Adult separation anxiety disorder in complicated grief: an exploratory study on frequency and correlates

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ScienceDirect Comprehensive Psychiatry 72 (2016) 6 – 12 www.elsevier.com/locate/comppsych

Adult separation anxiety disorder in complicated grief: an exploratory study on frequency and correlates Camilla Gesi a , Claudia Carmassi a,⁎, Katherine M. Shear b , Theresa Schwartz b , Angela Ghesquiere b , Julie Khaler b , Liliana Dell'Osso a a

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy b Columbia University School of Social Work, NY, U.S.A.

Abstract Introduction: Complicated grief (CG) has been the subject of increasing attention in the past decades but its relationship with separation anxiety disorder (SEPAD) is still controversial. The aim of the current study was to explore the prevalence and clinical significance of adult SEPAD in a sample of help-seeking individuals with CG. Methods: 151 adults with CG, enrolled in a randomized controlled trial comparing the effectiveness of (CG) treatment to that of interpersonal therapy, were assessed by means of the Inventory of Complicated Grief (ICG), the Structured Clinical Interview for DSM-IV, the Hamilton Rating Scale for Depression (HAM-D), the Work and Social Adjustment Scale (WSAS), the Adult Separation Anxiety Questionnaire (ASA-27), the Grief Related Avoidance Questionnaire (GRAQ), the Peritraumatic Dissociative Experiences Questionnaire (PDEQ), and the Impact of Events Scale (IES). Results: 104 (68.9%) individuals with CG were considered to have SEPAD (ASA-27 score ≥22). Individuals with SEPAD were more likely to have reported a CG related to the loss of another close relative or friend (than a parent, spouse/partner or a child) (p = .02), as well as greater scores on the ICG (p = b.001), PDEQ (p = .004), GRAQ (p b .001), intrusion (p b .001) and avoidance (p = b.001) IES subscales, HAM-D (p b .001) and WSAS (p = .006). ASA-27 total scores correlated with ICG (p b .0001), PDEQ (p b .001) GRAQ (p b .0001) scores and both the IES intrusion (p b .0001) and IES avoidance (p b .0001) subscale scores. People with SEPAD had higher rates of lifetime post-traumatic stress disorder (PTSD) (p = .04) and panic disorder (PD) (p = .01). Conclusions: SEPAD is highly prevalent among patients with CG and is associated with greater symptom severity and impairment and greater comorbidity with PTSD and PD. Further studies will help to confirm and generalize our results and to determine whether adult SEPAD responds to CG treatment and/or moderates CG treatment response. © 2016 Elsevier Inc. All rights reserved.

1. Introduction Separation anxiety disorder (SEPAD) has been classically described as a childhood condition, occasionally persisting until adulthood. Patients with SEPAD report impairing anxiety about actual or imagined separations from significant others and family environment, worry that harm would come to loved ones and need to maintain proximity to them [1–4].

⁎ Corresponding author at: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy. Tel.: +39 050 2219766; fax: +39 050 2219787. E-mail address: [email protected] (C. Carmassi). http://dx.doi.org/10.1016/j.comppsych.2016.09.002 0010-440X/© 2016 Elsevier Inc. All rights reserved.

While in DSM-IV TR this condition was included in the section ‘Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence’, over the last decades, researches conducted on adults have shown SEPAD not only to be often present across the entire lifespan, but also to have sometimes onset in adulthood. In these studies, the diagnosis of SEPAD was reliably made either by means of childhood DSM-IV criteria adapted to adults or by using a threshold level of symptoms, as evaluated by the Adult Separation Anxiety Checklist (ASA-27) [5–14]. In particular, the former criterion was adopted in one of the few epidemiological studies available, the National Comorbidity Survey-Replication (NCS-R) [7], where a lifetime prevalence of SEPAD in the adult general population of 6.6% was reported. Adult SEPAD also showed

