Curr Psychiatry Rep (2010) 12:290–297

DOI 10.1007/s11920-010-0131-9

Adult Separation Anxiety Disorder: A Disorder Comes

of Age
Vijaya Manicavasagar & Claire Marnane & Stefano Pini &
Marianna Abelli & Susan Rees & Valsa Eapen &
Derrick Silove

Published online: 16 June 2010

# Springer Science+Business Media, LLC 2010

Abstract This article explores accruing evidence support- Keywords Adult separation anxiety . Anxiety disorders .
ing the occurrence of an adult form of separation anxiety Diagnostic classification
disorder (ASAD), a category yet to be recognized by
international classification systems. ASAD can have its first
onset in adulthood, although in a portion of cases, it Introduction
represents a persistence or recurrence of the childhood-
onset type. Recent large-scale clinic studies have suggested The body of literature focusing on an adult form of
that ASAD is associated with high levels of disability. In separation anxiety disorder (ASAD) is relatively small,
addition, the presence of ASAD in individuals with anxiety largely because the condition has only been described in
disorders seems to signal a poor outcome to cognitive- recent years. Questions thus remain about the nosologic
behavioral therapy. The existing evidence suggests possible status and clinical significance of ASAD. Therefore, it is
grounds for removing the childhood-onset requirement for timely to assess whether separation anxiety disorder can
the category of separation anxiety disorder, thereby allow- occur in adulthood for the first time or as a continuation of
ing for first onset in adulthood. There is a pressing need to the childhood-onset form. Clarification of this issue is
design and test appropriate treatments for ASAD and to important in relation to the way in which separation anxiety
educate clinicians to identify and manage the condition. disorder is formulated in the forthcoming revisions of the
DSM and ICD. In addition, recognition of ASAD has
broader implications for understanding the developmental
V. Manicavasagar (*) psychopathology of anxiety, investigating possible psycho-
School of Psychiatry, Prince of Wales Hospital, logical and biological factors underlying attachment-related
University of New South Wales and Black Dog Institute,
Randwick, New South Wales 2031, Australia
disorders, and the development of treatments designed to
e-mail: [email protected] target specific forms of anxiety in adults.

C. Marnane : S. Rees : D. Silove

School of Psychiatry,
University of New South Wales and Psychiatry Research and
Background
Teaching Unit,
Liverpool, New South Wales 2170, Australia It has been a longstanding convention to regard separation
anxiety disorder as a condition confined to childhood and
S. Pini : M. Abelli
Department of Psychiatry,
adolescence [1]. This age-restricted formulation contrasts
University of Pisa, with overall trends in the classification of other anxiety
Pisa, Italy subtypes, in which it is increasingly acknowledged that
several disorders can have their onset across a broad age
V. Eapen
School of Psychiatry,
range spanning childhood and adulthood [2]. As a
University of New South Wales, consequence, there has been a growing convergence in
Liverpool, New South Wales 2170, Australia revisions of the classification systems between the juvenile
Curr Psychiatry Rep (2010) 12:290–297 291

