Interpersonal Stress Regulation and the Development of Anxiety Disorders: An Attachment-Based Developmental Framework

Article (PDF Available)inFrontiers in Behavioral Neuroscience 5:55 · September 2011with178 Reads
DOI: 10.3389/fnbeh.2011.00055 · Source: PubMed
Abstract
Anxiety disorders represent a common but often debilitating form of psychopathology in both children and adults. While there is a growing understanding of the etiology and maintenance of these disorders across various research domains, only recently have integrative accounts been proposed. While classical attachment history has been a traditional core construct in psychological models of anxiety, contemporary attachment theory has the potential to integrate neurobiological and behavioral findings within a multidisciplinary developmental framework. The current paper proposes a modern attachment theory-based developmental model grounded in relevant literature from multiple disciplines including social neuroscience, genetics, neuroendocrinology, and the study of family factors involved in the development of anxiety disorders. Recent accounts of stress regulation have highlighted the interplay between stress, anxiety, and activation of the attachment system. This interplay directly affects the development of social-cognitive and mentalizing capacities that are acquired in the interpersonal context of early attachment relationships. Early attachment experiences are conceptualized as the key organizer of a complex interplay between genetic, environmental, and epigenetic contributions to the development of anxiety disorders - a multifactorial etiology resulting from dysfunctional co-regulation of fear and stress states. These risk-conferring processes are characterized by hyperactivation strategies in the face of anxiety. The cumulative allostatic load and subsequent "wear and tear" effects associated with hyperactivation strategies converge on the neural pathways of anxiety and stress. Attachment experiences further influence the development of anxiety as potential moderators of risk factors, differentially impacting on genetic vulnerability and relevant neurobiological pathways. Implications for further research and potential treatments are outlined.

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BEHAVIORAL NEUROSCIENC
E
HYPOTHESIS AND THEORY ARTICLE
published: 21 September 2011
doi: 10.3389/fnbeh.2011.00055
Interpersonal stress regulation and the development of
anxiety disorders: an attachment-based developmental
framework
Tobias Nolte
1,2
*
, Jo Guiney
3
, Peter Fonagy
1,2
, Linda C. Mayes
2,4
and Patrick Luyten
1,5
1
Research Department of Clinical, Educational and Health Psychology, University College London, London, UK
2
Developmental Neuroscience Unit, Anna Freud Centre, University College London, London, UK
3
Royal Holloway, University of London, London, UK
4
Yale Child Study Center, Yale University, New Haven, CT, USA
5
Department of Psychology, University of Leuven, Leuven, Belgium
Edited by:
Luke R. Johnson, Uniformed Services
University of the Health Sciences,
USA
Reviewed by:
René Hurlemann, University of Bonn,
Germany
Kwang Choi, Uniformed Services
University of the Health Sciences,
USA
*Correspondence:
Tobias Nolte, Anna Freud Centre, 12
Maresfield Gardens, London NW3
5SU, UK.
e-mail: tobias.nolte@annafreud.org
Tobias Nolte and Jo Guiney share
joint first authorship.
Anxiety disorders represent a common but often debilitating form of psychopathology
in both children and adults. While there is a growing understanding of the etiology and
maintenance of these disorders across various research domains, only recently have inte-
grative accounts been proposed. While classical attachment history has been a traditional
core construct in psychological models of anxiety, contemporary attachment theory has
the potential to integrate neurobiological and behavioral findings within a multidisciplinary
developmental framework.The current paper proposes a modern attachment theory-based
developmental model grounded in relevant literature from multiple disciplines including
social neuroscience, genetics, neuroendocrinology, and the study of family factors involved
in the development of anxiety disorders. Recent accounts of stress regulation have high-
lighted the interplay between stress, anxiety, and activation of the attachment system.
This interplay directly affects the development of social–cognitive and mentalizing capaci-
ties that are acquired in the interpersonal context of early attachment relationships. Early
attachment experiences are conceptualized as the key organizer of a complex interplay
between genetic, environmental, and epigenetic contributions to the development of anx-
iety disorders a multifactorial etiology resulting from dysfunctional co-regulation of fear
and stress states. These risk-conferring processes are characterized by hyperactivation
strategies in the face of anxiety. The cumulative allostatic load and subsequent “wear
and tear” effects associated with hyperactivation strategies converge on the neural path-
ways of anxiety and stress. Attachment experiences further influence the development of
anxiety as potential moderators of risk factors, differentially impacting on genetic vulnera-
bility and relevant neurobiological pathways. Implications for further research and potential
treatments are outlined.
Keywords: stress, anxiety, anxiety disorders, mentalization, attachment, hyperactivation, allostasis
INTRODUCTION
Contemporary perspectives in developmental psychopathology
conceptualize attachment relationships as part of a complex net-
work of epigenetic factors which interact to confer risk of or
resilience to the development of stress-related psychopathology
(e.g., Fonagy and Luyten, 2009; van Ijzendoorn et al., 2010;Luyten
et al., submitted for publication). This paper presents a model of
the influence of attachment relationships on the development of
stress regulation strategies and discusses the role those relation-
ships play in the development and maintenance of anxiety dis-
orders, particularly the neurobiological alterations that underpin
them.
Anxiety disorders are characterized by a pronounced dysfunc-
tion of systems underpinning stress regulation and fear responses
(Mineka and Zinbarg, 1996; Rosen and Schulkin, 1998). It has
been hypothesized that individual styles of threat response and
stress regulation develop within the context of early caregiving
experiences (Luyten et al., submitted for publication). These styles
are thought to persist throughout the life cycle, providing a the-
oretical framework for linking early attachment to later anxiety
disorders (Gunnar and Quevedo, 2007; Sbarra and Hazan, 2008).
From this perspective, stressful experiences, physiological stress
regulation, and attachment relationships are inherently linked,
as the activation of the attachment system invariably follows the
early stages of detecting and processing fear-related cues, stress-
responses, and states of anxiety (e.g., Murgatroyd and Spengler,
2011; Luyten et al., submitted for publication). Specifically, the
biologically based activation of a child’s attachment system fol-
lowing distress entails coordinated behaviors that aim to address
the stress response by eliciting the attention, and by ensuring the
proximity and protection of attachment figures. When effective,
this process leads to a co-regulation of the child’s distress (Sbarra
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Nolte et al. Attachment-based framework of anxiety disorders
and Hazan, 2008). Hence, at least some of the mechanisms by
which stress-regulatory strategies are acquired are inherently inter-
personal in nature and, it is argued, these strategies persist into
adulthood and are relevant for the understanding of the nature
and development of anxiety disorders. In this paper we review evi-
dence from prospective human behavioral studies show ing that a
history of insecure–anxious infant–caregiver attachment, charac-
terized by an excessive intensification of distress signals to elicit
caregiver responsiveness and maintain proximity, is a risk factor
for developing anxiety disorders in middle childhood and adoles-
cence (Bosquet and Egeland, 2006), even when maternal anxiety
and temperament are controlled for (Warren et al., 1997). Based on
these and similar studies, we propose a theoretical model arguing
that the characteristic up-regulation of stress reactivity observed
in individuals classified as insecure–anxious may be an important
risk factor for the development of anxiety disorders (Vasey and
Dadds, 2001; Muris et al., 2003; Shaw and Dallos, 2005; Lee and
Hankin, 2009). Thus, we argue that an understanding of the nor-
mative and pathological development of stress-regulator y systems
within an attachment context is likely to be important for eluci-
dating the etiology and may also directly inform the treatment of
anxiety disorders.
In this context, the multiple levels of the stress response must
be taken into account. Research into stress and anxiety disorders
in past decades has tended to consider factors such as behavioral,
genetic, or physiological phenomena in isolation. Recently, how-
ever, more comprehensive developmental formulations have been
proposed that are notable for their integration of findings from
genetic and social neuroscience research in adults (e.g., Heim and
Nemeroff, 2001; Pine, 2007; Martin et al., 2009). With convergent
findings in adult research indicating that neurobiological under-
pinnings are broadly shared by most anxiety disorders (Martin
et al., 2009; Etkin, 2010) there have been calls for a comprehensive
integration of research findings from multiple levels of analysis
utilizing a developmental perspective (e.g., Gross and Hen, 2004;
Murray et al., 2009; Cicchetti, 2010).
