Lifetime comorbidity among anxiety disorders and between anxiety disorders and other mental disorders in adolescents

Journal of Anxiety

Disorders, VoI. 11, No. 4, pp. 377-394, 1997 Copyright 0 1997 Elsevier Science Ltd Printed in the USA. AII rights reserved 0887-6185/97 $17.00 + .OO

Pergamon

PII SO887-6185(97)00017-O

lifetime Comorbidity Among Anxiety Disorders and Between Anxiety Disorders and Other Mental Disorders in Adolescents M.

PETER

Oregon

LEWINSOHN, Research

RICHARD

JOHN Oregon

MARK Tualatin

PH.D.

of Oregon

R.

SEELEY,

Research

Valley Mental

Health

H.

M.S.

Institute

LEWINSOHN,

WILLIAM Oregon

Institute

ZINBARG,

University

PH.D.

PH.D. Health

SACK,

Sciences

Center

M.D. University

Abstract -

We examine the lifetime comorbidity among anxiety disorders, and between anxiety disorders and other mental disorders, in a large (n = 1,507) community sample of high school students on whom extensive diagnostic data were available. Three diagnostic groups were formed: those with a lifetime anxiety disorder (n = 134); those with a nonanxiety disorder (n = 510); and those who had never met criteria for a mental disorder (n = 863). The intra-anxiety comorbidity rate was relatively low (l&7%), and

This research is supported in part by NIMH grants MH40501 Requests for reprints should be sent to Peter M. Lewinsohn, 1715 Franklin Boulevard, Eugene, OR 97403-1983. 0 1997 Elsevier Science Ltd. All rights reserved. 377

and MH50522. Ph.D., Oregon

Research

Institute,

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was strongly associated with being female (92%). The lifetime comorbidity anxiety and other mental disorders (primarily MDD) was substantial (73.1%) not associated with being female. 0 1997 Elsevier Science Ltd

between and was

INTRODUCTION Comorbidity or the co-occurrence of mental disorders in adolescents is common in clinic and community samples(Biederman, Newcom, & Sprich, 1991; Brady & Kendall, 1992; Bukstein, Glancy, & Kaminer, 1992; Caron & Rutter, 1991; Feehan, McGee, & Williams, 1993; Lewinsohn, Hops, Roberts, Seeley, & Andrews, 1993). Indeed, the degree of comorbidity appearsto be higher in adolescencethan in adults (Rohde, Lewinsohn, & Seeley, 1991). Knowledge about comorbidity is recognized as important in the classification and etiology of mental disorders (e.g., Caron & Rutter, 1991; Maser & Cloninger, 1990). For example, if one disorder regularly precedesanother, the first disorder may be a risk factor or precipitant for the second;if two disorders are highly comorbid they may be manifestations of the samedisorder; if two disordersare not comorbid at all they are clearly separatedisorders. While there has been increasing interest in the occurrence of anxiety disordersduring childhood and adolescence(Angold & Costello, 1995; Bernstein & Borchard, 1991; Gittelman, 1986; Klein & Last, 1989; Last, 1993; March, 1995; Tuma & Maser, 1985) the extent of comorbidity of anxiety disordershas received only limited attention. With important exceptions (e.g., Cohen et al., 1993, Fleming, Boyle, & Offord, 1993; Gittelman, 1986; Kashani & Orvashel, 1988; Kessler et al., 1996; Regier, Burke, & Burke, 1990; for a review see Curry & Murphy, 1995)researchstudieson children and adults have focused on the clinical characteristicsof patients with “pure” disorders.Consequently, we know very little about the degreeto which anxiety disordersare comorbid with each other and with other mental disorders. An important limitation of the existing literature is that previous studieshave generally restricted their focus on comorbidity between two or relatively small subsetsof anxiety disorders, failing to examine the pattern of comorbidity within a wider array of anxiety disorders.An additional limitation is that patient samplesare known to have disproportionately high rates of comorbidity (Caron & Rutter, 1991) - a phenomenonthat has been labeled “Berkson’s fallacy” (Berkson, 1946) - and much of the available research is based on patient samples(e.g., Biederman et al., 1991; Fawcett & Kravits, 1983; Garvey & Cook, 1989; Grunhaus, 1988; Last et al., 1987; Lesser et al., 1988; Moreau, Wiessman, & Warner, 1989; Noyes et al., 1986; Prusoff & Klerman, 1974; Strauss,Last, Hersen, & Kazdin, 1988). This paper is one of a seriesreporting results from the Oregon Adolescent DepressionProject (OADP) a longitudinal investigation of the epidemiology of psychiatric disordersin a large, community-based cohort of high school students (e.g., Lewinsohn et al., 1993, 1994). In a previous publication from the

