Objective: To examine the association between separation anxiety disorder (SAD) and mental disorders in a community sample and to evaluate whether separation anxiety is specifically related to panic disorder with and without agoraphobia. Method: The data come from a 4-year, prospective longitudinal study of a representative cohort of adolescents and young adults aged 14–24 years at baseline in Munich, Germany. The present analyses are based on a subsample of the younger cohort that completed baseline and two follow-up investigations (n = 1,090). DSM-IV diagnoses were made using the Munich Composite International Diagnostic Interview. Cox regressions with time-dependent covariates were used to examine whether prior SAD is associated with an increased risk for subsequent mental disorders. Results: Participants meeting DSM-IV criteria for SAD were at an increased risk of developing subsequent panic disorder with agoraphobia (PDAG) (HR = 18.1, 95% CI = 5.6–58.7), specific phobia (HR = 2.7, 95% CI = 1.001–7.6), generalized anxiety disorder (HR = 9.4, 95% CI = 1.8–48.7), obsessive-compulsive disorder (HR = 10.7, 95% CI = 1.7–66.1), bipolar disorder (HR = 7.7, 95% CI = 2.8–20.8), pain disorder (HR = 3.5, 95% CI = 1.3–9.1), and alcohol dependence (HR = 4.7, 95% CI = 1.7–12.4). Increased hazard rates for PDAG (HR = 4.2, 95% CI = 1.4–12.1), bipolar disorder type II (HR = 8.1, 95% CI = 2.3–27.4), pain disorder (HR = 1.9, 95% CI = 1.01–3.5), and alcohol dependence (HR = 2.1, 95% CI = 1.1–4.) were also found for subjects fulfilling subthreshold SAD. Conclusions: Although revealing a strong association between SAD and PDAG, our results argue against a specific SAD-PDAG relationship. PDAG was neither a specific outcome nor a complete mediator variable of SAD.

1.
Silove D, Manicavasagar V, Curtis J, Blaszczynski A: Is early separation anxiety a risk factor for adult panic disorder? A critical review. Compr Psychiatry 1996;37:167–179.
2.
Klein DF: Delineation of two drug-responsive anxiety syndromes. Psychopharmacologia 1964;5:397–408.
3.
Gittelman-Klein R: Is panic disorder associated with childhood separation anxiety disorder? Clin Neuropharmacol 1995;18:7–14.
4.
Bowlby J: Attachment and Loss. London, The Hogarth Press, 1973, vol 2.
5.
Klein D: Anxiety reconceptualized. Compr Psychiatry 1980;21:411–427.
6.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 3. Washington, American Psychiatric Association, 1994.
7.
Ayuso JL, Alfonso S, Rivera A: Childhood separation anxiety and panic disorder: a comparative study. Prog Neuropsychopharmacol Biol Psychiatry 1989;13:665–671.
8.
Balon R, Yeragani VK, Pohl R: Higher frequency of separation in panic disorder patients. Am J Psychiatry 1989;146:1351.
9.
Battaglia M, Bertella S, Politi E, Bernardeschi L, Perna G, Gabriele A, Bellodi L: Age of onset of panic disorder: influence of familial liability to the disease and of childhood separation anxiety disorder. Am J Psychiatry 1995;152:1362–1364.
10.
Gittelman R, Klein DF: Relationship between separation anxiety and panic and agoraphobic disorders. Psychopathology 1984;17(suppl 1):56–65.
11.
Zitrin CM, Ross DC: Early separation anxiety and adult agoraphobia. J Nerv Ment Dis 1988;176:621–625.
12.
van der Molen GM, van den Hout MA, van Dieren AC, Griez E: Childhood separation anxiety and adult-onset panic disorders. J Anxiety Disord 1989;3:97–106.
13.
Yeragani VK, Meiri PC, Balon R, Patel H, Pohl R: History of separation anxiety in patients with panic disorder and depression and normal controls. Acta Psychiatr Scand 1989;79:550–556.
14.
Raskin M, Peeke HV, Dickman W, Pinsker H: Panic and generalized anxiety disorders. Arch Gen Psychiatry 1982;39:687–689.
15.
Thyer BA, Nesse RM, Cameron OG, Curtis GC: Agoraphobia: a test of the separation anxiety hypothesis. Behav Res Ther 1985;23:75–78.
