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Separation Anxiety in Adulthood

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 Chapter #

SEPARATION ANXIETY DISORDER IN ADULTHOOD

Stefano Pini1 , Marianna Abelli1, Angelo Bruschi2

∗

1
Department of Psychiatry, University of Pisa, Italy
2
Institute of Psychiatry, Catholic University Medical School of Rome, Italy

ABSTRACT
Separation anxiety disorder was described in DSM-IV-TR as a childhood disorder that rarely persists into
adulthood, but several empirical studies have demonstrated that adult separation anxiety disorder (ASAD) is
more common than suggested. This could be due to either of two possibilities: 1) a higher proportion of
childhood-onset cases persist into adulthood than was assumed in DSM-IV-TR; 2) a substantial proportion of
first onsets occur in adulthood (these subjects never having had childhood separation anxiety disorder). The
position of separation anxiety disorder in the DSM-5 is different. Indeed, the DSM-5 discontinues the section
for disorders that have their first onset in childhood, where separation anxiety disorder was previously
placed. Differently, in the DSM-5, it moves within the general section for anxiety disorders. Moreover, a
crucial change in the criteria is the removal of the assertion that onset of the disorder must be before the age
of 18 years, a modification that is consistent with clinical and population-level research evidence. Finally,
symptoms have been reworded to remove any implicit bias towards childhood. However, the relationships of
ASAD with other psychopathological conditions are not clear. In particular, studies of pathological
mechanisms, including the role of attachment, shared by both separation anxiety disorder and other anxiety
and mood disorders are needed and deserve further neurobiological and clinical research.
Finally, from a treatment perspective, there is increasing evidence that unaddressed separation anxiety
lessens the effects of both medication and psychotherapy.

INTRODUCTION
Separation Anxiety Disorder (SAD) is a disease that has been classically defined as a childhood
phenomenon. As well known, the discomfort arisen by the separation from an attachment figure is related to
the ordinary childhood development (Ainsworth, 1963; Bowlby, 1969; Bowlby, 1973), with a probable
evolutionary purpose: the retention of the human offspring, still inept, near its main caregiver.
Then, a physiological level of separation anxiety could be considered a universal dimension, expected in the
development of every child; it appears from the first months of life, becoming gradually more intense and
then it disappear with the growth.
In the first year of life, the fear of strangers is considered an important step of average social development as
well as the anxious reaction occurring at the first school placement.
Only if the sensitivity of the separation becomes excessive, prolonged, with an intense anxiety and
interference in daily life activities or normal development, we can diagnose a Separation Anxiety Disorder
(SAD) (American Psychiatric Association, 2000).
The SAD, Separation anxiety disorder of childhood (American Psychiatric Association, 2013), can be
defined as condition burdened by an excessive and inappropriate display of fear and distress when faced with

∗
Stefano Pini, Department of Psychiatry, University of Pisa, via Roma 67, S. Chiara Hospital, Pisa, Italy
e-mail: stefano.pini@med.unipi.it
situations of separation from home or from a specific attachment figure. The severity of the symptoms
ranges from anticipatory uneasiness to full-blown anxiety about separation.
From the clinical point of view there are generally developmental differences in the expression of the
disorder:
• Younger children resent separations and show concern when the mother leaves. In his presence they
make constant checks: they do not lose sight of her, are close to, touch her, cling to her clothes and
ask to get caught up in her arms. Even falling asleep requires the close proximity of the mother and
sleep may be disturbed by nightmares, waking up anxious, constant references and intrusions in bed
parents;
• At 5-8 years the symptoms are mainly behavioral and somatic: there are unrealistic fears of being
lost without parents, with ruminations of been damaged by this separation;
• In the following years takes priority the fear of possible accidents/diseases of the parents and the
school refusal;
• In adolescence are very frequent somatic and challenging behaviors, used by the adolescent to attract
the attention of parents.
The estimated prevalence of SAD, according to the international literature, is referred as 3-4% of school
aged children and 1% during teenage years (American Psychiatric Association, 2000).
The focus on the childhood onset, emphasized by the comment in the DSM-IV-TR, indicates that the first
appearance of the disorder during adolescence is extremely rare. However, the manual suggests that the
disease may persist after childhood and includes separation anxiety between the possible exclusion criterion
for certain disorders occurring mainly in adulthood as panic disorder (PD) and agoraphobia (Ag).
The key question, however, remains: may the separation anxiety disorder have its onset in adulthood?
The age-related formulation contrasts with the general classification trend of the various subtypes of anxiety,
in which it is increasingly recognized that different disorders can have their debut in a wide age range
(Kessler et al., 2005).To date, despite it’s not yet recognized by the international classifications, there is a
broad evidence regarding the existence of an adult form of the SAD, which may arise at any age even if,
sometimes, it represents a continuation or recurrence of the childhood disorder (Shear et al., 2006; Pini et
al., 2010).