The developmental model proposed in this paper attempts
to respond to such calls by highlighting, within an integra-
tive account, the role of early attachment relationships. In this
framework, individual differences in parental stress regulation are
conceptualized as impacting upon the stress regulation strate-
gies developed by the child. This process is proposed to confer
both risk of or resilience to the development of anxiety-related
psychopathology. More specifically, we propose that stress- and
fear-triggered co-regulatory processes between parent and child
within the attachment relationship are evolutionarily vital and
neurobiologically pre-wired adaptations to the child’s specific
early caregiving environment. These early adaptations are pre-
served to ensure the superior adaptation of the organism to likely
environmental challenges over the course of the life cycle.
Behavioral and physiological aspects of stress regulation
have been comprehensively described in adults (McEwen, 2007;
Chrousos, 2009), and this is increasingly the case in children (Gun-
nar and Quevedo, 2007). However, research focusing on the inter-
generational transmission of dysfunctional stress regulation, and
the role of this transmission in the subsequent emergence of anx-
iety disorders, is relatively underdeveloped. Stress in a child’s early
caregiving environment has been linked to lasting adverse effects
on both physiological and psychological domains of development
(National Scientific Council on the Developing Child, 2005; Gun-
nar and Quevedo, 2007; Nugent et al., 2011). These findings are
congruent with population-representative studies that have show n
that early adversity, and particularly attachment-related trauma, is
related to increased risk for anxiety disorders throughout the life
span (Green et al., 2010; Luyten et al., submitted for publication).
For example, early adversity, such as maltreatment and neglect,
have been consistently shown to lead to chronic alterations in
the function of the hypothalamic-pituitary–adrenal (HPA) axis,
both at a the level of basal activity and in response to stress
(De Bellis et al., 1999; Heim and Nemeroff, 2001; Lupien et al.,
2009). Hyperresponsiveness of this system is also implicated in
the anxiety disorders (Kallen et al., 2008; Etkin, 2010). Further
theory-driven research is required to link the interpersonal mech-
anisms invo lved in the emergence of childhood anxiety problems
with studies of the heterogeneity in stress responsivity (Luyten
et al., submitted for publication). This paper is an attempt to
provide a theoretical framework for such research and outlines
implications for intervention strategies. While the psychopharma-
cological treatment of anxiety is beyond the scope of this paper,
its central role in intervention is acknowledged. Rather, the model
presented here suggests how attachment-based interventions may
enhance a range of other treatments, including pharmacological
approaches.
PAPER OUTLINE
This paper covers three literatures. We begin by reviewing lit-
erature on anxiety disorders from the perspective of a number
of disciplines. Next, an account of the role of attachment in the
development of both normative and aberrant stress regulation is
explicated. Finally, an integrative developmental model for the eti-
ology of anxiety disorders is proposed based on constructs drawn
from the interface of modern attachment theory and neuroscience.
Differences i n the presentations of the various anxiety disorders
may reflect variations in etiological pathways, but we suggest that
the unregulated fear responses and subsequent hyp eractivation
of the attachment system is shared by these diagnostic entities.
For this reason, the focus of this paper is on the anxiety disor-
ders as a group. This is in line with studies concerning a tripartite
model showing that anxiety disorders empirically cluster together,
separate from depression for instance (Clark and Watson, 1991;
De Bolle and De Fruyt, 2010; Luyten and Blatt, 2011), and with
findings from recent studies based upon multivariate statistical
analyses indicating that anxiety disorders can be hierarchically
ordered as part of a spectrum of internalizing disorders (Krueger
et al., 2007).
ANXIETY DISORDERS
While fear is an evolutionarily preserved response to environ-
mental threat and enables appropriate defensive behaviors such
as escape and avoidance (Rosen and Schulkin, 1998) the excessive
fear responses that characterize pathological anxiety have been
conceptualized as a dysfunctional variant of these originally adap-
tive processes. (Mineka and Zinbarg,1996; LaBar and Phelps, 2005;
Shin and Liberzon, 2009). While resulting symptomatology can
Frontiers in Behavioral Neuroscience www.frontiersin.org September 2011 | Volume 5 | Article 55 | 2
Nolte et al. Attachment-based framework of anxiety disorders
range from the persistent and non-specific apprehension in Gen-
eralized Anxiety Disorder to the overwhelming terror present in
Panic Disorder, the presence of fear and stress states is common to
these presentations (Craske et al., 2009).
PREVALENCE
Lifetime prevalence data consistently shows anxiety disorders to
be the most commonly occurring class of mental disorders (e.g.,
Lépine, 2002; Kessler and Wang, 2008), usually with a chronic-
recurrent course (Kessler et al., 2010). Several population studies
attest to the high prevalence of anxiety disorders occurring before
adulthood (Breton et al., 1999; Canino et al., 2004) and though
estimates vary, at any given time approximately 2.5–5% of chil-
dren and adolescents meet criteria for an anxiety disorder (Ford
et al., 2003). Evidence from longitudinal studies suggests that the
life-interference associated with shyness and anxiety disorders in
childhood persists into early adulthood (Caspi et al., 1996; Last
et al., 1996), while studies demonstrating the longitudinal stability
of features predicting anxiety disorders from childhood to adoles-
cence (Bittner e t al.,2007) and from adolescence to early adulthood
(Pine et al., 1998) emphasize the importance of a developmental
approach.
COMORBIDITY
Estimates suggest that 40–60% of children and adolescents with a
specific anxiety disorder meet criteria for at least one other anxiety
disorder (Benjamin et al., 1990; Kendall et al., 2001). Such a high
level of comorbidity within the anxiety disorders likely reflects
both shared risk factors and common underlying fear processes
maintaining the presentation (Rapee et al., 2009).
Population studies also indicate high levels of comorbidity with
other psychiatri c disorders (Angold et al., 1999), with significant
associations existing between anxiety disorders and the subsequent
onset of other psychiatric (Beesdo et al., 2007) and substance use
(e.g., Zimmerman and Chelminski, 2003) disorders. However, the
most striking and consistent finding of population studies is the
marked comorbidit y of anxiety disorders and depression. It is esti-
mated that anxious children are between 8 and 29 times more
at risk of developing subsequent depression than non-anxious
children (Angold et al., 1999; Costello et al., 2003; Ford et al.,
2003).
Given the early onset of anxiety disorders, they commonly
represent the temporally primary disorder in comorbid profiles.
It is on this basis that some commentators have suggested that
early interventions to treat anxiety disorders might attenuate
risk for the onset, persistence, or severity of secondary disorders
such as depression and substance abuse (Wittchen et al., 2000;
Kessler, 2004) underscoring the value of developmental accounts
of etiology and course.
FACTORS CONTRIBUTING TO THE DEVELOPMENT OF
ANXIETY DISORDERS
Before outlining the key role of the attachment relationship in the
development of stress-regulatory processes in the face of threat
and anxiety, a review of the critical factors that have been impli-
cated in the development of anxiety disorders is presented. These
factors have been investigated across multiple disciplines and are
examined in turn.
GENETIC INFLUENCES ON THE DEVELOPMENT OF ANXIETY DISORDERS
A growing body of research supports the familial aggregation of
anxiety disorders (Hettema et al., 2001) with findings consistently
demonstrating that children with anxiety disorders are more likely
to have a parent with an anxiety disorder (Last et al., 1987, 1996;
Cooper et al., 2006; Schreier et al., 2008).
Twin studies have allowed for estimates of the actual contr ibu-
tion of genetic factors to the pathogenesis, or heritability, of anxiety
disorders and consistently report a genetic influence of a moder-
ate magnitude (Thapar and McGuffin, 1995; Hettema et al., 2001,
2005; Ehringer et al., 2006; Gregory and Eley, 2007). In consider-
ing transdiagnostic overlap of anxiety psychopathology accounted
for by genetic and environmental influences, estimates have var-
ied according to the form of anxiety investigated (Eley et al., 2003,
2010; Ehringer et al., 2006), with Obsessive–Compulsive and Shy-
ness/Inhibition behaviors most consistently indicated as highly
heritable and Separation Anxiety as more strongly influenced by
shared environmental factors.
This evidence for phenot ypic and genetic overlap in the various
behaviors associated with the anxiety disorders has provided the
basis for their common consideration as a group. However, while
the differentiation in genetic contributions can partially account
for the heterogeneity of presentations in the anxiety disorders,
environmental influences remain substantial in each diagnostic
entity. Defining the nature of the early experiences that may inter-
act with genetic risk factors to produce anxiety-related phenotypes
is therefore crucial (Norrholm and Ressler, 2009).
Furthermore, it has been argued that genetic and environ-
mental factors may be more or less influential depending on a
subject’s developmental stage, and that factors relating to the pri-
mar y caregiver will account for more variance during early to
middle childhood, when parents exert the strongest influence on
their children (Rapee and Spence, 2004). In line with this, varia-
tions in a polym orphism of the serotonin transporter gene have
been associated with anxiety sensitivity, but only in the presence
of childhood maltreatment (Stein et al., 2008).
