The Separation Anxiety Hypothesis of Panic Disorder Revisited: A Meta-Analysis
Abstract
Objective
Method
Results
Conclusions
Method
Search Strategy and Inclusion Criteria
Study | Group (Disorder) | Study Participants N | Mean Age or Range | SD | Female (%) | Study Design | Sample Type | Outcome | Comparison Group | Clinical Control Disorder | Separation Anxiety Disorder Measure | Separation Anxiety Disorder Measure Criteria | Informant | STROBE Score |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Aschenbrand et al. (2003) | Clinical control;separation anxiety disorder | 6718 | 19.3 (Total sample) | 1.7 | 36 | Prospective cohort | Clinical | Anxiety disorders; major depressive disorder; panic disorder | Clinical control | Generalized anxiety disorder; social phobia | Interview | DSM-III-R | Parent and child | 18.5 |
Ayuso et al. (1989) | Nonclinical control; panic disorder | 50 107 | No data 35.1 | 9.0 | 65 | Case control | Clinical | Panic disorder | Nonclinical control | Checklist | DSM-III | Proband | 11 | |
Balon et al. (1989) | Nonclinical control; | 100 | 29.5 | 5.9 | 55 | Case control | Clinical | Panic disorder | Nonclinical control | Checklist | DSM-III | Proband | 7 | |
panic disorder | 100 | 32.8 | 8.0 | |||||||||||
Bandelow et al. (2001) | Nonclinical control; panic disorder | 124 | 36.8 | 11.6 | 58 | Case control | Clinical | Panic disorder | Nonclinical control | Interview; checklist | DSM-IV | Proband | 16.5 | |
115 | 38.1 | 10.6 | ||||||||||||
Battaglia et al. (1995) | Nonclinical control; | 131 | 37.3 | 12.0 | 68 | Case control | Clinical | Panic disorder | Nonclinical control | Panic disorder; major depressive disorder; social phobia; simple phobia | Checklist | DSM-III-R | Proband | 14.5 |
panic disorder | 231 | 36.3 | 11.0 | |||||||||||
Biederman et al. (2005)b | Nonclinical control referred; | 61 | 38.3 | 5.1 | 48 | Case control | Population | Panic disorder | Nonclinical control | Interview | DSM-III-R | Proband | 17.5 | |
panic disorder in referred sample; | 131 | 38.8 | 5.4 | 85 | ||||||||||
nonclinical control nonreferred; | 587 | 42.4 | 5.8 | |||||||||||
panic disorder in nonreferred sample | 58 | 40.5 | 6.4 | |||||||||||
Biederman et al. (2005)c | Nonclinical control; | 686 | 42.1 | 6.0 | 51 | Case control | Population | Major depressive disorder; panic disorder | Nonclinical control | Interview | DSM-III-R | Proband | 15.5 | |
panic disorder; | 23 | 42.5 | 5.5 | |||||||||||
major depressive disorder | 225 | 41.8 | 5.9 | |||||||||||
Biederman et al. (2006) | Nonclinical control; | 960 | 42.0 | 6.0 | 51 | Case control | Population | Panic disorder | Nonclinical control | Interview | DSM-III-R | Proband | 17.5 | |
panic disorder | 58 | 40.5 | 6.4 | |||||||||||
Biederman et al. (2007) | Separation anxiety disorder; | 41 | 6.4 (Total sample) | No data | No data | Prospective cohort | Population | Major depressive disorder; panic disorder | Non-separation anxiety disorder | Interview | DSM-III-R | Parent and child | 16.5 | |
non-separation anxiety disorder | 192 | |||||||||||||
Bittner et al. (2007) | Separation anxiety disorder; | 68 | 9–19 (Total sample) | 50 | Prospective cohort | Population | Major depressive disorder; substance dependence | Non-separation anxiety disorder | Interview | DSM-IV | Parent and child | 17 | ||
non-separation anxiety disorder | 812 | |||||||||||||
Brückl et al. (2007) | Separation anxiety disorder; | 17 | 14–17 (Total sample) | 52 | Prospective cohort | Population | Anxiety disorders; major depressive disorder; panic disorder; substance dependence | Non-separation anxiety disorder | Interview | DSM-IV | Child | 15.5 | ||
subthreshold separation anxiety disorder; | 99 | |||||||||||||
symptomatic separation anxiety disorder; | 86 | |||||||||||||
non-separation anxiety disorder | 888 | |||||||||||||
