What do childhood anxiety disorders predict?

Antje Bittner,1,2 Helen L. Egger,3 Alaattin Erkanli,3 E. Jane Costello,3

Debra L. Foley,4 and Adrian Angold3

1Institute of Clinical Psychology and Psychotherapy, Technische Universitat Dresden, Dresden, Germany;2Department of Psychotherapy and Psycho-somatics, Universitat-Klinikum Carl Gustav Catus, Technische

Universitat Dresden, Germany; 3Department of Psychiatry and Behavioral Sciences, Duke University Medical Center,Durham, NC, USA; 4Psychiatry Department, University of Melbourne, Applied Genetics Unit, ORYGEN Research

Centre, Parkville, Australia

Background: Few longitudinal studies of child and adolescent psychopathology have examined thelinks between specific childhood anxiety disorders and adolescent psychiatric disorder. In this paper wetest the predictive specificity of separation anxiety disorder (SAD), overanxious disorder (OAD),generalized anxiety disorder (GAD), and social phobia. Methods: Data come from the Great SmokyMountains Study (GSMS). A representative population sample of children – ages 9, 11, and 13 years atintake – was followed to age 19. Diagnoses of both childhood (before age 13 years) and adolescentpsychiatric disorders (age 13 to 19 years) were available from 906 participants. Results: ChildhoodSAD predicted adolescent SAD, whereas OAD was associated with later OAD, panic attacks, depressionand conduct disorder (CD). GAD was related only to CD. Social phobia in childhood was associated withadolescent OAD, social phobia, and attention-deficit/hyperactivity disorder (ADHD). Conclusions:Anxiety disorders in childhood are predictors of a range of psychiatric disorders in adolescence.It appears that children meriting a well-defined diagnosis are missed by the current rules for thediagnosis of GAD. Future studies should examine whether OAD deserves reconsideration as a noso-logical entity. Keywords: Childhood, anxiety disorders, developmental epidemiology, longitudinalstudy. Abbreviations: SAD: separation anxiety disorder; OAD: overanxious disorder; GAD: general-ized anxiety disorder; SoPHO: social phobia; PA: panic attacks; SpPHO: specific phobia; AgPHO: ago-raphobia; DEP: depression; CD: conduct disorder; ODD: oppositional defiant disorder; ADHD:attention-deficit/hyperactivity disorder; SUD: substance use disorder.

Anxiety disorders occur frequently in childhood andadolescence, are associated with substantialimpairment and disability, and may have a chroniccourse (for a review see Costello, Egger, & Angold,2004). Studies investigating lifetime comorbidity ofchildhood anxiety disorders have revealed high levelsof comorbidity among ‘different’ anxiety disorders,and between anxiety disorders and other psychiatricdisorders – especially depression and alcohol usedisorders (Kashani & Orvaschel, 1988; Lewinsohn,Zinbarg, Seeley, Lewinsohn, & Sack, 1997; Simonoffet al., 1997).

However, there has been little prospective study ofanxiety disorders from childhood to adolescence andbeyond. Longitudinal community-based studies thatcover both childhood and adolescent psychiatricdisorders are rare, and the majority of prospectivecommunity studies have been able to consider onlyadolescent anxiety disorders. These indicate thatadolescent anxiety disorders predict a broad range ofsubsequent psychiatric disorders (Bittner et al.,2004; Cohen et al., 1993; Foley, Pickles, Maes,Silberg, & Eaves, 2004; Hayward, Killen, Kraemer, &Taylor, 2000; Orvaschel, Lewinsohn, & Seeley, 1995;Stein et al., 2001; Woodward & Fergusson, 2001).

The outcomes of childhood anxiety disorders havereceived less attention. Until recently, longitudinal

community-based studies have lumped togetherinternalizing disorders or investigated the outcomesof anxious symptoms rather than diagnoses(Goodwin, Fergusson, & Horwood, 2004; McGee,Feehan, Williams, & Anderson, 1992; Reinherz,Paradis, Giaconia, Stashwick, & Fitzmaurice, 2003).Behavioral inhibition (a consistent tendency of chil-dren to display fear and withdrawal in unfamiliarsituations) also deserves attention (Kagan, Reznick,Clarke, Snidman, & Garcia-Coll, 1984). That litera-ture suggests that an inhibited temperament in earlychildhood is associated with the later development ofanxiety disorders (Biederman et al., 2001; Schwartz,Snidman, & Kagan, 1999) as well as depression(Caspi, Moffitt, Newman, & Silva, 1996; Hayward,Killen, Kraemer, & Taylor, 1998). This in turnsuggests that there might be very long-lasting con-tinuities in at least some components of anxiety fromearly childhood to adulthood.

The possible consequences of childhood separationanxiety disorder (SAD) have attracted special interestas a result of thehypothesis that separation anxiety inchildhoodmightbea forerunner of panicdisorder (PD)during adolescence and adulthood (Gittelman &Klein, 1984). Whereas findings from early clinicalstudies supported this hypothesis (Klein, 1995;Silove, Manicavasagar, Curtis, & Blaszczynski,1996), more recent longitudinal studies have notfound an association between childhood SAD andConflict of interest statement: No conflicts declared.