TEMPERAMENT AND ANXIETY DISORDERS
Various nosologies of temperament have described a style in
infancy characterized by inhibition, shyness, withdrawal, and dis-
tress in response to novelty, and a tendency to stay within close
proximity to attachment figures (Windle and Lerner, 1986; Kagan
et al., 1988; Hirshfeld e t al., 1992; Sanson et al., 1996; Chorpita and
Barlow, 1998). As a result, although studies examining childhood
anxiety have utilized different classification criteria for tempera-
ment, nearly all employ measures of behavioral inhibition (BI)
and proneness to distress reactions when faced with novelty. For
purposes of clarity and because it is the most commonly used term
across disciplines, we refer to this temperament style as BI.
It has been suggested that BI might serve as a potential endophe-
notype in research into anxiety disorders (Smoller et al., 2005;
Norrholm and Ressler, 2009). Indeed, associations have been
found between BI in children and anxiety disorders in their par-
ents (Biederman et al., 1993; Rickman and Davidson, 1994), and
longitudinal studies have shown that BI in childhood predicts later
anxiety disorders (Hirshfeld e t al., 1992; Turner et al., 1996; Prior
et al., 2000).
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Nolte et al. Attachment-based framework of anxiety disorders
Although BI features have much in common with those
observed in children w ith an insecure–anxious attachment classi-
fication (Calkins and Fox, 1992), meta-analyses investigating this
overlap have indicated that individual differences in attachment
style cannot be explained by temperament constructs (Vaughn
and Bost, 1999). Rather, contemporary accounts posit that tem-
perament and attachment are distinct but interacting influences
on the child’s development (for a review, see Vaughn et al.,
2008).
In relation to the model proposed in the current paper, a BI
temperament style is conceptualized as one potential risk for the
development of anxiety disorders (Rapee and Coplan, 2010 ), and
a factor interacting with an individual’s attachment status.
ENDOCRINOLOGICAL, NEURAL, AND COGNITIVE MEDIATORS OF
STRESS REGULATION AND ANXIETY DISORDERS
HPA-axis sensitivity programming
The concept of developmental programming (Andrews and
Matthews, 2004; Meaney et al., 2007; Seckl, 2008) has been pro-
posed in response to a large body of research demonstrating
that environmental cues at sensitive periods of development can
result in permanent alterations in the functioning of the HPA-
axis (Matthews, 2002; De Kloet et al., 2005; Oitzl et al., 2010).
Preclinical and clinical evidence suggests that this programming
is relevant to an understanding of the etiology of anxiety disor-
ders in humans (Heim et al., 2004, 2008; Capitanio et al., 2005)
with a growing number of studies in human samples indicating
that stressors within the early caregiving environment are associ-
ated with alterations in the functioning of the HPA-axis and an
increased risk of heightened anxiety and psychopathology later in
life (Graham et al., 1999; Rinne et al., 2002; Heim et al., 2008).
It has been suggested that maternal care plays a key mediating
role in the regulation of the HPA-axis in offspring (e.g., Gun-
nar and Donzella, 2002; Taylor et al., 2011). Adequate care has
been associated with reduced cortisol levels and an attenuation
of HPA-axis responsiveness in children, together with a greater
cortisol recovery post-stress (Albers et al., 2008). These findings
are highly pertinent to the attachment framework applied in the
current paper as they underscore the interpersonal nature of st ress
regulation. The regulation of the HPA-axis as a primary function
of the attachment relationship is a key component of the cur rent
model.
The effects of prenatal anxiety on HPA-axis function. A number
of studies have demonstrated associations of antenatal maternal
anxiety with cognitive, behavioral, and emotional problems in
the child (Van den Bergh and Marcoen, 2004; O’Connor et al.,
2005; Bergman et al., 2010). In investigating potential physiolog-
ical mediators underpinning the sequelae of prenatal maternal
anxiety, attention has largely focused on its effects on the HPA-
axis of the offspring. Based on the ev idence for overactive and
dysregulated HPA axes in the offspring of prenatally stressed ani-
mals (Weinstock et al., 1992; McCormick et al., 1995; Huizink
et al., 2004), it has been hypothesized that exposure to anxiety and
stress in the prenatal environment may result in susceptibility to
psychopathology, such as anxiety disorders and/or depression, in
humans (Van den Bergh et al., 2008).
In a recent study examining outcomes associated with prena-
tal stress and the impact of attachment, Bergman et al. (2010)
documented that levels of maternal prenatal cortisol measured in
amniotic fluid were linked with impaired cognitive development
in children. However, mother–infant attachment moderated these
in utero effects: the negative outcome only held true when early
caregiving was characterized by attachment insecurit y. Further, it
has been shown that prenatal stress is associated with reduced hip-
pocampal volume only when combined with inadequate levels of
post-natal care from the mother (Buss et al., 2007).
Taken together, this body of research suggests that although
prenatal stress can confer risk for anxiety disorders through alter-
ing the set-point of the HPA-axis, this risk can be attenuated by
the early caregiving environment and attachment experiences in
particular.
Neural basis of anxiety
Current understanding of fear conditioning and threat responses
at a neural level derives mainly from animal research and sub-
sequent translational efforts that apply these animal models
to study fear and anxiety processes in nor mal human popula-
tions (LeDoux, 2000; Schiller et al., 2010; Schiller and Phelps,
2011). Phenomenologically, the arousal and avoidance responses
of subjects with anxiety disorders resemble the reactions of
normal subjects to conditioned fear cues (Grillon, 2002). Cru-
cially, both groups of subjects display the same accompanying
changes in the neural substrates that coordinate their defensive
responses to threats. Responses in humans with anxiety disor-
ders are therefore likely to represent extreme manifestations of
the normal, context-appropriate responses to stress and fear that
have proven evolutionarily successful (Rosen and Schulkin, 1998;
Gray and McNaughton, 2000; Rauch et al., 2000; Shekhar et al.,
2005).
Any account of the neurobiological underpinnings of anxiety
disorders should therefore be based on an understanding of the
neural circuitry underlying normal processing of fear and subse-
quent normative regulatory mechanisms. Neuroscientific evidence
has converged to delineate a well-established limbic-medial pre-
frontal system comprising three functionally interacting groups
of brain structures (Etkin and Wager, 2007; Kober et al., 2008;
Martin et al., 2009; Etkin, 2010). The complex interaction of these
structures is summarized here in brief.
First, detection of and early response to fear cues and/or neg-
ative emotional stimuli occur within the phylogenetically ancient
limbic structures of the amygdala and insula. The result is a first
integration of sensory, affective, and interoceptive processes (see
Etkin and Wager, 2007 for a quantitative meta-analysis of the
involvement of these areas in anxiety-relevant emotional process-
ing). In turn, these regions initiate and modulate activity in sev-
eral target structures (including the hypothalamus, periaqueductal
gray, sensory cortices, and the hippocampus) to carry out coordi-
nated physiological and behavioral responses. The hippocampus
exerts an important regulatory function via negative feedback to
the HPA-axis (Pruessner et al., 2010). Hippocampal volume and
neurogenesis have been implicated in stress resilience and in the
stress sensitivity associated with anxiety disorders (Lupien et al.,
2009; Roozendaal et al., 2009).
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Nolte et al. Attachment-based framework of anxiety disorders
Subsequent appraisal of the registered fear cues occurs in the
dorsal anterior cingulate and dorsomedial prefrontal cortices. This
detailed evaluation of the emotional stimulus has a potential
gate-keeping function that may admit the stimulus to conscious
awareness and may trigger the context-dependent inhibition or
enhancement of limbic activation. Finally, the engagement of a
third part of the circuit (involving rostral subregions of the ante-
rior cingulate and ventromedial prefrontal cortex) is responsible
for top-down-regulation of negative emotions and limbic process-
ing. Furthermore, executive regions within the lateral prefrontal
cortex activate medial prefrontal regulation of emotion processing.
The complexity of the interdependent functions of the regions
within the limbic prefrontal circuit suggests that anxiety pro-
cessing and responses do not rely on specific areas that perform
unique functions. Rather, anxiety processing and response should
be conceived of as emergent functions of interacting brain areas
(Morgane et al., 2005). Furthermore, these circuits are under the
modulatory influence of several other neural systems and neu-
ropeptides (e.g., Mathew et al., 2008; Joels and Baram, 2009).
Oxytocin, in particular, has been studied widely during the last
decade (Insel, 2010). Its crucial role in mediating attachment as
well as its influence on the neural circuits underpinning anxiety
are discussed further below.