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OADP data set, we have reported the prevalence (point and lifetime), incidence, and comorbidity of anxiety disorder with other mental disorders(Lewinsohn et al., 1993). In another publication (Lewinsohn, Rohde, & Seeley, 1995) we reported that those with a lifetime history of an anxiety disorder that is comorbid with major depressivedisorder (MDD) in particular, were more likely to have received treatment, to show evidence of academic problems, and to have madea suicideattempt comparedto noncomorbid anxiety cases.Recently, we examined gender differences in anxiety finding a female preponderanceof anxiety disordersand anxiety symptoms among current and recovered anxiety disorder cases(Lewinsohn, Gotlib, Lewinsohn, Seeley, & Allen, 1997). In this paper we present descriptive information about the degreeof comorbidity among certain (panic, social phobia, simple phobia, obsessivecompulsive, separation anxiety, and overanxious) anxiety disorders (intraanxiety comorbidity) and between these specific anxiety disorders and other mental disorders (extra-anxiety comorbidity) in a sample of high school students. Comorbidity can be defined as two or more disorders that are present during the sameperiod of time (concurrent comorbidity) or that are present,but not necessarilyoverlapping, during one’s life (lifetime comorbidity). Given the low prevalence rates of many of the disordersto be examined, we will focus exclusively on lifetime comorbidity. The available evidence from adult outpatients suggeststhe existence of substantial it&a-anxiety comorbidity at both the feature level (Zinbarg & Barlow, 1996) and the syndromal level (e.g., Barlow, Di Nardo, Vermilyea, Vermilyea, & Blanchard, 1986; De Ruiter, Rijken, Garssen, van Schaik, & Kraaimaat, 1989). Consequently, our expectation was that the lifetime comorbidity between specific anxiety disorders would be considerable. Based on considerations of similarity, as well as comorbidity, between anxiety and depression(Coryell, 1988; DiNardo & Barlow, 1990; Rachman & Hodgson, 1980; Regier et al., 1990; Watson & Clark, 1991; Weissman et al., 1984; Weissman & Merikangas, 1986), we expected a particularly high level of comorbidity between the specific anxiety disorders and depression.We were also interested in examining the lifetime comorbidity between specific anxiety disorders and externalizing disorders, such as substanceuse and disruptive behavior disorders. Finally, we were interested in the degree to which gender moderatesthe above-mentioned associations.Anxiety disorders are much more frequent in females(e.g., Lewinsohn et al., 1997; Weissman,1985) and there is evidence to suggest that comorbidity involving anxiety disorders may be moderated by gender (Ochoa, Beck, & Steer, 1992; Last et al., 1987). Consequently, gender was included as a factor in all of the analysesreported below.

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METHOD Subjects and Procedure

Participants were selectedin three cohorts from nine senior high schools (approximately 10,200 students) representative of urban and rural districts in western Oregon. Sampling fractions of lo%, l&5%, and 20% were used for each cohort; sampling within each school was proportional to the size of the school, size of the grade within the school, and the proportion of males and femaleswithin the grade (9th-12th). A total of 1,709 adolescentscompleted the initial (Tl) assessments (interview and questionnaires)between 1987and 1989, with an overall participation rate of 61% among those who were originally contacted. At the secondassessment(T2), 1,507 participants (88.1% of the Tl sample) returned for re-administration of the interview and questionnaires(M Tl - T2 interval = 13.8 months, SD = 2.3). Several checks on the representativenessof the samplewere made.First, we comparedthe demographic characteristicsof the samplewith the 1980 census and found no differences on gender, ethnic status, or parental education level. Not surprisingly, our samplehad significantly more children under 18 years of agein the home and a slightly higher proportion of two-parent families. Second, we compared our participants with those who declined on demographic information obtained from decliners by telephone. Differences were minimal. Families were similar on gender of head of household,family size, and number of parents in the household.Although the decliners’ mean socioeconomic status (SES; Hollingshead, 1975) was significantly lower than that of the participants, F( 1, 2023) = 97.0, p -=c.OOl, both representedthe middle class. Significant effects were found for grade and gender; 12th graders (67%) were more likely to participate than 9th graders (59%), x*(3, N = 2,571) = 10.5, p < .05, and female students (68%) were more likely to participate than male students (60%), x2(1, N = 2,575) = 17.3, p < .OOl. As an additional check on the representativenessof the sample,we assessed 100 subjects who refused initially but respondedto a $100 inducement. This sample did not differ on type or number of current and lifetime clinical diagnoses,number or extent of clinical symptoms, race, current employment status of parents, and questionnaire variables. However, compared with 100 randomly-selectedparticipants, decliners were lesslikely to be from two-parent families (66% vs. 74%), x*(1, N = 200) = 6.86, p < .05; their parentshad less education, F(1, 175) = 6.5, p < .05; and they reported a lower grade-point average (2.9 vs. 3.1), F( 1, 189) = 4.6, p -=c.05. All of theseanalysessuggested that, with minor exceptions, the studentsin our samplewere representative of high school studentsin western Oregon. To evaluate the degree to which the Tl-T2 panel (n = 1,507) might have becomebiased,we comparedthosewho did not participate at T2 (n = 202) with the panel subjectson critical Tl variables. There were small but statistically

