
1975) but do seem to be useful concepts or constructs autonomic arousal (flashbacks) and past trauma. Although
The Nature, Diagnosis, and Treatment of Neuroticism 353

each diagnostic category is linked to a prototypic dimen- is mixed. As noted earlier, Kagan (1989, 1994) described
sional profile, this classification system would allow clini- his conceptualization of behavioral inhibition as strongly
cians to determine the extent to which other key features heritable and stable; however, empirical evidence, includ-
are present that would potentially affect treatment plan- ing Kagan’s own work, has suggested that only 30% of
ning. A new measure, the multidimensional emotional children who clearly met criteria for this trait as young
disorder inventory (MEDI), recently was developed to children went on to develop anxiety disorders, although
assess these important vulnerabilities and characteristics some of the participants may have remained shy. Several
of emotional disorders with a single assessment tool; the additional studies have yielded similar results (e.g.,
ongoing MEDI validation study has suggested that this Hayward, Killen, Kraemer, & Taylor, 1998; Hirshfeld-
measure may be a reliable and valid method for assessing Becker et al., 2007; Schwartz, Snidman, & Kagan, 1999).
important emotional disorder dimensions (Rosellini, These results led Kagan to view behavioral inhibition as
2013). A representation of what a MEDI profile might look a constraining factor subject to environmental influences.
like is shown in Figure 1. These data present clinical esti- Such influences may include stress and having parents
mates of constructs composing the dimensional scheme diagnosed with anxiety disorders; behaviorally inhibited
from a patient seen at CARD with a principal diagnosis of third to sixth graders were more likely to experience
posttraumatic stress disorder (motor vehicle accident) and increased anxiety if they reported more daily hassles
additional diagnoses of generalized anxiety disorder and (Brozina & Abela, 2006) and were more likely to be diag-
subclinical depression. Under the current diagnostic sys- nosed with an anxiety disorder if their parents also expe-
tem, unless a patient meets full diagnostic criteria for a rienced such disorders (Biederman et al., 2001).
comorbid disorder, information on the dimensions not L. A. Clark (2009) has reviewed research examining
associated with the primary diagnosis are discarded. stability and change in personality disorders in adults.
Given that the rates of comorbidity among emotional dis- Contrary to the thinking of most personality theorists, as
orders are high, with even greater overlap at the subclini- well as a statement in the DSM-5, which holds that per-
cal level (T. A. Brown & Barlow 2009), a dimensional sonality traits are stable, inflexible, and pervasive, is
classification system would allow for the integration of Clark’s observation that the collection of traits and behav-
several important areas of functioning. iors that make up the definition of most personality dis-
orders do change, albeit slowly over time, with the
greatest change occurring in the behavioral manifesta-
Malleability of Neuroticism tions of these traits. Furthermore, researchers examining
The evidence regarding the malleability of personality longitudinal changes in negative traits, such as neuroti-
traits over time or in response to therapeutic intervention cism, in the normal population have observed gradual

100
90
80
70
60
Score

50
40
30
20
10
0
A/N BA/P DEP MAN SOM PAS IC SOC TRM AV-BI AV-CE

Fig. 1. Example profile of patient evaluated with a dimensional classification system. Higher scores on
the y-axis indicate higher levels of the x-dimension; otherwise, the y-axis metric is arbitrary and used for
illustrative purposes. A/N = anxiety/neuroticism; BA/P = behavioral activation/positive affect; DEP = uni-
polar depression; MAN = mania; SOM = somatic anxiety; PAS = panic and related autonomic surges; IC =
intrusive cognitions; SOC = social evaluation; TRM = past trauma; AV-BI = behavioral and interoceptive
avoidance; AV-CE = cognitive and emotional avoidance.
354 Barlow et al.

age-related decreases that continue long into old age also been examined (Eaton et al., 2011; Oltmanns &
(Roberts & Mroczeck, 2008; Roberts, Walton, & Viechtbauer, Balsis, 2011). Low levels of extraversion at Time 1 pre-
2006). Similar age-related decreases in the related higher- dicted poorer clinical outcome of major depressive disor-
order construct of internalizing have also been found; spe- der at the 8-month reassessment. Moreover, neuroticism
cifically, internalizing means and indicator intercepts were and extraversion were remarkably stable over time,
lower for older-aged cohorts (Eaton, Krueger, & Oltmanns, despite changes in clinical state. In fact, although more
2011; Oltmanns & Balsis, 2011). This pattern of results is than one third of depressed participants were classified
found at the mean level, which suggests that, summed as no longer depressed at the 8-month follow-up, neu-
across individuals, neuroticism decreases across time. In roticism and extraversion displayed the same high level
addition, change in neuroticism has been examined at the of temporal stability in this group as in a subgroup of
individual level using growth modeling (Mroczek & Spiro, participants who were depressed at both assessment
2003); results suggested that there is great variability in points. Despite these overall findings, because there was
extent of change on temperamental variables, with some no information available regarding what types of treat-
people remaining at stable levels and other people chang- ment patients received during this study, it is difficult to
ing a great deal (Helson, Jones, & Kwan, 2002; Small, determine how specific treatments may have affected the
Hertzog, Hultsch, & Dixon, 2003). temperamental constructs.
At CARD, we have also investigated longitudinal In contrast, other researchers have indeed found
change in neuroticism, with particular focus on respon- changes in neuroticism as a function of time and treat-
siveness to psychological intervention, and have encoun- ment. For example, we examined the temporal course
tered mixed findings. For example, in a study on the and temporal structural relationships of dimensions of
treatment of panic disorder (T. A. Brown & Barlow, 1995), temperament (neuroticism, extraversion) within DSM-IV-
comorbid anxiety and depressive diagnoses improved TR disorder constructs of depression, social anxiety dis-
immediately after successful treatment even though they order, and generalized anxiety disorder (T. A. Brown,
were not specifically targeted, which suggests, as 2007; T. A. Brown & Barlow, 2009). Outpatients with
described earlier, the existence of an underlying temper- these disorders (N = 606) were first examined at intake
amental vulnerability. But at a 2-year follow-up, comor- and then reassessed at 1- and 2-year follow-ups. The
bid diagnoses had returned to a level (30%) that was no majority (76%) of patients received some kind of treat-
longer significantly different from pretreatment. This ment after intake, although not all at CARD, of varying
result occurred despite the fact that, in the aggregate, duration and quality. The overall rate of diagnosed anxi-
patients maintained or improved on gains for panic ety and mood disorders declined significantly during
disorder across the follow-up interval, which indicates follow-up from 100% at intake to 58% at the 2-year fol-
considerable independence between panic disorder low-up. Despite the marked decline in DSM-IV-TR diag-
symptoms and related comorbidity. Although speculative, noses by the 2-year follow-up, test-retest correlations of
and contrary to the more usual interpretations offered the factors and unconditional latent growth models indi-
earlier, these findings may suggest that current cognitive- cated that extraversion evidenced a very high degree of
behavioral treatments are generally effective in address- temporal stability, consistent with its conceptualization as
ing the specific symptoms and maintaining processes of a trait vulnerability construct that is relatively unaffected
the targeted disorder (in this case, panic disorder) both by treatment. However, of the five constructs examined,
immediately and at follow-up but do not result in sub- neuroticism evidenced the greatest amount of temporal
stantial reductions in general predispositional features change and was the dimension associated with the larg-
(e.g., neuroticism), which leaves patients vulnerable to est treatment effect. In addition to its inconsistency with
the emergence or persistence of other disorders. These some prior research, such as that reviewed earlier (e.g.,
findings also raise the possibility that current psychologi- Kasch et al., 2002), this finding is clearly at odds with
cal treatments have become overly specialized because conceptual assumptions that core dimensions of temper-
they focus on disorder-specific features, such as panic ament are stable, inflexible, and more resistant to psy-
attacks in panic disorder or rituals connected to obses- chological treatment.
sional thought in obsessive-compulsive disorder, neglect- Levels of neuroticism and extraversion have also been
ing broader dimensions that might produce more explored in a more specified context across a large ran-
favorable long-term outcomes across all disorders. domized controlled trial of cognitive therapy compared
In a more direct evaluation of this issue, the temporal with placebo for adults with major depressive disorder
stability (8 months) and predictive utility of self-reported (Tang et al., 2009). Results indicated that cognitive ther-
levels of neuroticism and extraversion in 41 individuals apy produced greater changes in both neuroticism and
diagnosed with major depressive disorder (most of whom extraversion than did placebo, but contrary to T. A.
received some kind of treatment during this time) has Brown’s (2007) results, cognitive therapy maintained a
The Nature, Diagnosis, and Treatment of Neuroticism 355