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to be highly comorbid with other psychiatric disorders, especially panic disorder (PD) [2,8,10,15], and associated with substantial impairment in functioning. Data from clinical samples explored by means of the same methodology corroborated these findings showing SEPAD rates in psychiatric populations ranging between 23% and 40%. Silove et al. [8], in fact, found 23% SEPAD rates among 520 adult patients with anxiety disorders, with an over-representation of females in the SEPAD group. Some of us [10] reported a SEPAD prevalence as high as 46% in 508 adult patients with mood and anxiety disorders. Similarly, by means of the ASA-27 scores, Manicavasagar and colleagues showed a 40% rate of SEPAD among 70 patients with panic disorder or generalized anxiety [5]. In the light of this growing literature, the wording of diagnostic criteria for SEPAD has been adapted to adults and the disorder has been included in the section of anxiety disorders in the recently released DSM-5 [16–18]. Also addressed for the first time in the DSM-5 is the increasing literature on bereavement-related mental disorders, including a loss-related syndrome variously referred to as “complicated grief” (CG), “prolonged grief disorder” or “traumatic grief”. This condition is now included as “Persistent Complex Bereavement-Related Disorder” in the Section III of “Conditions Requiring Further Research” [16,19–21]. Besides the death of someone with whom the person had a close relationship (criterion A), proposed criteria for Persistent Complex Bereavement-Related Disorder include that the subjects experienced persistent yearning/ longing for the deceased, or intense sorrow and emotional pain, or preoccupation with the deceased or preoccupation with the circumstances of the death for at least 12 months (6 for bereaved children) (criterion B). Moreover, at least six symptoms indicating reactive distress to the death (marked difficulty accepting the death, disbelief or numbness over the loss, difficulty with positive reminiscing about the deceased, bitterness or anger, self-blame, avoidance of reminders of the loss) or social/identity disruption (desire to die in order to be reunited with the deceased, difficulty in trusting other people since the death, feeling that life is meaningless without the deceased, confusion about one's role in life, difficulty in pursuing interests or plan for future since the loss) must be present (criterion C) [16]. Existing studies suggest that 10% to 20% of bereaved persons may develop CG [22–24] and that it has a negative impact on physical and mental health and global functioning [25–34]. The attachment theory offers insight into links between separation anxiety and grief [35,36]. A few studies have reported an association between insecure attachment styles and CG [37,38]. Separation anxiety is a symptom of anxious insecure attachment [39]. According to attachment theory, the loss of a loved one is a potent trigger of separation anxiety symptoms. The syndrome of complicated grief has been conceptualized as being composed of separation-related and trauma-related symptoms, and a recent study showed separation distress to be the more prominent across different types of relationships and losses [40]. However, it is unclear

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whether and how bereaved individuals with or without CG might be more prone to adult SEPAD [1,8]. Available data examining the relationship between SEPAD and CG have shown mixed results. In one of the first studies, Vanderwerker and colleagues found that retrospective reports of childhood SEPAD were associated with an odds ratio of 3.2 for CG in adulthood and this relationship was mediated by adult SEPAD [41]. A more recent study found that CG was associated with adult but not childhood SEPAD in a sample of outpatients with mood and anxiety disorders [13]. The latter findings are consistent with our own unpublished data (Shear personal communication). However, in a sample of trauma-affected subjects, adult SEPAD was found to be associated with post-traumatic stress disorder (PTSD), but not with depression or CG [9]. We recently found higher SEPAD levels in patients with CG compared to healthy controls [42] and greater SEPAD among individuals with both CG and PTSD compared to those with either CG or PTSD alone [43]. However, subjects with CG either alone or with depression were shown to have lower SEPAD symptoms compared to subjects with major depression alone [44]. Mixed findings could be due to lack of standardization in the method of assessing both SEPAD and CG and raise questions about the prevalence and clinical significance of adult SEPAD among individuals with CG. The aim of the current study was to explore this question in a sample of help-seeking individuals who participated in a randomized controlled study of CG treatment [45]. Our hypothesis is to find a high prevalence of SEPAD among CG subjects. Furthermore, based on previous literature, we hypothesize that SEPAD will be associated with PD and PTSD. 2. Methods 2.1. Participants The study was conducted in a sample of treatmentseeking adults with CG enrolled in a randomized controlled trial [45] comparing the effectiveness of complicated grief treatment (CGT) to that of interpersonal therapy (IPT). The methodology of the parent randomized controlled trial has been reported in detail elsewhere [43]. Briefly, inclusion criteria required: the death of a loved one at least 6 months prior to enrollment, a score of at least 30 on the Inventory of Complicated Grief (ICG), and judgment that CG was the most important clinical problem by an independent evaluator. Exclusion criteria were: current substance abuse or dependence, history of psychotic disorder or bipolar I disorder, suicidality requiring hospitalization, pending lawsuit or disability claim related to the death, or concurrent psychotherapy. The study was approved by the University of Pittsburgh Institutional Review Board. Participants were enrolled between April 2001 and April 2004. One hundred and fifty-one study participants who completed measures of both CG and separation anxiety pre-randomization were included in these cross-sectional analyses.