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significant differences. The T2 participants were slightly higher on parental SES, F(1, 1431) = 11.6,p < .OOl; number in household,F(1, 1683) = 4.0, p < .05; proportion of female students(54% vs. 40%), x*(1, N = 1,709) = 13.2, p < .OOl; and parental educational level, F(1, 1544) = 14.1, p < .OOl. However, the two groups did not differ on measuresof psychopathology (e.g., number of suicide attempts, number of episodesof current and past disorders including depression),the self-report depressionmeasures,race, or grade level. Significantly higher attrition rates were noted, however, for subjectswho had a history of disruptive behavior disorders(16.8% vs. 10.8%): x2( 1, N = 1,709) = 30.7, p < .OOl. Also, male students with a history of substanceuse disorders had a significantly higher attrition rate (26.1% vs. 13.7%), x*(1, N = 819) = 7.7,~ < .Ol. Attrition was not significantly associatedwith current or lifetime history of anxiety disorder or with the current number of anxiety symptoms at Tl. Approximately half of the Tl-T2 panel samplewas female (53.7%),with an average Tl age of 16.6 (SD = 1.2, range = 14-19). A total of 8.9% were nonwhite; 71.3% were living with two parents and 53% were living with two biological parents; 12.3% had repeated a grade in school. Parental education level (maximum value for mother or father) was as follows: 1.9% did not complete high school, 16.1% completed high school, 35.1% had a partial college education, and 46.9% had an academicor professionaldegree. Diagnostic Interview Adolescents were interviewed at Tl with a version of the Schedule for Affective Disordersand Schizophrenia for School-Age Children (K-SADS) that combined features of the Epidemiologic version (K-SADS-E; Orvaschel et al., 1982) and the PresentEpisode version (K-SADS-P), which included additional items (generated in consultation with the late Dr. Puig-Antich) to derive diagnosesof most disorders as per DSM-III-R criteria (American Psychiatric Association, 1987). At T2, subjectswere diagnostically interviewed using the Longitudinal Interval Follow-up Evaluation (LIFE; Keller et al., 1987), which provides detailed information about the course of psychiatric symptoms and disorderssincethe initial K-SADS interview, with rigorous criteria for recovery from a disorder (i.e., symptom-free for 8 or more weeks). Interviewers (who had accessto the Tl diagnostic information) elicited information and rated the presenceand severity of depressionsymptoms and other psychiatric disorders since Tl using the K-SADS format. Therefore, lifetime diagnostic information was available regarding the occurrence and duration of all disordersprior to and at T2. Diagnostic interviewers were carefully trained and supervised; most had advanced degrees in clinical or counseling psychology or social work and completed a 70-hr didactic and experiential course in diagnostic interviewing. For reliability purposes,all interviews were either audio- or videotaped and a secondinterviewer reviewed the recordings of 12% of the interviews. Interrater

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reliability was evaluated by the kappa statistic (Cohen, 1960) for the anxiety disorders for which five or more subjects in the reliability sample met criteria per the original interviewer’s diagnosis. Thus, kappas for the current anxiety disorders were computed for social phobia (K = 57) and simple phobia (K = 56); kappas based on lifetime history of anxiety disorders at Tl were computed for social phobia (K = .56), simple phobia (K = .65), separation anxiety (K = .76), and overanxious (K = .59). The current and lifetime kappas for a diagnosis of any anxiety disorder were .60 and .53, respectively. These reliabilities are roughly comparable in magnitude to those that have been reported for adult patients by Barlow (1987) for current episodes of simple phobia (K = .56) and to those reported for child patients by Silverman (1993) for current episodes of overanxious (K = .54) and simple phobia (K = .64), and lower than that reported by Barlow (1987) for adult patients for current episodes of social phobia (K = .91). All of the kappas for the other disorders were equal to or greater than .80, with the exception of lifetime dysthymia (K = .58), lifetime eating disorders (K = .66), and current and lifetime bipolar disorder (KS = .50 and .49, respectively). Because of the low frequency of disorders at T2, kappas were computed across all disorders. Kappas for the presence of any disorder versus no disorder at T2 and for the occurrence of any disorder between Tl-T2 were .87 and .72, respectively.

