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The Separation Anxiety Hypothesis of Panic Disorder Revisited: A Meta-Analysis
Joe Kossowsky, Ph.D.; Monique C. Pfaltz, Ph.D.; Silvia Schneider, Ph.D.; Jan Taeymans, Ph.D.; Cosima Locher, B.Sc.; Jens Gaab, Ph.D.
Am J Psychiatry 2013;170:768-781. doi:10.1176/appi.ajp.2012.12070893
View Author and Article Information

The authors report no financial relationships with commercial interests.

From the Department of Clinical Psychology and Psychotherapy, University of Basel, Switzerland; Department of Psychology, Harvard University, Cambridge, Mass.; Faculty of Psychology, Ruhr University Bochum, Germany; and Bern University of Applied Sciences, Switzerland.

Address correspondence to Dr. Kossowsky (joe.kossowsky@unibas.ch).

Copyright © 2013 by the American Psychiatric Association

Received July 9, 2012; Revised October 25, 2012; Revised November 28, 2012; Accepted December 04, 2012.

Abstract

Objective  Evidence suggests that childhood separation anxiety disorder may be associated with a heightened risk for the development of other disorders in adulthood. The authors conducted a meta-analysis to examine the relationship between childhood separation anxiety disorder and future psychopathology.

Method  PubMed, PsycINFO, and Embase were searched for studies published through December 2011. Case-control, prospective, and retrospective cohort studies comparing children with and without separation anxiety disorder with regard to future panic disorder, major depressive disorder, any anxiety disorder, and substance use disorders were included in the analysis. Effects were summarized as pooled odds ratios in a random-effects model.

Results  Twenty-five studies met all inclusion criteria (14,855 participants). A meta-analysis of 20 studies indicated that children with separation anxiety disorder were more likely to develop panic disorder later on (odds ratio=3.45; 95% CI=2.37–5.03). Five studies suggested that a childhood diagnosis of separation anxiety disorder increases the risk of future anxiety (odds ratio=2.19; 95% CI=1.40–3.42). After adjusting for publication bias, the results of 14 studies indicated that childhood separation anxiety disorder does not increase the risk of future depression (odds ratio=1.06; 95% CI=0.78–1.45). Five studies indicated that childhood separation anxiety disorder does not increase the risk of substance use disorders (odds ratio=1.27; 95% CI=0.80–2.03). Of the subgroup analyses performed, differences in comparison groups and sample type significantly affected odds ratio sizes.

Conclusions  A childhood diagnosis of separation anxiety disorder significantly increases the risk of panic disorder and any anxiety disorder. These results support a developmental psychopathology conceptualization of anxiety disorders.

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FIGURE 1. Study Selection Procedure for a Meta-Analysis of the Association Between Childhood Separation Anxiety and Future Psychopathology

FIGURE 2. Meta-Analysis of Studies Investigating the Association Between Childhood Separation Anxiety Disorder (SAD) and Future Panic Disorder (Random Effects)a

a The red diamonds indicate the combined effect sizes for studies with clinical, nonclinical, and non-separation anxiety disorder comparison groups, as well as the overall effect size of the meta-analysis (top to bottom). An asterisk indicates that the study included two separate separation anxiety disorder samples, and the data were treated as belonging to separate cohorts.

FIGURE 3. Meta-Analysis of Studies Investigating the Association Between Childhood Separation Anxiety Disorder (SAD) and Future Major Depressive Disorder (Random Effects)a

a The red diamonds indicate the combined effect sizes for studies with clinical, nonclinical, and non-separation anxiety disorder comparison groups, as well as the overall effect size of the meta-analysis (top to bottom).

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TABLE 1.Selected Characteristics of Studies Investigating the Association Between Childhood Separation Anxiety Disorder and Subsequent Mental Illnessesa
Table Footer Note

a OCD=obsessive-compulsive disorder; STROBE=Strengthening the Reporting of Observational Studies in Epidemiology.

Table Footer Note

b The data refer to the Biederman et al. study on childhood antecedents to panic disorder (13).

Table Footer Note

c The data refer to the Biederman et al. study on patterns of comorbidity in panic disorder and major depression (17).

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TABLE 2.Selected Results of Publication Bias and Sensitivity Analyses
Table Footer Note

a The data represent the variance between studies as a proportion of the total variance; heterogeneity was tested using the I2 statistic (low heterogeneity=25%; moderate heterogeneity=50%; high heterogeneity=75%). The p values refer to significance of the Q statistic (the I2 statistic does not include a test of significance).

Table Footer Note

b Heterogeneity was tested using the tau2 statistic, which estimates the between-study variance.

Table Footer Note

c The data represent the Z value of the test of interaction between different categories of studies (Altman and Bland [42]).

Table Footer Note

* p≤0.05. ** p≤0.01. *** p≤0.001.

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