History of clinical classification

Since the mid-’90, psychiatrists from the New South Wales University of Sidney observed that, in some
adult patients followed by their anxiety clinic, the clinical picture was dominated by separation anxiety
symptoms (Manicavasagar et al., 1997). Early studies tried to correlate early separation anxiety with the
agoraphobic subset of PD (PD-Ag) (Silove et al., 1995a). However, as underlined by Manicavasagar and
colleagues, some adult patients reported that the main fears were focused on the separation from attachment
figures and the possibility that some event could affect this relationship. Associated symptoms included a
reluctance to leave places considered sure, sleep disorders (fear of sleep alone, nightmares of separation) and
an excessive focus on the maintenance of close proximity or contact with attachment figures.
Adult symptoms seems to be worsen by real or threatened breach of primary bonds, with interval of acute
anxiety similar to panic attacks triggered by situations that activated separation anxiety (Manicavasagar et
al., 2010).
Subsequently, additional studies of the same workgroup (Manicavasagar et al., 1997a-b; 2000; 2003; Silove
et al., 1995) and also by other authors (Cyranowski et al., 2002; Silove et al., 2007) have focused the SAD,
defining it more accurately. According to Kessler et al. the SAD should no longer be confined exclusively to
childhood and adolescence but, like other anxiety disorders, could be considered a disease that can have its
onset in every age (Kessler et al., 2005); moreover, the same authors argue that, although the SAD is a well
known phenomenon studied in childhood, it can persist in adulthood, showing symptoms characteristic of the
new context in which the disorder is manifested.

Assessment tools
Over the years we have developed numerous tools for the evaluation of the SAD, weather it is child or adult.
The first, The Adult Separation Anxiety Structured Interview (ASA-SI) is a semi-structured interview whose
items are derived from the criteria of the DSM-IV-TR for the SAD adapted to the adulthood and from other
sources (Manicavasagar et al., 1997). It has also been developed a self-administered evaluation scale, the
Adult Separation Anxiety-27 (ASA-27), which contains the same items of the ASA-SI and provides both a
dimensional score as well as a threshold value in order to make diagnoses (Manicavasagar et al., 2003). The
Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS) was developed for the
evaluation, through two distinct modules, of the childhood or adulthood SAD with items derived from the
DSM-IV-TR and modified in the adult form (Cyranowski et al., 2002).

MAIN STUDIES

General Population studies

The National Comorbidity Survey Replication (NCS-R) (Kessler et al., 2004a-b) was the first
epidemiological study including a questionnaire for Adult Separation Anxiety Disorder (ASAD) and a
retrospective form for the childhood SAD (Kessler et al., 2005). The results showed a 12 months ASAD
prevalence of 1, 9% and a lifetime prevalence of 6.6%, notably greater that the childhood SAD prevalence,
found to be 4.1% (Shear et al., 2006).

Clinical and volunteer samples

The first study on a sample of volunteers was conducted by a media campaign specifically drawn for the
recruitment of patients with a possible diagnosis of ASAD. Thirty-six of the forty-four enrolled subjects
fulfilled the criteria for the disorder and, although many of these patients remembered the onset in the
childhood, about a third reported an adulthood onset; moreover, were also frequent comorbid anxiety and
mood disorders (PD or MDD), but in about 75% of cases the symptoms of separation anxiety came first
(Manicavasagar et al., 1997).
The first study on a clinical sample was performed on a group of 70 patients with anxiety disorders (PD-Ag
and GAD) using ASA-27 (Manicavasagar et al., 2000): 46% of the sample met the criteria for ASAD. There
is a study on 86 elderly patients (62-87 years), with an ASAD prevalence of 6% (Wijeratne &
Manicavasagar, 2003). Recently it has been published the result of two clinical studies on larger samples: in
the first study, in Pisa, were observed 508 patients outpatients with anxiety and mood disorders, detecting an
overall ASAD prevalence of 40% (Pini et al., 2010); the second study, conducted in an anxiety disorders
clinic in Sidney on 520 outpatients, showed an ASAD prevalence of 23%, not excluding comorbidities with
other anxiety disorders including PD, the PD-Ag and the GAD (Silove et al., 2010a).