Diagnostic

Groups

Because relatively few subjects were in a current episode of psychopathology at the time of the Tl (9.6%) or T2 (7.8%) assessments (Lewinsohn et al., 1993), lifetime diagnoses, per DSM-HZ-R criteria, based on the Tl-T2 panel sample were used in the present study. Three diagnostic groups were formed for the purposes of this study: an Anxiety Disorder group (AD), a Nonanxiety Disorder Psychiatric control group (NAD), and a No Disorder control group (ND). The AD group consisted of 134 participants who had a lifetime diagnosis of at least one anxiety disorder at T2, which included panic disorder (n = 16), social (n = 22) or simple (n = 32) phobia, obsessive-compulsive disorder (OCD) (n = 9), separation anxiety disorder (n = 65), and overanxious disorder (n = 18). As only one subject met criteria for agoraphobia without history of panic, this disorder was not examined. The NAD group consisted of 510 participants who did not have a history of anxiety disorder who had a lifetime diagnosis of nonanxiety disorder at T2, which included major depressive disorder (MDD) (n = 354), dysthymia (n = 45), bipolar (n = 15), attention-deficit hyperactivity disorder (ADHD) (n = 43), conduct disorder (n = 41), oppositional-defiant disorder (ODD) (n = 31), alcohol abuse/dependence (n = 94), drug abuse/ dependence (n = 123), and eating disorder (n = 20). The ND group consisted of 863 participants who never met criteria for any DSM-III-R Axis I disorder.

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DLSORDERS

TABLE 1 CHARACIERISIICS OF THE TIIREE DIAGNOSTIC GROUPS Group

Variable

ND (n = 863) NAD

Female (%) White (%) Live with two biological parents (%) Parent with bachelor’s degree (%) Age (hf. SD)

48.0, 92.1 59.2, 50.2, 17.6,(1.2)

(n = 510) AD (n = 134)

58.8, 89.8 46.9, 43.4.i.b 17.9,, (1.2)

71.6, 90.3 49.3,, 38.1, 17.SJ1.2)

Note. ND = Never Mentally Ill; NAD = Nonanxiety Disorder; AD = Anxiety and means with different subscripts differ significantly at p < .05. “*p < .Ol: ***p < ,001.

Disorder.

Test x2=34.13*** x2= 2.28 x2=20.44*** X2’ 9.59** F=11.37*** Proportions

Statistical Analyses The associations between the psychiatric disorders were examined using contingency tables and logistic regression analyses. The degree of comorbidity was tested using the odds ratio (OR), which compares the odds of having a particular disorder for those with and without the other disorder. An OR of 1.O indicates no association between the two disorders being compared; an OR of 2.0 indicates that a particular disorder occurs twice as often among those who have the other disorder than those who do not. Although numerous comparisons were made, which inflates the probability of making a Type I error, the confidence bounds for the ORs were set to 95% (p < .05) given the low prevalence rates of several disorders.

RESULTS LImographic

Characteristics

As can be seen in Table 1, the AD group had a significantly greater proportion of females than both the NAD and ND groups and a smaller proportion of parents who completed college than the ND group but did not significantly differ from the other two groups in regard to race, living with both biological parents, or age. Among those living in a single parent home, the groups did not significantly differ in the proportions living in a single parentmother versus single parent-father home. Comparisons between those with two or more anxiety disorders (n = 25) and those with only one anxiety disorder (n = 109) showed the multiple anxiety disorder group to have a smaller proportion of parents who completed college (17% vs. 43%), x*(1, N = 134) = 5.77, p < .05. The multiple anxiety disorder group also had a greater proportion of females (92% vs. 67%), x2(1, N = 134) = 6.27,1> < .05. Viewed another way, among those with at least one anxiety disorder over the lifetime, 24% (23/96)