Journal of Child Psychology and Psychiatry 48:12 (2007), pp 1174–1183 doi:10.1111/j.1469-7610.2007.01812.x

� 2007 The AuthorsJournal compilation � 2007 Association for Child and Adolescent Mental Health.Published by Blackwell Publishing, 9600 Garsington Road, Oxford OX4 2DQ, UK and 350 Main Street, Malden, MA 02148, USA

later panic (Aschenbrand, Kendall, Webb, Safford, &Flannery-Schroeder, 2003; Hayward et al., 2000;Pine, Cohen, Gurley, Brook, & Ma, 1998). Neitherhave probands with SAD been found to be at higherrisk of subsequent panic compared to people withother childhood anxiety diagnoses.

Three longitudinal community-based studies haveconsidered the outcomes of one or more specificchildhood anxiety disorders. In the Virginia TwinStudy of Adolescent and Behavioral Developmentchildren with persistent SAD had a significantlyhigher prevalence of overanxious disorder (OAD),oppositional defiant disorder (ODD), depression,simple phobia, and ADHD at 18-months follow-upthan children without SAD (Foley et al., 2004). TheNew York Child Longitudinal Study investigated theassociations between anxiety disorders and laterpsychiatric disorders in 9- to 18-year-old childrenand adolescents (Pine et al., 1998). Phobias mainlypredicted later phobias, fearful spells were associ-ated with later generalized anxiety, and OAD wasrelated to subsequent major depression, social pho-bia, and generalized anxiety. However, separationanxiety did not predict any later psychiatric disorder.In an earlier article we examined homotypic andheterotypic continuity, from wave to wave, of a rangeof childhood psychiatric disorders (Costello,Mustillo, Erkanli, Keeler, & Angold, 2003). Con-tinuity of the same disorder was significant for allanxiety disorders except specific phobias. Transi-tions from one diagnosis to another were significantfrom depression to anxiety and anxiety to depres-sion, and from anxiety to substance abuse. However,that approach to examining continuity has somelimitations as a means of describing continuities anddiscontinuities from childhood to adolescence,because it pays no attention to when the continuityor discontinuity occurred. In particular, if there areparticular points of transition (‘turning points’), thenaveraging across all points will tend to obscure them.We also lumped the anxiety disorders together,which could have obscured effects specific toparticular anxiety disorders.

No community study has considered the implica-tions of DSM-IV childhood GAD for later outcomes.Between DSM-III-R and DSM-IV OAD (a childhooddiagnosis) was abolished, with the intention thatthese children would in future receive a diagnosis ofGAD. Since both OAD and GAD were diagnosed inGSMS, we are able to examine the actual overlapbetween the two, and their prediction to adolescentdisorders. Furthermore, no study has yet takenaccount of the fact that the transition from thechildhood pattern of roughly equal rates of anxietydisorders in boys and girls to an excess of disordersin females does not occur until around age 13. Inother words, there have been no community-basedpure studies of the implications of childhood anxietydisorders for later adolescent/adult anxiety dis-orders. It can also be seen that these studies either

lumped anxiety disorders together, or consideredonly a small subset of the relevant disorders.

The aim of the current paper is therefore to extendour earlier findings by focusing on the implicationsof specific childhood anxiety disorders (before age13 years – the age at which the transition to adultsex ratios for depressive and anxiety disorders oc-curs) (Angold & Costello, 2006) for adolescent (age13 to 19 years) disorders.

Methods

Sample

Data come from the Great Smoky Mountains Study(GSMS); an ongoing longitudinal study of the develop-ment of psychiatric disorders and need for mentalhealth services (Costello et al., 1996; Costello et al.,2003). Three cohorts of children – 9, 11, and 13 years atthe first assessment – were recruited from 11 countiesin western North Carolina. A multistage sampling de-sign was used. Potential participants were randomlyselected from the population of some 20,000 childrenusing a household equal probability, accelerated cohortdesign (Schaie, 1965). The initial random sample of4,067 yielded 3,896 screening questionnaires (95%),which consisted mainly of the externalizing problemsscale of the Child Behavior Checklist (Achenbach &Edelbrock, 1981) completed by a parent, by telephoneor in person. All children scoring above a predeterminedcutoff point (the top 25% of the total scores), plus a 1 in10 random sample of the rest, were recruited fordetailed interviews. The data were weighted by thereciprocal of each subject’s probability of selection, togenerate accurate population prevalence estimates. Allthe prevalence estimates presented in this paper arebased on weighted data.

