J Psychopathol Behav Assess (2009) 31:168177 DOI 10.

1007/s10862-008-9109-x

Associations Among Anxiety Disorders and Non-anxiety Disorders, Functional Impairment and Medication in Children and Adolescents
Lourdes Ezpeleta & Josep Toro

Published online: 14 November 2008 # Springer Science + Business Media, LLC 2008

Abstract This is a study of comorbid anxiety disorders and how they affect the clinical picture of comorbid cases. The sample consisted of 576 Spanish children aged 8 to 17 years receiving psychiatric outpatient consultation that were evaluated using a semi-structured diagnostic interview for both parents and children. A specific association of homotypic comorbidity among anxiety disorders that was independent of the presence of other disorders was found. There was heterotypic comorbidity between anxiety and depressive disorders, ADHD, anorexia and tic disorders. Relationships between non-anxiety disorders were, in general, independent of anxiety, but anxiety moderated the relationship between ADHD-Conduct disorder and Conduct disorder-enuresis. Comorbid anxiety increased difficulties in social interaction, was related with higher global impairment and had an impact on consultation and medication. Anxiety disorder comorbidity should be well recognized in order not to disregard the treatment of all present disorders. Keywords Anxiety disorders . Comorbidity . Functional impairment . Consultation . Medication

Abbreviations ADHD attention deficit hyperactivity disorder ANOR anorexia nervosa ANX Anxiety BUL bulimia nervosa CD conduct disorder DD dysthymia ENC encopresis ENU enuresis GAD generalized anxiety disorder MDD major depression OCD obsessive compulsive disorder ODD oppositional defiant disorder PTSD posttraumatic stress disorder SAD separation anxiety disorder SpPh specific phobia SoPh social phobia TIC any tic disorder

L. Ezpeleta (*) Unitat dEpidemiologia i de Diagnstic en Psicopatologia del Desenvolupament, Departament de Psicologia Clnica i de la Salut, Universitat Autnoma de Barcelona, 08193 Bellaterra, Barcelona, Spain e-mail: lourdes.ezpeleta@uab.es J. Toro Departament de Psiquiatria i Psicobiologia Clnica, Universitat de Barcelona, Barcelona, Spain

Anxiety disorders are, after disruptive disorders, the most prevalent psychiatric disorders in children and adolescents. In the general population reported prevalence oscillates between 1.7% and 9.2% (Costello et al. 2003; Ford et al. 2003; Gau et al. 2005; Mullick and Goodman 2005). Despite this high prevalence, anxiety disorders are often not treated (Chavira 2004). Furthermore, approximately one third of those with an anxiety disorder have more than one of the same (American Academy of Child and Adolescent Psychiatry 1997). Fifty-one percent of adolescents in the general population with anxiety have other psychiatric disorders (Essau 2003). Longitudinal studies indicate that anxiety disorders are associated with a risk of later disorders (Costello et al. 2003). The identification of the association of anxiety and non-

