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. Author manuscript; available in PMC: 2021 Apr 1.
Published in final edited form as: Depress Anxiety. 2020 Feb 25;37(4):386–395. doi: 10.1002/da.23003

Separation Anxiety in PTSD: A Pilot Study of Mechanisms in Patients Undergoing IPT

Barbara Milrod 1, John R Keefe 1, Tse-Hwei Choo 2, Shay Arnon 3, Sara Such 3, Ari Lowell 2,3, Yuval Neria 2,3, John C Markowitz 2,3
PMCID: PMC7207264  NIHMSID: NIHMS1574901  PMID: 32097526

Abstract

Introduction.

Separation anxiety disorder (SAD) comprises one aspect of attachment dysregulation or insecurity. Although SAD aggravates PTSD risk, no clinical research has tracked how many patients with PTSD have SAD, its clinical associations, or its response to PTSD treatment. Our open trial of Interpersonal Psychotherapy (IPT) for veterans with PTSD assessed these SAD domains.

Methods.

Twenty-nine veterans diagnosed with chronic PTSD on the Clinician-Administered PTSD Scale (CAPS-5) were assessed for SAD using the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS), and for Symptom-Specific Reflective Function (SSRF), another dysregulated-attachment marker capturing patients’ emotional understanding of their symptoms. Patients received 14 IPT sessions for PTSD with assessments at baseline, week 4 (SCI-SAS, SSRF), and termination for SAD, PTSD, and depression.

Results.

At baseline, 69% of patients met SAD criteria. Separation anxiety did not correlate with baseline PTSD severity, depressive severity, or age when traumatized; patients with and without SAD had comparable PTSD and depression severity. Patients with baseline comorbid SAD who completed IPT (N=17) reported significantly improved adult separation anxiety (p=.009). Adult SAD improvements predicted depressive improvement (p=0.049). Patients with SAD showed a stronger relationship between early SSRF gains and subsequent adult SAD improvement (p=.021) compared to patients without SAD.

Discussion.

This first exploration of dysregulated/insecure attachment features among PTSD patients found high SAD comorbidity, and adult SAD improvement among SAD patients following IPT. Highly-impaired attachment patients normalized attachment post-treatment: 14-session IPT improved attachment dysregulation. This small study requires replication but begins to broaden clinical understanding of separation anxiety, attachment dysregulation, and PTSD.

Introduction

Insecure attachment profoundly affects the development and treatment responsiveness of mood disorders, anxiety disorders, and PTSD (Milrod, Markowitz, Gerber, Cyranowski, Altemus, Shapiro, Hofer, & Glatt, 2014). It increases risk of developing PTSD post trauma (Koenen, Moffitt, Poulton, Martin, & Caspi, 2007; Silove, Ionso, Bromet, Gruber, Sampson, Scott, Andrade, Benjet, Caldas de Almeida, De Girolamo, de Jonge, Demyttenaere, Fiestas, Florescu, Gureje, He, Karam, Lepine, Murphy, Villa-Posada, Zarkov, & Kessler, 2015; Milrod, 2015; Besser, Neria, & Haynes, 2009; Besser & Neria, 2012). This study explores several measures reflecting insecure attachment, including separation anxiety and symptom-specific reflective function, in a cohort of patients with chronic PTSD treated with interpersonal psychotherapy (IPT; Markowitz, 2016). The broad respective literatures describing attachment and separation anxiety derive from historically distinct intellectual traditions, as do the literatures about mentalization, reflective function, and attachment per se. These literatures describe related, often overlapping, yet slightly differing aspects of the same set of developmental, attachment-derived relational phenomena that profoundly affect mental life. No one to our knowledge has previously combined these related, theoretically diverse phenomenological measures in a single clinical trial.

In early childhood, anxiety induced by separation from close attachment figures is normal and adaptive (Bowlby, 1973, 1988). Yet if separation anxiety continues into later childhood or adulthood, it engenders dysfunctional perceptions of self and others. Separation anxiety disorder (SAD) makes individuals feel unable to survive away from mother or another close attachment figure (Bowlby, 1973, 1988).