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2.2. Assessment instruments The 19-item Inventory of Complicated Grief (ICG) [46] was used to assess symptoms of CG. This scale has been well-validated and is widely used [47]. The Structured Clinical Interview for DSM-IV [48] was used to assess co-occurring Axis-I disorders. The Hamilton Rating Scale for Depression [49] (HAM-D) was administered to assess severity of depressive symptoms. The Work and Social Adjustment Scale (WSAS) [50] was used to assess the interference of grief symptoms with five areas of daily functioning: work, home management, private leisure, social leisure, and family relationships. 2.2.1. Separation anxiety The Adult Separation Anxiety Questionnaire (ASA-27) is a 27-item self-report inventory that explores symptoms of separation anxiety in adulthood, including, but not limited to, DSM-5 criteria for separation anxiety. This scale has been

shown to display concurrent validity with clinical assessments of adult separation anxiety [51]. In agreement with studies conducted before the inclusion of adult SEPAD in DSM-5 [5–14], we utilized a score of 22 to tentatively assign the diagnosis of adult SEPAD [51].

2.2.2. Grief-related dimensions Three additional instruments were administered to further characterize study participants. The Grief Related Avoidance Questionnaire (GRAQ) is a 6-item self-report scale [36], which measures avoidance behavior through 15 situations that bereaved individuals frequently refrain from doing. The Peritraumatic Dissociative Experiences Questionnaire (PDEQ) [52] is a 10-item self-report scale, which assesses dissociative experiences occurring during a traumatic event, including derealization, depersonalization, amnesia, altered time perception, confusion, and reduced awareness. The Impact of Events Scale (IES) is a 15-item self-report scale. It

Table 1 Baseline characteristics of CG subjects with and without SEPAD. No SEPAD⁎ (n = 47) Age 18–44 45–59 60+ Female Caucasian Marital status Never married Married Divorc./widow. Lost only one person Spouse/partner Parent Child Other How the death occurred Violent Non-violent Axis I comorbidity PTSD current † PTSD lifetime † PD current † PD lifetime † MDD current † MDD lifetime † Ham-D mean (SD) ICG mean (SD) PDEQ mean (SD) GRAQ mean (SD) IES Intrusion mean (SD) Avoidance mean (SD) WSAS

SEPAD⁎ (n = 104)

Chi 2

df

P

16 (34) 22 (47) 9 (19) 36 (77) 35 (75)

50 (48) 41 (39) 13 (13) 89 (86) 66 (65)

2.59 0.73 1.15 1.83 1.77

1 1 1 1 1

.11 .39 .28 .18 .18

13 (28) 16 (34) 18 (38) 19 (40) 14 (29) 14 (29) 16 (34) 3 (6)

30 (29) 24 (23) 50 (48) 38 (36) 27 (26) 33 (32) 21 (20) 22 (22)

0.02 2.00 1.25 0.21 0.24 0.06 3.36 5.11

1 1 1 1 1 1 1 1

.88 .16 .26 .65 .62 .81 .07 .02

8 (28) 21 (72)

16 (34) 31 (66)

0.07 3.17

1 1

.80 .07

18 (40,9) 21 (47,7) 0 2 (4,6) 22 (50,0) 33 (75,0)

54 (58,7) 61 (66,3) 19 (20,7) 27 (29,3) 58 (62,4) 74 (79,6)

1 1 1 1 1 1

.07 .04 − .01 .20 .66

17.4 (7.4) 42.5 (7.2) 28.4 (10.3) 17.8 (11.0)

22.5 (7.5) 48.3 (10.3) 33.6 (10.3) 27.8 (11.9)

3.79 4.29 − 10.91 1.88 0.36 t −3.68 −3.94 −2.90 −4.14

136 146 149 113

b.006 b.006 b.024 b.006

18.3 (8.1) 15.9 (8.5) 18.3 (9.4)

22.9 (7.3) 21.6 (9.0) 23.3 (10.5)

−3.45 −3.68 −2.79

149 148 144

b.006 b.006 .006

Bold is for statistically significant results at p b .05. ⁎ Data are expressed as number (%) unless otherwise indicated. † Data available in a subgroup of patients (n = 136). ‡ Bonferroni adjustment applied.