About 8% of area residents and the sample are Af-rican American, and less than 1% are Hispanic. Amer-ican Indians make up only about 3% of the populationof the study area, but were over-sampled from schoolrecords to constitute 25% of the study sample. We usedthe same screening procedure but recruited all Amer-ican Indian children irrespective of screen score. Of the456 American Indian children identified, screeningquestionnaires were obtained from 96%, and 81% (n ¼350) participated in the study; 33.7% (weighted; 46.0%of the observed sample) fell below poverty criteria on atleast one assessment during the study period. Ourinterviewers observed an impoverished environment in4.1% of cases (weighted; 7.1% unweighted). Unem-ployment of one or both parents occurred in 32.6%(weighted; 39.8% unweighted) at least at one assess-ment. In 28.7% (weighted; 38.6% unweighted) of ourparticipants one or both parents had left school before11th grade.

The study design and participation rates at eachwave are presented in Figure 1. Annual assessments ofthe 11- and 13-year-olds were conducted up to the ageof 16 years. Funding constraints prevented interview-ing the youngest cohort from January 1997 throughJune 1998. Because subjects were randomly selected,the cohort members interviewed between July andDecember 1998 are a random sample of the whole

Adolescents’ outcomes of childhood anxiety disorders 1175

� 2007 The AuthorsJournal compilation � 2007 Association for Child and Adolescent Mental Health.

cohort. All 3 cohorts were interviewed at age 19 years.Data were collected on 1 cohort at ages 9 and 10 years,2 cohorts ate ages 11, 12, and 13 years, and all 3cohorts at ages 14, 15, 16, and 19 years.

Diagnoses of childhood psychiatric disorders (beforeage 13 years) could only be obtained from the 1,008participants (N ¼ 439 girls, N ¼ 569 boys) in the twocohorts under age 13 when first recruited. So in thispaper we consider only the 906 probands (89.9%) (N ¼402 girls, N ¼ 504 boys) from these two cohorts forwhom diagnostic information was also obtained inadolescence (ages 13 to 19 years). We comparedparticipants for whom childhood and adolescentsdiagnoses could be obtained with subjects who onlyparticipated in childhood. We looked at 22 variables(sex, measures of SES, psychiatric disorders) and foundfew differences between these two groups. Individualsfor whom we had only information on childhoodpsychiatric disorders were less likely to have parentswho were teenagers at subject’s birth (7.0% vs. 20.3%,p ¼ .031), less likely to have ADHD (1.2% vs. 4.3%, p ¼.046), and more likely to have agoraphobia (3.5% vs..1%, p ¼ .004) than probands who participated beforeand after age 13 years.

Diagnostic assessment

Participants were interviewed with the Child andAdolescent Psychiatric Assessment (CAPA; Angold &Fisher, 1999; Angold et al., 1995). Parent and childwere interviewed separately by different interviewers,except at age 19, when only the ‘child’ was interviewed.We counted a symptom as present if it was reported byeither parent or the child or both, as is standard clinicalpractice. ADHD was an exception in that only theparent was interviewed about these symptoms. Thetime frame of the CAPA for determining the presence ofmost psychiatric disorders is the past 3 months (primaryperiod). Three months was chosen because of concernsabout the reliability ofmemory for longer periods (Angold& Costello, 2000). However, the date from which thesubject had suffered from a symptom that had been

present during the primary period was also recorded. Inthe case of a few rare and severe acts, such as fire-settingor assault, a lifetime frame of reference was used, asrequired by DSM-IV. Based on a test–retest reliabilitystudy (N ¼ 78) (Angold & Costello, 1995) two-weektest–retest reliability of CAPA diagnoses in children atages 10 through 18 years is comparable to that ofother highly structured child psychiatric interviews(Angold & Costello, 1995; Angold & Fisher, 1999)(Kappas: GAD – .79; OAD – .74; Depression – .82; CD –.55; Substance abuse/dependence–1.0). There were toofew cases of other diagnoses for kappas to be estimated.

Scoring programs for the CAPA, written in SASstatistical software (SAS Institute Inc, Cary, NC),combined information about the date of onset, duration,and intensity of each symptom to create diagnosesaccording to DSM-IV (American Psychiatric Association,1994).We also includedDSM-III-R overanxious disorder(OAD), because there has been no research on thecomparative predictive validity of these two, partiallyoverlapping, formulations of ‘generalized anxiety.’Reviews of the taxonomic properties of OAD concludedthat improvements in its diagnostic criteria were needed(Klein, Tancer, & Werry, 1997; Werry, 1991), butdiscarding OAD altogether in DSM-IV may have beenpremature, especially since the special childhoodcriteriafor GAD were not subjected to empirical testing prior totheir introduction into DSM-IV.

Interviews usually took place in the child’s home. Theparent gave signed informed consent for each interviewthrough age 16, and the child signed informed assentforms, except at age 19 when signed informed consentwas obtained only from the subject. The study wasapproved by the Duke institutional review board. Theparticipants were reimbursed for the time they spent onthe interview.