Flakierska-Praquin et al. (1997) | Nonclinical control | 35 | 7–12 (Total sample) | 54 | Prospective cohort | Clinical | Anxiety disorders; major depressive disorder; panic disorder; substance dependence | Clinical control, nonclinical control | Oppositional disorder; attention deficit disorder; dysthymia; anxiety disorders; OCD; tics; reading disorder; enuresis/encopresis; atypical stereotyped movement disorder; adjustment disorder | Medical records | DSM-III | No information provided | 15.5 | |
clinical control; | 35 | |||||||||||||
separation anxiety disorder | 35 | |||||||||||||
Gregory et al. (2007) | Nonclinical control; | 640 | 32 (Total sample) | No data | 62 | Case control | Population | Panic disorder | Non-separation anxiety disorder | Interview; checklist | DSM-III | Parent and child | 12 | |
clinical control; | 307 | |||||||||||||
panic disorder | 16 | |||||||||||||
Hayward et al. (2000) | Major depressive disorder; non-separation anxiety disorder | 1241,917 | 15.4 (Total sample) | 0.9 | 47 | Prospective cohort | Population | Major depressive disorder | Non-separation anxiety disorder | Interview | DSM-III-R | Child | 13.5 | |
Hayward et al. (2003) | Panic disorder; clinical control | 122,342 | 15.4 (Total sample) | 0.9 | 47 | Case control | Population | Panic disorder | Nonclinical control | No information provided | Interview | DSM-III-R | Child | 12.5 |
Lewinsohn et al. (2008) | Nonclinical control; | 457 | 16.1 (Total sample) | No data | No data | Prospective cohort | Population | Anxiety disorders; major depressive disorder; panic disorder; substance dependence | Clinical control, nonclinical control | Affective disorder; nonaffective disorder; psychotic disorder; adjustment disorder | Interview | DSM-III-R | Child | 17.5 |
clinical control; | 389 | |||||||||||||
separation anxiety disorder; | 42 | |||||||||||||
anxiety disorders | 88 | |||||||||||||
Lipsitz et al. (1994) | Panic disorder; | 156 | 34.5 (Total sample) | 8.4 | 59 | Case control | Clinical | Panic disorder | Clinical control | Panic disorder; social phobia; OCD | Interview | DSM-III-R | Proband | 13.5 |
social phobia; | 106 | |||||||||||||
OCD; | 51 | |||||||||||||
Mroczkowski et al. (2011) | Clinical control; | 390 | 42.2 | 14.7 | 71 | Retrospective cohort | Clinical | Major depressive disorder; panic disorder; substance dependence | Non-separation anxiety disorder | Interview | DSM-IV | Proband | 13 | |
separation anxiety disorder | 80 | 34.2 | 12.9 | |||||||||||
Otto et al. (2001) | Panic disorder; | 133 | 36.4 | 9.7 | 34 | Case control | Clinical | Panic disorder | Clinical control | Social phobia | Interview | DSM-III-R | Proband | 13.5 |
social phobia | 97 | |||||||||||||
Pine et al. (1998) | Non-separation anxiety disorder; | 601 | 9–18 (Total sample) | No data | 50 | Prospective cohort | Population | Major depressive disorder; panic disorder | Non-separation anxiety disorder | Interview | DSM-III; DSM-III-R | Parent and child | 15 | |
separation anxiety disorder | 111 | |||||||||||||
Pini et al. (2005) | Nonclinical control; | 15 | 27.1 | 6.0 | 54 | Case control | Clinical | Major depressive disorder; panic disorder | Nonclinical control | Interview | DSM-IV | Proband | 13.5 | |
panic disorder; | 24 | 32.5 | 9.3 | |||||||||||
major depressive disorder | 20 | 45.6 | 8.3 | |||||||||||
Pini et al. (2010) | Non-separation anxiety disorder; | 250 | 42.0 | 12.1 | 66 | Case control | Clinical | Major depressive disorder; panic disorder; anxiety disorders | Non-separation anxiety disorder | Interview | DSM-IV | Proband | 14.5 | |
adult separation anxiety disorder with history of childhood separation anxiety; | 110 | 39.4 | 13.3 | |||||||||||
separation anxiety disorder | 43 | 36.9 | 10.5 | |||||||||||