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TABLE 2 LIFETIME COMORBIDITY BETWEEN DSM-III-R ANXIETY DISORDERS FOR THE FEMALE SAMPLE Paired Disorders Disorder Panic Panic Panic Panic Social Social Social Simple OCD W Panic Social Simple Simple OCD

A

phobia phobia phobia phobia

phobia phobia phobia

Disorder

B

Social phobia OCD Separation anxiety Overanxious Simple phobia OCD Overanxious Si Overanxious Overanxious Simple phobia SA OCD Overanxious SA

Comorbid WI 2 1 3 2 3 1 3 5 1 5 0 3 0 0 1

Percent of A with B

Percent of B with A

OR

16.7 8.3 25.0 16.7 15.8 5.3 15.8 21.7 33.3 10.2 0 15.8 0 0 33.3

10.5 33.3 6.1 12.5 13.0 33.3 18.8 10.2 6.3 31.3 0 6.1 0 0 2.0

9.2* 36.2* 5.4* 11.2* 7.2* 21.9* 11.2* 4.7* 26.4* 7.7 nc 0.90 nc nc 2.5

95% CI 1.945.2 3.1-429.1 1.4-20.8 2.2-55.9 1.9-26.8 1.9-252.8 2.943.3 1.7-13.2 2.3-307.2 2.6-23.3 .3-3.3

0.2-27.9

Note. OR = odds ratio;, CI = confidence interval; OCD = obsessive-compulsive disorder; SA = separation anxiety; nc = not calculable; panic n = 12, social phobia n = 19, simple phobia n = 23, OCD n = 3, SA n = 49; overanxious n = 16. *p < .05.

of the female cases compared to 5% (2/38) of the male cases also had at least one additional anxiety disorder. None of the demographic differences between p.articipants with only anxiety disorder(s) (n = 36) and those whose anxiety was comorbid with another mental disorder (n = 98) attained statistical significance. Irma-Anxiety

Cotwrbidity

Of the 134 subjects with a lifetime history of an anxiety disorder, 109 (81.3%) were diagnosed as having only one, 21 (15.7%) were diagnosed as having two, and four (3.0%) as having three anxiety disorders. Because only two male subjects were diagnosed with more than one anxiety disorder compared to 23 female subjects, comorbidity between anxiety disorders could only be examined for fern* subjects. As only seven of the anxiety cases had more than one current anxiety disorder at Tl, and none had more than one current anxiety disorder at T2, comorbidity was examined only in regard to lifetime diagnoses.. The average comorbidity between a given anxiety disorder and any other anxiety disorder for females was 40,2% ranging from 30.6% for Separation Anxiety (15149) to 66.7% (2/3) for OCD. Lifetime comorbidity between spe-

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cific pairs of anxiety disorders and the associated OR are presented in Table 2. Of the 15 possible pairwise combinations, 10 were significant. Only the associations between panic, OCD and overanxious disorder with simple phobia, and between social phobia and OCD with separation anxiety did not attain statistical significance. Extra-Anxiety

ComorbidiQ

The degree of lifetime comorbidity between specific anxiety disorders and other mental disorders was extensive with 70.1% of the anxiety cases having another mental disorder; conversely, 15.6% of the subjects with a nonanxiety disorder also had an anxiety disorder. Having an anxiety disorder was significantly associated with six of the nine other mental disorders. Only the disruptive behavior disorders (i.e., ADHD, Conduct, and ODD) showed nonsignificant associations with the anxiety disorders as an aggregate. With the sole exception of OCD (5 of the 9 had a nonanxiety disorder), all of the specific anxiety disorders showed statistically significant comorbidity with the aggregate of any nonanxiety disorder.’ Of the 54 nonaggregated (i.e., specific) pairwise combinations, 20 attained statistical significance. MDD was the most comorbid of the other mental disorders with 53.7% of the anxiety cases also having MDD. Conversely, MDD was significantly associated with all of the specific anxiety disorders except for OCD and three of the OCD female subjects had MDD for which the OR was not calculable. Alcohol abuse/dependence had the next highest degree of comorbidity; 11.9% of the anxiety cases also had alcohol abuse/dependence. Alcohol abuse/dependence was significantly associated with all of the specific anxiety disorders except panic and simple for which the n’s were very small (3 and 1, respectively). Significant gender interactions were found for five of the specific combinations. Given that the odds ratios for three of the 54 specific combinations and one of the 16 aggregate combinations (i.e., six combinations between the specific anxiety disorders and the aggregate of any nonanxiety disorder, nine between the specific nonanxiety disorders and the aggregate of any anxiety disorder, and one between the anxiety and nonanxiety aggregates) would be expected to have been significant by chance alone, it would appear that gender did not exert a strong influence on extra-anxiety comorbidity and these findings will not be discussed further. Because of the known high rate of comorbidity between all mental disorders, but especially between MDD and other mental disorders in adolescents (Lewinsohn et al., 1993) it was possible that some of the observed comorbid associations with anxiety disorders were secondary to the other comorbid associations ‘A table that summarizes the seventy 2 X 2 contingency tables for the pairwise comparisons between the anxiety disorders and the nonanxiety disorders can be obtained by writing the authors.