Separation anxiety can precede and aggravate severity of mood disorder, other anxiety disorders, and PTSD (Milrod et al, 2014; Kossowsky, Pfaltz, Schneider, Taeymans, Locher, & Gaab, 2013). Cause and effect are unclear (Tamman, Sippel, Han, Neria, Krystal, Southwick, Gelernter, & Pietrzak, 2017). Silove et al. (2015), analyzing time-lagged associations (odds ratios) in a large cross-national WHO epidemiological study (N=38,993), found that pre-existing major depression, bipolar disorder, and other anxiety disorders led to developing SAD in adulthood. Reliable, trained raters in 18 countries assessed cross-sectional past month and historical symptoms. They found a non-reciprocal relationship between SAD and PTSD: SAD was a risk factor for developing PTSD, but not vice versa. The picture is likely more complicated, however, as risk factors for SAD included childhood adversity, “maladaptive family functioning,” and extreme childhood traumas that can engender early childhood PTSD-like syndromes (Lieberman, 2004). Separation anxiety is also a specific risk factor for PTSD in children with burns or exposure to missile attacks (Laor, Wolmer, Mayes, Golomb, Silverberg, Weitzman, & Cohen, 1996; Saxe, Stoddard, Hall, Chawla, Lopez, Sheridan, King, King, & Yehuda, 2005).

Assessment of attachment:

Systematic assessment of psychological attachment dysregulation mechanisms in clinical trials has been rare, partly because of feasibility. The definitive attachment measurements (namely the Adult Attachment Interview; George, Kaplan, & Main, 1996; Blatt, 1974) are extremely time- and labor-intensive, and overly burdensome to patients also undergoing diagnostic assessment, as each interview takes at least an hour. Thus, in psychotherapy trials treating DSM disorders, we have assessed briefer, more easily measurable attachment aspects (Markowitz, Petkova, Neria, Van Meter, Zhao, Hembree, Lovell, Biyanova, & Marshall 2015; Milrod, 2016) including Reflective Function (RF) and separation anxiety, a newly-accepted (DSM-5) diagnosis-marker for unstable attachment profiles (Milrod, 2015; Milrod, Altemus, Gross, Busch, Silver, Christos, Steiber, & Schneier, 2016; Milrod et al, 2014).

Separation anxiety (Milrod et al, 2014) does not capture the breadth of insecure attachment. Attachment encompasses psychological domains of “other” and “self” (Bowlby, 1973, 1988). Insecurely attached individuals have anxious, unstable relationships with other people (the “other” attachment domain) and impaired self-definition (“self” domain), affecting their abilities to self-soothe and to make sense of their own feelings and symptoms (Bowlby, 1973, 1988; George et al, 1996). Although these problems generate anxiety (Besser et al, 2009), evidence-based anxiolytic treatments rarely address them directly. This may partly reflect the ego-syntonic quality of separation anxiety (Milrod, 2015): because separation anxiety runs in families (Silove et al, 2015), separation difficulties can be externally reinforced, under-recognized by patients and close contacts, and normalized.

The Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS; Cyranowski, Shear, Rucci, Fagiolini, Frank, Grochocinski, Kupfer, Banti, Armani, Cassano, 2002), a scale comprising childhood and adult subscales, assesses separation anxiety. Our research group previously surveyed patients with DSM anxiety disorders non-responsive to at least one completed course of evidence-based treatment (Milrod et al, 2016), documenting 80% SAD prevalence (N=37 of 46). Treating a small sample (N=5) of these patients suffering from other anxiety disorders and comorbid SAD using brief, affect- and attachment-focused Panic-Focused Psychodynamic Psychotherapy-eXtended range (PFPP-XR; Busch, Milrod, Singer, & Aronson, 2012) improved their anxiety on the Hamilton Anxiety Rating Scale (Hamilton, 1960) and adult separation anxiety on the adult SCI-SAS subscale (Milrod et al, 2016). (Treating adults would expectedly change only the adult SCI-SAS subscale, as the complementary child SCI-SAS subscale is retrospective.)

Also partially capturing the normative developmental achievement of attachment stability is Reflective Function (RF; Fonagy & Target, 1997; Fonagy, Target, & Steele,1998), a construct delineating capacity to experience and understand internal emotional states and one’s own and others’ motivations. Individuals need relatively stable attachment patterns to develop normal RF. RF develops throughout the lifespan in response to life experiences, including psychotherapy (Clarkin, Foelsch, Levy, Hull, Delaney, & Kernberg, 2001; Fonagy, Leigh, Steele, Steele, Kennedy, Mattoon, Target, & Gerber, 1996). These cognitive capacities closely relate to attachment stability. Low RF levels indicate concrete views of relationships and emotionally charged events, and poor understanding of one’s own and others’ emotions. High RF indicates a complex view of relationships, interpersonal emotions, and their potential change over time. Evidence-based, mentalization-based psychotherapies (Fonagy & Target,1997; Bateman & Fonagy, 2008; Bosanac, Hamilton, Beatson, Trett, Rao, Mancuso, & Castle, 2015; Berthelot, Ensink, Bernazzini, Normandin, Luyten, Fonagy, & 2015; Jakobsen, 2014) target this psychological domain: principally for borderline personality disorder, for syndromes arising from child abuse, but notably they have not been developed for anxiety or PTSD.