Interviewers

Interviewers were residents of the study area and had atleast bachelor’s-level degrees. They received 1 month oftraining, constant monitoring of quality control, and

Wave

Cohort Age 1, 1993 2, 1994 3, 1995 4, 1996 5, 1997 6, 1998 7, 1999 8, 2000 9, 2001 10, 2002 11, 2003

A 9 A1

10 A2

B 11 B1 A3

12 B2 A4

C 13 C1 B3

14 C2 B4 A5

15 C3 B5 A6

16 C4 B6 A7

17

18

19 C5 B7 A8

94.2 90.5 88.0 78.0 80.3 75.0 75.2 80.7 80.5 71.3

Figure 1 Design of the Great Smoky Mountains Study (GSMS)

1176 Antje Bittner et al.

� 2007 The AuthorsJournal compilation � 2007 Association for Child and Adolescent Mental Health.

instruction by Department of Social Services staff inNorth Carolina’s requirements for reporting abuse orneglect. All suspected cases were referred to theappropriate agency. After training, quality control wasmaintained through post-interview reviews of eachschedule, weekly staff meetings to review audiotapesof randomly selected field interviews, and regularrefresher sessions with study faculty.

Data analysis

We defined each psychiatric disorder as being present inchildhood if a child met diagnostic criteria for thatdisorder at one or more observations before age 13.Adolescent psychiatric disorderswere defined as presentif the childmet diagnostic criteria betweenage13and19.There were very few cases of panic disorder, panicattacks, specific phobias, or agoraphobia in childhood(see Table 2). We therefore focused our analyses on theoutcomes of SAD, OAD, GAD, and social phobia, forwhich sufficient cases were available.

The Stata Software package (StataCorp., 2003) wasused to compute robust variances, confidence inter-vals, and p-values (by applying the Huber–Whitesandwich matrix), as required when basing analyses onweighted data (Royall, 1986). Logistic regression mod-els were used to examine the associations betweenchildhood anxiety disorders and subsequent psychiat-ric disorders during adolescence. First, the associa-tions between specific childhood anxiety disorders andadolescent psychiatric disorders were estimated inseparate models (bivariate associations). Second, allfour anxiety disorders (SAD, OAD, GAD, and socialphobia) were jointly entered in one multiple logisticregression model. In the prediction of panic attacks,specific phobia, agoraphobia, and non-anxiety out-comes, we also adjusted our analyses for the earlieroccurrence (before age 13 years) of the relevant out-come. All associations were also tested for interactionwith sex of respondents.

Results

A) Frequency of psychiatric disorders in childhoodand adolescence

Table 1 shows the prevalence rates for anxiety dis-orders, depression, disruptive behavior disorders,and substance use disorders. More than 16% of theparticipants met criteria for any anxiety disorder atsome point of the study period. The prevalence ofspecific phobia, CD, and ODD remained relativelystable from childhood to adolescence. The rates ofmost other disorders increased from childhood toadolescence, except for SAD and ADHD whichdecreased. Whereas girls had higher rates of anxietydisorders and depression in adolescence (see alsoAngold et al., 1998), boys more often met diagnosticcriteria for disruptive behavior disorders at all ages.

Almost 30% of those with an anxiety disorder metdiagnostic criteria for an anxiety disorder on morethan one assessment during the study period. From61 cases with childhood SAD, 11 (18%) had SAD at

more than one assessment during childhood(repeated SAD). From 21 OAD cases, 6 (28.6%)had repeated childhood OAD. Repeated childhoodGAD was observed in 1 proband (4.3%). From 14individuals with childhood social phobia, 2 had re-peated social phobia (14.3%).

Concurrent comorbidity between childhood anxi-ety disorders was considerable. From 61 cases withchildhood SAD, 12 (20%) had at least one of the otherthree anxiety disorders (OAD, GAD, social phobia).In OAD, 7 cases (33%) had another anxiety disor-ders, and 6 cases (43%) with social phobia met cri-teria for another childhood anxiety disorder. Thehighest comorbidity was seen in GAD, where 11cases (48%) had at least one of the other anxietydisorders. Given these high comorbidity rates, weconducted adjusted analyses to examine which ofthe specific anxiety disorders had independent pre-dictive value. We jointly entered all four childhoodanxiety disorders (SAD, OAD, GAD, and social pho-bia) into each logistic regression model. These anal-yses adjust statistically for the associations amongdisorders.