significant effect only for extraversion after controlling these findings suggest that neuroticism may be therapeu-
for changes in depression symptoms during treatment. tically malleable, and it is this malleability that mediates
Nevertheless, the Tang et al. (2009) study differs from the extent of change in the emotional disorders.
Brown’s study in the clinical features of the sample (pure Some authors have suggested that decreases in neu-
major depressive disorder vs. heterogeneous anxiety and roticism over time may partly reflect the fact that mea-
unipolar depressive disorders) and the degree of control sures of temperament overlap to some degree with
provided regarding the treatment condition (placebo symptomatic measures of anxiety and depression, which
controlled and with stringent adherence/fidelity proce- results in distortions on estimates of temperament (mood-
dures vs. naturalistic, heterogeneous treatment). state distortion; cf. L. A. Clark, Vittengl, Kraft, & Jarrett,
There is also evidence that neuroticism may operate 2003; Jylhä & Isometsä, 2006; Widiger, Verheul, & van
differently than the DSM-IV-TR disorder constructs in sev- den Brink, 1999). That is, the measurement of neuroti-
eral ways (T. A. Brown, 2007). For instance, uncondi- cism consists of some combination of stable tempera-
tional latent growth models of each DSM-IV-TR disorder mental variance (i.e., vulnerability) and variability
construct revealed inverse relations between the inter- attributable to generalized distress that would be subject
cept and the slope; that is, higher initial disorder severity to greater temporal fluctuation and would imply that
was associated with greater change over time. However, neuroticism is apt to covary with temporal fluctuations in
the intercept and the slope of neuroticism were positively the severity of disorders. However, results from a recent
correlated (r = .47), which indicated that patients with study have suggested that measures of neuroticism (and
higher initial levels of neuroticism tended to show less extraversion) primarily capture true temperamental vari-
change in this dimension over time, and, conversely, ance even in individuals with emotional disorders
patients with lower initial levels of neuroticism tended to (Naragon-Gainey, Gallagher, & Brown, 2013). In addi-
evidence greater change. Thus, unlike the DSM-IV-TR dis- tion, a number of longitudinal studies have controlled for
orders, the stability of neuroticism increased as a function the periodic occurrence of anxious or depressive symp-
of initial severity. In addition, parallel-process latent toms and still found that neuroticism acted independently
growth models indicated that higher initial levels of neu- in predicting anxiety and mood (Lahey, 2009; Spijker, de
roticism were associated with less change in the DSM-IV- Graf, Oldehinkel, Nolen, & Ormel, 2007).
TR constructs of generalized anxiety disorder and social In sum, the malleability of neuroticism and other tem-
anxiety disorder. Although neuroticism alone demon- peramental variables, particularly in response to treat-
strated no temporal relation with depression, the pres- ment, remains an unsettled question. The studies
ence of chronic stress moderated the relationship such described earlier, in which researchers have examined
that high neuroticism resulted in less improvement in changes in temperamental variables in the context of
depression as the level of chronic stress increased (T. A. naturalistic treatments or treatments targeting disorder-
Brown & Rosellini, 2011). These results are consistent specific symptoms, have yielded mixed findings. In some
with results from earlier work, as well as theory, that studies, temperament dimensions appeared to change
showed that neuroticism has directional temporal effects during the course of treatment in the expected directions
on Axis I psychopathology (cf. Gershuny & Sher, 1998; (e.g., T. A. Brown, 2007; Kennedy, Rapee, & Edwards,
Kasch et al., 2002; Meyer, Johnson, & Winters, 2001) but 2009), whereas in other studies, no changes in tempera-
that the converse does not seem to occur; that is, initial ment occurred (e.g., Kasch et al., 2002). Inconsistencies
levels of the DSM-IV-TR disorders did not predict increases also exist in the degree to which the different dimensions
in temperament over time. of temperament respond to treatment across studies.
Finally, evidence has suggested that change in DSM Indeed, the research reviewed raises questions about the
disorder constructs (e.g., depression, social anxiety disor- nature and mechanisms of change of temperament dur-
der, and generalized anxiety disorder) is significantly ing treatment of emotional disorders, how best to mea-
related to change in neuroticism (T. A. Brown, 2007). Of sure temperament, and whether directly targeting
particular interest is the finding that all the temporal temperament therapeutically would lead to more defini-
covariance of the DSM-IV-TR disorder constructs was tive results.
accounted for by change in neuroticism; that is, when
neuroticism was specified as a predictor, there was no Prevention and Treatment of
temporal overlap among disorder constructs. The corre-
lational nature of these findings precludes firm conclu-
Neuroticism
sions about the direction of these effects. Nevertheless, In most of the studies in which researchers have exam-
and counter to some earlier evidence and conceptualiza- ined changes in temperament in response to psychologi-
tions (T. A. Brown et al., 1995; Kasch et al., 2002), all of cal interventions, including the studies described in the
356 Barlow et al.

previous section, researchers have not provided a priori that treatments can be designed to selectively target tem-
hypotheses regarding how and why the study treatment peramental variables. As a corollary, the pharmacologic
might affect temperament other than as a by-product of results also suggested that treatments, whether pharma-
symptom reduction. The interventions used were not cological or psychological, should not be expected to
designed to target features of temperament but, rather, to produce equivalent changes in temperament. Some treat-
address symptoms. Within such studies, it is difficult to ments may produce no effects on temperament, whereas
interpret changes in temperament. One explanation for other treatments may produce generalized or specific
the mixed findings across studies is that there may be effects on dimensions of temperament.
specific interactions between the intervention and Behavioral interventions designed to specifically
the dimensions of temperament that influence which address temperamental vulnerabilities are limited in num-
temperament variables respond and to what extent. Such ber. Rapee, Kennedy, Ingram, Edwards, and Sweeney’s
interactions have been largely unexplored in studies of (2005) intervention for children identified as behaviorally
psychological-treatment outcomes. However, recent inhibited was designed with the purpose of preventing
research from pharmacological-treatment studies has sup- the later onset of anxiety and related disorders and serves
ported this treatment-temperament interaction hypothe- as one example. The program consists of a parent-focused
sis, and emerging research from our own laboratory has intervention that includes psychoeducation about the
suggested that dimensions of temperament can be more nature of anxiety, traditional cognitive-behavioral strate-
directly targeted through specialized treatments. In this gies (i.e., exposure and cognitive restructuring) directed
section, we review recent evidence for treatments specifi- toward personal concerns, and training in behavior man-
cally designed to affect temperament and discuss briefly agement techniques that prevent an overprotective par-
our own efforts to develop a psychological treatment enting style. Results from randomized controlled trials
focused on directly addressing neurotic temperament. (Rapee et al., 2005; Rapee, Kennedy, Ingram, Edwards &
Most of the studies in which researchers examine Sweeney, 2010) have indicated that this program is clearly
interventions specifically designed to target temperament successful at preventing anxiety disorders, but for our
have come from the literature on psychopharmacology purposes, the most interesting findings are those on the
(for a review, see Soskin, Carl, Alpert, & Fava, 2012). effects of the program on temperament.
Results from these studies have provided some evidence Specifically, using a brief version of this program,
for specific interactions between treatment agents and Rapee et al. (2010) found that levels of behavioral inhibi-
temperament variables. To summarize, this research has tion did not differ significantly on the basis of either par-
indicated that serotonergic drug agents (i.e., selective ent report or laboratory observation, despite the success
serotonin reuptake inhibitors) produce dampening in preventing the later onset of anxiety disorders.
effects on neuroticism (Fu et al., 2004; Harmer et al., However, when the program was administered in a more
2009; Harmer, Mackay, Reid, Cowen, & Goodwin, 2006; intensive format with higher risk children, compared
Murphy, Yiend, Lester, Cowen, & Harmer, 2009; Quilty, with a group that did not receive the treatment, reduc-
Meusel, & Bagby, 2008) and possibly to a lesser extent on tions in measures of temperament did occur (Kennedy
extraversion (McCabe, Mishor, Cowen, & Harmer, 2010), et al., 2009). Rapee et al. also noted that differences
whereas catecholaminergic (i.e., noradrenergic/dopami- among groups seemed to increase with time, which sug-
nergic) agents produce specific enhancement of extraver- gested to them that interventions directed at tempera-
sion (McCabe et al., 2010; Tomarken, Dichter, Freid, ment (and related risk factors) might produce an
Addington, & Shelton, 2004). The specific neurobiologi- increasing trajectory of change in temperament over the
cal properties of these agents have been hypothesized to years, at least in children.
mediate such observed effects on temperament variables. In addition, some work has been conducted in an
For example, serotonergic agents have been shown to effort to identify intervention strategies specifically for
decrease hyperreactivity of the amygdala in response to targeting positive affect (extraversion). For example, in
fear-inducing stimuli and to inhibit dopaminergic neuro- an experience-sampling study, Mata et al. (2012) found
transmission in areas of the prefrontal cortex. In contrast, that both participants diagnosed with major depressive
catecholaminergic agents upregulate noradrenergic and disorder and control participants reported increases in
dopaminergic neurotransmission, particularly within the positive affect directly following physical activity and
mesolimbic reward circuitry (Soskin et al., 2012). Despite that depressed participants in particular demonstrated
the obvious differences between pharmacological and a dose-response effect such that longer and more
psychological treatments, the studies on preferential intense instances of physical activity led to greater
effects of pharmacological agents on dimensions of tem- increases in positive affect. Speisman, Kumar, Rani,
perament have provided some support for the notion Foster, and Ormerod (2012) recently demonstrated in
The Nature, Diagnosis, and Treatment of Neuroticism 357