Adult separation anxiety in family and attachment studies

Over recent decades, attachment theory has expanded its scope beyond infancy and childhood to attachment
styles in adulthood and related relevance to psychopathology in later life. A small study on 54 children and
their parents showed that a child with SAD has a higher chance of having a parent affected by ASAD (odds
ratio = 11.1) (Manicavasagar et al., 2001). The correlation was stronger for mothers and daughters, in
agreement with previously published data on higher genetic female load for the SAD (Silove et al., 1995b).
Recently it has been tried to clarify the link between attachment styles and psychiatric disorders in
adulthood, primarily the PD-Ag. Manicavasagar et al. (2009) studied 83 patients with PD-Ag and ASAD,
highlighting that the style of anxious attachment, using the Attachment Style Questionnaire (ASQ) (Feeney
et al., 1994), was more prevalent in patients with separation anxiety and panic than in patients only with
panic attacks. This is in disagreement with the previous theory of a link between anxious attachment styles
and PD-Ag, confirming the lack of supports between early separation anxiety and PD-Ag (Lipsitz et al.,
1994; Silove et al., 1996). The authors instead hypothesize a model of continuity for the SAD, which states
that hereditary factors and an early overprotective attitude of parents can lead to the development of high
levels of separation anxiety (Silove et al., 1995b; Manicavasagar et al., 1999).
Separation anxiety disorder in adulthood may be regarded as a parallel development that consolidates the
notion that anxious and other forms of distorted attachments are of fundamental importance to human
adaptation across the lifespan – and not simply an issue of relevance to understanding developmental
psychopathology originating in infancy. Notwithstanding, it is important to keep in mind that SAD and an
anxious attachment style are not synonymous constructs. As a diagnostic category, SAD is a nomothetic
construct based on the coexistence of operational symptoms (Marnane and Silove, 2013). Conversely,
anxious attachment is an idiographic construct whose meaning and assessment varies according to different
attachment theories. Although several studies showed that persons with adult SAD score higher on indices of
anxious attachment, the association is modest (Manicavasagar et al., 2009). Furthermore, it is not clear
whether adult SAD may predispose to anxious/insecure attachment or viceversa.
In addition, some of the findings in the recent literature point to associations between SAD and other forms
of psychopathology that may be unanticipated.
For example, in a study of trauma-exposed refugees, adult SAD was strongly associated with PTSD (see also
paragraph on comorbidity) (Silove et al., 2010b).
Fears for the safety and security of the self are closely linked to fears for others amongst the symptoms of
SAD, offering a possible explanation for its overlap with PTSD. Indeed, in some instances, SAD may be the
opposite side of the coin of PTSD, particularly in settings where the initiating trauma posed a threat to close
others. As such, as a diagnostic category, SAD may prove to have complex origins that are not necessarily
aligned with the constructs of attachment theory.

Neurobiology
A significant neurobiological line of research has focused on the correlation between SAD, protein
translocator-protein (TSPO) and oxytocin (OXT). TSPO is a polypeptide implicated in the synthesis of
neurosteroids that can influence the cognitive and behavioral functions associated to anxiety (Birzniece et al.,
2006), probably through the allosteric modulation of the complex GABAA/BDZ.
Oxytocin, instead, is a neurotransmitter that influences attachment processes in a large variety of animals.
The traditional view of OXT as an endocrine hormone acting on peripheral organs (i.e., to induce labor and
milk ejection) has been revised such that this neuropeptide is now considered to be a neurotransmitter or
neuromodulator with central actions in the limbic system, the forebrain and the autonomic centers of the
brainstem. Oxytocin plays a role in a variety of central functions, such as sexual behavior, maternal behavior,
affiliation, social memory, satiety and stress responsiveness. In particular, there is strong evidence
concerning the involvement of OXT in attachment processes in animals (Insel and Young, 2001) and, despite
a limited amount of detailed experimental data, some evidence to support similar behavioral effects in
humans as well (Marazziti et al., 2008).
Different studies have showed that the peripheral density values of the TSPO are associated with stress or
anxiety: the up-regulation of TSPO occurs after acute stress, while the down-regulation after chronic stress
(Weizman et al., 1995; Johnson et al., 1998). It has been investigated the link between the density of TSPO
and symptoms of ASAD (Pini et al., 2005a; Chelli et al., 2008; Abelli et al., 2010) and the associated genetic
polymorphisms (Costa et al., 2009a). Pini et al. found that only PD patients with ASAD comorbidity showed
low platelet density values of TSPO but not those with PD without ASAD.
Similarly, some studies reported low platelet density values of TSPO in patients with MDD or bipolar
disorder (BD) only in the presence of comorbidity for ASAD (Pini et al., 2005; Chelli et al., 2008). The
possible link between SAD and dysregulation of neurobiological mechanisms of attachment led the focus of
the research on oxytocin, particularly on polymorphisms of oxytocin gene (OXT) and its receptor (OXTR).
In the first study, no mutations were found in the coding region or in the promoter regions of OXT in
patients with SAD; probably, as suggested by the authors, since oxytocin is crucial for the homeostasis of the
organism it could be highly preserved among species (Costa et al., 2009b). The search for mutations in the
promoter OXT (healthy vs mood patients) has revealed the existence of two different single nucleotide
polymorphisms: 6930G> A (rs53576) and 9073G> A (Rs2254298). In particular, the carriers of the genotype
GG seem to have an higher probability of being affected by MDD and show higher levels of anxious
attachment and separation anxiety (Costa et al., 2009c).
In sum, findings indicate moderate heritability of separation anxiety symptoms and stronger influence for
SAD, especially in females. The degree of heritability of SAD cannot be estimated yet. Its underlying causal
factors and mechanisms likely include genetic and environmental components that are strongly correlated
with those of other anxiety disorders. The question of which genes or polymorphisms may be involved in the
etiology of separation anxiety, beyond the association between ASAD and oxytocin peptide and receptor
polymorphisms, is still unknown. Further analyses, allowing also for the effects of age on the expression of
genetic and environmental factors, are needed.