Accruing evidence suggests that the neural correlates of anxi-
ety disorders involve an abnormally elevated activation pattern in
the limbic st ructures. This leads to hypoactivation in prefrontal
regions aimed at normalizing limbic response, and thus to regu-
latory failures. In a normal population, the neuronal processing
of participants who scored higher on an anxiety measure, already
appears to involve, via activation of the basolateral amygdala, a
more generalized dysregulation and distorted detection of nega-
tive affect (Etkin et al., 2004; Campbell-Sills et al., 2010). Studying
the regulation of negative affect in a sample of older adults, Urry
et al. (2006) reported an inverse coupling of amygdala and ventro-
medial prefrontal cortex activation. This association also predicted
diurnal cortisol secretion.
These findings, in particular the role of increased amygdala acti-
vation provoked by anxiety-producing unpredictable or ambigu-
ous stimuli, are indicative of “hyperarousal and hypervigilance”
(Etkin et al., 2004). These states are similar to behavioral responses
found in anxiety disorders. This is of particular relevance, since
most anxiety disorders are characterized by intolerance of uncer-
tainty or ambiguity (Holaway et al., 2006; Boelen and Reijntjes,
2009) and a bias toward negative interpretations of ambiguous
cues (Bishop, 2007). Additionally, success in interpreting negative
stimuli as less threatening is associated with increased PFC and
decreased amygdalar activity (Bishop, 2007) implying the cen-
tral role of inter pretation of experience. These processes reflect-
ing normal social cognition or mentalizing capacities will be
explained in detail below. Investigating the structural integrity of
the amygdala–prefrontal pathway with diffusion tensor imaging,
Kim and Whalen (2009) found evidence for an inverse correlation
with participants’ trait anxiety levels. This linked higher pathway
strength with lower anxiety. In addition, studies on the resting
brain showed that the level of anxiety can dissociate ventrome-
dial prefrontal cortex functional connectivity with the amygdala,
resulting in compromised interactions between these two brain
regions (Kim et al., 2011). This may partly explain the failure to
downregulate anxiety-provoked stress states,especially when these
occur in interpersonal contexts as our model will show.
Taking these findings together, it appears likely that the
prefrontal–amygdala circuit mediates basic mechanisms involved
in human anxiety. These mechanisms include:attention to threat,
interpretation of stimuli, and acquisition and extinction of condi-
tioned fear” (Bishop, 2007). Ultimately, this mediation can lead
to a pathological bias in favor of negative representations of
external and internal cues and to a failure to a ctivate alternative
non-threatening representations.
Evidence from recent functional neuroimaging research in clin-
ical populations suggests commonalities in the functional anatomy
underpinning most anxiety disorders (van den Heuvel et al., 2005;
Pine, 2007; Ressler and Mayberg, 2007; Martin et al., 2009; Etkin,
2010; Shin and Liberzon, 2009 for review of the overlap w ith neural
circuits of depression). Additionally, there are disorder-specific
features in pathologies such as obsessive–compulsive disorder
(Martin et al., 2009; Etkin, 2010). In the most comprehensive
meta-analysis on negative emotional processing, Etkin and Wager
(2007) demonstrated that limbic hyperactivation in patients with
PTSD, social anxiety, or specific phobia was similar to anxiety
experimentally induced through fear conditioning in healthy indi-
viduals. The finding that amygdala and insula hyperactivation is
common to all three anxiety disorders is suggestive of patients’
excessive engagement of fear- or negative emotion-related cir-
cuitry” and reflects a neural phenotype of anxiety (Etkin and
Wager, 2007) as well as of alterations in interoceptive processing of
anxiety-induced affect (Paulus and Stein, 2006; Stein et al., 2007).
Future research, however, is needed to address whether these func-
tional perturbations represent acquired characteristics of anxiety
disorders or reflect vulnerability factors that precede the onset
of psychopathology. A growing body of developmental research
investigates neuro-structural correlates of exposure to stressors in
the early environment, finding for example, corticostriatal-limbic
gray matter reductions in adolescents reporting maltreatment in
childhood (Edmiston et al., in press) and decreases in corpus cal-
losum volume in maltreated children and adolescents compared
to their non-maltreated peers (Jackowski et al., 2008). Preliminary
evidence suggests such str u ctural differences in response to early
life stress might be mediated by gender (Teicher et al., 2004).
Attentional bias to threat
Cognitive accounts have suggested that development of an atten-
tional bias to threatening stimuli is both a mechanism by which
early experience shapes an individual’s stress responsivity and a
risk factor for the development of anxiety disorders (MacLeod
et al., 2002). It is now well-established that attentional biases are
present in individuals diagnosed with a range of anxiety disorders
(Bar-Haim et al., 2007) as indexed by heightened and sustained
vig ilance for visual stimuli conveying threat (Mogg and Bradley,
2002). Attentionalbiases have also been associated with heightened
HPA-axis activity (Ellenbogen et al., 2002; Roelofs et al., 2007)pro-
viding a basis for cognitive-biological accounts of mood disorders
(Beck, 2008). Furthermore, a genetic mechanism for attentional
biases has emerged through its association with variations in the
serotonin transporter gene (Perez-Edgar et al., 2010).
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Nolte et al. Attachment-based framework of anxiety disorders
It has, however, been proposed that a child who is genetically
vulnerable to anxiety may or may not develop an attentional bias
toward threat depending upon the early caregiving environment
(Fox et al., 2007). This research demonstrated that caregivers who
highlight or identify negative events in their child’s environment
are contributing to the child’s own development of a negative bias.
It is interesting therefore that recognition and modification of
attentional biases has been a central aspect of Cognitive Behav-
ioral approaches to the treatment of the anxiety disorders (e.g.,
Beck, 1976; Beck and Emery, 1985).
ENVIRONMENTAL INFLUENCES
Early adversity
Although there is evidence indicating that children diagnosed with
an anxiety disorders experience more negative events preceding
diagnosis when compared to non-anxious controls (Goodyer et al.,
1988; Phillips et al.,2005), such findings are called into question by
studies indicating reciprocal influences. For example, it has been
demonstrated that childhood anxiety predicts the occurrence of
subsequent negative events (Swearingen and Cohen, 1985). Simi-
larly, longitudinal research by Kim et al. (2003) demonstrated that
internalizing problems such as anxiety and depression followed,
but were also followed by, negative life events.
The processes whereby adverse events lead to the develop-
ment of an anxiety disorder are therefore likely to be mediated
by multiple factors, including attachment experiences (Cicchetti
and Rogosch, 1997). Studies have in fact demonstrated that, in
the presence of risk factors such as early adversity (Carlson and
Sroufe, 1995) and stressful events (Heinrichs et al., 2003; Powers
et al., 2006), secure attachment can act as a protective factor mod-
erating the potential for development of psychopathology via the
impact on stress regulation (Gunnar et al., 1996; Nachmias et al.,
1996).
Parenting influences
Modeling and information transfer. A child’s observation of
anxiety in others has been proposed as a route for the intergen-
erational transmission of anxiety disorders (Mineka, 1985). Such
learning-theory accounts posit that caregiver modeling allows the
child to vicariously acquire behaviors, and that this is likely to
be evolutionarily advantageous because it prepares the child for
environmental challenges without exposing him to direct threat
(Mineka, 1988). For example, in a sample of mothers without anx-
iety disorders and their 15 to 20-month-old infants, fear modeling
by the mothers was found to be associated with the subsequent fear
responses of the infants (Gerull and Rapee,2002).Inamorerecent
longitudinal study comparing mothers with and without an anxi-
ety disorder (Murray et al., 2008), the level of anxiet y expressed by
the mother toward a stranger in front of their 10-month-old infant
predicted the infant’s subsequent avoidance of the same stranger
at 14 months.
Research examining features of child–parent discussions has
shown that anxious mothers are more likely to make comments of
a catastrophic nature to their children (Whaley et al., 1999; Moore
et al., 2004) and less likely to refer to positive emotions (Suveg
et al., 2008). Further, compared to discussions in non-clinical fam-
ilies, discussions regarding ambiguous situations within families
of anxious children appear to be characterized by reciprocal rein-
forcement of comments regarding risk and have been shown to
magnify the extent of a child’s anxiety and avoidance behavior in
subsequent situations (Barrett et al., 1996).
This body of literature links parental behavior to anxiety in chil-
dren via parental displays of anxiety or verbal behaviors empha-
sizing threat in the environment. These instances of “modeling
may also in part be seen as failures of the attachment system
since the parent does not (or is unable to) show appropriate
caregiving behavior within a stressful situation, and thus fails to
effectively co-regulate the child’s stress. Rather, the caregiver mod-
els to the child their own strategies for evaluating and responding
to threat.