‡ ‡ ‡ ‡ ‡ ‡

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consists of two subscales, intrusion and avoidance, measuring current stress related to a specific event [53].

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χ =10.91, p = .01) but not MDD current (62.4% vs. 50%, χ = 1.88, p = .20) or lifetime (79.6% vs. 75%, χ 2=0.36, p = .66). 2

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2.3. Statistical analyses Statistical differences between people with and without adult SEPAD were reported using chi-square test for categorical variables (such as socio-demographic variables, grief-related variables and Axis I diagnoses) and t-test for continuous variables (such as HAM-D, GRAQ, PDEQ, IES and WSAS scores). Correlations between continuous variables were reported using Pearson's correlation test. In order to avoid Type I error, Bonferroni adjustment was applied to multiple comparisons lacking a priori hypotheses. All tests were two-tailed and a p value b0.05 was considered statistically significant. Statistical tests were performed with STATA (Rel. 10. 2007. College Station, TX: StataCorpLP) for Windows. 3. Results One hundred and four of the 151 study participants who completed the ASA-27 endorsed a score ≥22 and were considered to have evidence of adult SEPAD. Socio-demographic, grief and clinical correlates of CG patients with and without SEPAD are shown in Table 1. Groups did not differ significantly with respect to gender, race, age, education or marital status. There were no differences between people with SEPAD and those without on total number of losses or type of loss (violent/non violent). Individuals with SEPAD were more likely to report a diagnosis of CG related to the loss of another close relative or friend than a parent, spouse/partner or a child, with respect to subjects without SEPAD (22% vs. 6%, χ 2=5.11, p = .02). However, this result is likely to be unstable because this was the smallest and most heterogeneous of the relationships to the deceased and there were only 3 people in the no SEPAD group. Study participants with SEPAD had higher scores on all clinical measures, including the ICG (48.3 vs. 42.5, t = −3.94, p = b.006), the PDEQ (33.6 vs. 28.4, t = −2.90, p = b.024), the GRAQ (27.8 vs. 17.8, t = −4.14, p b .006), both the intrusion (22.9 vs. 18.3, t = −3.45, p b .006) and avoidance (21.6 vs. 15.9, t = −3.68, p = b.006) subscales of IES, HAM-D score (22.5 vs. 17.4, t = −3.68, p b .006) and the WSAS (23.3 vs. 18.3, t = −2.79, p = .006). Additionally, ASA-27 total score correlated significantly with each of the other self-report measures, including ICG (r = 0.48, p b .0001), PDEQ (r = 0.29, p b .001), GRAQ (r = 0.44, p b .0001) scores and both the IES intrusion (r = 0.37, p b .0001) and IES avoidance (r = 0.38, p b .0001) subscale scores. The strong correlation with ICG score is especially notable given the limited range of ICG scores in this sample. People with SEPAD, compared to those without, had a higher rate of comorbidity with lifetime PTSD (66.3% vs. 47.7%, χ 2=4.29, p = .04) and lifetime PD (29.3% vs. 4.6%,

4. Discussion We found that nearly 70% of help-seeking adults with CG endorsed scores on the ASA-27, consistent with adult SEPAD. This rate is higher than previously reported. Other studies found estimates of adult SEPAD that ranged from 23% to 54% [5,8,10]. However, ours is the first study examining a clinical sample of help-seeking individuals. ASA-27 scores correlate with ICG in our study as well as others and the ICG score in our study was substantially higher than that in other studies. Our results are consistent with Pini et al. [13] who reported that the mean ICG score was about 38 among subjects with CG and 56% were positive for adult SEPAD. Given the correlation between ICG and ASA-27, a mean ICG score 10 points higher could reasonably be associated with about 10% more SEPAD. The fact that insecure attachment and childhood SEPAD increase the risk of developing both adult SEPAD [5] and CG [37,54] supports the possibility of high rates of co-occurrence. Additionally, loss of an attachment figure is a potent stimulus for separation distress and a recent study showed that separation distress symptoms are core symptoms of CG [40]. In other words, while CG and SEPAD have been shown to be distinct disorders, they seem to share some phenomenological features [55]. Given the importance of separation distress as a symptom of CG, the high frequency of SEPAD found in our sample is not surprising. A possible explanation may be that CG and SEPAD are both rooted in attachment theory [35]. The central assumption of this latter, in fact, is that humans show an inborn, neuro-biologically mediated motivation to form and maintain close emotional bonds [35]. The brain's instinctive attachment system facilitates the development of the cognitive-affective circuitry that Bowlby called ‘internal working model’, which is a mental representation of significant others derived from our history with them. We use the ‘internal working model’ to make predictions that guide our expectations of these important people while developing an intuitive, implicit knowledge of them. Acute grief symptoms are manifestations of activation of the attachment system, which are gradually deactivated as information about the death is integrated into the internal working model of the deceased. However, sometimes, this process is waylaid and CG develops [36,56]. The attachmentbased theory of CG postulates that the derailed process of transition from acute to integrated grief that occurs in CG is based on a mechanism of incomplete processing of information about the death. Specifically, the mental representation of the attachment figure is disrupted, such that the loss is acknowledged in declarative memory but not in implicit memory, leading to a lack of acceptance of the finality of the loss; further, the exploratory system does not re-engage, so that the grieving individual can become distanced from other