To further characterize attachment dysregulation in anxious patients, we developed a now widely-used, anxiety-specific RF mentalization submeasure, Symptom-Specific Reflective Function (SSRF). Focusing on the “self” attachment domain, SSRF assesses patient self-understanding of emotional meanings of mood or anxiety symptoms. SSRF measures capacity to reflect on one’s own symptoms and their relation to self-definition, a sense of stable identity (Berthelot et al 2015; Rudden, Milrod, Meehan, & Falkenstrom, 2009; Rudden, Milrod, & Aronson, 2008; Rudden, Milrod, Target, Ackerman, & Graf, 2006). How emotionally understandable are the person’s symptoms to the person? Research demonstrated SSRF improvement as a change mechanism in panic disorder patients treated with affect-focused, anxiety-targeted time-limited PFPP (Rudden et al, 2006; Barber, Gallop, & Milrod, 2016; Barber, Milrod, Gallop, Solomonov, Rudden, & Chambless, in press). In the current open trial of time-limited, symptom-focused, attachment-based interpersonal psychotherapy (IPT; Markowitz, 2016) for PTSD, we expected SSRF to more sensitively measure impairment and short-term change than RF, and hence focused hypotheses on SSRF.

Separation anxiety seems important in PTSD inasmuch as both limit access to social support. Social support protects against developing PTSD post trauma and can facilitate its treatment (Brewin, Andrews, & Valentine, 2000; Ozer, Best, Lipsey, & Weiss, 2003). Confiding in someone allows processing of a traumatic event, which likely protects against PTSD. Insecure attachment, embodied by SAD, leads to having fewer and less trusting relationships than securely attached individuals, leaving the insecurely attached less likely to seek support, and thus at greater risk for PTSD. The premise of IPT for PTSD hinges on this: using one’s emotions to guide interpersonal relationships helps formerly numb patients to gauge whether they can trust others and seek their support (Markowitz, Milrod, Bleiberg, & Marshall, 2009).

Despite the importance of separation anxiety in PTSD and the persistence of anxiety and mood disorders (Milrod,et al, 2014; Shear, 1996; Cassano, Michelini, Shear, Coli, Maser, & Frank, 1997; Rucci, Miniati, Oppo, Mula, Calugi, Frank, Shear, Mauri, Pini, & Cassano, 2009; Frank, Shear, Rucci, Cyranowski, Endicott, Fagiolini, Grochocinski, Houck, Kupfer, Maser, & Cassano, 2000; Benvenuti, Rucci, Calugia, Cassano, Miniata, & Frank, 2010; Frank, Cyranowski, Rucci, Shear, Fagiolini, Thase, Cassano, Grochocinski, Kostelnik, & Kupfer, 2002; Coryell, Fiedorowicz, Solomon, Leon, Rice, & Keller, 2012), no treatment studies have assessed how common SAD is in patient samples, tracked its clinical correlates, or evaluated whether it responds to treatment. Now that IPT (Weissman, Markowitz, & Klerman, 2018), an affect-, attachment-, and life-event-focused psychotherapy, has demonstrated efficacy for PTSD (Markowitz et al, 2015; US Department of Veterans Affairs, 2017; Krupnick, Green, Stockton, Miranda, Krause, & Mete, 2008; Campanini, Schoedl, Pupo, Costa, Krupnick, & Mello, 2010), exploring these relationships in PTSD patients seems compelling.

Interpersonal Psychotherapy.

IPT (Weissman et al, 2018) is a time-limited, efficacious psychotherapy for depression, eating disorders, some anxiety disorders (Markowitz, Lipsitz, Milrod, 2014), and PTSD (Markowitz, 2016; Markowitz et al, 2015; US Department of Veterans Affairs, 2017). Unlike the more commonly studied cognitive behavioral PTSD therapies, which habituate patients to traumatic experiences via exposure (e.g., Foa & Rothbaum, 1998), IPT focuses on affects, interpersonal relationships, and life circumstances, and on addressing the interpersonal consequences of trauma rather than revisiting traumatic events themselves. Although its mechanisms are understudied, IPT may work partly through improving underlying attachment dysregulation (Markowitz et al, 2009; Lipsitz & Markowitz, 2013; Markowitz, Milrod, Luytens, & Holmqvist, 2019; Markowitz, Lowell, Milrod, Lopez-Yianilos, & Neria, in press). In a chronic depression trial (Ekeblad, Falkenstrom, & Holmqvist, 2016), IPT improved Reflective Function (Fonagy et al, 1998). Delineating active elements of psychotherapies is clinically important, permitting refinement to strengthen therapies for particular patient groups and elucidating differential therapeutics by better targeting therapies toward patients more likely to respond.