Nosological implications
The main question is whether ASAD is not simply the manifestation of another disorder: in fact it could be
argued that the desire to be close to another person appears rather common in many disorders for different
reasons. According to Pini et al. (2010) the symptoms of separation anxiety do not merely represent a
secondary manifestation of a primary condition, as for example the dependent personality disorder in which
the dependence is a pervasive and indiscriminate tendency to rely excessively on others, whereas separation
anxiety refers to a limited array of concern about the proximity and safety of key attachment figures. In some
cases, fears of separation may also pose a problem of differential diagnosis of borderline personality
disorder. However, in this case, clinical picture is characterized by pervasive instability in mood,
interpersonal relationships, self-image and behavior (Reisch et al., 2008).
More complex is the relationship existing between separation anxiety, PD and Agoraphobia: it is well known
that subjects with ASAD may experience symptoms similar to panic attacks (Manicavasagar et al., 2009).
According Manicavasagar (Manicavasagar et al., 2010) separation anxiety and agoraphobia differ in the
main core: an agoraphobic subject feels an irrational and uncontrolled fear of being overwhelmed by panic
attack or panic-like symptoms, whereas separation anxiety is triggered by the fear of a temporary separation,
real or imagined, from significant attachment figures.
Once highlighted symptoms and phenomenological peculiarities of the disorder (Table 1), we must take into
account that ASAD nosology cannot fail to take into account the general revision in the classification of
anxiety disorders.

Table 1: Differential Diagnosis of ASAD vs other psychiatric disorders a

Behavioural aspects Adult Panic Generalized Dependent Borderline

linked to Separation Disorder Anxiety Personality Disorder
separation anxiety Anxiety with Disorder Disorder
Agoraphobia
Childhood YES YES YES NO NO
Separation Anxiety

Fear of Panic Attack NO YES NO NO NO

Excessive fear of YES NO YES NO NO

something bad
happening to the
attachment figure
Difficult to stay YES NO NO YES NO
away from the main
figures
Difficulty accepting YES NO NO NO YES
the end of a
relationship
Difficulty to YES NO NO NO YES / NO
discontinue
psychotherapy even
if therapist does not
believe
it is still necessary
Sensitivity to NO YES NO NO NO
reassurance
Agoraphobia NO YES NO NO NO

Symptoms related to Floating or Worsening of Not specific Increased Feelings of

separation critical agoraphobia liability anger,
(or fear of anxiety emotional
separation) emptiness,
impulsivity
a
Modified from: Pini S, Abelli M. (2008). Ansia di separazione in età adulta: manifestazioni cliniche e
rapporti con i disturbi affettivi. In: Cassano GB, Tundo A (Eds). Lo spettro dell’umore. Psicopatologia e
clinica. Milano: Elsevier.
In fact, taxonomic analysis, consistent with other anxiety disorders, suggest a dimensional model of
separation anxiety (Silove et al., 2007), in which ASAD can be represented in a more realistic construct with
a continuous distribution, as an extreme point on a dimensional continuum.
The results of the study also suggest that the pattern of symptoms, by himself, may not be sufficient for a
diagnosis, but there are still needed additional criteria such as, for example, the onset and the progression of
symptoms, family history, the clinical impact of separation anxiety in comparison to other symptoms and
disability associated with the disorder.
There is, however, another model that fits the separation anxiety, together with other symptoms of anxiety,
within the panic-agoraphobic spectrum (Shear et al., 2002). In the model developed by Cassano et al. (1999)
there is a specific subset of items for the separation anxiety dimensions that refers to a whole series of
symptoms directly linked to the separation from attachment figures.
In any case, since the separation anxiety disorder may have its onset in adulthood and it seems also relatively
common in this phase, there will be no reason to enter the SAD in the section of disorders that begin only in
childhood (Kessler et al., 2005).

Separation anxiety disorder in the DSM-5

Modifications to the proposed criteria in DSM-5 reflect the aforementioned findings of research undertaken
on SAD over the past 15 years. First, DSM-5 discontinues the section for disorders that have their first onset
in childhood, where SAD was located in DSM-IV-TR. Instead, SAD now joins the other subtypes of anxiety
disorders in the general section for the anxiety disorders (see Table 2).

Table 2. Anxiety Disorders in the DSM-5

Diagnosis Age of onset

Separation anxiety Disorder More frequent before 18 years of age, but may occurs first
time in adulthood

Selective Mutism Typically before 5 years of age

Specific Phobia Peak between 7 and 11 years of age

Social Anxiety Disorder Median age 13 years (75% have an age at onset between 8
and 15 years)

Panic Disorder Median age at onset is 20-24 years; overall prevalence is

low before age 14 years (<0.4%)

Panic attack specifier (panic attacks in the Mean age at onset is 22-23 years. Can occur in children
context of any mental disorder) but are relatively rare until puberty

Agoraphobia The overall mean age at onset is 17 years.