animal laboratories that exercise increases neurogenesis, changes in temperament as they affect treatment out-
which could possibly be one mechanism of action in suc- comes. Neuroticism and extraversion contributed to both
cessful psychological treatments using exercise. Despite shared and distinct treatment outcomes. Decreased neu-
strong preliminary evidence, this theory must now roticism at posttreatment and at 6-month follow-up pre-
undergo the slow process of scientific confirmation. dicted decreased anxiety and depressive symptoms.
Given the clinical promise of therapeutically address- Increased extraversion was associated with decreased
ing temperamental vulnerabilities, we have devoted more depressive symptoms at posttreatment and decreased
than a decade to developing a psychological treatment anxiety symptoms at 6-month follow-up, and changes in
that targets the putative, fundamental, underlying pro- both temperament variables predicted reductions in
cesses of anxiety and mood disorders that may be more functional impairment at 6-month follow-up. Finally,
closely related to temperament. This treatment, the uni- extraversion alone was associated with higher quality of
fied protocol for transdiagnostic treatment of emotional life at posttreatment and at 6-month follow-up. Although
disorders (UP), which has been described in detail else- preliminary, these results suggest that there are both
where (Barlow et al., 2011), is a cognitive-behavioral common and differentiated outcomes associated with
intervention designed to address core temperamental changes in specific dimensions of temperament. Although
processes in emotional disorders. The UP targets identifi- both neuroticism and extraversion can affect depression
cation and modification of the strong negative reactions and anxiety symptoms and functional impairment, only
to emotions that lead to problematic, avoidant coping extraversion appears to directly influence quality of life.
across emotional disorders (Ellard, Fairholme, Boisseau, In future research, it will be important to investigate and
Farchione, & Barlow, 2010). Amelioration of negative gain a better understanding of what accounts for the vari-
reactions to emotions in turn changes the frequency and ability in the effects of these temperamental predictors
intensity of future emotional experiences and thereby on treatment outcomes.
affects temperamental constructs. In summary, contrary to traditional conceptions, a
The UP has now been evaluated for its efficacy in variety of research has suggested that dimensions of tem-
treating anxiety disorders in a series of preliminary trials perament may be malleable over time or in response to
culminating with a small randomized controlled trial (N = treatment, but such findings have been mixed, which
37) comparing a treatment group with a wait list control indicates that more research is required to identify spe-
group (Ellard et al., 2010; Farchione et al., 2012). Results cific conditions that affect temperament. Specifically,
from these studies have indicated that the UP is an effica- recently developed interventions that target dimensions
cious treatment for a range of anxiety disorders with sta- of temperament more directly have provided preliminary
ble improvements out to an 18-month follow-up (Bullis, support for the notion that psychological interventions
Fortune, Farchione, & Barlow, 2013). We have also can address temperamental vulnerabilities and that such
recently begun a large randomized controlled equiva- improvements are associated with a range of beneficial
lence trial (N = 250) comparing the UP with four well- treatment outcomes (Carl et al., 2013; Farchione et al.,
established single anxiety disorder treatment protocols 2012; Kennedy et al., 2009). If confirmed, these findings
on the basis of patients’ principal diagnoses (generalized may shift the focus of investigation into the nature, diag-
anxiety disorder, obsessive-compulsive disorder, social nosis, and treatment of emotional disorders.
anxiety disorder, or panic disorder with or without
agoraphobia).
Future Research Directions
In following with the goal of assessing the extent to
which the UP addresses temperamental vulnerabilities in The construct of neuroticism is almost as old as the study
addition to current symptoms, we have also conducted of psychopathology itself, but recent developments
an investigation of the effects of the UP on dimensions of described herein suggest fresh, new directions for
temperament (see Carl, Gallagher, Sauer-Zavala, Bentley, research. Considered broadly, can we develop targeted
& Barlow, 2013) in the context of the randomized con- psychological interventions for neuroticism? If so, will
trolled trial mentioned in the previous paragraph (i.e., these interventions provide a more efficient and effective
Farchione et al., 2012). In brief, our results indicated that way to affect the broad sweep of phenomena across the
in the treatment group, compared with the wait list group, spectrum of emotional disorders, including common pat-
the UP produced small to moderate effects on both neu- terns of comorbidity and subthreshold symptomatic pre-
roticism and extraversion from pre- to posttreatment, and sentations? Will these conceptions move us further along
these changes in temperament are associated with toward the goal of a more satisfactory dimensional sys-
improvements in core symptomatology, functional tem for classifying the emotional disorders and facilitate
impairment, and quality of life (Carl et al., 2013). The the development of diagnostic instruments that will
results of this investigation suggest the importance of greatly simplify the process of assessment? And can we
358 Barlow et al.

usefully extend these research objectives to other rele- Baer, R. A., Smith, G. T., Hopkins, J., Kritemeyer, J., & Toney,
vant temperaments, such as positive affect and perhaps L. (2006). Using self-report assessment methods to explore
constraint? The accumulation of important basic research facets of mindfulness. Assessment, 13, 27–45.
covered briefly in this review suggests that it may now be Baker, R., Holloway, J., Thomas, P., Thomas, S., & Owens,
M. (2004). Emotional processing and panic. Behaviour
possible to translate these concepts into a fundamentally
Research and Therapy, 42, 1271–1287.
new approach to the diagnosis, assessment, and treat-
Barlow, D. H. (1988). Anxiety and its disorders: The nature and
ment of emotional disorders. treatment of anxiety and panic. New York, NY: Guilford
Press.
Author Contributions Barlow, D. H. (1991). Disorders of emotion. Psychological
D. H. Barlow developed the main thesis of the manuscript. Inquiry, 2, 58–71.
D. H. Barlow, S. Sauer-Zavala, J. R. Carl, J. R. Bullis, and K. K. Barlow, D. H. (1996). The effectiveness of psychotherapy:
Ellard all contributed substantially to the literature review and Science and policy. Clinical Psychology: Science and
subsequent drafting of the manuscript in support of this thesis. Practice, 3, 236–240.
Barlow, D. H. (2000). Unraveling the mysteries of anxiety
Acknowledgments and its disorders from the perspective of emotion theory.
American Psychologist, 55, 1247–1263.
Portions of this article were presented by D. H. Barlow as the Barlow, D. H. (2002). Anxiety and its disorders: The nature and
James McKeen Cattell Address at the Annual Meeting of the treatment of anxiety and panic (2nd ed.). New York, NY:
Association for Psychological Science, May 2012. Guilford Press.
Barlow, D. H. (2004). Psychological treatments. American
Declaration of Conflicting Interests Psychologist, 59, 869–878.
The authors declared that they had no conflicts of interest with Barlow, D. H. (2008). Clinical handbook of psychological dis-
respect to their authorship or the publication of this article. orders: A step-by-step treatment manual (4th ed.). London,
England: Oxford University Press.
Note Barlow, D. H., Cohen, A. S., Waddell, M. T., Vermilyea, B. B.,
Klosko, J. S., Blanchard, E. B., & DiNardo, P. A. (1984).
1. We henceforth refer to this construct as neuroticism; how-
Panic and generalized anxiety disorders: Nature and treat-
ever, it should be noted that the individual studies described
ment. Behavior Therapy, 15, 431–449.
may have used alternate terms.
Barlow, D. H., Ellard, K. K., Fairholme, C., Farchione, T. J.,
Boisseau, C., Allen, L., & Ehrenreich-May, J. (2011). Unified
References protocol for the transdiagnostic treatment of emotional dis-
Abramowitz, J., Tolin, D., & Street, G. (2001). Paradoxical effects orders. New York, NY: Oxford University Press.
of thought suppression: A meta-analysis of controlled stud- Barlow, D. H., Ellard, K. K., Sauer-Zavala, S., Bullis, J. R., & Carl,
ies. Clinical Psychology Review, 21, 683–703. J. R. (2013). The origins of trait neuroticism. Manuscript in
Aldao, A., Nolen-Hoeksema, S., & Schweizer, S. (2010). preparation.
Emotion-regulation strategies across psychopathology: A Barlow, D. H., Gorman, J. M., Shear, M. K., & Woods, S. W.
meta-analytic review. Clinical Psychology Review, 30, 217– (2000). Cognitive-behavioral therapy, imipramine, or their
237. doi:10.1016/[Link].2009.11.004. combination for panic disorder: A randomized controlled
Allen, L. B., White, K. S., Barlow, D. H., Shear, K. M., Gorman, trial. Journal of the American Medical Association, 283,
J. M., & Woods, S. W (2010). Cognitive-behavior therapy 2529–2536.
(CBT) for panic disorder: Relationship of anxiety and Begotka, A., Woods, D., & Wetterneck, C. (2004). The rela-
depression comorbidity with treatment outcome. Journal of tionship between experiential avoidance and the sever-
Psychopathology and Behavioral Assessment, 32, 185–192. ity of trichotillomania in a nonreferred sample. Journal of
American Psychiatric Association. (1980). Diagnostic and sta- Behavior Therapy and Experimental Psychiatry, 35, 17–24.
tistical manual of mental disorders (3rd ed.). Washington, Berking, M., Neacsiu, A., Comtois, K., & Linehan, M. (2009).
DC: Author. The impact of experiential avoidance on the reduction of
American Psychiatric Association. (2000). Diagnostic and sta- depression in treatment for borderline personality disorder.
tistical manual of mental disorders (4th ed., text rev.). Behaviour Research and Therapy, 47, 663–670.
Washington, DC: Author. Biederman, J., Hirshfeld-Becker, D., Rosenbaum, J., Herot, C.,
American Psychiatric Association. (2013). Diagnostic and statis- Friedman, D., Snidman, N., . . . Farone, S. (2001). Further
tical manual of mental disorders (5th ed.). Arlington, VA: evidence of the association between behavioral inhibi-
American Psychiatric Publishing. tion and social anxiety in children. American Journal of
Andrews, G. (1990). Classification of neurotic disorders. Journal Psychiatry, 158, 1673–1679.
of the Royal Society of Medicine, 83, 606–607. Biederman, J., Rosenbaum, J. F., Bolduc-Murphy, E. A., Faraone,
Andrews, G. (1996). Comorbidity in neurotic disorders: The S. V., Chaloff, J., Hirshfeld, D. R., & Kagan, J. (1993). A
similarities are more important than the differences. In 3-year follow-up of children with and without behavioral
R. M. Rapee (Ed.), Current controversies in the anxiety dis- inhibition. Journal of the American Academy of Child and
orders (pp. 3–20). New York, NY: Guilford Press. Adolescent Psychiatry, 32, 814–821.
The Nature, Diagnosis, and Treatment of Neuroticism 359