B) Associations between childhood and adolescentdisorders

Table 2 shows the relations between childhood anxi-ety disorders and later psychiatric disorders. In termsof bivariate associations, childhood SAD was associ-ated with subsequent SAD. OAD in childhood wasrelated to OAD, panic attacks, depression, and CD inadolescence. GAD was significantly associated withsubsequent CD. Childhood social phobia predictedadolescent social phobia and ADHD. After includingall four anxiety disorders simultaneously, SADremained associatedwith SAD.OADwas still signific-antly associated with later OAD, panic attacks,depression and CD. GAD remained significantlyrelated to later CD. Social phobia remained related toadolescent social phobia. The association betweenchildhood social phobia and adolescent OAD reachedstatistical significance in the multiple logistic regres-sion model. The relation between social phobia andADHD lost statistical significance. In addition, wereran our analyses with SES as a covariate in alllogistic regression models. The patterns of associa-tions were almost identical (detailed results areavailable from the first author). To examine possiblerace differences all associations were tested forinteractionwith race of respondents (American Indianversus non-American Indian). We found only twosignificant race-by-predictor interactions. The asso-ciation between childhood separation anxiety disor-der andsubsequent overanxiousdisorder (ORAI ¼ 8.8[1.7–43.1]; ORnonAI ¼ 1.4 [.4–4.4]; ORinter ¼ 9.3 [1.3–64.2]) and the relation between childhood separationanxiety disorder and later conduct disorder (ORAI ¼5.1 [1.2–21.5]; ORnonAI ¼ .2 [.0–1.7]; ORinter ¼ 11.3[1.3–91.1] were significantly higher in American

Adolescents’ outcomes of childhood anxiety disorders 1177

� 2007 The AuthorsJournal compilation � 2007 Association for Child and Adolescent Mental Health.

Indians than in the rest of the study sample (detailedresults are available from the first author).

We initially defined panic attacks according toDSM-IV criteria (‘a discrete period of intense fear ordiscomfort, in which four or more symptoms devel-oped abruptly and reached a peak within 10 min-utes’) but ‘spontaneous’ panic attacks are ofoverriding importance to the diagnosis of panic dis-order. Accordingly, we reanalyzed the associationswith ‘spontaneous’ panic attacks. The associationsbetween SAD (OR ¼ 2.9 [.6–13.1]), GAD (OR ¼ .2[.0–2.9]), and social phobia (OR ¼ 6.2 [.5–75.9]) andspontaneous panic attacks did not change signific-antly. There was no significant association between

OAD and spontaneous panic attacks (OR ¼ 4.0 [.6–26.0]).

To examine possible gender differences, all asso-ciations were tested for interaction with sex ofrespondents. We found only one formally significantsex-by-predictor interaction. The association be-tween childhood generalized anxiety disorder andsubsequent substance use disorder was significantlyhigher in girls than in boys (OR ¼ .06 [.00–.52])(ORgirls ¼ 16.0 [3.1–82.7]; OR boys ¼ .4 [.0–3.3]).Statistical power for these interactions was limitedand the results for boys and girls actually appearedto be substantially different when separate analysesby sex were conducted. In girls, childhood SAD was

Table 1 Frequency of childhood and adolescent psychiatric disorders

Total (N ¼ 906) Girls (N ¼ 402) Boys (N ¼ 504)

Sex diff.N %w N %w N %w

Any anxiety disorder 154 16.07 87 20.29 67 11.99 G > B<13 years 79 6.57 40 8.17 39 5.01 NS‡13 years 92 10.57 56 13.6 36 7.64 NS

Separation anxiety disorder 68 4.9 37 5.6 31 4.2 NS<13 years 61 4.6 33 5.3 28 3.9 NS‡13 yearsa 10 .4 4 .3 6 .5 NS

Overanxious disorder 56 6.6 33 8.9 23 4.4 NS<13 years 21 1.7 10 2.4 11 1.0 NS‡13 years 41 5.5 27 7.6 14 3.5 NS

Generalized anxiety disorder 55 5.8 33 6.6 22 5.0 NS<13 years 23 1.8 10 .9 13 2.7 NS‡13 years 32 4.0 23 5.7 9 2.3 NS

Panic attacks 35 3.1 24 4.7 11 1.7 NS<13 years 5 .2 3 .2 2 .2 NS‡13 years 32 3.0 22 4.5 10 1.6 NS

Spontaneous panic attacks 17 1.5 11 1.7 6 1.3 NS<13 years 0 .0 0 .0 0 .0 -‡13 years 17 1.5 11 1.7 6 1.3 NS

Specific phobia 12 .6 7 .7 5 .4 NS<13 years 7 .4 5 .5 2 .2 NS‡13 years 5 .2 2 .2 3 .2 NS

Social phobia 25 1.5 13 2.1 12 1.0 NS<13 years 14 .6 7 .6 7 .6 NS‡13 years 13 1.0 6 1.4 7 .6 NS

Agoraphobia 16 2.5 7 2.8 9 2.2 NS<13 years 3 .1 0 .0 3 .2 –‡13 years 13 2.4 7 2.8 6 2.0 NS

Any depression 122 10.6 63 13.2 59 8.1 NS<13 years 45 2.7 19 2.3 26 3.1 NS‡13 years 88 8.7 51 12.1 37 5.3 G > B

Conduct disorder 131 9.1 29 4.0 102 14.1 B > G<13 years 92 5.5 20 1.8 72 9.2 B > G‡13 years 61 5.3 16 2.8 45 7.7 B > G

Oppositional defiant disorder 222 15.7 76 11.7 146 19.6 B > G<13 years 159 9.6 56 6.9 103 12.2 B > G‡13 years 111 8.7 39 7.4 72 10.0 NS

Attention-deficit/hyperactivity disorderb 70 4.9 15 1.5 55 8.1 B > G<13 yearsb 57 4.3 14 1.4 43 7.1 B > G‡13 yearsc 24 1.1 3 .3 21 1.9 B > G

Substance use disorder 112 12.2 38 9.7 74 14.5 NS<13 years 1 .1 0 .0 1 .1 –‡13 years 112 12.2 38 9.7 74 14.5 NS

Notes: %w ¼ weighted %; NS ¼ not significant; G ¼ girls; B ¼ boys.atotal N ¼ 880; girls N ¼ 390; boys N ¼ 490.btotal N ¼ 905; girls N ¼ 402; boys N ¼ 503.ctotal N ¼ 841; girls N ¼ 376; boys N ¼ 465.