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anxiety disorders can help to improve the outcomes of anxiety disorders. Research into associations between anxiety disorders has addressed both the topic of comorbidity within anxiety disorders (Last et al. 1987; Lewinsohn et al. 1997), showing a considerable degree of homotypic comorbidity, and comorbidity of anxiety disorders with other psychiatric disorders (heterotypic comorbidity). The disorder that is most commonly associated with anxiety is depression, both sharing negative affect (Clark and Watson 1991). Rates of comorbidity between anxiety and depression oscillate between 30 and 75% (Angold and Costello 1993). The age range, race and socioeconomic class of the subjects, or informants used, may explain the wide range in the rates of comorbidity. The cooccurrence of both depression and anxiety is indicative of poor prognosis (Masi et al. 1999) and discriminates suicidal youth (Foley et al. 2006). An association has been also reported between generalized anxiety disorder (GAD) and attention deficit/hyperactivity disorder (ADHD) and other externalizing disorders, but this relationship has been more controversial, having been confirmed in some studies (Biederman et al. 1991; George et al. 1993; Last et al. 1991) but not in others (Lpez et al. 2004; Masi et al. 1999; Mattison and Bagnato 1987; Verduin and Kendall 2003). Eating disorders form another group linked with anxiety disorders (Godart et al. 2002). Kaye et al. (2004) reported that 2/3 of patients with eating disorders had anxiety disorders (Obsessivecompulsive disorders (OCD) and social phobia (SP)). Finally, anxiety has been related with tic disorders and their severity (Coffey et al. 2000; Gaze et al. 2006). A review of the literature shows heterotypic comorbidity in anxiety disorders, with both a positive (increasing) and a negative (protective) association (Mamorstein 2007). Maughan et al. (2004) found that the presence of anxiety diminished the dysfunctional behaviour associated to an oppositional defiant disorder and indicate that some aspects of anxiety may inhibit the appearance of other problems, while others promote it. However, few studies have examined the role of anxiety disorders when they are associated with other disorders. Lilienfeld (2003) pointed out that a substantive reason for comorbidity is that one disorder causes another. It could be that the presence of anxiety moderated the relationships between non-anxiety disorders as a result of shared common factors such as inhibitory control deficits, genetic factors, common risk factors or common symptoms (such as irritability or fidgetiness) (Boylan et al. 2007). For instance, negative affect explains, in part, comorbidity between anxiety and depression (Clark and Watson 1991; Jacques and Mash 2004). At the same time, irritability and negative affect could lead to oppositional and aggressive behaviour, leading to the simultaneous occurrence of anxiety, depression and oppositional or conduct disorder.

Changes in the effectiveness of treatment are among the reported consequences of comorbid anxiety. For instance, in the case of the association between anxiety and dexpression some researchers report more difficulties for treatment (Young et al. 2006) while others do not find differences (Kendall et al. 2001; Rapee 2003). Comorbid anxiety has been related with functioning, such as higher proportions of academic problems or conflict with parents (Lewinsohn et al. 1995), though others suggest a beneficial effect of comorbid anxiety that ameliorates the outcomes evaluated (James and Javaloyes 2001). Furthermore, children with comorbid anxiety conditions are significantly more psychologically distressed (Essau 2003) but only a few families seek treatment for their problems (Essau et al. 2000). The attenuating or aggravating role of anxiety when it co-occurs with others disorders could facilitate or hinder families from seeking professional help for a childs problems and a clinicians decision to prescribe medication. Given the high frequency of anxiety disorders in referred children, and the fact that they pre-date other disorders,suggesting that anxiety disorders may predispose towards other disorders (Essau 2003; Kaye et al. 2004)the aim of this paper is to provide data on the homotypic and heterotypic comorbidity of anxiety disorders and, specifically, their modifying role in the comorbidity between non-anxiety disorders. The study also reports how comorbid cases of anxiety disorders affect the daily functioning of a child as well as the familys decision to seek professional help and the clinicians decision to prescribe medication. These issues are analyzed in a broad sample of Spanish children receiving public mental health services.

Method Participants The children participating in the study were recruited from two psychiatric outpatient settings forming part of the public health network in Barcelona (Spain). The original sample was composed of 576 consecutive admissions that represent 96.4% of those invited to participate. The children were between 8 and 17 years of age (mean age=13.7; SD= 2.5) and 265 (46%) were girls. Socioeconomic status (Hollingshead 1975) was distributed as follows: 13.4% high/high average; 58% average/low average; and 28.6% low. Ninety-seven percent were Caucasian. The first row in Table 1 shows the distribution of disorders in the sample. Fifty-four percent presented some kind of anxiety disorder. There were significantly more girls than boys with some kind of anxiety disorder (62.3% vs. 46.9%; p<.001), GAD (40.7% vs. 22.2%; p<.001) or

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Table 1 Distribution (%) of disorders in the sample and distribution of anxiety disorders in non-anxiety disorders by sex Non-anxiety disorders ADHD (N=254) ODD (N=280) CD (N=80) Drugs (N=32) MDD (N=191) Dysth. (N=61) ANOR. (N=30) BUL. (N=11) ENU. (N=124) ENC. (N=34) TIC (N=62)