Biederman, J., Rosenbaum, J., Hirshfeld, D., & Faraone, S. the DSM-IV anxiety and mood disorders: Implications for
(1990). Psychiatric correlates of behavioral inhibition in assessment and treatment. Psychological Assessment, 21,
young children of parents with and without psychiatric dis- 256–271.
orders. Archives of General Psychiatry, 47, 21–26. Brown, T. A., Campbell, L. A., Lehman, C. L., Grisham, J. R., &
Blair, K., Shaywitz, J., Smith, B. W., Rhodes, R., Geraci, M., Mancill, R. B. (2001). Current and lifetime comorbidity of
Jones, M., . . . Pine, D. S. (2008). Response to emotional the DSM-IV anxiety and mood disorders in a large clinical
expressions in generalized social phobia and generalized sample. Journal of Abnormal Psychology, 110, 49–58.
anxiety disorder: Evidence for separate disorders. American Brown, T. A., Chorpita, B. F., & Barlow, D. H. (1998). Structural
Journal of Psychiatry, 165, 1193–1202. doi:10.1176/appi relationships among dimensions of the DSM-IV anxiety and
.ajp.2008.0707106 mood disorders and dimensions of negative affect, posi-
Boelen, P., Vrinssen, I., & van Tulder, F. (2010). Intolerance of tive affect, and autonomic arousal. Journal of Abnormal
uncertainty in adolescents: Correlations with worry, anxi- Psychology, 107, 179–192.
ety, social anxiety, and depression. Journal of Nervous and Brown, T. A., & McNiff, J. (2009). Specificity of autonomic
Mental Disease, 198, 194–200. arousal to DSM-IV panic disorder and post-traumatic
Borkovec, T. D., Abel, J. L., & Newman, H. (1995). Effects stress disorder. Behaviour Research and Therapy, 47,
of psychotherapy on comorbid conditions in general- 487–493.
ized anxiety disorder. Journal of Consulting and Clinical Brown, T. A., & Rosellini, A. J. (2011). The direct and interac-
Psychology, 63, 479–483. tive effects of neuroticism and life stress on the severity and
Boswell, J. F., Farchione, T. J., Sauer-Zavala, S. E., Murray, H. longitudinal course of depression. Journal of Abnormal
W., Fortune, M., & Barlow, D. H. (2013). Anxiety sensitiv- Psychology, 120, 844–856.
ity and interoceptive exposure: A transdiagnostic construct Brozina, K., & Abela, J. (2006). Behavioral inhibition, anx-
and change strategy. Behavior Therapy, 44, 417–431. ious symptoms, and depressive symptoms: A short-term
Boswell, J. F., Thompson-Hollands, J., Farchione, T. J., & prospective examination of the diathesis-stress model.
Barlow, D. H. (2013). Intolerance of uncertainty: A com- Behaviour Research and Therapy, 44, 1337–1346.
mon factor in the treatment of emotional disorders. Journal Bullis, J. R., Fortune, M. R., Farchione, T. J., & Barlow,
of Clinical Psychology, 69, 630–645. doi:10.1002/jclp.21965 D. H. (2013). Long-term outcome of the unified protocol
Bouton, M., Mineka, S., & Barlow, D. H. (2001). Modern learn- for the transdiagnostic treatment of emotional disorders.
ing theory perspective on the etiology of panic disorder. Manuscript submitted for publication.
Psychological Review, 108, 4–32. Butler, L., & Nolen-Hoeksema, S. (1994). Gender differences
Brown, K., & Ryan, R. (2003). The benefits of being pres- in responses to depressed mood in a college sample. Sex
ent: Mindfulness and its role in psychological well-being. Roles, 30, 331–346.
Journal of Personality and Social Psychology, 84, 822–848. Calmes, C., & Roberts, J. (2007). Repetitive thought and emo-
Brown, K., Weinstein, N., & Creswell, D. (2011). Trait mind- tional distress: Rumination and worry as prospective predic-
fulness modulates neuroendocrine and affective responses tors of depressive and anxious symptomatology. Cognitive
to social-evaluative threat. Psychoneuroendocrinology, 37, Therapy and Research, 31, 343–356.
2037–2041. Campbell-Sills, L., Barlow, D., Brown, T., & Hofman, S. (2006).
Brown, T. A. (2007). Temporal course and structural relation- Acceptability and suppression of negative emotion in anxi-
ships among dimensions of temperament and DSM–IV anx- ety and mood disorders. Emotion, 6, 587–595.
iety and mood disorder constructs. Journal of Abnormal Campbell-Sills, L., Liverant, G. I., & Brown, T. A. (2004).
Psychology, 116, 313–328. Psychometric evaluation of the behavioral inhibition/
Brown, T. A., Antony, M. M., & Barlow, D. H. (1995). Diagnostic behavioral activation scales in a large sample of outpatients
comorbidity in panic disorder: Effect on treatment outcome with anxiety and mood disorders. Psychological Assessment,
and course of comorbid diagnoses following treatment. 16, 244–254.
Journal of Consulting and Clinical Psychology, 63, 408–418. Carl, J. R., Gallagher, M. W., Sauer-Zavala, S. E., Bentley, K. H.,
Brown, T. A., & Barlow, D. H. (1995). Long-term outcome in & Barlow, D. H. (2013). A preliminary examination of the
cognitive-behavioral treatment of panic disorder: Clinical effects of the unified protocol on temperament. Manuscript
predictors and alternative strategies for assessment. Journal submitted for publication.
of Consulting and Clinical Psychology, 63, 754–765. Cash, M., & Whittingham, K. (2010). What facets of mindful-
Brown, T. A., & Barlow, D. H. (2002). Classification of anxiety ness contribute to psychological well-being and depressive,
and mood disorders. In D. H. Barlow (Ed.), Anxiety and its anxious, and stress-related symptomatology? Mindfulness,
disorders: The nature and treatment of anxiety and panic 1, 177–182.
(2nd ed., pp. 292–327). New York, NY: Guilford Press. Cheavens, J., & Heiy, J. (2011). The differential roles of affect
Brown, T. A., & Barlow, D. H. (2005). Dimensional versus cat- and avoidance in major depressive and borderline person-
egorical classification of mental disorders in the fifth edition ality disorder symptoms. Journal of Social and Clinical
of Diagnostic and Statistical Manual of Mental Disorders Psychology, 30, 441–457.
and beyond: Comment on the special section. Journal of Cheavens, J., Rosenthal, M., Daughters, S., Novak, J., Kosson,
Abnormal Psychology, 114, 551–556. D., & Lynch, T. (2005). An analogue investigation of the
Brown, T. A., & Barlow, D. H. (2009). A proposal for a dimen- relationships among perceived parental criticism, nega-
sional classification system based on the shared features of tive affect, and borderline personality disorder features:
360 Barlow et al.