and adult categories of anxiety. For example, the DSM-III The Structured Clinical Interview for Separation Anxiety
category of overanxious disorder of childhood has been Symptoms was developed by an independent research group
removed in the DSM-IV, with the diagnosis of generalized [7]. The measure has sound reliability and has been validated
anxiety disorder now being applied to all age groups. against the ASA-27. The instrument assesses CSAD and
Separation anxiety disorder remains the only category ASAD based on DSM-IV criteria, with symptoms modified
retained in the section for “disorders that usually have their for the adult module. It is noteworthy, therefore, that
onset in childhood” in the DSM-IV-TR [1]. Both the DSM- diagnostic measures developed at two separate centers show
IV-TR and ICD-10 explicitly require that onset of this convergence in identifying ASAD [6, 7]. More recently, the
disorder occur prior to 18 years of age. The emphasis on National Comorbidity Survey Replication (NCS-R) added its
childhood onset is emphasized by the comment in the own module for ASAD to the Composite International
DSM-IV-TR indicating that even the first occurrence of the Diagnostic Interview, based on the Structured Clinical
disorder in adolescence is rare. Nevertheless, the manual Interview for Separation Anxiety Symptoms [8].
does suggest that the disorder can persist beyond childhood,
and separation anxiety disorder is included as a possible
exclusion criterion for disorders that manifest primarily in Volunteer and Clinic-Based Studies
adulthood, such as panic disorder (PD) and agoraphobia
(Ag). The key issue, however, is that there is no reference The first quantitative study in the literature was based on
in the DSM or ICD systems to the possibility that separation respondents to a media campaign aimed at recruiting
anxiety disorder can have its first onset in adulthood. individuals with possible ASAD [5]. At the interview, 36
Observations of patients attending an anxiety clinic at respondents proved to have severe symptoms of adult
the University of New South Wales in Sydney, Australia, in separation anxiety. Participants recognized that their anxi-
the mid-1990 s alerted members of the team to the eties were excessive, ego-dystonic, and imposed extreme
possibility that separation anxiety symptoms could domi- limitations on their lives. For example, they needed to
nate the clinical presentation in adults [3]. Our research maintain proximity to or contact with attachment figures by
focus at the time was on early separation anxiety as a phoning key family members several times per day to
precursor to adult PD [4]. We noted, however, that in some check on their safety. Some respondents described “shad-
adult patients, the core fears focused on separations from owing” their attachments from afar or serially checking on
key attachment figures and the likelihood that harm would their whereabouts, often using complex strategies. Many
befall these individuals. Associated symptoms included a reported that their symptoms had adversely impacted their
reluctance to leave places of safety, sleep difficulties (fear careers. Those who reached the attention of mental health
and avoidance of sleeping alone, and nightmares about professionals had been given diagnoses such as PD, Ag, or
separation), and an excessive focus on maintaining prox- major depression, but none had been diagnosed with
imity to or contact with close attachments. Adult symptoms separation anxiety disorder. All reported that the treatments
seemed to be exacerbated by actual or threatened ruptures they received had proven ineffective. When comorbid
to primary bonds, with periods of acute anxiety akin to conditions were present, longitudinal histories suggested
panic being precipitated by situations or cognitions that that for most (75%), separation anxiety disorder had
triggered separation anxiety. preceded the other disorders. In the first clinic-based study
focusing on ASAD, 70 patients attending an anxiety service
with intake diagnoses of PD-Ag or generalized anxiety
Measurement disorder were administered the ASA-27 [9]. A total of 46%
met the criteria for ASAD, a remarkably similar prevalence
Several diagnostic instruments have been developed to to that reported for CSAD in anxiety clinics for children
measure ASAD. The Adult Separation Anxiety Structured [10]. A further Sydney-based study investigated the
Interview (ASA-SI) contains items derived from the DSM- occurrence of ASAD among older adult patients [11]. Of
IV criteria for childhood separation anxiety disorder 86 consecutive patients (age range, 62–87 years) recruited
(CSAD) and other sources, with symptoms modified for from a primary medical care setting, 6% (n=5) were
adulthood [3]. A self-report measure, the Adult Separation diagnosed with ASAD. Drawing on three case vignettes,
Anxiety-27 (ASA-27) contains the same items as the ASA- the authors described the same array of separation anxiety
SI, providing both a dimensional score and a threshold symptoms as found in younger adult counterparts with
score for caseness [5]. The ASA-27 has sound internal ASAD. None had received treatment for the disorder.
consistency (Cronbach’s α=0.89) and test–retest reliability Two large clinic-based studies were published recently.
(0.86; P<0.001) and has shown a high level of concordance Of 520 consecutive patients attending an outpatient
with the ASA-SI (area under the curve, 0.90) [6]. anxiety clinic in Sydney, 23% were assigned a diagnosis
292 Curr Psychiatry Rep (2010) 12:290–297