% of disorders in the whole sample (N=576) Girls 25.7 42.6 8.7 Boys 59.8* 53.7* 18.3* Total 44.1 48.6 13.9 % of separation anxiety disorder (N=65) Girls 11.8 11.5 8.7 Boys 12.4 12.0 10.5 Total 12.2 11.8 10.0 % of generalized anxiety disorder (N=176) Girls 27.9** 37.2* 30.4 Boys 16.7 20.4 19.3 Total 19.7 27.1 22.5 % of specific phobia (N=158) Girls 27.9 26.5 26.1 Boys 28.5 26.9 19.3 Total 28.3 26.8 21.3 % of social phobia (N=78) Girls 10.3 11.5 13.0 Boys 14.0 12.6 8.8 Total 13.0 12.1 10.0 % of obsessivecompulsive disorder (N=43) Girls 7.4 10.6** 8.7 Boys 4.3 3.6 5.3 Total 5.1 6.4 6.3 % of posttraumatic stress disorder (N=15) Girls 7.4* 5.3* 8.7** Boys 0 0 0 Total 2.0 2.1 2.5 Significant sex differences: *p=.001; **p=.05

7.5 3.9 5.6 5.0 0 3.1 35.0 25.0 31.3 5.0 16.7 9.4 20.0 16.7 18.8 5.0 0 3.1 0 0 0

46.4* 21.9 33.2 7.3 25.0* 13.6 51.2 45.6 49.2 26.0 50.0* 34.6 13.8 25.0 17.8 12.2 5.9 9.9 7.3 1.5 5.2

16.2* 5.8 10.6 16.3 27.8 19.7 61.9 50.0 58.3 27.9 50.0 34.4 20.9 38.9 26.2 16.3 11.1 14.8 11.6 0 8.2

10.3* 1.0 5.2 14.8 33.3 16.7 57.7 0 51.7 29.6 33.3 30.0 33.3 66.7 36.7 7.4 0 6.7 3.7 0 3.3

4.2* 0 1.9 9.1 0 9.1 45.5 0 45.5 9.1 0 9.1 9.1 0 9.1 9.1 0 9.1 0 0 0

18.1 24.4 21.5 12.5 13.2 12.9 45.8 15.8 27.4 25.0 27.6 26.6 8.3 15.8 12.9 10.4 3.9 6.5 4.2 0 1.6

2.3 9.0* 5.9 0 14.3 11.8 33.3 21.4 23.5 16.7 39.3 35.3 33.3 17.9 20.6 0 3.6 2.9 0 0 0

6.4 14.5* 10.8 11.8 15.6 14.5 47.1 26.7 32.3 29.4 22.2 24.2 15.6 23.5 17.7 23.5 11.1 14.5 5.9 2.2 3.2

posttraumatic stress disorder (PTSD) (4.9% vs. 0.6%; p=.001). Measures Diagnostic Interview for Children and Adolescents-IV The Diagnostic Interview for Children and Adolescents (Entrevista Diagnstica para Nios y Adolescentes; EDNAIV) (Reich 2000), was used to assess psychopathology. The EDNA-IV is a semi-structured diagnostic interview that covers the most frequent diagnostic categories according to DSM-IV (American Psychiatric Association 1994) and has been adapted and validated for the Spanish population and shown to offer satisfactory psychometric properties (Ezpeleta et al. 1997a, b). There are three versions, one for children, one for adolescents and one for parents. The interview should be administered by trained interviewers with a knowledge of child psychopathology. The training procedure consisted of the study of the interview, simulated practice

interviews, codification of audio registered interviews and observation and codification of in vivo interviews. Kappa indices of inter-interviewer reliability for anxiety disorders ranged from .73 for GAD to 1 for phobias, PTSD and OCD (de la Osa et al. 1996). Diagnoses were generated by combining the information from parents and children at the symptom level, i.e. a symptom was regarded as being present if the parent or the child reported it. If symptoms of a disorder are present, the interviewer then asks about functional impairment, distress, consultation and medication (the latter two only when appropriate). Questions about impairment at home, at school or with friends were registered in a four-alternative format (1: Not at all; 2: A little; 3: Fairly; 4: A lot). Levels 3 and 4 were grouped as one variable (impairment present) combining the information from the parent and child. The same was done for the distress question. Psychological distress refers to the personal feelings of discomfort, unpleasantness, or emotional pain caused by psychological symptoms, whereas functional impairment refers to the consequences that psychological