The role of thought suppression. Behaviour Research and development and initial outcome data. Cognitive and
Therapy, 43, 257–268. Behavioral Practice, 17, 88–101. doi:10.1016/[Link].2009
Chorpita, B. F., Albano, A. M., & Barlow, D. H. (1998). The .06.002
structure of negative emotions in a clinical sample of chil- Etkin, A., Prater, K. E., Hoeft, F., Menon, V., & Schatzberg,
dren and adolescents. Journal of Abnormal Psychology, A. F. (2010). Failure of anterior cingulate activation and
107, 74–85. connectivity with the amygdala during implicit regulation
Chorpita, B. F., Brown, T. A., & Barlow, D. H. (1998). Perceived of emotional processing in generalized anxiety disorder.
control as a mediator of family environment in etiologi- American Journal of Psychiatry, 167, 545–554. doi:10.1176/
cal models of childhood anxiety. Behavior Therapy, 29, [Link].2009.09070931
457–476. Etkin, A., & Wager, T. D. (2007). Functional neuroimaging of
Clark, D. M. (1986). A cognitive approach to panic. Behaviour anxiety: A meta-analysis of emotional processing in PTSD,
Research and Therapy, 24, 461–470. social anxiety disorder, and specific phobia. American
Clark, L. A. (2005). Temperament as a unifying basis for per- Journal of Psychiatry, 164, 1476–1488. doi:10.1176/appi.
sonality and psychopathology. Journal of Abnormal ajp.2007.07030504
Psychology, 114, 505–521. Eysenck, H. J. (1947). Dimensions of personality. Oxford,
Clark, L. A. (2009). Stability and change in personality disorder. England: Kegan Paul.
Current Directions in Psychological Science, 18, 27–31. Eysenck, H. J. (1961). The handbook of abnormal psychology.
Clark, L. A., Vittengl, J., Kraft, B., & Jarrett, D. (2003). Separate New York, NY: Basic Books.
personality traits from states to predict depression. Journal Eysenck, H. J. (1981). A model for personality. New York, NY:
of Personality Disorders, 17, 152–172. Springer-Verlag.
Clark, L. A., & Watson, D. (1991). Tripartite model of anxiety and Eysenck, H. J., & Eysenck, S. B. G. (1975). Manual of the
depression: Psychometric evidence and taxonomic implica- Eysenck Personality Questionnaire (adult and junior).
tions. Journal of Abnormal Psychology, 103, 103–116. London, England: Hodder & Stoughton.
Clark, L. A., & Watson, D. (2008). Temperament: An organizing Farchione, T. J., Fairholme, C. P., Ellard, K. K., Boisseau, C. L.,
paradigm for trait psychology. In O. P. John, R. R. Robins, Thompson-Hollands, J., Carl, J., . . . Barlow, D. H. (2012).
& L. A. Pervin (Eds.), Handbook of personality: Theory and Unified protocol for the transdiagnostic treatment of emo-
research (3rd ed.). New York, NY: Guilford Press. tional disorders: A randomized controlled trial. Behavior
Clark, L. A., Watson, D., & Mineka, S. (1994). Temperament, Therapy, 43, 666–678.
personality, and the mood and anxiety disorders. Journal Freud, S. (1924). Collected papers. New York, NY: International
of Abnormal Psychology, 103, 103–116. Psychoanalytic Press.
Collimore, K., McCabe, R., Carelton, N., & Asmundson, G. Fu, C. H. Y., Williams, S. C. R., Cleare, A. J., Brammer, M. J.,
(2008). Media exposure and dimensions of anxiety sensitiv- Walsh, N. D., Kim, J., . . . Bullmore, E. T. (2004). Attenuation
ity: Differential associations with PTSD symptom clusters. of the neural response to sad faces in major depression by
Journal of Anxiety Disorders, 22, 1021–1028. antidepressant treatment. Archives of General Psychiatry,
Cox, B., Enns, M., Walker, J., Kjernisted, K., & Pidlubny, S. 61, 877–889.
(2001). Psychological vulnerabilities in patients with major Gallagher, M. W., Payne, L. P., White, K. S., Shear, K. M., Woods,
depression versus panic disorder. Behaviour Research and S. W., Gorman, J. M., & Barlow, D. H. (2013). Mechanisms
Therapy, 39, 567–573. of change in cognitive-behavioral therapy for panic disor-
Cox, B., Taylor, S., & Enns, M. (1999). Fear of cognitive dys- der: The unique effects of self-efficacy and anxiety sensitiv-
control in relation to depressive symptoms: Comparisons ity. Manuscript submitted for publication.
between original and alternative measures of anxiety sen- Gershuny, B. S., & Sher, K. J. (1998). The relation between
sitivity. Journal of Behavior Therapy and Experimental personality and anxiety: Findings from a 3-year prospective
Psychiatry, 30, 301–311. study. Journal of Abnormal Psychology, 107, 252–262.
Creswell, D., Way, B., Eisenberger, N., & Leiberman, M. (2007). Goldberg, L. (1993). The structure of phenotypic personality
Neural correlates of dispositional mindfulness during affect traits. American Psychologist, 48, 26–34.
labeling. Psychosomatic Medicine, 69, 560–565. Gray, J. A. (1982). The neuropsychology of anxiety. New York,
Cuijpers, P., Smit, F., Penninx, B. W. J. H., de Graaf, R., ten NY: Oxford University Press.
Have, M., & Beekman, A. T. F. (2010). Economic costs of Gray, J. A. (1991). The neuropsychology of temperament. In
neuroticism: A population based study. Archives of General J. Strelau & A. Angleitner (Eds.), Explorations in tempera-
Psychiatry, 67, 1086–1093. ment: International perspectives in theory and measure-
Digman, J. (1990). Personality structure: Emergence of the five- ment (pp. 105–128). New York, NY: Plenum.
factor model. Annual Review of Psychology, 41, 417–440. Gray, J. A., & McNaughton, N. (1996). The neuropsychology of
Eaton, N., Krueger, R., & Oltmanns, T. (2011). Aging and the anxiety: A reprise. In D. A. Hope (Ed.), Nebraska Symposium
structure and long-term stability of the internalizing spec- on Motivation: Vol. 43. Perspectives on Anxiety, Panic, and
trum of personality and psychopathology. Psychology and Fear (pp. 61–134). Lincoln: University of Nebraska Press
Aging, 26, 987–993. Griffith, J. W., Zinbarg, R. E., Craske, M. G., Mineka, S., Rose,
Ellard, K. K., Fairholme, C. P., Boisseau, C. L., Farchione, R. D., Waters, A. M., & Sutton, J. M. (2010). Neuroticism
T. J., & Barlow, D. H. (2010). Unified protocol for the as a common dimension in the internalizing disorders.
transdiagnostic treatment of emotional disorders: Protocol Psychological Medicine, 40, 1125–1136.
The Nature, Diagnosis, and Treatment of Neuroticism 361

Harmer, C. J., Mackay, C. E., Reid, C. B., Cowen, P. J., & Hudson, J. I., & Pope, H. G. (1990). Affective spectrum disor-
Goodwin, G. M. (2006). Antidepressant drug treatment der: Does antidepressant response identify a family of dis-
modifies the neural processing of nonconscious threat orders with a common pathophysiology? American Journal
cues. Biological Psychiatry, 59, 816–820. of Psychiatry, 147, 552–564.
Harmer, C. J., O’Sullivan, U., Favaron, E., Massey-Chase, R., John, O. P. (1990). The “Big Five” factor taxonomy: Dimensions
Ayres, R., Reinecke, A., . . . Cowen, P. J. (2009). Effect of of personality in the natural language and in questionnaires.
acute antidepressant administration on negative affective In L. A. Pervin (Ed.), Handbook of personality: Theory and
bias in depressed patients. American Journal of Psychiatry, research (pp. 66–100). New York, NY: Guilford Press.
166, 1178–1184. John, O. P., & Srivastava, S. (1999). The Big Five trait taxonomy:
Hayes, S. C., Luoma, J. B., Bond, F. W., Masuda, A., & Lillis, J. History, measurement, and theoretical perspectives. In
(2006). Acceptance and commitment therapy: Model, pro- L. A. Pervin & O. P. John (Eds.), Handbook of personality:
cesses and outcomes. Behaviour Research and Therapy, Theory and research (2nd ed., pp. 102–138). New York,
44, 1–25. NY: Guilford Press.
Hayes, S. C., Wilson, K. G., Gifford, E. V., Follette, V. M., & Jylhä, P., & Isometsä, E. (2006). The relationship of neuroticism
Strosahl, K. (1996). Experiential avoidance and behavioral and extraversion to symptoms of anxiety and depression in
disorders: A functional dimensional approach to diag- the general population. Depression and Anxiety, 23, 281–289.
nosis and treatment. Journal of Consulting and Clinical Kabat-Zinn, J. (1982). An outpatient program in behavioral
Psychology, 64, 1152–1168. medicine for chronic pain patients based on the practice
Hayward, C., Killen, J. D., Kraemer, H. C., & Taylor, C. B. of mindfulness meditation: Theoretical considerations and
(1998). Linking self-reported childhood behavioral inhibi- preliminary results. General Hospital Psychiatry, 4, 33–47.
tion to adolescent social phobia. Journal of the American Kagan, J. (1989). Temperamental contributions to social behav-
Academy of Child and Adolescent Psychiatry, 37, 1308– ior. American Psychologist, 44, 668–674.
1316. Kagan, J. (1994). Galen’s prophecy: Temperament in human
Heimberg, R. G., Liebowitz, M. R., & Hope, D. A. (1998). nature. New York, NY: Basic Books.
Cognitive behavioral group therapy versus phenelzine Kagan, J., & Snidman, N. (1991). Infant predictors of inhibited
therapy for social phobia: 12-week outcome. Archives of and uninhibited profiles. Psychological Science, 2, 40–44.
General Psychiatry, 55, 1133–1141. Kasch, K. L., Rottenberg, J., Arnow, B. A., & Gotlib, I. H.
Helson, R., Jones, C., & Kwan, V. S. (2002). Personality change (2002). Behavioral activation and inhibition systems and
over 40 years of adulthood: Hierarchical linear modeling the severity and course of depression. Journal of Abnormal
analyses of two longitudinal samples. Journal of Personality Psychology, 111, 589–597.
and Social Psychology, 83, 752–766. Kashdan, T. B., Breen, W. E., Afram, A., & Terhar, D. (2010).
Hirshfeld-Becker, D. R., Biederman, J. F., Henin, A., Faraone, Experiential avoidance in idiographic, autobiographi-
S. V., Davis, S., Harrington, K., & Rosenbaum, J. (2007). cal memories: Construct validity and links to social anxi-
Behavioral inhibition in preschool children at risk is a spe- ety, depressive, and anger symptoms. Journal of Anxiety
cific predictor of middle childhood social anxiety: A five- Disorders, 24, 528–534.
year follow-up. Journal of Developmental and Behavioral Keightley, M. L., Seminowicz, D. A., Bagby, R. M., Costa, P. T.,
Pediatrics, 28, 225–233. Fossati, P., & Mayberg, H. S. (2003). Personality influences
Hirshfeld-Becker, D. R., Rosenbaum, J. F., Biederman, J. F., limbic-cortical interactions during sad mood induction.
Bolduc, E. A., Faraone, S. V., Snidman, N., . . . Kagan, J. NeuroImage, 20, 2031–2039.
(1992). Stable behavioral inhibition and its association with Kendell, R. E. (1975). The role of diagnosis in psychiatry.
anxiety disorder. Journal of the American Academy of Child Oxford, England: Blackwell Scientific.
and Adolescent Psychiatry, 31, 103–111. Kennedy, S. J., Rapee, R. M., & Edwards, S. L. (2009). A selective
Hoehn-Saric, R., Schlund, M. W., & Wong, S. H. Y. (2004). Effects intervention program for inhibited preschool-aged children
of citalopram on worry and brain activation in patients with of parents with an anxiety disorder: Effects on current anxi-
generalized anxiety disorder. Psychiatry Research, 131, 11– ety disorders and temperament. Journal of the American
21. doi:10.1016/[Link].2004.02.003 Academy of Child and Adolescent Psychiatry, 48, 602–609.
Hofmann, S. G., Heering, S., Sawyer, A. T., & Asnaani, A. doi:10.1097/CHI.0b013e31819f6fa9
(2009). How to handle anxiety: The effects of reap- Kessler, R. C., Berglund, P., & Demler, O. (2003). The epide-
praisal, acceptance, and suppression strategies on anxious miology of major depressive disorder: Results from the
arousal. Behaviour Research and Therapy, 47, 389–394. National Comorbidity Survey Replication (NCS-R). Journal
doi:10.1016/[Link].2009.02.010 of the American Medical Association, 289, 3095–3105.
Holmes, A. J., Lee, P. H., Hollinshead, M. O., Bakst, L., Roffman, Kessler, R. C., Cox, B. J., Green, J. G., Ormel, J., McLaughlin,
J. L., Smoller, J. W., & Buckner, R. I. (2012). Individual dif- K. A., Merikangas, K. R., . . . Zaslavsky, A. M. (2011). The
ferences in amygdala-medial prefrontal anatomy link nega- effects of latent variables in the development of comor-
tive affect, impaired social functioning, and polygenetic bidity among common mental disorders. Depression and
depression link. Journal of Neuroscience, 32, 18087–18100. Anxiety, 28, 29–39.
Hong, R. Y. (2007). Worry and rumination: Differential associa- Kessler, R. C., Gruber, M., Hettema, J. M., Hwang, I., Sampson,
tions with anxious and depressive symptoms and coping N., & Yonkers, K. A. (2008). Comorbid major depres-
behavior. Behaviour Research and Therapy, 45, 277–290. sion and generalized anxiety disorders in the National
362 Barlow et al.