Parenting styles. A related body of research has considered the
impact of a range of parenting practices on the de velopment of
anxiety disorders in children. The two major facets of parent-
ing considered in these studies are lack of warmth (or parental
rejection) and overcontrol. Within a cognitive framework, lack
of warmth and rejecting behaviors can be seen as likely to rein-
force a child’s expectations that the world and others are hostile
and unsupportive (Bögels and Tarrier, 2004). Overcontrol and the
concomitant discouragement of independence are likely to limit
the child’s sense of agency and competence and to reinforce avoid-
ance of potentially threatening situations (Parker, 1983; Chorpita
and Barlow, 1998).
Evidence for associations of such parenting factors with child-
hood anxiety has been mixed (Wood et al., 2003; DiBartolo and
Helt, 2007; McLeod et al., 2007), but with stronger and more
reliable associations generally found for overcontrolling parent-
ing. Inconsistencies in findings may partly reflect different study
designs and measurement contexts and methods. Direct observa-
tion of parenting, in samples of children with diagnosed anxiety
disorders rather than proxy symptoms, produces the most robust
associations. A meta-analysis of studies accounting for these fac-
tors suggested that of all aspects of parenting style, a low level of
autonomy granting (a feature of overcontrol) was the one most
reliably associated with anxiety disorders in children (McLeod
et al., 2007).
These associations can be considered in relation to quality of
parent–child attachment. Attachment theory has long held that
rejecting and overcontrolling parental behaviors are related to
the child’s level of attachment security. This general hypothesis
is well supported in observations of mothers and children (Crow-
ell and Feldman, 1991). More specifically, attachment theorists
have hypothesized that limited autonomy granting and/or reject-
ing parental styles engender an anxious style of attachment in the
child (Ainsworth and Bell, 1974; Sroufe et al., 1983). This spe-
cific hypothesis has been consistently supported in observational
research (e.g., Sroufe et al., 1993).
Child-driven effects and parenting factors
While studies examining parenting styles have established that
certain features are more commonly found in the context of
childhood anxiety and insecure–anxious attachment (for review
see Bögels and Brechman-Toussaint, 2006), researchers have
attempted to establish whether such styles cause anxiety in the
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Nolte et al. Attachment-based framework of anxiety disorders
child, are the effect of having an anxious child, or result from an
interaction between parent and child.
Studies pertaining to support a causal model of parenting styles
that use sibling controls are problematic (Hudson and Rapee, 2002;
Barrett et al., 2005) given that the controls often have considerable
levels of anxiety themselves. This leaves open the possibility that
parenting style is provoked by a child’s anxiety. Evidence for child-
driven effects was provided in a study by Moore et al. (2004) in
which parenting styles such as lack of warmth and catastrophiz-
ing were found to show a main effect of child diagnosis. Further,
Ghera et al. (2006) found that 4-month-old infants who responded
negatively to novel stimuli and were viewed by their mothers as
difficult to soothe received low levels of maternal sensitivity
(see also Hane and Fox, 2006 ). The same group reported that
9-month-old infants who showed high levels of behavioral avoid-
ance to ominous stimuli and a corresponding pattern of right
frontal electroencephalogram (EEG) asymmetry (itself a correlate
of continued inhibition across early childhood; see Fox et al.,2001),
received low levels of maternal sensitivity (Hane et al., 2008). This
result was replicated in a follow-up study of the same sample in
early childhood (Hane et al., 2010).
There is therefore some evidence that child-driven effects can
potentially influence the quality of the early caregiving environ-
ment by provoking a certain style of parenting response. Other
than child-driven effects, however, these studies do not adequately
address potential influences on maternal behavior that could be
impinging on mothers’ abilities to provide sensitive care. Social
support and maternal anxiety are two examples of such factors
and are considered in turn.
It has long been established that reported level of social support
correlateswith quality of caregiver behavior (e.g ., Crockenberg and
McCluskey, 1986), with the level of social support being of particu-
lar importance for mothers of distress-prone infants (Crockenberg
and McCluskey, 1986). One study demonstrated that maternal
insensitivity was predicted by the joint effect of infant distress-
proneness and low social support (Pauli-Pott et al., 2004) while
Hirshfeld et al. (1997) demonstrated that parenting styles associ-
ated with anxiety disorders in children emerged only in anxious
mothers with BI infants. Taken together, these studies suggest that
infant temperament (BI) predicts later child anxiety only when
accompanied by certain anxiogenic parenting styles. These styles
are more readily provoked in mothers who are themselves anxious,
an interaction that is more likely to occur against a background of
low social support. Recent longitudinal research offers support for
this complex pattern of interaction effects (Warren and Simmens,
2005; Murray et al., 2008).
Regarding parenting effects, research over the last decade has
largely focused on the impact of maternal factors. In order to
understand the development more comprehensively the role of
fathers should also be considered (Bögels and Phares, 2008).
While this is a relatively under-researched area, there is prelim-
inary evidence for the role of paternal anxiety as a moderator of
treatment outcomes for children with anxiety disorders (Rapee,
2000). Rapidly changing patterns of parenting in Westerns coun-
tries make delineation of the shared and gender specific parenting
influences on emotional development an urgent social as well as
psychological issue (Grossmann et al., 2005, 2006).
SECTION SUMMARY
Given their high prevalence, associated functional impairments
and robust associations with the onset of other debilitating dis-
orders, anxiety disorders warrant continued, multidisciplinary
attention. While further elucidation of the genetic substrates and
related biological processes by which anxiety disorders are inher-
ited will no doubt offer exciting insights, greater understanding of
the processes by which such genetic v ulnerabilities may be modu-
lated by the early environment will afford the most comprehensive
etiological account.
ATTACHMENT EXPERIENCES AND STRESS REGULATION
Having reviewed literature pertinent to anxiety disorders, we now
transition to integrating these finding s in an attachment frame-
work. First, we discuss normative co-regulation of stress and
threat in the secure attachment relationship. We then propose
a model for the dysfunction of regulation in anxious attach-
ment and how this moderates genetic vulnerabilities and biolog-
ical pathways that underpin subsequent development of anxiety
disorders.
Contemporary attachment theory posits attachment as a
behavioral and physiological system that is biologically based and
dynamically adapting to meet the needs of the individual’s particu-
lar environment (Mikulincer and Shaver, 2007). It responds to the
stress provoked by environmental threats by promoting strategies
that best maintain proximity to the caregiver.
Recent literature has conceptualized the stress response as an
interpersonal process (Sbarra and Hazan, 2008; Luyten et al., sub-
mitted for publication), and has proposed an empirically testable
and integrative framework of individual differences in stress regu-
lation and susceptibility to anxiety disorders. Because it provides a
developmental account of both normative and maladaptive stress
regulation, attachment theory is best positioned to integrate find-
ings that are proliferating in the various fields investigating stress
and anxiety disorders (for a comprehensive review, see Luyten et
al., submitted for publication).
SECURE ATTACHMENT AND THE REGULATION OF STRESS AND
ANXIETY
Perceived threats and fear activate an individual’s attachment sys-
tem, prompting a series of processes that ultimately aim to regulate
the stress response (Mikulincer and Shaver,2007). These processes
include primary attachment behaviors such as separation dis-
tress and subsequent proximity seeking (Sbarra and Hazan, 2008).
Experimental and naturalistic studies have demonstrated this in
children, adolescents, and adults (Sbarra and Hazan, 2008 for
review , Mikulincer and Shaver, 2007).
If these behaviors successfully elicit the safety-promoting
response of the attachment figure, the attachment system is deac-
tivated. Over time, if the attachment figure is reliably available,
attentive, and responsive, a secure attachment develops. This
attachment is characterized by experiences of reassurance, a sense
of safety and, ultimately, effective affect regulation. These repeated
experiences become generalized as experience-expectant predic-
tions of interactions and lead to a reduced reliance on external
cues of safety (Mikulincer and Shaver, 2007). Individuals become
increasingly capable of effectively regulating their stress-responses
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Nolte et al. Attachment-based framework of anxiety disorders
by calling upon mental representations of internalized attach-
ment figures so-called “internal working models (Bowlby, 1973;
Bretherton and Munholland, 2008). Recently, research studies
have operationalized the effects of the working model as support-
seeking, self-esteem, and self-worth (e.g., Lee and Hankin, 2009).