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symptoms or disorders have on the life of the child with respect to their performance of everyday functions (stun and Chatterji 1997). Child and Adolescent Functioning Assessment Scale (CAFAS) The CAFAS records the extent to which a young persons mental health disorder is disruptive of their functioning in each of eight psychosocial areas, reported by the children and parents (Hodges 1997). The following functional areas were analyzed: role performance at school, at home, in the community, behaviour toward others and total score. With the extensive information obtained after clinical examination, interviewers are required to rate the lowest level of functioning in each area, taking into account the childs age, sex and social class, as well as the norms for the community in which the child is living. Each scale is scored on 4 levels of impairment. For the purposes of this study, the higher (worse) of the two scores resulting from the information from the parent or child was used. The resulting score was then dichotomized as (0) mild or no impairment (0 and 10), and (1) moderate and severe (20 and 30). The psychometric properties of the instrument have been extensively studied by its author (Hodges 1999) and in the Spanish population (Ezpeleta et al. 2006). Procedure The project was approved by the ethics review committee of the Universitat Autnoma de Barcelona. Written consent from parents and oral consent from children to participate in the study were obtained. Different interviewers, who were unaware of the childrens diagnoses, simultaneously interviewed the children and the parents. Interviewers (undergraduate psychology students and doctoral students) were trained in the use of all the assessment instruments. The interviewers compliance with the interview protocol was checked through weekly conference revisions. All of the raters had a clinical background and knowledge of child development and psychopathology. After completing the diagnostic interview, the interviewers administered the CAFAS. Statistical Analysis The data was analyzed using SPSS 14.0 for Windows. The association between sex, functional impairment, distress consultation, medication and diagnosis in anxiety and nonanxiety disorders was analyzed through chi-square tests. Age differences, adjusted by sex and the presence of other disorders, were analyzed through multiple linear regression.

Homotypic (coexistence of anxiety disorders) and heterotypic (coexistence of anxiety disorders with non-anxiety disorders) anxiety comorbidity was examined with logistic regression adjusted by sex, age, sex by age, non-anxiety disorders and individual anxiety disorders. To test whether comorbidity between non-anxiety disorders was dependant on anxiety disorders, logistic regressions adjusted by sex, age, and other disorders were performed, including the interaction between anxiety with non-anxiety disorders in the model.

Results Sex and Age Differences of Anxiety Disorders in Non-anxiety Disorders Table 1 presents the distribution of anxiety disorders and sex differences. Girls with ADHD and oppositional defiant disorder (ODD) had a higher frequency of GAD than boys. Also, girls with ODD presented a higher prevalence of obsessive compulsive disorder (OCD) and those with externalizing disorders (ADHD, ODD and conduct disorder (CD)) had higher percentages of PTSD. Boys with major depression (MDD) presented significantly more separation anxiety (SAD) and specific phobia (SpPh) than girls. GAD and SpPh were the most frequent anxiety disorders present along with other disorders. Children with SAD were younger than those without SAD in ADHD (Adjusted mean of age difference 1.1 years; 95% CI: .252.0), CD (1.9 years; 95% CI: .473.4), MDD (1.9 years; 95% CI: 1.02.8) and enuresis (1.4 years; 95% CI: .262.5). Children with social phobia were older than those without in ADHD (.91 years; 95% CI:.081.7). Comorbidity Among Anxiety Disorders Adjusting by sex, age, non-anxiety disorders and individual anxiety disorders, logistic regression resulted in the following significant associations: SAD and GAD (OR= 6.7; 95% CI: 3.413.0); SAD and SpPh (OR=5.2; 95% CI: 2.89.7); GAD and SpPh (OR=1.7; 95% CI: 1.12.8); GAD and OCD (OR=3.0; 95% CI: 1.56.0); SpPh and SoPh (OR=3.7; 95% CI: 2.16.6); and SpPh and PTSD (OR=3.6; 95% CI: 1.311.2). Association Between Anxiety and Non-anxiety Disorders Associations between individual anxiety disorders and other psychopathologies were studied through logistic regressions. A model was run for each anxiety disorder as a dependent variable. Independent variables were all of the