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between the nonanxiety disorders. For example, the comorbidity between separation anxiety and alcohol and drug abuse could have been due to comorbidity between depression and these disorders. Consequently, in addition to examining the association of the specific anxiety disorders with each of the other mental disorders individually (i.e., the univariate associations), multiple logistic regression (MLR) analyses were performed to examine the associations between each of the specific anxiety disorders and each of the other mental disorders while controlling for all the other mental disorders. Separate MLR analyses were conducted for each of the anxiety disorders and for the aggregate of any anxiety disorder. The results showed that when controlling for all other disorders and gender, MDD remained significant for all of the anxiety disorders with the exception of OCD, for which neither the main effect nor the interaction between MDD and gender attained statistical significance. The adjusted ORs remaining significant for MDD were 5.4 (95% CI = 1.7-17.1) with panic, 3.3 {95% CI = 1.3-8.1) with social phobia, 2.9 (95% CI = 1.3-6.1) with simple phobia, 3.6 (95% CI = 2.1-6.3) with separation anxiety, and 3.0 (95% CI = 1.1-8.8) with overanxious disorder. Other disorders with significant adjusted ORs were ADHD with simple phobia (OR = 4.2; 95% CI = 1.2-15.6), oppositional defiant disorder with OCD (OR = 7.1; 95% CI = 1.243.4), and alcohol abuse/dependence with overanxious disorder (OR = 5.5; 95% CI = 1.4-22.3) and, for male subjects only, bipolar disorder with separation anxiety (OR = 39.6; 95% CI = 4.7-330.6). Thus, of the 20 significant univariate pairwise combinations, nine remained significant in the MLR analyses and five of these were with MDD. The MLR analyses of having any anxiety disorder with each of the nonanxiety disorders indicated that when controlling for all other disorders, MDD (OR = 4.0; 95% CI = 2.7-5.8), dysthymia (OR = 2.7; 95% CI = 1.3-5.5) and bipolar disorder (OR = 5.0; 95% CI = 1.5-16.6) remained statistically significant. Temporal Order of Comorbid Disorders Because the number of cases with comorbid disorders was small on a pair-wise basis for many of the nonanxiety disorders, temporal order was examined statistically only for the comorbidity between the specific anxiety disorders and MDD. MDD was significantly more likely to follow simple phobia (13 of the 14 cases) [Z = 2.93, p < .OOl], and separation anxiety (32 of the 37 cases, with four indeterminate cases) [Z = 4.29, p < .OOl]. Although not attaining conventional levels of statistical significance, a similar trend for MDD to be more likely to follow the specific anxiety disorder also emerged for social phobia (8 of the 12 cases, with one indeterminate case) [Z = .87, p > .05], and Overanxious disorder (9 of the 11 cases, with one indeterminate case) [Z = 1.80, p > .05]. On the other hand, the results did not suggest a temporal pattern for MDD and Panic (MDD preceded panic disorder in 6 of the 11 cases, with two indeterminate cases).

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DISCUSSION Intra-Anxiety

Comorbidity

We found modest levels of comorbidity among the anxiety disorders; only 18.7% of cases with at least one anxiety disorder had more than one anxiety disorder: 24% in females and 5% in males. On the one hand, these results appear to provide strong justification for the recognition of several distinct anxiety disorder diagnoses in the DSM. On the other hand, our intra-anxiety comorbidity figures are markedly lower than the rates in nonreferred samples reported by Costello and Angold (1995) for adolescents, and Weissman, Myers, and Harding (1978) for adults, and should be interpreted with some caution. Although these discrepancies raise many questions, we believe that one can have considerable confidence in the finding that almost all of the cases of multiple anxiety disorder were female. This adds an important fact to our knowledge about the interaction between sex and psychopathology. It is already well known that among those with anxiety disorders there is a preponderance of females in adult (Weissman, 1985) and adolescent samples (Last & Strauss, 1989; Lewinsohn et al. 1993). The results of the present study suggest that in a nonreferred sample, having more than one anxiety disorder during childhood/ adolescence is an almost exclusively female phenomenon. Extra-Anxiety