Thus, securely attached individuals can efficiently regulate stress
and anxiety either by seeking proximity to a reliable attachment
figure in their actual environment or by mentally drawing upon
past experiences in which stress was effectively co-regulated. In this
way, stress regulation remains an inherently interpersonal process
(Diamond and Aspinwall, 2003; Luyten et al., submitted for pub-
lication) with the attenuation of anxiety embedded in all close
relationships.
Ganzel et al. (2010) have modeled the stress response in an
allostasis framework that accounts for: (a) ongoing e valuations of
internal resources and external demands; (b) advance physiolog-
ical adjustment through anticipatory arousal; and (c) adaptation
to environmental circumstances over time. This notion has been
greatly enriched in contemporar y attachment theory by the elab-
oration of the concept of mentalization (Fonagy, 1998; Fonagy
et al., 2002). The role of mentalization, that is, to conceive of
self and others as social agents whose thoug hts, feelings, desires,
and behaviors are underpinned by intentional mental states (Fon-
agy et al., 2002), has been highlighted as a potent factor in social
cognition and particularly in stress-related interpersonal contexts
(Fonagy and Luyten, 2009). There is accruing evidence that effec-
tive mentalization that enables infants to regulate negative affect,
threat cues, separation anxiety, and the resulting stress states and
thus subjective as well as physiological distress follows a pat-
tern of intergenerational transmission (Sharp and Fonagy, 2008).
A mother’s mentalizing ability, that is, the parents ability to treat
the child as an psychological agent with mental states indepen-
dent of their own (Fonagy and Target, 1997) predicts both secure
attachment and their child’s own capacity to mentalize (Meins
et al., 2002; Slade et al., 2005). For instance, a distinctive marker
of secure attachment is the capacity to tolerate negative affect
(Sroufe, 1996). Crucial to these processes is the caregiver’s capacity
to attenuate the child’s stress or anxiety once its attachment sys-
tem has been activated. A child’s general sense of a secure base not
only enables them to explore their environment freely but, more
importantly, enhances their ability to contemplate own mental
states and those of others. Studies have demonstrated attachment
security to be a predictor of performance on diverse theory of
mind (ToM) tasks, including false belief tasks in preschoolers (e.g.,
Arranz et al., 2002), and of the development of socio-cognitive
capacities which support ToM, such as internal state language (i.e.,
emotion regulation and self-awareness vocabulary) in toddlers
(e.g., Lemche et al., 2007). In critical contexts, these mentalizing
capacities are online only once the attachment system has been
downregulated after a threat or stressor has abated (Luyten et al.,
submitted for publication). This in turn, creates positive feed-
back loops for the possibility of the adjustment and regulation
of impending stress response. In an attachment-based approach
secure attachment is therefore viewed as the interpersonal train-
ing g round for the infant in which social cognition or mentalizing
and their concomitant neural correlates are developed. These
capacities allow for allostatic accommodation by enabling indi-
viduals to recognize and to regulate stress-related states (Schulkin,
2010).
As noted earlier, there is increasing e vidence that attachment
security serves a protective function by promoting resilience to
the impact of stress mainly via anxiolytic and trust-enhancing
effects mediated by the neuropeptide oxytocin ( Heinrichs et al.,
2003; Powers et al., 2006; Feldman et al., 2007; Heinrichs and
Domes, 2008). Moreover, studies investigating stress responsiv-
ity in both human and animals have demonstrated that a secure
attachment leads to an “adaptive hypoactivity” of the HPA-axis
(Gunnar and Quevedo, 2007). Conversely, in a study of human
adults low-quality parenting was found to be linked w ith elevated
salivary cortisol levels during experimentally induced psychoso-
cial stress (Gunnar et al., 2007). Such parenting was also linked to
an increased release of dopamine in ventral striatal areas, which
is a factor in the response to aversive stressful stimuli (Pruessner
et al., 2004).
A further feature of a secure attachment is its encouragement of
effective seeking of supportive attachment relationships through-
out the lifespan. This is in line with contemporary attachment
theor y which posits that a attachment security leads to a cyclical
process of “broaden and build” (Fredrickson, 2001) in which the
individual experiences a sense of personal agency, can effectively
regulate emotions and conflicts and engage in exploratory behav-
iors (Mikulincer and Shaver, 2007). Such behaviors direct the
individual into new environments (broaden) that require adapt-
ing to new challenges (build). Moreover, broadening exper i ences
have been shown to result in the recruitment of suppor tive rela-
tionships (Hauser et al., 2006) which further enhances resilience
in the face of stress (Masten and Obradovic, 2008). Additional
evidence for this notion is provided by functional neuroimaging
studies that demonstrate an inverse relationship between partic-
ipants’ cortisol levels during social stress and the extent of their
supportive social network (Eisenberger et al., 2007), with indi-
vidual differences in activity of brain areas associated with social
separation (Brodmann area 8, dorsal anterior cingulate cortex)
found to mediate this relationship indicating a “protective effect
of social support on the neural processing of social threat and
subsequent HPA reactivity. Furthermore, secure attachment has
been associated with stronger decreases in state anxiety levels fol-
lowing laboratory-induced stress exposure (Ditzen et al., 2008).
More interestingly, an interaction effect between combined social
support and secure attachment resulted in even lower post-stress
anxiety levels. Secure attachment and a normative stress response,
in the current model, are closely linked with adaptive allostasis
and neural plasticity (Ganzel et al., 2010;
McEwen and Gianaros,
2010), a process conceived of as a buffer against future environ-
mental challenge and conferring resilience to the development of
psychopathology (Gluckman et al., 2007). The capacity to retain
high levels of mentalization when faced with threat or anxiety is
supposed to play a key mediating role therein, mainly by keeping
regulatory brain regions such as the prefrontal cortex engaged dur-
ing experiences of stress and attachment activation and by enabling
a fast recover y from the momentary loss of this capacity. This, is
turn, results in a reinforced feeling of attachment security, a sense
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Nolte et al. Attachment-based framework of anxiety disorders
of agency and autonomy during successful affect regulation, facil-
itated by undistorted perception and representation of self and
others (Fonagy and Luyten, 2009).
There is increasing evidence that the interplay between attach-
ment activation, stress-related arousal, and continuing mental-
izing is subserved by both the activation of mesocorticolimbic
dopaminergic reward circuits and stress attenuating (Neumann,
2008; Fonagy and Luyten, 2009) and anxiolytic effects of oxytocin
(Heinrichs et al., 2003; Kirsch et al., 2005; Ditzen et al., 2009;
Kubzansky et al., 2009; Quirin et al., 2010). Given that oxytocin
has been implicated in the parent–infant attachment relationship
(e.g., Gordon et al., 2008; Strathearn e t al., 2008), the attachment
system may play a key role in the functioning of neural systems
involved in anxiety processing. Oxytocin thus provides a link to
the attachment system and has been shown to enhance experi-
ences of secure attachment in an experimental setting (Buchheim
et al., 2009). Because of the impairments in attachment in inse-
curely attached indiv i duals, the quality of early experiences seems
to have differential effects on the oxytonergic system (Heim et al.,
2009; Bartz et al., 2010) and peripheral oxytocin levels in mothers
watching cues of their infants ( Strathearn et al., 2009).
INSECURE ATTACHMENT, DYSFUNCTIONAL STRESS REGULATION, AND
THE DEVELOPMENT OF ANXIETY DISORDERS
Given that the primary evolutionary function of the attachment
system is to maintain an infant’s proximity to the caregiver, the
system has to allow for adaptation to sub-optimal caregiving, as
in cases where the caregiver is inconsistently responsive, unavail-
able, or abusing. Therefore, when faced with stress or threat and
the primary attachment strategies have failed to elicit appropri-
ate caregiving behaviors, the infant utilizes so-called secondary
strategies in order to promote proximity and regulate anxiety.
These secondary strategies are characterized by “hyperactivating”
or deactivating
1
modes of stress and anxiety regulation (Cassidy
and Kobak, 1988; Mikulincer and Shaver, 2007; Roisman, 2007).