Accordingly, this study had five aims: to 1) evaluate the proportion of SAD in a sample of patients with PTSD; 2) further explore elements of attachment dysregulation/mentalization impairment, captured by impaired SSRF; 3) determine whether adult separation anxiety improves among patients with comorbid SAD following 14 weeks of IPT for PTSD; 4) explore whether early (baseline to week 4) improvements in mentalization (i.e., SSRF) facilitate greater subsequent improvements in separation anxiety, PTSD, and depression, particularly among patients with attachment insecurity indexed by separation anxiety; and 5) determine the correlation between SAD and PTSD outcome. Analyses for questions 3–5 focused on post-baseline SCI-SAS and SSRF. We analyzed all data available in the ITT sample; but as dropouts were relatively few and only attended M= 4.6 (3.8) sessions, most post-baseline attachment data were available. We hypothesized in this exploratory study that 1) patients with PTSD would have high SAD comorbidity, and 2) brief IPT treatment would ameliorate adult separation anxiety symptoms among patients with SAD in targeting PTSD.

Methods

Setting.

The Military Family Wellness Center (MFWC) provides no-cost evidence-based treatment to military veterans and their family members at the Columbia University Irving Medical Center/New York State Psychiatric Clinic. The Center treats individuals who do not qualify for or decline treatment at Veterans Administration hospitals, recruited by outreach to military organizations, web advertisement, flyers, and word of mouth. With American Psychoanalytic Fund for Psychoanalytic Research funding to study mechanisms in IPT, we offered study participation to veterans with PTSD who opted to receive brief IPT.

Twenty-nine veterans presenting to the MFWC with primary PTSD diagnosed on the Clinician-Administered PTSD Scale-5 (CAPS-5; Weathers, Blake, Schnurr, Kaloupek, Marx, & Keane, 2013) were offered 14 weekly sessions of manualized IPT treatment (Markowitz, 2016). To assess whether SSRF change might precede and predict PTSD symptom change, we assessed attachment measures (SCI-SAS and SSRF) at baseline, week 4, and week 14, with PTSD and depressive symptom outcome measures at baseline, week 7, and week 14. Patients signed informed written consent for this NYSPI IRB-approved protocol. Subjects were considered study completers if they attended the 14 week termination assessment. Completers attended M=13.5 (SD=1.0) sessions.

Assessments.

Clinician-Administered PTSD Scale for DSM-5

(Weathers et al, 2013). Developed at the National Center for PTSD, the canonical CAPS-5 was the primary study symptom outcome measure. Its 30 items cover the DSM-5 PTSD criteria; its accompanying Life Events Checklist (LEC-5) assesses trauma history. CAPS-5 interrater reliability was excellent (ICC=0.99).

Hamilton Depression Rating Scale (Ham-D).

The Ham-D (Hamilton, 1960) is the most widely used observer rating scale for depressive symptoms. Interrater reliability on the 17-item version was adequate (ICC=.75).

Structured Clinical Interview for Separation Anxiety Symptoms

(Cyranowski et al, 2002). Total SCI-SAS score ≥8 defines clinically significant, syndromal SAD. DSM5 diagnosed SAD can also be determined based on endorsing three symptoms at the “2, often” level for either current adult SAD or retrospective childhood SAD. Designed to assess separation anxiety in adults, the SCI-SAS displays excellent psychometric properties in discretely assessing retrospective childhood and current adult separation anxiety. To assess separation anxiety change, severity was assessed by summing together scores of 0–2 for each of the 8 adult SAD items (Cyranowski et al, 2002).

Reflective Function/Symptom-Specific Reflective Function.

The RF Scale (Fonagy et al, 1998), modified for PTSD patients (SSRF; Rudden et al, 2009), is a brief, semi-structured interview. SSRF specifically for PTSD was developed and tested by Rudden and Milrod. RF score is independent of social class, socioeconomic status, ethnicity, education, and verbal intelligence (Levy, Meehan, Kelly, Reynoso, Weber, Clarkin, & Kernberg, 2006). Trained research assistants interviewed and taped RF/SSRF interviews. Blinded RF/SSRF raters rated audiotaped transcriptions. Both RF and SSRF scales, scored like the far longer Adult Attachment Interview (George et al, 1996), yield ratings ranging from −1 (bizarre, extremely unreflective) to 9 (extremely reflective), where 5 signifies normal reflective capacity. Studied in various psychiatric disorders (Rudden et al, 2009), SSRF is scored and normed like general RF. An example of unreflective SSRF might be: “I get flashbacks when I eat Chinese food.” A more reflective example: “When I feel guilty and useless the way I did when my men were blown up, like the way I’ve been feeling with my daughter, I notice I have flashbacks to that time.” Small numerical score changes indicate significant improvements in ability to reflect on one’s internal life (the attachment “self” domain) and, for RF, understanding of others (“other” domain). Intraclass correlationreliability ratings among three independent coders ranged from acceptable to excellent [General RF is always administered with SSRF, General RF did not form part of our hypotheses, so these data are not presented here]: RF= 63.91, SSRF= .72−.80. (Shrout & Fleiss, 1979)

Treatment.