of ASAD (including those with comorbidity) [12•]. In can persist into an adult form, ASAD. In the NCS-R study,
Pisa, Italy, 20% of a sample of 508 outpatients with 36% of those with ASAD reported a history of CSAD [8].
anxiety and mood disorders were assigned to the category The association has been stronger in clinic settings, with
of ASAD with a history of CSAD, and an equal number to ASAD patients consistently reporting heightened levels of
that of ASAD without CSAD [13•]. The discrepancy in separation anxiety in early life [12•]. This discrepancy
prevalence rates across these studies may relate to the across studies may be accounted for by the possibility that
more stringent threshold set for assigning cases to ASAD individuals with ASAD have heightened separation anxiety
in the Australian study. Nevertheless, the results of both symptoms in childhood, but only a portion reach the
studies suggest that the ASAD diagnosis can be assigned symptom threshold for CSAD.
to a substantial number of adults attending clinics for Preliminary evidence indicates that separation anxiety
affective disorders. In both studies, ASAD was associated disorder may also follow differing trajectories depending on
with severe role impairment in personal, work, and social the age at onset. It seems that early-childhood–onset
functioning, even after controlling for possible confound- separation anxiety disorder is more likely to remit, whereas
ing factors such as comorbidity [12•, 13•]. Hence, ASAD those with middle-childhood–onset are more likely to
seems to rank high among the anxiety subtypes as a cause develop ASAD [13•]. Therefore, it is possible that
of dysfunction. individuals with severe separation anxiety spanning the
period of middle- to late-childhood and early-adolescence
have the worst overall prognosis. They may account for
Epidemiologic Studies most of the ASAD group who report a history of CSAD.
That group in turn seems to experience a higher frequency
The NCS-R, involving more than 5000 adults in the of affective episodes in adulthood, greater comorbidity with
United States, was the first epidemiologic study to include other anxiety disorders [13•], and a tendency to develop
a module for ASAD and a retrospective index of CSAD personality disorders [22].
[2]. The 12-month prevalence of ASAD was 1.9%, In summary, contemporary evidence, although incomplete,
whereas the lifetime prevalence was 6.6%, greater than suggests that elevated separation anxiety symptoms may
that for CSAD (4.1%) as measured retrospectively [8]. occur at any point in the lifespan, including old age, although
ASAD was associated with severe role impairment in 50% onset is most likely in childhood, adolescence, and early-
of comorbid and 25% of pure cases. adulthood. The large discrepancy between lifetime and
12-month prevalence rates indicated by the NCS-R suggests
that the disorder typically may follow a pattern of remission
Developmental Models of Separation Anxiety and relapse. Hence, the diathesis for separation anxiety may
be evident from early development, but whether or not
An important question is why has ASAD been overlooked by individuals reach the clinical threshold for symptoms may
psychiatric classification systems? A prevailing view based on depend on the extent and nature of the stress experienced at
the attachment theory proposed by Bowlby [14, 15] has been particular junctures in their lives (a diathesis-stress model).
that CSAD is the precursor of adult Ag. Subsequent to the
DSM-III, the focus of this model shifted to the relationship
between CSAD and PD with or without Ag [16–18]. The Nosologic Implications
model was essentially transformational in character (ie, it
postulated that one set of symptoms [CSAD] transmogrified Contemporary classifications systems are based on the
into another [PD-Ag] during the course of maturation [the assumption that the anxiety disorders form discrete, if
separation anxiety–PD hypothesis]). overlapping categories. A perennial debate revolves around
This hypothesis has come under increasing scrutiny, whether a categorical approach ignores the inherent
however, with studies conducted during the past four dimensionality of phenomena such as anxiety [23]. Taxo-
decades yielding inconsistent results [4, 19–21]. In partic- metric analysis [24] favors a model of adult separation
ular, many studies suggest that heightened early separation anxiety that is dimensional, consistent with most other
anxiety may be a nonspecific risk factor for the develop- forms of anxiety [23, 25, 26]. An alternative model that has
ment of a range of anxiety and other disorders. It seems been proposed is that separation anxiety, along with a range
possible that this inconsistency in findings has arisen at of other symptoms of stress, form part of a panic spectrum
least in part from a failure to account for ASAD as a disorder [27]. Nevertheless, it seems unlikely that formal
possible outcome of early separation anxiety. classification systems will depart from the established
Emerging evidence now favors the continuity hypothesis categorical approach in representing the anxiety disorders.
of separation anxiety, namely that early separation anxiety As such, there are grounds to reconsider how separation
Curr Psychiatry Rep (2010) 12:290–297 293