1178 Antje Bittner et al.

� 2007 The AuthorsJournal compilation � 2007 Association for Child and Adolescent Mental Health.

Table

2Associationsbetw

eenchildhoodanxiety

disord

ers

andadolescentpsychiatric

disord

erin

girls

andboys

Adolescent

disord

ers

Childhoodanxiety

disord

ers

SAD

OAD

GAD

SoPHO

unadj.model

adj.model

unadj.model

adj.model

unadj.model

adj.model

unadj.model

adj.model

OR

95%

CI

OR

95%

CI

OR

95%

CI

OR

95%

CI

OR

95%

CI

OR

95%

CI

OR

95%

CI

OR

95%

CI

SAD

6.3*(1.2–3

0.9)

6.2*(1.02–3

7.9)

##

2.7

(.2–2

4.5)

.7(.0–1

7.5)

8.7

(1.0–7

6.5)

7.0

(.6—81.0)

OAD

1.5

(.5–4

.2)

1.6

(.5–4

.5)

9.8**

(1.9–4

9.5)

9.9**

(1.8–5

3.2)

.5(.0–4

.0)

.2(.0–1

.1)

3.9

(.9–1

6.9)

3.6*(1.1–1

1.3)

GAD

1.0

(.3–3

.6)

1.0

(.3–3

.3)

2.4

(.5–1

0.9)

2.3

(.5–9

.4)

##

2.9

(.5–1

6.6)

2.5

(.5–1

2.0)

PA

1.8

(.5–5

.9)

1.8

(.5–6

.6)

14.1**

(2.2–9

0.1)

14.1**

(1.9–1

00.2)

.6(.1–3

.3)

.2(.0–1

.7)

4.1

(.7–2

4.4)

3.1

(.2–3

7.4)

SpPHO

6.8

(.7–6

5.3)

6.8

(.7–6

5.3)

##

##

##

SoPHO

1.6

(.2–1

0.9)

1.4

(.2–9

.7)

##

##

13.8**

(1.9–9

6.8)

13.3**

(1.9–9

1.9)

AgPHO

1.1

(.2–5

.2)

1.1

(.2–5

.0)

1.3

(.1–1

2.5)

1.3

(.1–1

1.7)

##

##

DEP

2.5

(.8–7

.7)

2.6

(.8–8

.4)

6.7*(1.4–3

0.8)

6.4*(1.3–3

0.9)

1.2

(.3–4

.6)

.6(.1–3

.0)

2.9

(.7–1

0.7)

2.2

(.5–8

.1)

CD

.6(.1–2

.1)

.4(.0–1

.7)

7.6*(1.2–4

4.9)

7.5*(1.1–4

9.3)

3.6*(1.02–1

2.8)

4.3*(1.1–1

6.7)

1.5

(.1–1

2.5)

.5(.0–9

.1)

ODD

1.2

(.5–3

.0)

1.3

(.5–3

.3)

.8(.1–3

.6)

.8(.1–3

.5)

.6(.1–3

.0)

.5(.0–2

.5)

2.1

(.4–9

.8)

2.4

(.5–1

1.7)

ADHD

2.9

(.7–1

1.6)

2.7

(.6–1

1.3)

##

##

9.6*(1.1–7

8.4)

8.6

(.9–7

8.3)

SUD

2.0

(.6–6

.3)

1.8

(.5–6

.4)

3.9

(.8–1

8.7)

3.6

(.7–1

8.5)

2.1

(.6–7

.1)

1.5

(.3–6

.0)

1.6

(.4–6

.7)

1.1

(.2–4

.3)

Notes:OR¼

oddsra

tio;95%

CI¼

95%

confidenceinterval.

unadj.¼

unadjustedanalyses(bivariate

associations).

adj.¼

adjustedanalyses(m

ultiple

model,controlledforoth

erchildhoodanxiety

comorb

idityaswellasoccurrenceofoutcomebefore

age13years).

#empty

cells,i.e.th

ere

wasnoindividualwhohadth

erelevantdisord

erin

both

childhoodandadolescence.

*p<.05,**p<.01,***p

<.001.