Seven psychologists (1 licensed Ph.D., 4 post-doctoral Ph.D.’s, 2 psychology interns) and one psychiatric social worker provided treatment. Therapists followed the IPT for PTSD manual (Markowitz, 2016) and received weekly supervision of videotaped sessions from its author. Beyond supervision there was no formal adherence monitoring.

IPT for PTSD resembles standard IPT (Weissman et al, 2018) but recognizes that patients with PTSD often present benumbed, affectively distanced, and hence (unlike depressed patients) struggle to connect feelings to events. Thus early sessions of this 14-week manualized adaptation focus on helping patients to recognize and name their emotional responses, and to understand that their feelings (e.g., anger at mistreatment) are useful emotional cues about interpersonal encounters rather than problems to fear and suppress. IPT therapists normalize such emotional responses and role play with patients so they can employ them effectively. Once patients can better identify feelings, they can proceed with standard IPT maneuvers (Markowitz, 2016), which often involve confronting, or asserting their needs or anger to, others-- encounters with evident attachment substrates.

Data Analysis.

Process analyses were run in the R statistical computing environment using the R packages “lme4” and “lmerTest” (Bates, Maechler, Bolker, Walker, Christensen, Singmann, Dai, Schepi, Grothendieck, Green, Fox, & Bolker, 2016; Kuznetsova, Brockhoff, & Christensen, 2016) or SAS version 9.4. Baseline differences between patients with versus without baseline comorbid SAD were assessed using chi-square or t-tests, as appropriate.

An intention-to-treat analysis included all patients initiating treatment (n=29), incorporating all collected data. Aim 1 was a simple proportion of patients presenting with PTSD who met criteria for SAD. Aim 2 tracked baseline SSRF in patients with PTSD. For Aims 3–5, analyses were conducted in mixed linear models with a random effect of person and fixed effect of time (represented for baseline, mid-treatment, and termination; coded 0, 1, and 2). We examined symptom change both in the total sample and among patients with comorbid SAD (SCI-SAS total ≥8), analyzing change in adult SCI-SAS, CAPS-5, and Ham-D. To examine whether patients with comorbid SAD experienced different rates of change in these three outcomes (Aim 3), we tested the interaction between qualifying for SAD (coded 0/1) and time. To assess with temporal sequencing the effect of early SSRF changes on outcome, we examined whether early SSRF changes (between baseline and week 4) predicted later (mid-treatment to termination) SCI-SAS, CAPS-5, and Ham-D symptom change (Aim 4). We explored whether SAD influenced degree of improvement following SSRF gains, using an interaction term between SAD diagnosis and early SSRF change to predict later symptom change. A significant interaction indicates that early changes in SSRF differentially predict later symptom change as a function of a patient being SAD+ or SAD-.

A significant interaction indicates that slopes for a given outcome reliably differ between SAD+ and SAD− patients. We examined covariation between adult SCI-SAS change and other symptoms by including pre-to-post SCI-SAS change as a fixed effect in predicting symptom change, controlling for baseline SCI-SAS score (Aim 5).

Results

Mean age of the 29 patients was 43.3 (s.d.=14.1). Nine (31%) were women, 31% were African-American, and 4 (13.8%) identified as Hispanic. Twenty of 29 (69%) subjects who presented with PTSD met clinically significant SAD diagnostic criteria using SCI-SAS norms (total SCI-SAS≥8) at baseline (Aim 1; see Table 1). Meeting this definition can include elements of both child and adult SAD. [An alternative (novel) method is to score “2”s on the adult and childhood SCI-SAS interviews to indicate meeting the corresponding DSM-5 SAD criteria. Based on this scheme, 10 (34.5%) had DSM-5 adult SAD, 3 (10.3%) reported retrospective childhood SAD, including N=2 overlapping child +adult and 11 (37.9%), met criteria for at least one of the two independently scored SAD criteria.] We used the former method (SCI-SAS ≥8) as our a priori definition of SAD.

Table 1.