First onset in childhood is rare.
Without preceding panic attacks or panic disorder is 25-29
years

Generalized Anxiety Disorder Median age at onset is 30 years (later than that for the
other anxiety disorders). However, age at onset is spread
over a very broad range from childhood to elderly.

From: American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th
ed.). Arlington, VA: American Psychiatric Publishing.
The DSM-5 chapter on anxiety disorder no longer includes obsessive-compulsive disorder (which is
included with the obsessive-compulsive and related disorders), post-traumatic stress disorder and acute stress
disorder (both are now included with the trauma- and stressor-related disorders).
Although in DSM-IV, separation anxiety disorder was classified in the section “Disorders Usually First
Diagnosed in Infancy, Childhood, or Adolescence,” it is now classified as an anxiety disorder. The core
features remain mostly unchanged, although the wording of the criteria has been modified to more
adequately represent the expression of separation anxiety symptoms in adulthood (see Table 3). For example,
attachment figures may include the children of adults with separation anxiety disorder, and avoidance
behaviors may occur in the workplace as well as at school. Also, in contrast to DSM-IV, the diagnostic
criteria no longer specify that age at onset must be before 18 years, because a substantial number of adults
report onset of separation anxiety after age 18. Also, a duration criterion—“typically lasting for 6 months or
more”—has been added for adults to minimize overdiagnosis of transient fears.

Table 3. DSM-5: Separation Anxiety Disorder Diagnostic Criteria 309.21 (F93.0)

A. Developmentally inappropriate and excessive fear or anxiety concerning separation from those to whom
the individual is attached, as evidenced by at least three of the following:
1. Recurrent excessive distress when anticipating or experiencing separation from
home or from major attachment figures.
2. Persistent and excessive worry about losing major attachment figures or about possible harm to them,
such as illness, injury, disasters, or death.
3. Persistent and excessive worry about experiencing an untoward event (e.g., getting lost, being kidnapped,
having an accident, becoming ill) that causes separation from a major attachment figure.
4. Persistent reluctance or refusal to go out, away from home, to school, to work, or elsewhere because of
fear of separation.
5. Persistent and excessive fear of or reluctance about being alone or without major attachment figures at
home or in other settings.
6. Persistent reluctance or refusal to sleep away from home or to go to sleep without being near a major
attachment figure.
7. Repeated nightmares involving the theme of separation.
8. Repeated complaints of physical symptoms (e.g., headaches, stomachaches, nausea, vomiting) when
separation from major attachment figures occurs or is anticipated.
B. The fear, anxiety, or avoidance is persistent, lasting at least 4 weeks in children and adolescents and
typically 6 months or more in adults.
C. The disturbance causes clinically significant distress or impairment in social, academic,
occupational, or other important areas of functioning.
D. The disturbance is not better explained by another mental disorder, such as refusing to leave home
because of excessive resistance to change in autism spectrum disorder; delusions or hallucinations
concerning separation in psychotic disorders; refusal to go outside without a trusted companion in
agoraphobia; worries about ill health or other harm befalling significant others in generalized anxiety
disorder; or concerns about having an illness in illness anxiety disorder.
From: American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th
ed.). Arlington, VA: American Psychiatric Publishing.

Therefore, the key change in the criteria is the removal of the stipulation that onset of the disorder must be
before the age of 18 years, a modification that is consistent with clinical and population-level research
evidence (Manicavasagar et al., 1997a; Shear et al., 2006). In addition, symptoms have been reworded to
remove any implicit bias towards childhood, for example by widening the target of SA fears to a range of
attachment figures instead of only listing parents, and by expanding the repertoire of avoidance behaviors to
adult settings such as work, rather than focusing primarily on school refusal. In concert, these changes have
the important effect of aligning SAD with the existing anxiety subtypes, particularly by removing any
reference to age of onset in the criteria for diagnosing the disorder. These changes have a far-reaching impact
on the interpretation of past epidemiological and clinical studies involving the anxiety disorders. In effect,
the changed status of SAD means that the epidemiology, patterns of comorbidity and risk factor profiles of
the anxiety disorders need to be updated because it is likely that past studies that have not taken into account
persons with adult SAD have overlooked or misdiagnosed a substantial number of individuals included in
the analyses. It is of interest, therefore, that the modifications proposed for SAD have not attracted any
public or professional debate, possibly because the evidence supporting these changes is relatively strong.
Yet the maturation of SAD has profound implications for research and practice, opening up important
questions about the origins, patterns of comorbidity and consequences in relation to disability for adults who
can now legitimately be assigned that diagnosis. As yet, there are no treatment studies testing interventions
for SAD in adulthood, a remarkable hiatus in itself. Hopefully, the changes ushered in by DSM-5 will act as
a catalyst for research aimed at establishing interventions for SAD in adulthood.