anxiety disorder should be represented in future revisions of close link between the constructs of complicated or
international taxonomies. If it is acknowledged that traumatic grief and separation anxiety disorder, both in
separation anxiety disorder can have its onset in adulthood terms of precipitating events—namely traumatic losses—
and that it is relatively common during that phase, then and overlapping symptom descriptors. In a community
there would be no grounds for retaining the category in the study, 33% of 36 participants with ASAD reported that the
section for disorders that commence in childhood. This onset of their symptoms followed a major loss (death,
modification would then bring complete symmetry to the divorce, changes of caregivers) [5]. Vanderwerker et al.
early-onset and adult anxiety disorders; separation anxiety [28] found a substantial association between complicated
disorder could be located with the other anxiety subcate- grief in adulthood and a history of CSAD (OR, 3.2), with
gories, obviating the need for a special section for the mediating factor being a current diagnosis of ASAD. In
childhood-onset anxiety. In so doing, the existing criteria contrast, a study of Bosnian refugees failed to find a
for separation anxiety disorder might need some modifica- connection between complicated grief and ASAD, although
tion to ensure that they apply equally to childhood and a weak link was found between ASAD and experiences of
adulthood. traumatic loss [29]. Instead, the strongest association that
emerged was between ASAD and PTSD, with almost all
individuals with ASAD having comorbid PTSD (al-
Comorbidity though∼50% of those with PTSD did not have comorbid
ASAD).
Anxiety and Stress-Related Disorders Interestingly, the NCS-R study also reported that PTSD
showed one of the strongest patterns of comorbidity with
In keeping with other anxiety subtypes, ASAD shows a ASAD, suggesting that trauma may be a common factor in
pattern of comorbidity with other anxiety and mood triggering both disorders [2]. Such a possibility is supported
disorders. Nevertheless, in the NCS-R study, the level of by studies of CSAD among disaster-affected children [28].
comorbidity between ASAD and other anxiety subcatego- These findings raise important questions about whether fear
ries was somewhat lower than for categories such as PD for personal safety is the common factor underlying PTSD
and post-traumatic stress disorder (PTSD) [2]. The study and separation anxiety disorder. In those with ASAD, this
found an inverse association of obsessive-compulsive fear constellation may be a substantial motivator driving the
disorder with ASAD (r=-0.79; OR, 8.1), an observation need to maintain proximity to attachment figures.
that remains to be explained [8]. The anxiety category that
showed the greatest comorbidity with ASAD was Ag Mood Disorders
without panic (OR, 5.8), whereas for those with a history
of CSAD, the strongest association was with specific An unexpected finding of the NCS-R study was the
phobia (OR, 4.3). It is possible that some of the overlap association that emerged between separation anxiety disor-
of these categories reflects the contemporary wording of der and bipolar disorder (with CSAD: OR, 4.3; with
diagnostic criteria. For example, individuals with both ASAD: OR, 7.1) [2, 8]. Following up this finding, Pini
ASAD and Ag may avoid leaving home, but there are and coworkers [30] reported that a history of CSAD was
differences in their motivation: those with Ag anticipate associated with earlier onset of bipolar disorder; conversely,
experiencing heightened anxiety in specified settings, ASAD symptoms were more severe in those with comorbid
whereas individuals with ASAD are concerned with being bipolar disorder and PD compared with those with pure PD.
separated from attachment figures. In addition, unless Furthermore, among patients with depression, those with
explicitly inquired into, the salient precipitants and cogni- comorbid ASAD (and a history of CSAD) had a greater
tive fears relating to separation may be overlooked in number of affective episodes compared with those in whom
differentiating acute episodes of separation anxiety from ASAD was absent [13•]. The relationship between separa-
those of panic attacks. Hence, there may be a need to tion anxiety disorder and affective disorders (especially
ensure that criteria for Ag, separation anxiety disorder, and bipolar disorder) therefore warrants closer investigation.
PD are revised to ensure that there is minimal or no As yet, there are no longitudinal studies involving
definitional overlap among these categories. ASAD. Hence, when comorbidity is recorded, the question
remains about whether separation anxiety preceded and was
Loss, Grief, and Post-Traumatic Stress Disorder implicated in the pathogenesis of other symptom constella-
tions or vice versa. In a phenomenologic study, most of
Relatively little attention has been paid to investigating the those with ASAD reported that their separation anxiety
impact of loss and bereavement in precipitating or predated other symptoms (eg, panic or depression) [5]. The
exacerbating ASAD [8]. Conceptually, there seems to be a sample was selected, however, on the basis of their
294 Curr Psychiatry Rep (2010) 12:290–297