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associated with adolescent specific phobia (OR ¼20.5 [1.1–349.9]). OAD was related to later OAD(OR ¼ 10.1 [1.1–85.6)], panic attacks (OR ¼ 15.4[1.4–161.7]), and conduct disorder (OR ¼ 25.8 [1.7–379.7]). GAD predicted later SAD (OR ¼ 19.5 [1.7–219.8]) and SUD (OR ¼ 16.0 [3.1–82.7]). In boys,homotypic continuity was seen for SAD (OR ¼ 14.4[2.2–93.2]) and social phobia (OR ¼ 73.0 [9.7–549.6]. Childhood OAD was associated with adoles-cent depression (OR ¼ 7.2 [1.7–30.1]), and socialphobia predicted later SAD (OR ¼ 14.1 [2.1–93.8]),panic attacks (OR ¼ 16.7 [1.3–213.6]), and ADHD(OR ¼ 19.5 [1.9–191.4]).

Discussion

The aim of the study was to examine the associationbetween individual anxiety disorders in childhoodand later psychiatric disorders in adolescence. Weextended our own and others’ work in this area(Costello et al., 2003) by investigating homotypic andheterotypic continuity of specific anxiety disorders.Childhood anxiety disorders predicted a variety ofsubsequent disorders, including both anxiety andother disorders.

Childhood SAD predicted adolescent SAD. As hasbeen the case in previous community-based longitudinal studies (Hayward et al., 2000; Pine et al.,1998), we did not find an association betweenchildhood SAD and subsequent panic attacks

(whether spontaneous or not). Even the unadjustedbivariate ORs for this putative association were verysmall. In our study, OAD predicted later panicattacks in general (although none of the childhooddisorder associations with spontaneous panicattacks reached statistical significance). It shouldbe noted that there were too few subjects withpanic disorder for predictive analyses to be run.Thus, our results on the association between SADand panic are rather preliminary. Future prospective community studies should further examine ifSAD is a specific risk factor for subsequent panicdisorder as suggested by Gittelman and Klein(1984).

Beside DSM-IV GAD we also included DSM-III-ROAD in our analyses, because there has been noresearch on the comparative predictive validity ofthese two, partially overlapping, formulations of‘generalized anxiety.’ We found different associationsfor the two disorders, and it was notable that OADwas, on the whole, a better predictor of later anxietydisorders than was GAD. Whereas childhood OADwas associated with later OAD, panic attacks (ofwhich it was the sole predictor in both sexes),depression, and CD, GAD was related only to ado-lescent CD. The finding that OAD predicted variouspsychiatric disorders is partially in line with previousresults from Pine and his colleagues (Pine et al.,1998). They found somewhat different associations

from ours (OAD was related to later major depres-sion, social phobia, and generalized anxiety). How-ever, their results combined prediction fromchildhood/adolescence (substantially the latter) toadulthood, and it is perfectly possible that predictivepatterns are different across these three develop-mental stages.

Our data also provide the first longitudinalevidence that we are aware of that the deletion ofOAD from DSM-IV, and the substitution of specialchildhood and adolescent rules for GAD, is likely tolead to underestimation of the impact of childhoodanxiety disorders in studies using DSM-IV criteria.In fact, only 14% of children with OAD also metdiagnostic criteria for childhood GAD in our sampleand we did not find a relation between childhoodOAD and adolescent GAD or vice versa. It is thereforequestionable whether the DSM-IV category of GADreally includes the majority of children with sig-nificant generalized anxiety symptoms (see alsoCostello et al., 2004). Longitudinal studies of clinicalsamples could be informative on this question.

Childhood social phobia also was a strong pre-dictor of subsequent psychopathology. Social phobiawas associated with adolescent OAD, social phobia,and ADHD. Whereas the association between socialphobia and subsequent anxiety disorders is a well-known phenomenon (Pine et al., 1998), to ourknowledge there are no previous findings revealingan association between social phobia and ADHD.One longitudinal study found an associationbetween SAD and ADHD (Foley et al., 2004). Find-ings from the Dunedin study also suggest an asso-ciation between internalizing disorders in childhoodand adolescent externalizing disorders (McGee et al.,1992). On the other hand, Pine and colleagues foundthat higher levels of social phobia symptoms atten-uated the continuity of CD symptoms over time(Pine, Cohen, Cohen, & Brook, 2000), a finding thatis in line with the non-significant adjusted OR of .5for the relationship between social phobia and CD inthis study.