Comorbidity

Compared to the modest degree of comorbidity among the anxiety disorders, the degree of comorbidity of the anxiety disorders with other psychiatric disorders in our sample was very high - 70.1% of those with an anxiety disorder also have a nonanxiety mental disorder. Our extra-anxiety comorbidity rate is comparable to the rate found by Last et al. (1987) in a child clinical sample and the rates reported by De Ruiter et al. (1989) and Sanderson, Di Nardo, Rappee, & Barlow (1990) in adult clinical samples (also see Brown & Barlow, 1992). To put this 70.1% extra-anxiety comorbidity rate in perspective, we have previously reported that 42.8% of those with depression in this sample have another mental disorder (Lewinsohn et al., 1993). The overall comorbidity rates for other disorders in this same sample were 60.0% for disruptive behavior disorders and 66.2% for substance use disorders. It appears that the rate of extra-anxiety comorbidity is similar to the overall comorbidity rates for disruptive behavior and substance use disorders, whereas the comorbidity rate for MDD was substantially lower. As expected, MDD is the most common comorbid diagnosis among those with an anxiety disorder diagnosis. It is interesting to note that, in fact, anxiety was more likely to be comorbid with depression than with another anxiety disorder. Taken together with the finding that the association between major depression and anxiety disorders remained significant when adjusting for the other disorders, this suggests a strong unique association between major de-

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pression and anxiety disorders. Given these findings, models of the relation between anxiety and depressive disorders, such as that of Roth (1992) and his colleagues (Gurney, Roth, Garside, Kerr, & Schapira, 1972; Roth & Barnes, 1981; Roth & Mountjoy, 1982) that emphasize the distinctness of these syndromes appear to be overly simplistic. Certainly the current findings disconfirm the suggestion by Roth and Mountjay (1982) that “the presence of an anxiety syndrome diminishes the likelihood that there is also a depressive syndrome, and vice versa” (p, 158). It is also important to note, however, that the degree of overlap between major depression and the anxiety disorders while greater than chance is far Iess than complete. The current results are therefore consistent with models of the relation between anxiety and depression, which suggests that there is both significant overlap and considerable differentiability between anxiety and depression, such as Clark and Watson’s (1991) tripartite model. Clark and Watson suggested that anxiety and depressive syndromes share a nonspecific component of generalized affective distress or negative affect. The other two factors in Clark and Watson’s model are: (a) anhedonia or diminished positive affect, a factor containing features specific to depression; and (b) physiological symptoms of hyperarousal, a factor specific to anxiety. Of course, the results reported here are silent with respect to the nature of the factor common to anxiety and depression or the nature of the specific factors that provide the basis for their discrimination. The finding that alcohol abuse/dependence had a significant association with the anxiety disorders, taken as an aggregate, is consistent with adult studies that have consistently shown elevated rates of alcoholism among individuals with anxiety disorders (Cloninger, Bohman, & Sigvardsson, 1981; Noyes et al., 1986; Reich & Chaudry, 1987; for a review see Winokur, 1988). According to Brown and Barlow (1992), the lifetime prevalence of clinically significant anxiety disorders among individuals with a diagnosis of alcoholism is between 25 and 45% (compared with 17% in our adolescent sample). We are not aware of any findings from the adult literature, however, that would lead one to expect this association to lose its significance when controlling for MDD as revealed by the MLR analyses. This pattern of findings suggests that comorbidity with MDD may mediate the elevated risk for alcoholism among individuals with anxiety disorders. The current findings also suggest that any comorbidities between the anxiety disorders, taken as an aggregate, on the one hand and ADHD, conduct disorder and ODD on the other hand are no greater than one would expect from the chance co-occurrence of independent disorders. That there does not appear to be a unique association between the anxiety and the externalizing disorders (as per the MLR) supports the distinction between internalizing and externalizing disorders (Quay & Werry, 1979). Regarding the comorbidity between specific anxiety disorders and other mental disorders, only four emerged as significant unique associations in the