CLINICAL IMPLICATIONS

Symptoms
Manicavasagar and Silove (1997a), in their seminal article, described three patients with the prototypical
criteria of separation anxiety. The clinical picture was dominated by marked levels of separation anxiety
from the main attachment figures, intense fear that some adverse event could happen to their loved ones and
a strong desire to return home when away. As stressed by the authors, this framework is similar to the
clinical picture that predominates the infantile form of the disorder, obviously with differences related to the
new context in which the disorder is expressed.

The ASAD is characterized by: significant distress, worry and fear at the thought of or event of separation
from an attachment figure; fear of harm coming to the attachment figure or the self when separated; somatic
symptoms including complaints of stomachaches, nausea, or headaches, which, may or may not actually be
occurring. Other symptoms may occur, such as difficulty in being away from home for many hours, starting
on long trips without the attachment figure, excessive fear on the health of loved ones, and to their safety
(Pini & Abelli, 2008).

Clinical Vignette

A case of adult separation anxiety

Sharon, age 32, began experiencing debilitating anxiety symptoms a few months
after marriage when she moved form parents’ home to her new own home with
her husband. She felt extremely anxious about her parents’ health experiencing
intrusive thoughts about the fact that one day both her parent would have died.
After some months, she also started to polarize on her husband's health, ruminated
about his safety, and experienced acute anxiety episodes with physical symptoms
(panick attacks) when he left for work each morning. She had trouble sleeping
when he was away on a business trip. She called his cell phone repeatedly each
day, and when he did not answer, she felt compelled to go to his office to find
him. After a couple of years, she presented a major depressive episode with the
characteristic of the atypical depression. At this point she decided to consult a
psychiatrist. She started an antidepressant treatment that, after some weeks, made
her to switch into an attenuated mixed state, with dysphonic mood, reactivity,
mood lability and some verbal dyscontrol episodes. Within this contest, separation
anxiety symptoms became more severe and led her to aggressive behaviors
towards her husband. Only at work, she was able to maintain calm, efficiency and
excellent level of functioning. She never presented or complained symptoms of
dependency from her husband in terms of self-confidence at work or capacity to
make free choices in different areas of functioning.
Comorbidity
Comorbidity is the rule rather than the exception in mental disorders, commonly as high as 50–60%. By
investigating the pattern of comorbidities of ASAD with other disorders, more insight can be obtained into
whether manifestations of ASAD are unique and autonomous or whether they are multiform and
heterogeneous to other disorders (Klein & Riso, 1993).
Several studies have investigated the levels of comorbidity between ASAD and other psychiatric disorders
(Pini et al., 2005b; Shear et al., 2006; Pini et al., 2010; Silove et al., 2010a; Dell’Osso et al., 2011). Despite
this, we still lack a full comprehension of the general framework for two reasons: the first is that the
comorbidity levels are reliable only in general population studies (and we have only one on ASAD based on
the National Comorbidity Survey Revised) (NCS-R), while clinical samples allow us to formulate
assumptions; the second, perhaps more important, is that no one knows if the degree of overlapping between
ASAD and other conditions, the inaccurate diagnostic criteria or other factors may exert in methodological
bias.
The vast majority of respondents classified in the NCS-R as having either childhood SAD (86.1%) or adult
SAD (88.5%) have a history of at least one of the other DSM-IV disorders assessed in the survey. Strength
of comorbidities, as indicated by ORs, does not differ markedly in magnitude between estimated childhood
SEPAD (with a median OR of 2.9) and adult SEPAD (median OR of 3.9). Moreover, the strength of
comorbidity between estimated SEPAD and other anxiety disorders (ORs in the range 4.9-5.3) is not
markedly different from the strength of comorbidities with mood disorders (ORs in the range 4.3-7.5),
although somewhat higher than comorbidities with impulse control disorders (ORs in the range 3.0-4.3) and
substance use disorders (ORs in the range 2.2-3.3).

Anxiety disorders
The NCS-R study highlights the patterns of comorbidity between ASAD and other psychiatric disorders. For
anxiety disorders, it showed high level of comorbidity between ASAD and other disorders such as PD and
post-traumatic stress disorder (PTSD) (Kessler et al., 2005). It also underlines an inverse relationship
between OCD and DASA (r = -0.79, OR = 8.1), that needs, as called from the authors, further investigations.
Among the various anxiety disorders, the one with higher ASAD comorbidity is the Agoraphobia without
panic with an OR of 5.8, although this might result from an overlapping of some diagnostic criteria between
these two categories (Shear et al., 2006): in both disorders is present, as a diagnostic criterion, the difficulty
of leaving home without the presence of a companion (or an attachment figure in the case ASAD), although
from a psychopathological point of view, the basic fears that underlie the two disorders differ.
Kossowsky et al. (2013) in a meta-analysis addressed the possible development of panic disorder, any
anxiety disorder, major depressive disorder, and substance use disorders in children with separation anxiety
disorder. The results indicate that a childhood diagnosis of separation anxiety disorder significantly increases
the risk of panic disorder but also of other anxiety disorders. Conversely, no association with major
depression or substance use disorders was found.