Hyperactivating strategies are centr al to an attachment account
of anxiety disorders given their initiation in response to anxiety
states, and are typically observed in anxiously attached individu-
als. Such strategies are characterized in infancy by frantic attempts
to gain the attention of the attachment figure and develop when
the infant’s previous interactions have required up-regulation of
seeking behaviors in response to an inattentive, preoccupied, or
anxious caregiver (Mikulincer and Shaver, 2008). If repeated over
time, these experiences serve to consolidate expectations of unre-
liable and unpredictable responses from the attachment figure and
therefore create anticipatory anxiety and heightened vigilance for
threat rather than successfully regulating anxiet y states. The frantic
demanding of support and constant activation of the attachment
1
Deactivating (minimizing) strategies are typically observed in individuals with a
avoidant style of attachment, and are characterized by attempts to downregulate and
suppress the attachment system in times of stress. Behaviorally, deactivating strate-
gies are observable in self-soothing activities, assertions of independence, and the
denial of attachment needs (Cassidy and Kobak, 1988). Deactivating strategies are
derived from a history of attachment experiences in which the caregiver was reject-
ing, emotionally distant, or prone to withdrawal when called upon. A reliance upon
deactivating strategies strengthens expectations of attachment figures as unavailable,
characteristic of a dismissive attachment in adulthood.
system may only allow for temporarily effective stress regulation
but in the long run “undermine the goal of recruiting a soothing
figure (Luyten et al., submitted for publication) and compromise
the establishment of social networks to provide supportive care
(Campbell et al., 2005). At the intrapersonal level, these dynam-
ics are characterized by autonomy-dependency conflicts which
in turn affect interpersonal functioning Joraschky and Petrowski
(2008). Furthermore,Mikulincer and Shaver (2007) demonstrated
that secondary strateg ies impact on the primary attachment strat-
egy of fear and threat appr aisal via inhibitory or excitatory feed-
back loops (with the latter being of particular relevance regarding
hypervigilance and HPA-axis functioning in anxiety disorders).
Anxiety therefore increases the seeking of proximity, while sepa-
ration from the attachment figure in turn increases anxiety and
withdrawal (Luyten et al., submitted for publication).
While evolutionarily advantageous in early childhood, these
strategies are associated with maladaptive outcomes in later life
due to their detrimental impact on interpersonal functioning
(Mikulincer et al., 2010). The resulting anxious pattern of attach-
ment is then likely to persist into adulthood (anxious–ambivalent
attachment) and represents the predominant mode of stress regu-
lation. In individuals who have experienced highly unpredictable
and abusive caregiving environments, attempts to regulate anxi-
ety states are observed to be characterized by a chaotic oscillation
between both hyperactivating and deactivating strategies so-
called disorganized attachment (Main and Solomon, 1986; Main
and Hesse, 1990). Both anxious and disorganized attachment
patterns have been associated with the development of anxiety
disorders (Manassis et al., 1994; Warren et al., 1997).
ATTACHMENT RESEARCH IN RELATION TO ANXIETY DISORDERS
Whilst not considered inherently pathological, insecure infant
attachment patterns, and the reliance upon secondary strategies
increases the likelihood of psychopathology. Specifically, anxious
attachment has been consistently associated with internalizing
problems (e.g., Colonnesi et al., 2011)andagrowingbodyof
research lends support to the view that anxious attachment, and
therefore the use of hyperactivating strategies, predisposes an indi-
vidual to various anxiety disorders (Colonnesi et al., 2011 for
meta-analysis). For example, it has been shown that a history of
anxious attachment measured at 12 months of age puts children
at risk of de veloping anxiety disorders in childhood and adoles-
cenceeven when maternal anxiety and temperament are controlled
for (Warren et al., 1997 ). Bosquet and Egeland (2006) found
attachment history was moderately correlated with self-reports of
anxiety at the age of 16. Further, childhood anxiety classification
was predictive of negative adolescent peer relationships which in
turn predicted anxiety sy mptoms. In another longitudinal study,
Bar-Haim et al. (2007) linked anxious–ambivalent attachment at
the age of 12 months with higher levels of school phobia 10 years
later. This association was, however, only found in boys.
Hyperactivating strategies therefore hold a relatively unique
position of predicting an array of transdiagnostic anxiety behav-
iors. Anxiously attached children experience constant worry
about being abandoned and left alone when fear is experienced
(Sroufe, 1996). This response is characterized by chronic hyper-
vigilance toward the social environment which may give rise to
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Nolte et al. Attachment-based framework of anxiety disorders
the development of anxiety symptoms (Cassidy and Berlin, 1994;
Weinfield et al., 1999).
In adulthood, the manifestation of anxiety disorders is linked
with ambivalent (anxious) attachment classification (Fonagy et al.,
1996; Rosenstein and Horowitz, 1996; Dick et al., 2005; Colon-
nesi et al., 2011) and negative attachment-related experiences such
as overprotective parenting or abandonment and separation dis-
tress (DeRuiter and van Ijzendoorn, 1992; Cassidy,1995; Bandelow
et al., 2002). In some of these studies (Manassis et al., 1994; Fon-
agy et al., 1996) and particular when investigating PTSD (Kobak
et al., 2004; Stovall-McClough and Cloitre, 2006 for review), there
seems to be a high prevalence of disorganized attachment sug-
gesting that childhood trauma or loss can give rise to particular
anxiety disorders.
More importantly, the study by Manassis et al. (1994) demon-
strates, albeit with a small sample, that 80% of the children
of mothers diagnosed with anxiety disorders were classified as
insecurely attached with 65% of them matching their mother’s
attachment classification.
In line with our fr amework it has to be noted that anxious
attachment itself is, at least in part, influenced by genetic con-
tributions. This seems to be more relevant when the style of
attachment is assessed via self-reports. Brussoni et al. (2000) found
that 25% of the variability in a dult attachment measured with the
Relationship Scales Questionnaire was accounted for by genes.
Using a twin study design, Crawford et al. (2007) demonstrated
that 40% of the variance was attributable to heritable factors, a
finding recently confirmed by Picardi et al. (2010) who reported
45% heritability. Behavioral genetics studies focusing on attach-
ment classifications obtained with interview-based instruments, in
contrast, highlight the role of shared environmental factors with
only little influence accounted for by genes in the contribution
to the transgenerational transmission of attachment in children
(Bokhorst et al., 2003; Fearon et al., 2006; Bakermans-Kranenburg
and Ijzendoorn, 2007). These inconsistencies might result from
different methodological approaches and the differential effect of
gene x environmental interplay depending on the timing of when
genetic effects come into play.
CONSEQUENCES OF HYPERACTIVATING STRATEGIES
As indicated earlier, secondary attachment str ategies might be
temporarily adaptive in a specific context or even at a societal
level (Simpson and Belsky, 2008 ; Ein-Dor et al., 2010), but in the
long run fail to attenuate stress effectively and result in increased
allostatic load. More specifically, the heightened subjective and
physiological stress reactivity found to be associated with hyper-
activation has been shown to affect core processes involved in
allostatic adaptation on a behavioral, endocrinological, and neural
level.
Compromised broaden and build features
The attachment-based coping strategies associated with hyper-
activation prohibit the ability of the individual to “broaden and
build.” Potentially supportive and competent others, especially
in close relationships, are experienced as untrustworthy and/or
unpredictable in their support and these expectations are com-
bined with chronic worry about abandonment (Campbell et al.,
2005; Miculincer and Shaver, 2009). Psychodynamic accounts fur-
thermore highlight the role of conflictuous interpersonal func-
tioning (e.g., Joraschky and Petrowski, 2008). Further, the use
of such strategies inhibits motivational systems responsible for
exploratory, affiliative, and caregiving behaviors (Mikulincer and
Shaver, 2005). Other factors characterizing hyperactivating behav-
ior, such as a negative view of self, a lack of self-efficacy, and
the tendency to avoid fears all inversely correlated with find-
ings regarding resilience (Cicchetti, 2010) reinforce the systems
responsible for hyperreactivity to stress.
Dysfunctional HPA-axis
The excessive use of behavioral hyperactivation has been linked
to physiological and neuroendocrinological hyperresponsivity
(Lupien et al., 2009). In a large prospective cohort study, for
instance, insecure–anxious (resistant) children displayed elevated
cortisol levels after being exposed to a separation paradigm (Luijk
et al., 2010). Similarly, in adults, hyperactivation has been found
to result in an altered and more sensitive HPA-axis (Powers et al.,
2006; Diamond et al., 2008; Gordon et al., 2008) and to have direct
effects on reducing hippocampal cell density (Quirin et al., 2011)
which might reflect a stress-driven neurotoxic impact on the gluco-
corticoid system. These indicators of allostatic load together with
the previously reviewed effects of stress and anxiety on HPA-axis
functioning suggest that chronic wear and tear entails that the once
regulatory and anticipatory functions of the HPA-axis are ren-
dered to conferring vulnerability to psychopathology (Schulkin,
2010). Most notably, the acquisition of prior allostatic load as
observed in attachment experiences characterized by anxiety and
ineffective stress regulation might impair the individual’s capac-
ity to accommodate to a current or future stressor (Ganzel et al.,
2010).