Results of previous studies with adolescent andadult samples suggest that anxiety disorders arestrong predictors of subsequent depression (Bittneret al., 2004; Stein et al., 2001; Woodward & Fer-gusson, 2001). Examining the outcomes of child-hood anxiety disorders we found associationsbetween OAD and adolescent depression which isconsistent with previous studies of childhood anxi-ety disorders (Pine et al., 1998), but neither child-hood SAD nor social phobia were related tosubsequent depression. These results are in linewith findings from the New York Child LongitudinalStudy (Pine et al., 1998), and suggest that moreattention needs to be paid to the specificity of asso-ciations between comorbid childhood anxiety dis-orders and depression, because not all types ofchildhood anxiety are strongly associated withdepression. In contrast, Foley et al. (2004) found

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that persistent SAD was associated with a highersubsequent risk of depression. An explanation forthese different findings could be that Foley et al.(2004) used a sample with a fairly broad age range(age 8–17 years), and did not control for the presenceof comorbid disorders. Neither did they examineseparate associations for different age groups. Wemight suppose, therefore, that they were dealingwith prediction from a mixture of childhood andadolescent anxiety disorders. In Beesdo et al.’s(2007) recent work, which found a strong associationbetween ‘social anxiety’ and later depression, par-ticipants were aged 14–24 at their first interviews,and the study relied upon lifetime (or since the lastinterview) retrospective interviews for onset timing(Beesdo et al., 2007). That study was, therefore,largely dealing with a mixture of adolescent andadult onset disorders (as the cumulative incidencecurves presented there clearly demonstrate). As wehave already noted, it is possible that childhood andadolescent anxiety disorders are different conditionswith different course and outcomes. It is also poss-ible that depression and anxiety might cross-predictwithin childhood and/or adolescence, but not pre-dict from childhood to adolescence. The same can besaid of our previous study from the GSMS (Costelloet al., 2003). Our analyses there ‘averaged’ across allpossible transitions, with no regard for any particu-lar question of developmental timing. That suggestsa new question for further analysis: When indevelopment does GAD predict depression?

Conclusions from these results should be drawn inlight of the strengths and limitations of the study.The major strengths are the prospective-longitudinaldesign and the community-based sample. Mostprevious findings regarding the course of childhoodanxiety disorders come from studies using clinicalsamples and have, therefore, been subject to help-seeking biases (Cohen & Cohen, 1984). Many anxietydisorders have their onsets in early to late childhood.An important strength of our work is that we exam-ined childhood anxiety disorders and followed thesechildren up to adolescence. However, some limita-tions should also be considered. First, the GSMSsample comes from a small and predominantly ruralarea of the southeastern United States, and thereforemight not represent the whole American population.The observed poverty rate in our study differs fromthe annual poverty rate for the US which is around12–13%. The average cross-sectional poverty rate(i.e., the probability of being in poverty at eachobservation) was 19.5% (weighted estimate; 29.3% ofthe observed sample); 33.7% (weighted; 46.0% of theobserved sample) fell below poverty criteria on atleast one assessment during the study period. Sec-ond, probands were 9 to 13 years at study intakeand it might be that we have missed cases withanxiety disorders (perhaps especially SAD) thatoccurred before the age of 9 years and remittedbefore study intake. Third, subjects were 19 at

follow-up and, therefore, had not completely passedthrough the age of risk for developing some of theoutcomes we investigated in our study. This concernmight apply especially to panic attacks. Fourth, theCAPA assesses only the 3-month period precedingthe interview and can be expected have underes-timated the total occurrence of psychiatric disordersin the time between any two waves. Fifth, althoughwe found some evidence of selective attrition, indi-viduals who only participated before age 13 yearswere less likely to have ADHD, and had more likely tohave agoraphobia than probands who participatedbefore and after age 13 years. This might have led tosome bias in our results, but such effects cannot beexpected to have been very large. Finally, despite afairly large overall sample size, the statistical powerfor interaction (e.g., by sex or race) analyses waslimited by small cell sizes. The large confidenceintervals in some of the associations are an indica-tion of a high level of uncertainty about the truevalue of the OR. However, inspection of the ORssuggests that there were very substantial differencesamong the outcomes of different anxiety disorders,and that these outcome patterns were gender-dif-ferentiated. It also indicates that the lack of associ-ation between SAD and panic attacks was not simplythe result of its being too easy to accept the nullhypothesis in the face of large, but still non-signi-ficant ORs. The ORs were small.

In conclusion, anxiety disorders in childhood–especially OAD and social phobia–were strongpredictors of psychiatric disorders in adolescence,but GAD was not. Insofar as GAD was predictive, itfailed to identify children at risk for continuinganxiety, but rather identified a group of children atrisk for CD. This suggests that the DSM-IV’s ap-proach to the diagnosis of GAD (and its exclusion ofOAD) may need to be rethought for subsequentrevisions.

Acknowledgements

This study was supported by grants DA11301 andMH57761 and Independent Scientist AwardMH01167 from the National Institutes of Health,Bethesda, MD, and faculty Scholar Awards from theWilliam T. Grant Foundation, New York (Drs CostelloandAngold).DrBittner’sworkwassupportedbygrantWI 709/7-1 from the German Research Foundation(Deutsche Forschungsgemeinschaft, DFG).

Correspondence to

Antje Bittner, Department of Psychotherapy andPsychosomatics, Universitatsklinikum Carl GustavCarus, Technische Universitat Dresden, Fetscherstr.74, D-01307 Dresden Germany; Tel: +49 3514583295; Fax: +49 351 4585713; Email: antje.bitt-ner@uniklinikum-dresden.de

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Manuscript accepted 22 May 2007

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