Mood disorders
The NCS-R study revealed that the association between ASAD and mood disorders is similar to that of
anxiety disorders (Shear et al., 2006). In particular, individuals with major depression with ASAD
comorbidity had suffered a higher number of mood episodes compared to MDD patients without ASAD
(Pini et al., 2010).
A strong association between SAD and Bipolar Disorder (BD) (childhood OR = 4.3; adult OR = 7.1) has
also been reported in the literature. In particular, symptoms of separation anxiety were more pronounced in
patients who had both BD and PD comorbidity compared to those who had only PD or BD. A history of
childhood SAD was correlated to an early onset of the BD (Pini et al., 2005b).
In Pini et al’s study (2005b), two findings suggest a link between SA and BD. First, a stronger correlation
between adult SA and a history of SA during childhood in the bipolar group than in the PD group was found.
Previous longitudinal data suggested that although many juveniles who suffer from SA disorder appear to
make a good recovery, a substantial number continue to suffer from severe psychosocial impairments
(Lipsitz et al., 1994; Silove et al., 1996). Whether such continuity might be more likely to occur in patients
with BD with respect to individuals with other psychiatric disorders is an interesting objective for further
research. Secondly, linear regression analysis showed that adult SA was predictive of an earlier age at onset
of BD. This is in line with research suggesting that anxiety comorbidity is more frequently associated with
early-onset than late-onset BD. It would be useful to further investigate, in larger and more representative
samples, to what extent SA may contribute to the characterization of more homogeneous subtypes of BD
(Pini et al., 2005b).

PTSD and Complicated Grief

Exposure to a traumatic event may precipitate fears and insecurities related to ASAD (Dell’Osso et al., 2011;
Pini et al., 2012).
In a seminal study (Manicavasagar et al., 1997b) 33% of 36 ASAD patients reported that the first symptoms
arose following a loss (change of caregiver, divorce, mourning). Silove et al. (48) investigated associations
between ASAD, trauma and other psychological reactions, PTSD and complicated grief (CG) and depression
in a group of 126 Bosnian war refugees in Australia. The results showed a strong association between ASAD
and PTSD (OR = 4.9) but not with the CG nor with depression. Moreover even if ASAD was connected to a
traumatic loss, this association was unspecific. The association between ASAD and PTSD has previously
been found in the NCS-R study, suggesting that trauma may be an ethiopatogenetic factor for the two
conditions (Kessler et al., 2005).
However, regarding specifically the relationship between CG and ASAD, further evidences enlighten a
possible association, but, due to the limited information available, we are not allowed to settle the etiological
relationship between the two clinical conditions: even if the pre-existence of an overt childhood SAD or
latent psychopathological traits could predispose the manifestations of CG in the adult, the ASAD
appearance could happen after the exposure to stressors with connotations of loss, as supported by the first
hypothesis of Australian researchers (Manicavasagar & Silove, 1997a; Manicavasagar et al., 1997b ).
In a survey conducted on a limited subset of patients with CG in comparison to healthy controls with recent
loss (Dell’Osso et al., 2011), the CG was associated with high levels of separation anxiety; the high
prevalence of depressive and hypomanic symptoms in these patients suggests that cyclothymia may
represent an element of vulnerability to ASAD. In another study carried out on a larger sample of anxiety or
mood disorders patients (Pini et al., 2012), the association with CG is only significant in subjects with
ASAD, but not with childhood SAD and is associated with unsecured adult attachment styles.

Personality disorders
The prevalence rate of personality disorders between patients suffering from ASAD is quite similar to that of
anxiety disorders (Manicavasagar et al., 2000). Silove et al. (2011) conducted a clinical study on 397 patients
suffering from anxiety disorders and the results have shown that patients with ASAD, who reported higher
scores of childhood SAD, had a higher rate of cluster C personality disorders than patients with ASAD
without early SAD. In addition, patients in the ASAD group with high levels of early separation anxiety
reported a higher rate of both cluster B and cluster C personality disorders, compared to anxious patients
who reported low levels of early separation anxiety and were not affected by ASAD. Therefore, it is likely
that high levels of early SAD may increase the probability of impairment in the personality development,
altering the safety in interpersonal relationships.