16.
Thyer BA, Nesse RM, Curtis GC, Cameron OG: Panic disorder: a test of the separation anxiety hypothesis. Behav Res Ther 1986;24:209–211.
17.
Silove D, Manicavasagar V, O’Connell D, Blaszczynski A: Reported early separation anxiety symptoms in patients with panic and generalised anxiety disorders. Aust NZ J Psychiatry 1993;27:489–494.
18.
Lipsitz JD, Martin LY, Mannuzza S, Chapman TF, Liebowitz MR, Klein DF, Fyer AJ: Childhood separation anxiety disorder in patients with adult anxiety disorders. Am J Psychiatry 1994;151:927–929.
19.
Aschenbrand SG, Kendall PC, Webb A, Safford SM, Flannery-Schroeder E: Is childhood separation anxiety disorder a predictor of adult panic disorder and agoraphobia? A seven-year longitudinal study. J Am Acad Child Adolesc Psychiatry 2003;42:1478–1485.
20.
Silove D, Manicavasagar V: Adults who feared school: is early separation anxiety specific to the pathogenesis of panic disorder? Acta Psychiatr Scand 1993;88:385–390.
21.
Silove D, Harris M, Morgan A, Boyce P, Manicavasagar V, Hadzi-Pavlovic D, Wilhelm K: Is early separation anxiety a specific precursor of panic disorder-agoraphobia? A community study. Psychol Med 1995;25:405–411.
22.
Silove D, Manicavasagar V, Drobny J: Brief report: associations between juvenile and adult forms of separation anxiety disorder: a study of adult volunteers with histories of school refusal. J Nerv Ment Dis 2002;190:413–415.
23.
Pine DS, Cohen P, Gurley D, Brook J, Ma Y: The risk for early-adulthood anxiety and depressive disorders in adolescents with anxiety and depressive disorders. Arch Gen 1998;55:56–64.
24.
Foley DL, Pickles A, Maes HM, Silberg JL, Eaves LJ: Course and short-term outcomes of separation anxiety disorder in a community. J Am Acad Child Adolesc Psychiatry 2004;43:452–460.
25.
Wittchen H-U, Perkonigg A, Lachner G, Nelson CB: Early developmental stages of psychopathology study (EDSP): objectives and design. Eur Addict Res 1998;4:18–27.
26.
Lieb R, Isensee B, von Sydow K, Wittchen H-U: The early stages of psychopathology study (EDSP): a methodological update. Eur Addict Res 2000;6:170–182.
27.
Wittchen H-U, Pfister H (eds): DIA-X-Interviews: Manual für Screening-Verfahren und Interview; Interviewheft Längsschnittuntersuchung (DIA-X-Lifetime); Ergänzungsheft (DIA-X-Lifetime); Interviewheft Querschnittuntersuchung (DIA-X-12 Monate); Ergänzungsheft (DIA-X-12 Monate); PC-Programm zur Durchführung des Interviews (Längs- und Querschnittuntersuchung). Auswertungsprogramm. Frankfurt, Swets & Zeitlinger, 1997.
28.
Lachner G, Wittchen H-U, Perkonigg A, Holly A, Schuster P, Wunderlich U, Türk D, Garczynski E, Pfister H: Structure, content and reliability of the Munich-Composite International Diagnostic Interview (M-CIDI). Substance use sections. Eur Addict Res 1998;4:28–41.
29.
Reed V, Gander F, Pfister H, Steiger A, Sonntag H, Trenkwalder C, Hundt W, Wittchen H-U: To what degree does the Composite International Diagnostic Interview (CIDI) correctly identify DSM-IV disorders? Testing validity issues in a clinical sample. Int J Methods Psychiatr Res 1998;7:142–155.
30.
Wittchen H-U, Lachner G, Wunderlich U, Pfister H: Test-retest reliability of the computerized DSM-IV version of the Munich-Composite International Diagnostic Interview (M-CIDI). Soc Psychiatry Psychiatr Epidemiol 1998;33:568–578.
31.
Wittchen H-U, Lieb R, Schuster P, Oldehinkel T: When is onset? Investigations into early developmental stages of anxiety and depressive disorders; in Rapoport JL (ed): Childhood Onset of ‘Adult’ Psychopathology, Clinical and Research Advances. Washington, American Psychiatric Press, 1999, pp 259–302.