Raskin et al. (1982) | Clinical control; | 16 | 21–54 | No data | 70 | Case control | Clinical | Panic disorder | Clinical control | Generalized anxiety disorder | No information provided | DSM-III | Proband | 10.5 |
panic disorder | 17 | 24–60 | ||||||||||||
Silove et al. (2002) | Non-separation anxiety disorder; | 20 | 45.0 (Total sample) | 15.0 | 65 | Retrospective cohort | Population | Major depressive disorder; panic disorder | Non-separation anxiety disorder | Interview; checklist | DSM-IV | Proband | 14 | |
separation anxiety disorder | 52 | |||||||||||||
Yeragani et al. (1989) | Nonclinical control; | 30 | 33.4 | 6.2 | 54 | Case control | Clinical | Major depressive disorder; panic disorder | Nonclinical control | Checklist | DSM-III | Proband | 7.5 | |
panic disorder; | 35 | 29.6 | 6.3 | |||||||||||
major depressive disorder | 24 | 31.7 | 5.1 |
Quality Assessment
Data Extraction and Analysis
Results
Study Selection
Association Between Separation Anxiety Disorder and Future Mental Disorders
Sensitivity Analyses and Moderator Variables
Variable | Outcome | |||
---|---|---|---|---|
Panic Disorder | df or 95% CI | Major Depressive Disorder | df or 95% CI | |
Publication bias | ||||
Funnel plot distribution | Symmetrical | Asymmetrical | ||
Begg’s adjusted-rank correlation (p value) | 0.45 | 0.29 | ||
Classic fail-safe N | 782 | 26 | ||
Comparison group | ||||
Separation anxiety disorder compared with clinical control | ||||
Heterogeneitya | 0.00 | 3 | 0 | 0 |
Heterogeneityb | 0 | 0 | ||
Odds ratio | 0.89 | 0.58–1.37 | 0.96 | 0.39–2.38 |
Separation anxiety disorder compared with non-separation anxiety disorder | ||||
Heterogeneitya | 71.09** | 6 | 53.28* | 7 |
Heterogeneityb | 0.51 | 0.09 | ||
Odds ratio | 3.70 | 1.87–7.34 | 1.04 | 0.87–1.24 |
Separation anxiety disorder compared with nonclinical control | ||||
Heterogeneitya | 0.00 | 10 | 0.00 | 2 |
Heterogeneityb | 0 | 0 | ||
Odds ratio | 5.73 | 4.15–7.92 | 3.69 | 1.85–7.35 |
Odds ratio of nonclinical control compared with odds ratio of clinical controlc | 6.78*** | 2.32* | ||
Odds ratio of nonclinical control compared with odds ratio of non-separation anxiety disorderc | 1.13 | 3.49*** | ||
Odds ratio of clinical control compared with odds ratio of non-separation anxiety disorderc | 3.45*** | 0.17 | ||
Study type | ||||
Case control | ||||
Heterogeneitya | 74.80*** | 15 | 79.71*** | 4 |
Heterogeneityb | 0.58 | 0.63 | ||
Odds ratio | 3.36 | 2.09–5.41 | 1.43 | 0.59–3.45 |
Prospective | ||||
Heterogeneitya | 68.50** | 6 | 12.57 | 7 |
Heterogeneityb | 0.79 | 0.02 | ||
Odds ratio | 4.08 | 1.75–9.52 | 1.43 | 1.11–1.86 |
Retrospective cohort | ||||
Heterogeneitya | 0 | 0 | 0 | 0 |
Heterogeneityb | 0 | 0 | ||
Odds ratio | 2.60 | 0.98–6.93 | 1.10 | 0.80–1.51 |
Odds ratio of case control compared with odds ratio of prospectivec | 0.39 | 0 | ||
Odds ratio of case control compared with odds ratio of retrospectivec | 0.46 | 0.55 | ||
Odds ratio of prospective compared with odds ratio of retrospectivec | 0.68 | 1.25 | ||
DSM criteria | ||||
DSM-III/DSM-III-R | ||||
Heterogeneitya | 69.61*** | 18 | 70.85*** | 8 |
Heterogeneityb | 0.47 | 0.24 | ||
Odds ratio | 3.18 | 2.11–4.81 | 1.45 | 0.94–2.23 |
DSM-IV/DSM-IV-TR | ||||
Heterogeneitya | 82.65*** | 3 | 1.51 | 4 |
Heterogeneityb | 1.58 | 0 | ||
Odds ratio | 4.79 | 1.13–20.29 | 1.14 | 0.87–1.50 |
Odds ratio of DSM-III compared with odds ratio of DSM-IVc | 0.53 | 0.92 | ||
Sample type | ||||
Clinical | ||||
Heterogeneitya | 67.55*** | 13 | 3.14 | 5 |
Heterogeneityb | 0.38 | 0.01 | ||
Odds ratio | 2.40 | 1.53–3.76 | 0.77 | 0.55–1.07 |
Population | ||||
Heterogeneitya | 68.22*** | 10 | 56.51* | 7 |
Heterogeneityb | 0.65 | 0.10 | ||
Odds ratio | 5.63 | 3.01–10.50 | 1.63 | 1.18–2.25 |
Odds ratio of clinical compared with odds ratio of populationc | 2.17* | 3.17** |
Discussion
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