Baseline characteristics of subjects with PTSD with and without separation anxiety disorder

Total Sample (n=29) BL SAD+ (n=20) BL SAD(n=9)
Variables N % n % n % prob
Age at consent [Mean (SD)] 29 43.3 (14.1) 20 42.1 (13.2) 9 46.1 (16.4) 0.4838
Gender 0.6749
Male 20 69.0% 13 65.0% 7 77.8%
Female 9 31.0% 7 35.0% 2 22.2%
Race 0.8087
White 13 44.8% 9 45.0% 4 44.4%
Black 9 31.0% 6 30.0% 3 33.3%
Asian 1 3.4% 1 5.0% 0 0.0%
White/American Indian 1 3.4% 0 0.0% 1 11.1%
Biracial 2 6.9% 2 10.0% 0 0/0%
Other 1 3.4% 1 5.0% 0 0.0%
Unknown 2 6.9% 1 5.0% 1 11.1%
Ethnicity 0.4989
Hispanic 4 13.8% 3 15.0% 1 11.1%
Non-Hispanic 24 82.8% 17 85.0% 7 77.8%
Unknown 1 3.4% 0 0.0% 1 11.1%
CAPS_5_BL [Mean (SD)] 29 35.0 (8.2) 20 33.7 (8.6) 9 38.1 (6.5) 0.1789
MDD Diagnosis 0.0502
No 15 51.7% 13 65.0% 2 22.2%
Yes 14 48.3% 7 35.0% 7 77.8%
PTSD Diagnosis 1.0000
No 1 3.4% 1 5.0% 0 0.0%
Yes 28 96.6% 19 95.0% 9 100.0%
HAM_D_BL [Mean (SD)] 29 15.7 (6.3) 20 15.6 (6.8) 9 15.9 (5.2) 0.9108
UseRF_BL [Mean (SD)] 29 4.5 (1.1) 20 4.6 (0.8) 9 4.5 (1.5) 0.9085
UseSSRF_BL [Mean (SD)] 29 3.7 (1.2) 20 3.8 (0.8) 9 3.4 (1.7) 0.1964
Child_Adult_SCI_SAS_BL [Mean (SD)] 29 10.4 (5.9) 20 13.2 (4.7) 9 4.1 (2.4) <.0001
Adult_SCI_SAS_BL [Mean (SD)] 29 6.9 (3.8) 20 8.7 (3.1) 9 3.1 (2.1) <.0001
Child_SCI_SAS_BL [Mean (SD)] 29 3.5 (3.1) 20 4.6 (3.0) 9 1.0 (1.1) 0.0021
CTQ Total Visit -1-Pre-Baseline [Mean (SD)] 24 65.9 (24.4) 16 67.6 (26.4) 8 62.5 (21.0) 0.6426
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Note: Completers defined as those with Week 14 data

Baseline mean CAPS-5 was 35.0 (s.d.=8.2) and mean Ham-D was 15.7 (6.3). Baseline SCI-SAS was 10.4 (5.9); baseline SSRF was quite impaired: 3.7 (1.2). Baseline SAD, CAPS-5 and Ham-D scores did not differ between patients with and without SAD. Baseline SCI-SAS in the SAD subsample was 13.2 (4.7) and baseline SSRF 3.8 (0.8), indicating impairment (Aim 2; Table 1).

Symptom change-treatment sample.

Of 29 patients initiating treatment, seven (24%) dropped out. Dropouts attended M= 4.6 (3.8) sessions.

SAD improved with IPT for PTSD. Among patients with comorbid SAD, adult SCI-SAS separation anxiety scores improved reliably during treatment (B= −1.0 [95% CI: −1.78, −0.28], t[48.8]= −2.71, p=0.009, total change= −2.1; Table 2). The difference in rate of adult SCI-SAS improvement between patients with versus without SAD achieved statistical significance (t[51.9]= −3.18, p=0.002). By contrast, the total sample with and without SAD showed no overall adult SCI-SAS improvement (B= −0.38 [95% CI: −1.08, 0.35], t[49.0]= −1.04, p=0.302) (Table 2). Of 17 patients with baseline SAD having termination SCI-SAS scores, 6 fell below criteria for significant SAD (35%) and 6 reported an adult SCI-SAS decrement of ≥50%, indicating response (35%); 5 patients met both criteria (29%). Of the 9 completers with DSM-5-defined SAD, 5 patients fell under diagnostic threshold following treatment (55.6%, Aim 3).

Table 2.