Comorbidity Survey follow-up. Psychological Medicine, 38, Mathews, A., & McLeod, C. (2005). A cognitive vulnerability to
365–374. emotional disorders. Annual Review of Clinical Psychology,
Kessler, R. C., Nelson, C. B., McGonagle, K. A., Lui, J., Swartz, 1, 167–195.
M., & Blazer, D. G. (1996). Comorbidity of DSM-III-R major Mayberg, H. S., Liotti, B. M., Brannan, S. K., McGinnis, S.,
depressive disorder in the general population: Results Mahurin, R. K., Jerabek, P. A., . . . Fox, P. T. (1999).
from the National Comorbidity Survey. British Journal of Reciprocal limbic-cortical function and negative mood:
Psychiatry, 168, 17–30. Converging PET findings in depression and normal sad-
Kessler, R. C., Stang, P. E., Wittchen, H. U., Ustun, T. B., Roy- ness. American Journal of Psychiatry, 156, 675–682.
Byrne, P. P., & Walters, E. E. (1998). Lifetime panic-depres- McCabe, C., Mishor, Z., Cowen, P. J., & Harmer, C. J. (2010).
sion comorbidity in the National Comorbidity Survey. Diminished neural processing of aversive and rewarding
Archives of General Psychiatry, 55, 801–808. stimuli during selective serotonin reuptake inhibitor treat-
Kotov, R., Watson, D., Robles, J. P., & Schmidt, N. B. (2007). ment. Biological Psychiatry, 67, 439–445.
Personality traits and anxiety symptoms: The multilevel McCrae, R. R., & Costa, P. T. (1987). Validation of the five-fac-
trait predictor model. Behaviour Research and Therapy, 45, tor model of personality across instruments and observers.
1485–1503. Journal of Personality and Social Psychology, 52, 81–90.
Krueger, R. F. (1999). The structure of common mental disor- McHugh, R. K., & Barlow, D. H. (2010). The dissemination and
ders. Archives of General Psychiatry, 56, 921–926. implementation of evidence-based psychological treat-
Lahey, B. B. (2009). Public health significance of neuroticism. ments: A review of current efforts. American Psychologist,
American Psychologist, 64, 241–256. 65, 73–84.
Lee, J. K., Orsillo, S. M., Roemer, L., & Allen, L. B. (2010). McLaughlin, K. A., Mennin, D. S., & Farach, F. J. (2007). The con-
Distress and avoidance in generalized anxiety disorder: tributory role of worry in emotion generation and dysregu-
Exploring relationships with intolerance of uncertainty and lation in generalized anxiety disorder. Behaviour Research
worry. Cognitive Behaviour Therapy, 39, 126–136. and Therapy, 45, 1735–1752. doi:10.1016/[Link].2006.12.004
Lewis, A. (1970). The ambiguous word “anxiety.” International McNally, R. J. (1996). Methodological controversies in the treat-
Journal of Psychiatry, 9, 62–79. ment of panic disorder. Journal of Consulting and Clinical
Lilienfeld, S. O. (1999). Anxiety sensitivity and the structure of Psychology, 64, 88–91.
personality. In S. Taylor (Ed.), Anxiety sensitivity: Theory, Mennin, D. S., Heimberg, R. G., Turk, C. L., & Fresco, D. M.
research and treatment of the fear of anxiety (pp. 149–182). (2005). Preliminary evidence for an emotion dysregulation
Mahwah, NJ: Erlbaum. model of generalized anxiety disorder. Behaviour Research
Lorberbaum, J. P., Kose, S., Johnson, M. R., Arana, G. W., and Therapy, 43, 1281–1310. doi:10.1016/[Link].2004.08
Sullivan, L. K., Hamner, M. B., . . . George, M. S. (2004). .008
Neural correlates of speech anticipatory anxiety in general- Merikangas, K. R., Zhang, H., & Aveneoli, S. (2003). Longitudinal
ized social phobia. NeuroReport, 15, 2701–2705. trajectories of depression and anxiety in a prospective com-
Lyubomirsky, S., & Nolen-Hoeksema, S. (1995). Effects of self- munity study. Archives of General Psychiatry, 60, 993–1000.
focused rumination on negative thinking and interper- Meyer, B., Johnson, S. L., & Winters, R. (2001). Responsiveness
sonal problem solving. Journal of Personality and Social to threat and incentive in bipolar disorder: Relations of the
Psychology, 69, 176–190. BIS/BAS scales with symptoms. Journal of Psychopathology
Lyubomirsky, S., Tucker, K., Caldwell, N., & Berg, K. (1999). and Behavioral Assessment, 23, 133–143.
Why ruminators are poor problem solvers: Clues from Mineka, S., Watson, D., & Clark, L. A. (1998). Comorbidity of
the phenomenology of dysphoric rumination. Journal of anxiety and unipolar mood disorders. Annual Review of
Personality and Social Psychology, 77, 1041–1060. Psychology, 49, 377–412.
Maack, D. J., Tull, M. T., & Gratz, K. L. (2012). Experiential Moore, S. A., Zoellner, L. A., & Mollenholt, N. (2008). Are
avoidance mediates the association between behavioral expressive suppression and cognitive reappraisal associ-
inhibition and posttraumatic stress disorder. Cognitive ated with stress-related symptoms? Behaviour Research and
Therapy and Research, 36, 407–416. Therapy, 46, 993–1000. doi:10.1016/[Link].2008.05.001
MacLeod, C., & Mathews, A. (2012). Cognitive bias modifica- Mroczek, D., & Spiro, A. (2003). Modeling intraindividual
tion approaches to anxiety. Annual Review of Clinical change in personality traits: Findings from the Normative
Psychology, 8, 189–217. Aging Study. Journals of Gerontology Series B: Psychological
Maller, R. G., & Reiss, S. (1992). Anxiety sensitivity in 1984 Sciences and Social Sciences, 58, 153–165.
and panic attacks in 1987. Journal of Anxiety Disorders, 6, Murphy, S. E., Yiend, J., Lester, K. J., Cowen, P. J., & Harmer,
214–247. C. J. (2009). Short-term serotonergic but not noradrenergic
Manos, R. C., Kanter, J. W., & Busch, A. M. (2010). A critical antidepressant administration reduces attentional vigilance
review of assessment strategies to measure the behavioral to threat in healthy volunteers. International Journal of
activation model of depression. Clinical Psychology Review, Neuropsychopharmacology, 12, 169–179.
30, 547–561. Naragon-Gainey, K. (2010). Meta analysis of the relations of
Mata, J., Thompson, R. J., Jaeggi, S. M., Buschkuehl, M., Jonides, anxiety sensitivity to the depressive and anxiety disorders.
J., & Gotlib, I. (2012). Walk on the bright side: Physical Psychological Bulletin, 136, 128–150.
activity and affect in major depressive disorder. Journal of Naragon-Gainey, K., Gallagher, M. W., & Brown, T. A. (2013).
Abnormal Psychology, 121, 297–308. doi:10.1037/a0023522 Stable “trait” variance of temperament as a predictor of
The Nature, Diagnosis, and Treatment of Neuroticism 363