separation anxiety. Only longitudinal studies will be able to with other anxiety and depressive disorders in depicting
examine the chronological onset of symptoms and to what their parents as uncaring.
extent separation anxiety disorder is implicated in the To date, little is known about the neurobiology of
genesis of disorders known to have a predominantly adult separation anxiety in humans. Several studies undertaken by
onset (eg, PD-Ag). the Pisa group have shown that translocator protein (TSPO)
density values are associated with states of stress and anxiety.
Personality Disorders The question explored by a series of studies undertaken in Pisa
was whether TSPO density may be specifically associated
The relationship between ASAD and personality disorders, with ASAD [34–36]. The first study of PD patients found
particularly dependent personality disorder, warrants con- that lower-density platelet TSPO was present only where
sideration. Bowlby [14] distinguished between dependency, there was comorbid ASAD. A relationship between TSPO
which he defined as a pervasive and indiscriminate density and severity of separation anxiety symptoms gave
tendency to rely excessively on others, and separation further weight to the findings. In a second study, TSPO
anxiety, which referred to a more constrained array of fears platelet density was found to be lower in patients with major
and proximity-seeking behaviors focused on key attach- depression, but this effect was exclusively accounted for by
ments in a person’s immediate circle. Those with ASAD the presence of comorbid ASAD; again, there was an inverse
seem to conform to the latter pattern, reporting excessive relationship between TSPO density values and the severity
attachments to one or only a limited range of individuals of separation symptoms. A third study found an association
and experiencing their fears as ego-dystonic and a source of between lower platelet TSPO density and the presence and
frustrating limitations in functioning [5]. In a study severity of ASAD in bipolar patients.
conducted in an adult anxiety clinic, ASAD patients These findings suggest that ASAD may be linked to a
exhibited similar rates of personality disorder as those with dysregulated neurobiological mechanism relevant to attach-
other anxiety disorders [9]. Nevertheless, in a larger clinic ment and separation anxiety for which there are extensive
study, there was a distinction between patients with ASAD animal models [37]. Genetic studies have added to this
alone and those with ASAD and heightened early separa- evidence by identifying a possible mutation (polymorphism
tion anxiety. The latter were assigned a larger number of 439GàA) of the TSPO gene in bipolar patients with ASAD
comorbid personality disorders (clusters B and C) com- [38]. The genetic variant may influence the uptake and
pared with those with adult-onset ASAD and patients with translocation of cholesterol into mitochondria [39]. The
other anxiety disorders [22]. Hence, it seems likely that impact on neurosteroid biosynthesis in turn could influence
early separation anxiety of a severe type increases the cognitive functioning and behaviors associated with emo-
likelihood that the developing personality will undergo tional states such as anxiety [40].
distortions, particularly in areas related to interpersonal The focus of research by the Pisa group has turned to
insecurity. This possibility is supported by the findings of a oxytocin, a neurotransmitter or neuromodulator that influ-
recent study suggesting that individuals with ASAD report ences attachment processes in animals [41] and possibly
enduring styles of anxious attachment—bonding character- humans [42]. It was postulated that ASAD may mediate the
istics that are likely to be established in early development well-established link between specific adult attachment
[31]. styles (apprehension over rejection and abandonment) and
depression [43]. However, in the first study to explore this
issue, no evidence was found of mutations in the promoter
Psychological and Biological Correlates of ASAD and coding regions of the oxytocin gene among ASAD
patients [44]. A further study examining the oxytocin
As yet, limited data are available concerning the possible receptor gene yielded interesting findings in relation to
etiologic factors underlying ASAD. A small study based on two single nucleotide polymorphisms: 6930G > A
an anxiety clinic showed that children with CSAD were (rs53576) and 9073G > A (rs2254298). Those with the
much more likely to have one parent with ASAD [32]. GG genotype for these single nucleotide polymorphisms
Familial concordance seemed particularly strong for moth- were more likely to have unipolar depression, and within
ers and daughters, a finding that is in accord with a twin the depressed group, GG individuals showed high scores on
study suggesting that females may have a stronger genetic dimensions of anxious attachment and ASAD [45]. Al-
loading for separation anxiety (measured by a retrospective though these biological inquiries are in their early phase,
measure of early separation anxiety, the Separation Anxiety the preliminary results offer support for a link involving
Symptom Inventory) [33]. In addition, ASAD patients ASAD, anxious styles of attachment, and neurobiological
characterized their parents as overprotective, whereas those markers thought to be relevant to the process of bond
with PD conformed to the general pattern of individuals formation.
Curr Psychiatry Rep (2010) 12:290–297 295