Symptom outcome and attachment measure scores for SAD+ and SAD− patients

Baseline Week 4 Week 7 Termination (Week 14)
Separation Anxiety + Adult SCI-SAS 8.7 (3.1); n = 20 8.5 (3.4); n = 19 6.6 (3.4); n = 17
SSRF 3.8 (0.8); n = 20 3.7 (n = 1.1); n = 19 3.9 (1.0); n = 17
CAPS 33.7 (8.6); n = 20 28.3 (10.1); n = 19 22.9 (14.1); n = 17
HAMD 15.6 (6.8); n = 20 14.5 (4.8); n = 19 11.4 (7.0); n = 17
Separation Anxiety - Adult SCI-SAS 3.1 (2.1); n = 9 5.4 (2.8); n = 7 6.0 (4.8); n = 5
SSRF 3.4 (1.7); n = 9 3.4 (1.2); n = 7 3.4 (0.5); n = 5
CAPS 38.1 (6.5); n = 9 27.4 (7.8); n = 7 22.6 (15.6); n = 5
HAMD 15.9 (5.2); n = 9 14.6 (6.1); n = 7 10.2 (9.1); n = 5
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CAPS PTSD symptoms (B= −6.10 [95% CI: −8.04, −4.16], t[50.7]= −6.20, p<.001; change= −12.2) and Ham-D depression symptoms (B= −2.28 [95% CI: −3.60, −0.96], t[52.2]= −3.42, p=.001; change= −4.6) improved in treatment, without significant SAD subsample differences (interactions p=0.310 and p=0.678, respectively).

SSRF change and symptom change.

Among PTSD patients with comorbid SAD, early SSRF improvement only predicted later improvement in adult SCI-SAS scores at a nonsignificant trend level (Aim 4) (B= −1.67 [95% CI: −3.30, 0.03], t[19.5]= −1.88, p=0.075, r =−0.39). Patients without comorbid SAD showed no significant relationship (B = 2.32 [95% CI: −0.14, 4.73], t[22.1]= 1.69, p=0.105, r=0.34). While SSRF improvement did not predict SCI-SAS improvement, the interaction reflecting difference in predictive value of SSRF improvements between the two groups reached statistical significance (B= −3.97 [95% CI: −6.88, −0.98], t[21.3]= −2.50, p=0.021). Interactions between SAD and early SSRF change did not significantly predict CAPS or Ham-D improvements, although interactions for the difference between groups moved in the same direction (ps= 0.123 for CAPS; 0.213 for Ham-D). SSRF itself did not reliably improve across the sample (B = 0.01 [95% CI: −0.17, 0.19], t[48.7] = 0.10, p = 0.917), although there was substantive variability in degree of pre-to-post SSRF change over the trial (M = −0.03, SD = 0.82).

Covariation of SCI-SAS and outcome change.

CAPS improvements did not significantly correlate with adult SCI-SAS improvement (Aim 5) (B= 0.54 [95% CI: 0.09, 1.17], t[41.0] = 1.67, p=0.103, r=0.25), whereas Ham-D improvement in this small sample appeared significantly correlated with adult SCI-SAS score reduction (B= 0.44 [95% CI: 0.02, 0.85], t[41.0]= 2.03, p=0.049, r=0.30). Neither relationship differed based on baseline SAD (interaction ps >0.771).

Discussion

Attachment dysregulation, a broad set of problems arising from insecure or unstable early formative childhood attachments (Bowlby, 1973, 1988), understandably has far-reaching effects on PTSD vulnerability. Treatment outcome research has not adequately tracked the effects of attachment problems on developing PTSD nor assessed the impact of treatment interventions addressing insecure attachment features, although our group has previously described their connection in several samples of civilians exposed to terrorism (Besser & Neria, 2010; 2012), and US (Tamman et al, 2017) and Israeli veterans (Dekel, Solomon, Ginzburg, & Neria, 2004). This is the first study to evaluate both comorbid SAD, and SSRF impairment, two aspects of dysregulated/insecure attachment, among patients with PTSD. The high (69%) rate in this clinical sample converges with Silove et al.’s (2015) epidemiological observations indicating elevated PTSD risk among individuals with SAD, or alternatively, SAD comorbidity with PTSD. The small study sample precludes predicting whether this high proportion might generalize to other populations of patients with PTSD. SSRF was quite impaired in this sample.

It is heartening that for patients with SAD and PTSD, brief IPT treatment not only improved CAPS-5 PTSD symptoms, but also SCI-SAS adult separation anxiety, an attachment dysregulation/insecurity marker. IPT, affect- and attachment-focused, may improve attachment dysregulation in patients with PTSD, paralleling the improvement of anxiety patients in PFPP-XR (Busch et al, 2012). This makes clinical sense: the IPT focus on articulating and relieving interpersonal difficulties with others and linking symptoms to mood and interpersonal relationships seems bound to address impaired attachment in relationships with others. Treatment implications are intriguing. To better personalize PTSD treatments, a study might treat a patient cohort with SAD and PTSD, comparing affect-focused treatment like IPT with exposure-based treatment like prolonged exposure to determine differential outcome for separation anxious PTSD patients. Such a study might delineate preferential response in sub-populations for specific evidence-based interventions.