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people and the world in general. From such a perspective, separation anxiety might play a role in preventing the attachment system from being deactivated, favoring a delayed integration of grief. Importantly, the presence of SEPAD was associated with greater severity of a range of associated symptom and impairment measures, not just the ICG. This is consistent with findings from other clinical populations, such as panic and other anxiety disorders showing that SEPAD was associated with earlier onset, greater severity and poorer outcomes of co-occurring disorders [57–59]. The treatment that MK Shear developed for CG relieves separation distress. However, it is not clear whether further methods may be needed to target SEPAD in these patients. Our data indicated that SEPAD is associated with comorbid PTSD in CG patients. This finding is consistent with reports from Silove and colleagues [9] showing a strong association between SEPAD and PTSD in trauma-affected refugees, with almost all individuals with SEPAD having co-morbid PTSD. Also consistent with our results, Dell'Osso and colleagues [43] found greater SEPAD symptoms in patients with co-occurring CG and PTSD than those with one or the other of these conditions. Similarly, epidemiological data from the NCS-R study [7] found that PTSD had high rates of co-morbidity with SEPAD compared to other Axis I disorders. Intense personal insecurity has been suggested to be the common factor underlying both PTSD and SEPAD [9]. Fear for personal safety may drive the need to maintain proximity to attachment figures that characterizes SEPAD, as well as increasing the likelihood of experiencing PTSD symptoms after a traumatic event, such as a significant loss [60]. We also found an association between SEPAD and PD among individuals with CG, findings that are again consistent with other studies [1,8]. The relationship between SEPAD and PD has long been of interest. Separation sensitivity has been considered a dimension of PD and it is included in the panic-agoraphobic spectrum [2,61,62]. However, SEPAD clearly occurs in association with a range of mood and anxiety disorders without PD comorbidity [3,7,54]. In our study sample, there were 29 individuals with lifetime panic and all but two met our criteria for SEPAD. One could speculate that the agoraphobic-like dimension of SEPAD might account for the high comorbidity between SEPAD and PD. In this regard, however, a recent study demonstrated that the high level of overlap between PD-Ag and SEPAD may represent a true form of comorbidity and that the ASA-27 discriminates strongly between the two disorders [14].

5. Limitations Several limitations need to be acknowledged in interpreting our findings. We used a threshold instrument instead of a criteria-based instrument to assess the presence of SEPAD. Although a score of 22 or greater on ASA-27 has been

shown to have good sensitivity and specificity with respect to a diagnosis yielded by a semi-structured clinical interview [51], it is possible that some cases may have been misclassified. A further limitation is the use of a relatively small sample that consists only of help-seeking individuals diagnosed with CG. Our results may not be suitable for generalizing with other groups of CG. Finally, though some interesting associations emerged, the cross-sectional design of the study did not allow us to clarify the temporal sequencing of onset between CG and SEPAD, highlighting the need for further, longitudinal investigations. In the context of these limitations, our data show that SEPAD is highly prevalent among patients with CG and is associated with greater symptom severity, greater impairment and more comorbidity with PTSD and PD. Further studies will be necessary in order to confirm and generalize our results and to determine whether adult SEPAD responds to CG treatment and/or moderates CG treatment response.

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