Adult separation anxiety and pregnancy

It is well reported in the literature that there is a relationship between the separation anxiety in adult life and
insecure attachment style. From such a perspective, it has been hypothesized that women with adult
separation anxiety may experience exacerbations of symptoms in the perinatal period when they anticipate or
actually become responsible for the health and care of an infant. If confirmed, this hypothesis would have
contributed to explain why some mothers become particularly anxious in pregnancy, a response that in turn
may lead onto bonding problems that could generate anxious attachment and insecurity in their infants and
toddlers.
Frequency and clinical correlates of adult SAD has been investigated in 331 pregnant women in a study
conducted in Australia (Eapen et al., 2012). The findings suggest that ASA is not uncommon, occurring in a
quarter of the women screened. For the majority, ASA symptoms seemed to reflect a general psychological
response pattern not associated with dysfunction, but for around one-third of those with ASA, the symptoms
were reported to be causing significant impairment in functioning. Whether pregnancy is a key event that
precipitates or exacerbates separation anxiety symptoms is still to b clarified. Similarly, what the trajectory
of ASA is through the phases of pregnancy, childbirth, and the postpartum period; and, importantly,
what the impact of maternal ASA is on the maternal–infant bond (Eapen et al., 2012). In particular, given
that early mother–infant interactions are crucial in the development and quality of attachment styles, it is
vital to determine whether ASA exerts a specific and potent influence in shaping early mother–infant
interaction patterns and infant outcomes.

Impairment of functioning
The NCS-R study shows that most of the 40% of patients affected by ASAD in the last 12 months, referred a
severe discomfort in (at least) one of the domains assessed by the Sheehan Disability Scale SDS (Sheehan,
1983), especially in the domains related to personal and social life. Even if , not surprisingly, SAD patients
with psychiatric comorbidity reported higher level of impairment of functioning, an high percentage (29.8%)
of patients without psychiatric comorbidity showed a severe disability in at least one functional domain.
Moreover two different studies (Pini et al., 2010; Silove et al., 2010a) reported a higher level of functional
impairment (social, working and individual) in ASAD comorbid patients, even after correcting every
potential confounding bias. This could demonstrate that separation anxiety can itself constitute a factor of
disability (Shear et al., 2006).

Therapeutical Implications for Adult Separation Anxiety Disorder

Several studies show that high levels of separation anxiety are linked to a lower benefit of psychotherapies
and psychopharmacological treatments (Aaronson et al., 2008; Kirsten et al., 2008; Miniati et al., 2012).
Aaronson et al. have reported that, between PD patients treated with CBT (Cognitive Behavioral Therapy),
those with ASAD comorbidity have a chance four times greater of a poor treatment outcome. This effect
persists even taking into account all of the concurrent factors: severity of anxiety symptoms, number of
comorbid anxiety disorders, socio-economic status, duration of the disease and severity of agoraphobia.
Kirsten et al., studying a sample of patients suffering from different anxiety disorders (Social phobia, GAD,
PD) treated with group CBT, showed that a lower improvement in the scores at the symptoms scale (for
anxiety and depression) correlates with higher rates of separation anxiety.
Recently, Miniati et al. investigated, using the panic-agoraphobia spectrum model developed by Cassano
(Rucci et al., 2009), the factors that may influence the outcomes of drug therapies in PD patients. The results
show that high scores of separation anxiety, assessed by a structured interview for the panic-agoraphobic
spectrum (PAS-SR Last-Month), may predict a poor response to drug treatment after 12 months of therapy.
Milrod et al. (2014) added that many individuals may be unaware of separation anxiety, as it clusters in
families and may be considered normal behavior. However, those who develop anxiety and mood disorders
respond more poorly to both pharmacological and psychotherapeutic interventions.

CONCLUSION
Since the first descriptions and the development of specific assessment tools, an ever-growing body of
evidence has shown great interest in the separation anxiety disorder, not only for the obvious taxonomic and
nosological implications, but also especially for his significant clinical and therapeutic impact. ASAD has
been proved as a not so uncommon disease, with a lifetime general population prevalence of 6.6% (Shear et
al., 2006). Even if there is a severe impact of this disorder on the quality of life of patients, only a small part
of them referred separation anxiety as the main focus of treatment. This goes by the acknowledged poor
outcome of ASAD patients on CBT and psychopharmacological treatment.
The identification of this disorder allows a better comprehension of the relationship between early separation
anxiety and psychiatric disorders in adulthood, leading to hypothesize a model of continuity according to
which, if separation anxiety persists into adulthood, may lead to the development of the ASAD (to confirm
this assumption it are still needed more longitudinal studies).
Of course, despite the genetic and neurobiological evidences, the focus on attachment styles and on family
context, we still need further studies for a better characterization of the disease, in attempt to explain the
etiology and the specificity of ASAD.
From a clinical point of view, ASAD showed specific features that distinguish it from other psychiatric
disorders; it could be necessary, in the future, a revision of the diagnostic criteria in order to avoid confusing
overlaps, starting with the PD-Ag and the dependent personality disorder; this appear evident reconsidering
the results of the NCS-R: the majority (91.1%) of subjects with ASAD met the criteria for at least one other
psychiatric disorder.
In conclusion, we hope future revisions of the classification systems and the removal of age-related
restrictions actually present for the SAD, as it turns out, from the current state of knowledge, that the
disorder may have its onset to any ages. Furthermore, we consider essential, especially among those who
deal with anxiety disorders, an increased awareness and knowledge of this clinical disorder, for a better
identification and for a more specific and much more effective treatment.

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