Patients with comorbid SAD experienced marked adult separation anxiety improvement after IPT following early improvements in SSRF, another attachment dysregulation/mentalization impairment marker. This further indicates that particularly impaired patients can normalize their attachment profiles, hopefully imparting greater resilience. Thus, people with SAD who learn to reflect in a more nuanced way about their symptoms experience more trustful attachment (improvement in separation anxiety). This is an important domain for patients with PTSD, who often struggle with interpersonal trust.

The relationship between insecure attachment, SAD, and PTSD remains complex and underexplored (Milrod et al, 2014; Silove et al, 2015; Milrod, 2015; Milrod, 2016). CAPS and HDRS scores did not differ between patients with and without SAD, indicating separation anxiety is not simply an artifact of greater anxiety or depression severity. This research did not address salient questions: Do SAD symptoms observed post trauma correspond to “state” or “trait”? Are they a traumatic reactivation of earlier childhood separation anxiety, or is adult traumatic SAD an adult phenocopy of the childhood syndrome, produced by chronic PTSD? Our prior research found that apparent comorbid personality disorders regressed in 14 weeks of acute PTSD psychotherapy; SAD might represent a similar, trait-like “comorbidity” in this context (Markowitz, Petkova, Biyanova, Ding, Suh, & Neria, 2015).

While anxious attachment and separation anxiety can predispose to developing PTSD after trauma exposure, separation anxiety and insecure attachment can also emerge after PTSD onset, potentially only reaching threshold criteria after trauma. Two factors complicate the relationship between SAD and attachment:

First, even more than other anxiety disorders and PTSD, separation anxiety occurs in a relational context. By definition, separating from a close attachment figure feels unsafe (Bowlby, 1973, 1988). Because separation anxiety is often ego-syntonic and culturally syntonic, its presence can go unrecognized until it becomes debilitating. Differing cultures and families may deem it normal (Silove et al, 2015), as it occurs in families with both genetic and epigenetic risks (Milrod et al, 2014; Milrod, 2015). This backdrop has clinical importance, because anxious attachment contributes to psychopathological burden in mood and anxiety disorder severity and chronicity (Milrod et al, 2014, Kossowsky et al, 2013).

Second, as further complication, separation anxiety is normal in early mammalian development. Pathological persistence of a developmentally inappropriate, burdensome attachment profile is apparently not ubiquitous in people facing trauma. Unlike other anxiety disorders and PTSD, specific situations and developmental phases make separation anxiety appropriate: it is essential for survival in early childhood, and during adulthood during times of illness.

This study is small, uncontrolled, and exploratory. Funding limitations precluded gathering all desired data, including follow-up data beyond week 14, relevant biomarkers (e.g., oxytocin), neuroimaging, and formal treatment fidelity. Because the sample was small, we opted not to use alpha protection for multiple comparisons in this exploratory study, potentially leading to greater inaccuracy. The assessment schedule precluded determining whether or not CAPS symptoms improved before week 7. A large literature exists on timing of assessment measures in the context of mechanism studies; ideally we would have measured attachment measures and CAPS at the same time (Barber et al, in press; Kraemer, 2014).These pilot results are promising in defining a potentially large subgroup of PTSD patients whom IPT may broadly help: patients with separation anxiety, and hence a troubled, dysregulated attachment profile.

Acknowledgments

Supported by the Fund for Psychoanalytic Research of the American Psychoanalytic Association (Dr. Markowitz, PI); the New York-Presbyterian Hospital (Dr Neria, PI), Stand for the Troops Foundation (Dr Neria, PI), and the Bob Woodruff Foundation (Drs Neria and Lowell, C0-PIs). Drs. Markowitz and Neria receive salary support from New York State Psychiatric Institute. Dr. Milrod receives support from a Fund in the New York Community Trust established by DeWitt Wallace and grants from the Weill Cornell Clinical Sciences Translation Center NIMH UL1-TR-002348 and the International Psychoanalytic Association and the American Psychoanalytic Association Fund for Psychoanalytic Research. Dr. John Keefe is supported by NIH/NCATS Grant # TL1-TR002386 through the Clinical & Translational Science Center at Weill Medical College of Cornell University.

Footnotes

Data Sharing: The data supporting the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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