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MLR that did not involve MDD (i.e., ADHD with simple phobia, ODD with OCD, alcohol abuse/dependence with overanxious disorder and, for male subjects, bipolar disorder with separation anxiety). Given that none of these specific pairwise associations had been predicted, and given that each of these combinations contained fewer than five comorbid cases, they must be regarded as tentative until they are replicated in an independent sample. Finally, in contrast to the results showing a strong association between gender and intra-anxiety comorbidity, there were few instances in which gender moderated extra-anxiety comorbidity relationships. Thus, the current results suggest that gender is more strongly associated with intra-anxiety comorbidity than extra-anxiety comorbidity. This pattern is particularly interesting in light of findings from the behavioral inhibition literature demonstrating sex differences in the direction of greater inhibition for girls (Bates, 1989) and preliminary evidence suggesting that behavioral inhibition is a risk factor for multiple anxiety disorders (Biederman, Rosenbaum, Chaloff, & Kagan, 1995). Taken together with our findings, this pattern of results suggests the following two hypotheses: (a) females’ substantially greater risk for the development of multiple anxiety disorders may be mediated by their higher levels of behavioral inhibition; and (b) behavioral inhibition may be specifically associated with intra-anxiety comorbidity. Temporal Pattern Just as we (Rohde et al., 1991) and others (Alloy, Kelly, Mineka, & Clements, 1990; Breslau, Schultz, & Peterson, 1995) have found previously, anxiety disorders typically precede MDD. The current results show that this happens almost all the time for simple phobia, separation anxiety, overanxious disorder, and social phobia but less so for panic and OCD. The modal temporal pattern suggests that in many cases the anxiety disorder may play a role in the chain of events leading to depression. Although some theories of the relation between anxiety and depression (Alloy et al., 1990) address the fact that the anxiety typically precedes depression, the modal temporal pattern is not addressed in other theoretical formulations, such as Clark and Watson’s (1991) tripartite model. It is possible that the etiology of depression that follows anxiety may be different from the etiology of depression that precedes anxiety or which occurs by itself. To our knowledge, no current theory of depression has raised this question. Limitations Finally, we note a number First, the fact that there were (especially OCD and bipolar confidence intervals. There

of limitations associated with the present study. very few subjects in some diagnostic categories disorder) resulted in odds ratios with very large were very few subjects meeting criteria for a

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diagnosis of agoraphobia without history of panic disorder, or schizophrenia, and this limits the generalizability of the findings. The dearth of subjects meeting criteria for agoraphobia without history of panic disorder is consistent with Kendler et al.‘s (1992) finding that agoraphobia has a later onset age than other phobic disorders and with the findings reviewed by Scupi (1994) indicating that agoraphobia without history of panic disorder is extremely rare even in adult samples. We relied exclusively on diagnostic information provided by the adolescent. This differs from the standard procedure for the K-SADS (Chambers et al., 1985), which calls for diagnostic information elicited from the adolescent to be combined with information from a parent (typically the mother) for a summary diagnosis; or to go with the “or” rule (i.e., the adolescent has the disorder if either self or parent indicate it). We felt justified relying exclusively on the information provided by the adolescent for several reasons. For one, recent findings indicate that the reliability of diagnostic information from the child increases with age, that the reliability of the parents’ report decreases sharply, and that the agreement between adolescent and parent declines with age, especially for internalizing disorder (e.g., Edelbrock, Costello, Dulcan, Kalas, & Conover, 1985; Kazdin, 1989). Studies suggesting that unique information is added by parents are typically based on younger children (ages 7-12), for problematic behaviors involving inattention and hyperactivity (e.g., Loeber, Green, Lahey, & Stouthamer-Loeber, 1990), and Kashani and Orvaschel(l990) and Weissman et al. (1987) have shown that diagnoses of anxiety and affective disturbances based on data from older children are more reliable than diagnoses based on reports from parents. In another publication based on the same data set (Cantwell, Lewinsohn, Rohde, & Seeley, 1997 ), we reported on findings for the first 281 subjects who were entered into the study for whom diagnostic information was also obtained from the mother and from the adolescent. The analyses showed that the adolescents reported themselves as experiencing a greater number of cases of anxiety disorder than did their mothers. We estimate that if we had obtained diagnostic information from all mothers, we would have identified an additional 15% cases with the “or” rule. Put another way, with adolescent self-report, we detected 85% of the anxiety disorder cases. As a related point, we should note that, although we only had modest reliability for the diagnostic interviews, our kappas are comparable to those obtained in other community studies (e.g., Cohen et al., 1993). Another noteworthy limitation is that most of the disorders that were examined were based on retrospective information and relied on the adolescent’s memory. Fendrich, Weissman, & Mufson (1990) have reported relatively poor recall for anxiety disorders that occurred 2 years earlier. It is also important to note that our study did not specifically address the degree of concurrent comorbidity between specific anxiety disorders and between the latter and other mental disorders.

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