Clinical Implications concerning the separation anxiety–PD model. Clearly,

however, only longitudinal studies can provide final
Some evidence indicates that a failure to identify and treat confirmation of the continuity model.
ASAD may be important in limiting treatment outcomes in The discovery of ASAD brings into question whether an
anxiety clinic patients in general. Aaronson et al. [46•] found age criterion should be retained in the diagnosis of
that patients receiving cognitive-behavioral therapy for PD separation anxiety disorder. Indeed, this has been a source
were about four times more likely to have a poor outcome if of debate in the process of revising the category of
they had comorbid ASAD. This effect remained even after separation anxiety disorder in preparation for the DSM-V
taking into account other prognostic factors, including the [48]. Existing data would suggest that separation anxiety
overall severity of anxiety symptoms, number of comorbid disorder may be best classified as a condition that can have
anxiety disorders, socioeconomic status, severity of Ag, and its onset at any age. By removing the age restriction,
duration of illness. Kirsten and colleagues [47] investigated complete symmetry could be achieved in the classification
the treatment outcomes for patients with social phobia, PD, of the adult and juvenile anxiety disorders, obviating the
or generalized anxiety disorder. Those with comorbid ASAD need for a special category for the latter age group. The
were less likely to show reductions in indices of general term ASAD therefore may prove to have a limited nosologic
anxiety and depression following cognitive-behavioral ther- lifespan, with the reasons for its inception (to indicate the
apy. These findings suggest that the presence of ASAD is a importance of recognizing that separation anxiety disorder
poor prognostic factor among the anxiety disorders in can have its onset throughout the life course) ultimately
general and/or that the failure to address the core separation dictating the need for its early removal.
anxiety fears of this group prevents them from achieving Although some evidence indicates that specific genetic,
substantial recovery. familial, bonding, and attachment factors may be relevant
to the genesis of ASAD, much more research in this area is
needed. Similarly, the early findings of biological research
Conclusions can only be regarded as preliminary.
From a clinical perspective, the failure to identify and
Although the body of existing research concerning ASAD address the symptoms of ASAD may be a key factor that is
is not as extensive as for other subtypes of anxiety, some responsible for limiting the effectiveness of cognitive-
tentative conclusions can be drawn based on existing data. behavioral therapy in treating anxiety patients as a whole.
The development of psychometrically tested measures has Therefore, it seems imperative to design and test treatments
made it possible to confirm initial clinical impressions by that may be specific to ameliorating separation anxiety
allowing the reliable identification of ASAD across symptoms in adulthood. At the same time, it is important to
populations (clinic and community) and countries. An raise awareness and the knowledge base of clinicians
epidemiologic study that has included the diagnosis of working with adult anxiety patients so that they accurately
ASAD has revealed a lifetime prevalence of the disorder of identify individuals with ASAD.
6.6% [8]. Once identified, ASAD assignments are common
among patients attending anxiety clinics, with the diagnosis
being made as frequently as for the combined categories of
Disclosure No potential conflicts of interest relevant to this article
PD and PD-Ag. This finding is even more noteworthy were reported.
given that patients, referral agents, and most clinicians are
not yet familiar with the diagnosis of ASAD. For that
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