Effects of allostatic load on the neural circuits mentalization
deficits under heightened stress and in the face of anxiety
biobehavioral switch
The core emotional regions of the brain (the fronto-limbic cir-
cuit), as outlined above, are the primary and central mediator of
allostatic load as they are involved in the immediate stress response
but also iteratively update evaluations of stress and threat-related
environmental challenge (Ganzel et al., 2010). Together they coor-
dinate physiological and behavior al responses to stress and require
the effective recruitment of additional neural resources due to
increased attentional and processing load. (Vuilleumier et al., 2001;
Davidson et al., 2004). As these neural circuits represent the main
interface between changes in the environment and the individ-
ual’s accommodation to it they have been shown to be vulnerable
to accrual of stress load and resulting wear and tear (LeDoux, 1996;
Phelps, 2006; McEwen, 2007; Fonagy and Luyten, 2009; Rodrigues
et al., 2009; Ganzel et al., 2010) and are most malleable during
fetal and early childhood periods (National Scientific Council on
the De veloping Child, 2005). Arnsten (2009) has drawn attention
to the stress signaling pathways and the neuromodulatory alter-
ations that markedly impair PFC functioning, the ventromedial
section in particular. More specifically, the impact of allostatic
load can damage brain circuits due to an overproduction of neu-
rochemicals involved in the stress response (Bremner et al., 1995;
Frontiers in Behavioral Neuroscience www.frontiersin.org September 2011 | Volume 5 | Article 55 | 10
Nolte et al. Attachment-based framework of anxiety disorders
Gould et al., 1997; Ganzel et al., 2010). These effects of signifi-
cantly stressful events on neural processing have been studied in
great detail in fear consolidation and fear extinction paradigms
which are associated with anxiety and affected by hyp eractivation
strategies (Wellman, 2001; Izquierdo et al., 2006; Milad et al., 2009;
Rodrigues et al., 2009).
More importantly, following the biobehavioral model put for-
ward by Luyten e t al. (submitted for publication), sustained hyper-
activation in the face of anxiety or stress is directly linked to a
relative switch in activation from cortical to subcortical brain sys-
tems, from slow, reflective regulation to a rapid, reflexive response
(see also Mayes, 2006; Fonagy and Luyten, 2009; Johnson et al.,
2011). This arousal-dependent switch furthermore affects the
capacity to mentalize and modulates the neural network under-
pinning this faculty. More broadly, on a neural level, what can
be observed is a “switch from non-stress to stress conditions”
(Arnsten, 2009). Brain areas that have been consistently shown
to underpin mentalization include the medial PFC, superior tem-
poral sulcus, and temporal lobes (Gallagher and Frith, 2003; Frith
and Frith, 2006; Lieberman, 2007). In keeping with this notion,
Fraley et al. (2006) showed that anxious attachment is associated
with hypervigilance in p erception of emotional expression and
poorer affect judgments.
Beyond the well-established effects on neural circuitry under-
pinning anxiety, there is strong evidence from electrophysiology
studies and functional neuroimaging that anxiously attached indi-
viduals employing hyperactivating st rategies under-recruit pre-
frontal brain regions involved in emotion regulation, display a
neurobiologically supported bias toward memor ies of negative
valence and respond with amygdala hyperactivation to negative
social feedback (Gillath et al., 2005; Zilber et al., 2007; Vrticka
et al., 2008; Zhang et al., 2008). Moreover, it has been shown that
when comparing the effect of a general stress induction versus an
attachment-related (interpersonal) stress induction, only the latter
results in a relative deactivation of core areas associated with men-
talization. In this study of a normal population, when inferring
mental states of others during the Reading the Mind in the Eyes
Test (Baron-Cohen et al., 2001), Nolte et al. (under review) found
that it was only after exposure to attachment stress that activation
decreased i n the inferior frontal gyrus (a part of the prefrontal
cortex), the posterior temporal sulcus, and the temporoparietal
junction combined with stress-driven alterations of functional
connectivity. It can be hypothesized that these stress-related alter-
ations will be more pronounced in anxious individuals, although
this has yet to be investigated.
Together, these findings provide preliminary evidence that the
mitigating role of mentalizing is reduced in anxious individuals
due to excessive use of hyperactivating strategies. Consistent with
this theory, Milrod and colleagues (Rudden et al., 2008)report
preliminary evidence that individuals with Panic Disorder dis-
play no general deficits in mentalizing but markedly impaired
mentalization related to threat and anxiety cues.
SECTION SUMMARY
The hallmarks of hyperactivation st rategies in response to stress
and anxiety states are a low threshold for activation of the
attachment system, a low threshold for relative deactivation of
brain areas involved in controlled, reflective social cognition,
and mentalization as well as amygdala hyperreactivity result-
ing in neuroendocrinological hyperresponsivity. The current
model locates the main “programming” of these circuits and the
neural acquisition of allostatic adaptation (i.e., plasticity) in the
early attachment experiences. The ineffective down-regulation of
stress which is linked with impaired interpersonal functioning
and long-term consequences of allostatic load can lead to an
exhaustion and dysfunction of the stress response system with
increased risk for stress-related psychopathologies such as anxiety
disorders.
AN ATTACHMENT-BASED DEVELOPMENTAL FRAMEWORK
OF ANXIETY DISORDERS
We conceptualize the attachment system as a central organizer of
biological, genetic, and environmental influences on the devel-
opment of dysfunctional stress-regulatory processes and fear
responses that underpin anxiety disorders. The model, based on
the preceding review is presented in Figure 1. Component sections
are discussed in turn.
CHILD FACTORS
Genetic influences have been demonstrated to account for tem-
peramental factors (BI) which may, in some instances, represent
child-driven effects in the evocation of certain parenting styles.
Individual differences in attachment have also been demonstrated
to be influenced by genetic factors, although to a lesser degree.
The direct contribution to anxiety disorders accounted for by
genes is most likely the result of multiple loci additive and/or
interactive gene effects (Norrholm and Ressler, 2009; Figure 1,
Box 1).
However, as we have seen, stress sensitivity, and temperament
at birth, is modifiable by the effects of prenatal environment given
that, maternal st ress and anxiety during pregnancy can lead to
a sensitization of the HPA-axis. Thus, characteristics the infant
is born with could represent an in utero adaptation to the stress
regulation style of the mother.
PARENTAL FACTORS
Multiple parental factors have been outlined as possible contribu-
tors to the development of dysfunctional stress regulation of the
child. Such factors have been delineated as the presence of an
anxiety disorder (or preclinical anxiety, both entailing HPA-axis
alterations), low social support, parental insecure attachment, and
low mentalization capacity (Figure 1, Box 2).
THE ATTACHMENT RELATIONSHIP AS A DIALECTICAL SYSTEM
ORGANIZING EARLY EXPERIENCES
Together, or individually, parental factors interact with child fac-
tors outlined above, within the context of the early attachment
relationship. The proposed mechanisms by which these factors
can affect the parent’s capacity to effectively co-regulate the child’s
stress include the modeling of anxiety responses, the reinforce-
ment of threat cues in the environment (and their avoidance)
and parenting styles characterized by overcontrol of the child and
limited autonomy granting as observed in caregiver responses to
anxiously attached children (Figure 1, Box 3).
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Nolte et al. Attachment-based framework of anxiety disorders
EARLY ATTACHMENT
EXPERIENCES
Caregiver:
Inconsistant
Unpredictable
Anxious
DYSFUNCTI ONAL
STRESS REGULATION
ANXIOUS-AMBIVALENT
ATTACHMENT
Modelling of anxiety
Reinf orcement of threat cues
Overcontrolling
Reinforcement of avoidance
CONSOLI DATION
OVERGENERALIZATION
INTERNALIZATION
CHILD FACOTRS
Genetic vulnerability
Temperament
Prenatal sensitization
of HPA
Box 1
PARENTAL FACOTRS
AD/ anxiety
Low social support
Insecure attachment
Impaired mentalizing
HPA
Box 2
Box 3
ANXIOUS CHILD
Hyperactivation
HPA
Low mentalizing under stress
Altered neural circuit
Attentional Bias
Broaden and Build
Lack of secure base
Hypervigilance
Box 4
ANXIETY DISODER
Box 5
FIGURE 1 | A developmental model of the attachment-moderated
interaction of risk factors in the development of anxiety
disorders. Black bolts from one box to another indicate either
uni- or bidirectional effects and refer to the box as a whole. Blue bolts inside
boxes indicate either an increase or decrease of the magnitude of the
respective feature.
FROM EARLY ATTACHMENT EXPERIENCE TO A RISK PROFILE
It is proposed that the development of a stress