the temporal course of depression and social phobia. attacks, and panic disorder: A prospective study. Journal
Manuscript in preparation. of Anxiety Disorders, 16, 455–473. doi:10.1016/S0887-6185
Nathan, P. E., & Gorman, J. M. (Eds.). (2007). A guide to (02)00129-9
treatments that work (3rd ed.). London, England: Oxford Porto, P. R., Oliveira, L., Mari, J., Volchan, E., Figueira, I., &
University Press. Ventura, P. (2009). Does cognitive behavioral therapy
Nemeroff, C. (2013). Psychoneuroimmunoendocrinology: The change the brain? A systematic review of neuroimag-
biological basis of mind-body physiology and pathophysi- ing in anxiety disorders. Journal of Neuropsychiatry and
ology. Depression and Anxiety, 30, 285–287. doi: 10.1002/ Clinical Neurosciences, 21, 114–125. doi:10.1176/appi
da.22110 .neuropsych.21.2.114
Newman, M., & Llera, S. (2011). A novel theory of experien- Purdon, C. (1999). Thought suppression and psychopathol-
tial avoidance in generalized anxiety disorder: A review ogy. Behaviour Research and Therapy, 37, 1029–1054.
and synthesis of research supporting a contrast avoidance doi:10.1016/S0005-7967(98)00200-9
model of worry. Clinical Psychology Review, 31, 371–382. Quilty, L. C., Meusel, L. A., & Bagby, R. M. (2008). Neuroticism
Nolen-Hoeksema, S. (1991). Responses to depression and their as a mediator of treatment response to SSRIs in major
effects on the duration of depressive episodes. Journal of depressive disorder. Journal of Affective Disorders, 111,
Abnormal Psychology, 100, 569–582. 67–73. doi:10.1016/[Link].2008.02.006
Nolen-Hoeksema, S. (2000). The role of rumination in depres- Rachman, S., & de Silva, P. (1978). Abnormal and normal
sive disorders and mixed anxiety/depressive symptoms. obsessions. Behaviour Research and Therapy, 16, 233–248.
Journal of Abnormal Psychology, 109, 504–511. doi:10.1016/0005-7967(78)90022-0
Nolen-Hoeksema, S., Larson, J., & Grayson, C. (1999). Explaining Rapee, R. M., Kennedy, S., Ingram, M., Edwards, S., & Sweeney,
the gender difference in depressive symptoms. Journal of L. (2005). Prevention and early intervention of anxiety disor-
Personality and Social Psychology, 77, 1061–1072. ders in inhibited preschool children. Journal of Consulting
Nolen-Hoeksema, S., Wisco, B. E., & Lyubomirsky, S. (2008). and Clinical Psychology, 73, 488–497. doi:10.1037/0022-
Rethinking rumination. Perspectives on Psychological 006X.73.3.488
Science, 3, 400–424. Rapee, R. M., Kennedy, S. J., Ingram, M., Edwards, S. L., &
Norton, G. R., Rockman, G. E., Ediger, J., Pepe, C., Goldberg, Sweeney, L. (2010). Altering the trajectory of anxiety in at-
S., Cox, B. J., & Asmundson, G. J. G. (1997). Anxiety sen- risk young children. American Journal of Psychiatry, 167,
sitivity and drug choice in individuals seeking treatment 1518–1525. doi:10.1176/[Link].2010.09111619
for substance abuse. Behaviour Research and Therapy, 35, Rasmussen, M. K., & Pidgeon, A. M. (2011). The direct and
859–862. indirect benefits of dispositional mindfulness on self-
O’Connor, D. B, O’Connor, R. C., & Marshall, R. (2007). esteem and social anxiety. Anxiety, Stress and Coping: An
Perfectionism and psychological distress: Evidence of International Journal, 24, 227–233. doi:10.1080/10615806
the mediating effects of rumination. European Journal of .2010.515681
Personality, 21, 429–452. Rassin, E., Muris, P., Schmidt, H., & Merkelbach, H.
Oltmanns, T. F., & Balsis, S. (2011). Personality disorders in (2000). Relationship between thought action fusion, thought
later life: Questions about the measurement, course, and suppression, and obsessive-compulsive symptoms: A
impact of disorders. Annual Review of Clinical Psychology, structural equation model approach. Behaviour Research
7, 321–349. and Therapy, 38, 889–897. doi:10.1016/S0005-7967(99)
Paquette, V., Levesque, J., Mensour, B., Leroux, J. M., Beaudoin, 00104-7
G., Bourgouin, P., & Beauregard, M. (2003). “Change the Rassovsky, Y., Kushner, M. G., Schwarze, N. J., & Wangensteen,
mind and you change the brain”: Effects of cognitive- O. D. (2000). Psychological and physiological predictors of
behavioral therapy on the neural correlates of spider pho- response to carbon dioxide challenge in individuals with
bia. NeuroImage, 18, 401–409. panic disorders. Journal of Abnormal Psychology, 109,
Paulesu, E., Sambugaro, E., Torti, T., Danelli, L., Ferri, F., 616–623. doi:10.1037//0021-843X.109.4.616
Scialfa, G., . . . Sassaroli, S. (2010). Neural correlates of Reardon, J. M., & Williams, N. L. (2007). The specificity of
worry in generalized anxiety disorder and in normal con- cognitive vulnerabilities to emotional disorders: Anxiety
trols: A functional MRI study. Psychological Medicine, 40, sensitivity, looming vulnerability, and explanatory style.
117–124. doi:10.1017/S0033291709005649 Journal of Anxiety Disorders, 21, 625–643. doi:10.1016/j
Phan, K. L., Fitzgerald, D. A., Nathan, P. J., & Tancer, M. E. .janxdis.2006.09.013
(2006). Association between amygdala hyperactivity Reiss, S. (1991). Expectancy model of fear, anxiety, and panic.
to harsh faces and severity of social anxiety in general- Clinical Psychology Review, 11, 141–153. doi:10.1016/0272-
ized social phobia. Biological Psychiatry, 59, 424–429. 7358(91)90092-9
doi:10.1016/[Link].2005.08.012 Reiss, S. (1997). Trait anxiety: It’s not what you think it is.
Pickett, S. M., Lodis, C. S., Parkhill, M. R., & Orcutt, H. K. Journal of Anxiety Disorders, 11, 201–214. doi:10.1016/
(2012). Personality and experiential avoidance: A model of S0887-6185(97)00006-6
anxiety sensitivity. Personality and Individual Differences, Reiss, S., Peterson, R. A., Gursky, D. M., & McNally, R. J. (1986).
53, 246–250. doi:10.1016/[Link].2012.03.031 Anxiety sensitivity, anxiety frequency, and the prediction
Plehn, K., & Peterson, R. A. (2002). Anxiety sensitivity as a of fearfulness. Behaviour Research and Therapy, 24, 1–8.
predictor of the development of panic symptoms, panic doi:10.1016/0005-7967(86)90143-9
364 Barlow et al.