32.
Höfler M, Lieb R, Perkonigg A, Schuster P, Sonntag H, Wittchen H-U: Covariates of cannabis use progression in a representative population sample of adolescents: a prospective examination of vulnerability and risk factors. Addiction 1999;94:1679–1694.
33.
Stata Corporation: Stata Statistical Software: Release 8.0. College Station, Stata Corporation, 2003.
34.
Royall RM: Model robust confidence intervals using maximum likelihood estimators. Int Stat Rev 1986;54:221–226.
35.
McCullagh P, Nelder JA: Generalized Linear Models, ed 2. London, Chapman & Hall, 1989.
36.
Therneau TM, Grambsch PM: Modeling Survival Data – Extending the Cox Model. Berlin, Springer, 2000.
37.
Höfler M, Brückl T, Lieb R, Wittchen H-U: Calculating control variables with age at onset data to adjust for conditions prior to exposure. Soc Psychiatry Psychiatr Epidemiol 2005;40: 731–736.
38.
Manicavasagar V, Silove D, Franzcp JC, Wagner R: Continuities of separation anxiety from early life into adulthood. J Anxiety Disord 2000;14:1–18.
39.
Kraemer HC: Current concepts of risk in psychiatric disorders. Curr Opin Psychiatry 2003;16:421–430.
40.
Lewinsohn PM, Zinbarg R, Seeley JR, Lewinsohn M, Sack WH: Lifetime comorbidity among anxiety disorders and between anxiety disorders and other mental disorders. J Anxiety Disord 1997;11:377–394.
41.
Pini S, Abelli M, Mauri M, Muti M, Iazzetta P, Banti S, Cassano GB: Clinical correlates and significance of separation anxiety in patients with bipolar disorder. Bipolar Disord 2005;7:370–376.
42.
MacKinnon DF, McMahon FJ, Simpson SG, McInnis MG, DePaulo JR: Panic disorder with familial bipolar disorder. Biol Psychiatry 1997;42:90–95.
43.
MacKinnon D, Xu J, McMahon F, Simpson S, Stine O, McInnis M, DePaulo J: Bipolar disorder and panic disorder in families: an analysis of chromosome 18 data. Am J Psychiatry 1998;155:829–831.
44.
Kaplow JB, Curran PJ, Angold A, Costello EJ: The prospective relation between dimensions of anxiety and the initiation of adolescent alcohol use. J Clin Child Psychology 2001;30:316–326.
45.
Lieb R, Zimmermann P, Friis RH, Höfler M, Tholen S, Wittchen H-U: The natural course of DSM-IV somatoform disorders and syndromes among adolescents and young adults: a prospective-longitudinal study. Eur Psychiatry 2002;17:321–331.
46.
Lieb R, Pfister H, Mastaler M, Wittchen H-U: Somatoform syndromes and disorders in a representative population sample of adolescents and young adults: prevalence, comorbidity and impairments. Acta Psychiatr Scand 2000;101:194–208.
47.
Livingston R, Taylor JL, Crawford SL: A study of somatic complaints and psychiatric diagnosis in children. J Am Acad Child Adolesc Psychiatry 1988;27:185–187.
48.
Egger HL, Costello EJ, Erkanli A, Angold A: Somatic complaints and psychopathology in children and adolescents: stomach aches, musculoskeletal pains, and headaches. J Am Acad Child Adolesc Psychiatry 1999;38:852–860.
49.
Last CG, Petrin S, Hersen M, Kazdin AE: A prospective study of childhood anxiety disorders. J Am Acad Child Adolesc Psychiatry 1996;39:1502–1510.
50.
Angold A, Erkanli A, Costello J, Rutter M: Precision, reliability and accuracy in the dating of symptom onsets in child and adolescent psychopathology. J Child Psychol Psychiatry 1996;37:657–664.
51.
Schwab-Stone M, Shaffer D, Dulcan M, Jensen P, Fisher P, Bird H, Goodman S: Criterion validity of the NIMH Diagnostic Interview Schedule for Children Version 2.3 (DISC-2.3). J Am Acad Child Adolesc Psychiatry 1996;35:878–888.
52.
Manassis K, Bradley S: The development of childhood anxiety disorders: toward an integrated model. J Appl Dev Psychol 1994;15:345–366.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.