Roberts, B. W., & Mroczeck, D. (2008). Personality trait change Shahar, B., & Herr, N. R. (2011). Depressive symptoms predict
in adulthood. Current Directions in Psychological Science, inflexibly high levels of experiential avoidance in response
17, 31–35. doi:10.1111/j.1467-8721.2008.00543.x to daily negative affect: A daily diary study. Behaviour
Roberts, B. W., Walton, K. E., & Viechtbauer, W. (2006). Research and Therapy, 49, 676–681. doi:10.1016/[Link]
Patterns of mean-level change in personality traits across .2011.07.006
the life course: A meta-analysis of longitudinal stud- Shin, L. M., & Liberzon, I. (2010). The neurocircuitry of fear,
ies. Psychological Bulletin, 132, 1–25. doi:10.1037/0033- stress, and anxiety disorders. Neuropsychopharmacology,
2909.132.1.1 35, 169–191. doi:10.1038/npp.2009.83
Robinson, J. L., Kagan, J., Reznick, J. S., & Corley, R. (1992). Shin, L. M., Wright, C. I., Cannistraro, P. A., Wedig, M. M.,
The heritability of inhibited and uninhibited behavior: A McMullin, K., Martis, B., . . . Rauch, S. L. (2005). A functional
twin study. Developmental Psychology, 28, 1030–1037. magnetic resonance imaging study of amygdala and medial
doi:10.1037/0012-1649.28.6.1030 prefrontal cortex responses to overtly presented fearful
Roemer, L., Salters, K., Raffa, S., & Orsillo, S. M. (2005). Fear and faces in posttraumatic stress disorder. Archives of General
avoidance of internal experiences in GAD: Preliminary tests Psychiatry, 62, 273–281. doi:10.1001/archpsyc.62.3.273
of a conceptual model. Cognitive Therapy and Research, Slater, E. (1943). The neurotic constitution: A statistical study of
29, 71–88. doi:10.1007/s10608-005-1650-2 two thousand neurotic soldiers. Journal of Neurology and
Rosellini, A. J. (2013). Initial development and validation of a Psychiatry, 6, 1–16. doi:10.1136/jnnp.6.1-2.1
dimensional classification system for the emotional disor- Small, B. J., Hertzog, C., Hultsch, D. F., & Dixon, R. A. (2003).
ders (Unpublished doctoral dissertation). Boston University, Stability and change in adult personality of 6 years:
Boston, MA. Findings from the Victoria Longitudinal Study. Journals
Rosellini, A. J., Lawrence, A., Meyer, J., & Brown, T. A. (2010). of Gerontology Series B: Psychological Sciences and Social
The effects of extraverted temperament on agoraphobia Sciences, 58, 166–176. doi:10.1093/geronb/58.3.P166
in panic disorder. Journal of Abnormal Psychology, 119, Soskin, D. P., Carl, J. R., Alpert, J., & Fava, M. (2012).
420–426. doi:10.1037/a0018614 Antidepressant effects on emotional temperament: Toward
Sarin, S., Abela, J., & Auerbach, R. (2005). Response a biobehavioral research paradigm for major depressive
styles theory of depression: A test of specificity and disorder. CNS Neuroscience & Therapeutics, 18, 441–451.
causal mediation. Cognition & Emotion, 19, 751–761. doi:10.1111/j.1755-5949.2012.00318.x
doi:10.1080/02699930441000463 Speisman, R. B., Kumar, A., Rani, A., Foster, T. C., & Omerod,
Sauer, S. E., & Baer, R. A. (2009). Responding to negative inter- B. K. (2012). Daily exercise improves memory, stimulates
nal experience: Relationships between acceptance and hippocampal neurogenesis and modulates immune and
change-based approaches and psychological adjustment. neuroimmune cytokines in aging rats. Brain, Behavior, and
Journal of Psychopathology and Behavioral Assessment, 31, Immunity, 28, 25–43.
378–386. doi:10.1007/s10862-009-9127-3 Spijker, J., de Graf, R., Oldehinkel, A. J., Nolen, W. A., & Ormel,
Sauer-Zavala, S., Boswell, J. F., Gallagher, M. W., Bentley, K. J. (2007). Are the vulnerability effects of personality and
H., Ametaj, A., & Barlow, D. H. (2012). The role of negative psychosocial functioning on depression accounted for by
affectivity and negative reactivity to emotions in predicting subthreshold symptoms? Depression and Anxiety, 24, 472–
outcomes in the unified protocol for the transdiagnostic 478. doi:10.1002/da.20252
treatment of emotional disorders. Behaviour Research and Straube, T., Mentzel, H. J., & Miltner, W. H. (2006). Neural
Therapy, 50, 551–557. doi:10.1016/[Link].2012.05.005 mechanisms of automatic and direct processing of phobo-
Schmidt, N. B., Keough, M. E., Timpano, K. R., & Richey, J. A. genic stimuli in specific phobia. Biological Psychiatry, 59,
(2008). Anxiety sensitivity profile: Predictive and incremen- 162–170. doi:10.1016/[Link].2005.06.013
tal validity. Journal of Anxiety Disorders, 22, 1180–1189. Strupp, H. (1973). The future of research in psychotherapy. In
doi:10.1016/[Link].2007.12.003 H. Strupp (Ed.), Psychotherapy: Clinical, research, and the-
Schwartz, C. E., Snidman, N., & Kagan, J. (1999). Adolescent oretical issues (pp. 733–756). Lanham, MD: Jason Aronson.
social anxiety as an outcome of inhibited tempera- doi:10.1037/11523-027
ment in childhood. Journal of the American Academy Tang, T. Z., DeRubeis, R. J., Hollon, S. D., Amsterdam, J.,
of Child and Adolescent Psychiatry, 38, 1008–1015. Shelton, R., & Schalet, B. (2009). Personality change during
doi:10.1097/00004583-199908000-00017 depression treatment: A placebo-controlled trial. Archives
Segal, Z. V., Williams, J. M. G., & Teasdale, J. D. (2002). of General Psychiatry, 66, 1322–1330. doi:10.1001/archgen
Mindfulness-based cognitive therapy for depression: A new psychiatry.2009.166
approach to preventing relapse. New York, NY: Guilford Taylor, S. (1999). Anxiety sensitivity: Theory, research and treat-
Press. ment of the fear of anxiety. Mahwah, NJ: Erlbaum.
Segerstrom, S. C., Tsao, J. C. I., Alden, L. E., & Craske, M. G. Tellegen, A. (1985). Structures of mood and personality and
(2000). Worry and rumination: Repetitive thought as a con- their relevance to assessing anxiety, with an emphasis on
comitant and predictor of negative mood. Cognitive Therapy self-report. In A. H. Tuma & J. D. Maser (Eds.), Anxiety and
and Research, 24, 671–688. doi:10.1023/A:1005587311498 the anxiety disorders (pp. 681–706). Hillsdale, NJ: Erlbaum.
Selby, E. A., Anestis, M. D., & Joiner, T. E. (2008). Understanding Tillfors, M., Furmark, T., Marteinsdottir, I., & Fredrikson, M.
the relationship between emotional and behavioral dys- (2002). Cerebral blood flow during anticipation of public
regulation: Emotional cascades. Behaviour Research and speaking in social phobia: A PET study. Biological Psychiatry,
Therapy, 46, 593–611. doi:10.1016/[Link].2008.02.002 52, 1113–1119. doi:10.1016/S0006-3223(02)01396-3
The Nature, Diagnosis, and Treatment of Neuroticism 365

Tolin, D. F., Abramowitz, J. S., Brigidi, B. D., & Foa, E. B. Watson, D. (2005). Rethinking mood and anxiety disorders:
(2003). Intolerance of uncertainty in obsessive-compul- A quantitative hierarchical model for DSM-V. Journal of
sive disorder. Journal of Anxiety Disorders, 17, 233–242. Abnormal Psychology, 114, 522–536. doi:10.1037/0021-
doi:10.1016/S0887-6185(02)00182-2 843X.114.4.522
Tomarken, A. J., Dichter, G. S., Freid, C., Addington, S., Watson, D., & Clark, L. A. (1993). Behavioral disinhibition ver-
& Shelton, R. C. (2004). Assessing the effects of bupro- sus constraint: A dispositional perspective. In D. M. Wegner
pion SR on mood dimensions of depression. Journal of & J. W. Pennebaker (Eds.), Handbook of mental control
Affective Disorders, 78, 235–241. doi:10.1016/S0165-0327 (pp. 506–527). New York, NY: Prentice Hall.
(02)00306-3 Watson, D., Clark, L. A., & Carey, G. (1988). Positive and nega-
Tsao, J. C. I., Lewin, M. R., & Craske, M. G. (1998). The effects of tive affectivity and their relation to anxiety and depressive
cognitive-behavior therapy for panic disorders on comor- disorders. Journal of Abnormal Psychology, 97, 346–353.
bid conditions. Journal of Anxiety Disorders, 12, 357–371. doi:10.1037//0021-843X.97.3.346
doi:10.1016/S0887-6185(98)00020-6 Wegner, D. M., Schneider, D. J., Carter, S. R., & White, T. L.
Tsao, J. C. I., Mystkowski, J. L., & Zucker, B. G. (2002). Effects (1987). The paradoxical effects of thought suppression.
of cognitive-behavioral therapy for panic disorder on Journal of Personality and Social Psychology, 53, 5–13.
comorbid conditions: Replication and extension. Behavior doi:10.1037//0022-3514.53.1.5
Therapy, 33, 493–509. doi:10.1016/S0005-7894(02)80013-2 Weiss, N. H., Tull, M. T., Davis, L. T., Dehon, E. E., Fulton, J. J.,
Tull, M. T., Gratz, K. L., Salters, K., & Roemer, L. (2004). The & Gratz, K. L. (2012). Examining the association between
role of experiential avoidance in posttraumatic stress symp- emotion regulation difficulties and probable posttraumatic
toms and symptoms of depression, anxiety, and somatiza- stress disorder within a sample of African Americans.
tion. Journal of Nervous and Mental Disease, 192, 754–761. Cognitive Behaviour Therapy, 41, 5–14. doi:10.1080/1650
doi:10.1097/[Link].0000144694.30121.89 6073.2011.621970
Tull, M. T., & Roemer, L. (2007). Emotion regulation difficulties Widiger, T. A., & Crego, C. (2013). Diagnosis and classifica-
associated with the experience of uncued panic attacks: tion. In I. B. Weiner, G. Stricker, & T. A. Widiger (Eds.),
Evidence of experiential avoidance, emotional nonaccep- Handbook of psychology: Clinical psychology (2nd ed.,
tance, and decreased emotional clarity. Behavior Therapy, pp. 3–18). Hoboken, NJ: John Wiley & Sons.
38, 378–391. doi:10.1016/[Link].2006.10.006 Widiger, T. A., Verheul, R., & van den Brink, W. (1999).
Turk, C. L., Heimberg, R. G., Luterek, J. A., Mennin, D. S., & Personality and psychopathology. In L. A. Pervin & O. P.
Fresco, D. M. (2005). Emotion dysregulation in generalized John (Eds.), Handbook of personality: Theory and research
anxiety disorder: A comparison with social anxiety disorder. (2nd ed., pp. 347–366). New York, NY: Guilford Press.
Cognitive Therapy and Research, 29, 89–106. doi:10.1007/ Zinbarg, R. E., & Barlow, D. H. (1996). Structure of anxiety
s10608-005-1651-1 and the anxiety disorders: A hierarchical model. Journal
Tyrer, P. J. (1989). Classification of neurosis. Chichester, of Abnormal Psychology, 105, 181–193. doi:10.1037/0021-
England: John Wiley & Sons. 843X.105.2.181