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non-anxiety disorders, anxiety disorders (except the disorder considered in the dependent variable), and sex, age, sex by age as covariates. There were only significant associations between GAD and MDD (OR=2.3; 95% CI: 1.53.6), GAD and ADHD (OR=0.5; 95% CI: 0.30.8), SoPh and anorexia (OR=3.8; 95% CI: 1.69.3), SoPh and dysthymia (DD) (OR=2.2; 95% CI: 1.14.5) and OCD and tics (OR= 2.7; 95% CI: 1.16.4). Moderating Role of Anxiety in Comorbidity Between Nonanxiety Disorders Anxiety was kept constant in order to discern its modifying role in comorbidity in non-anxiety disorders. For this purpose logistic regression models were adjusted by introducing any anxiety disorder as an interaction variable and controlling for all the other disorders, sex, age and sex by age; the dependent variable was the non-anxiety disorder. Table 2 synthesizes significant relations between non-anxiety disorders in the presence/absence of anxiety disorders. Most of the significant relationships between non-anxiety disorders were independent of anxiety disorders. However, relationships between ADHD and CD, and CD and enuresis were only significant in the presence of anxiety disorders. When anxiety was present, the probability of an association between ADHD and CD increased four times, while the probability of an association between CD and enuresis decreased 7.7 times (1/0.13). Functional Impairment and Distress in Non-anxiety Disorders in Children with and Without Anxiety Children in the sample were separated into two groups: those with any anxiety disorder (N=311) and those without any anxiety disorder (N =265) in order to study the differences in functional impairment in both groups

(Table 3). Oppositional and enuretic children with anxiety had fewer difficulties at school than those without anxiety. At home, enuretic children with anxiety disorder had fewer difficulties than non-anxious children. In the community, dysthymic children with anxiety had fewer difficulties than their anxious counterparts. In the relationships with others, enuretic children with anxiety had fewer difficulties than enuretic children without anxiety. The total CAFAS score was significantly higher in the cases of ADHD, CD and drug abuse or dependence that also suffered comorbid anxiety disorders in comparison with non comorbid cases. Children suffering from anxiety disorders presented significantly more impairment and more distress associated to the anxiety disorder than those that had not been diagnosed as having an anxiety or that only had anxiety symptoms (Table 3). However, for dysthymia, eating disorders and encopresis there were no significant differences between the distress associated to the anxiety: the frequency of those diagnosed with anxiety experiencing distress associated to the anxiety was comparable to that of those with only symptoms. Distress and impairment associated to the non-anxiety disorder was also compared in the groups (Table 3). The presence of an anxiety disorder did not significantly modify the impairment (data not shown) or the psychological distress associated to the non-anxiety disorder except in the case of enuresis: enuretic children with anxiety were more distressed by enuresis than those without anxiety. Consultation and Medication After asking questions about the symptoms of each disorder, the interviewer asks whether the family has consulted any professionals and whether medication for the disorder/ symptoms has been prescribed. Clearly, the group with anxiety consulted professionals significantly more frequently

Table 2 Role of anxiety disorders in the comorbidity between non-anxiety disorders (OR; CI 95%)a With anxiety Association independent of anxiety 3.4 (2.75.1) 4.0 (1.610.0) 2.7 (1.64.3) 8.3 (3.917.6) 1.6 (1.02.5) .13 (.03.62) 3.2 4.6 2.5 3.5 9.8 (1.28.7) (2.39.0) (1.016.6) (1.67.8) (1.373.3) 1.7 (.773.6) 1.2 (.532.5) Without anxiety

ADHDODD ADHDCD ADHDENURESIS ODDCD ODDMDD CDENURESIS CDDRUGS MDDDYSTHYMIA DRUGSENURESIS ENURESISENCOPRESIS BULIMIATICS
a

Logistic regression controlling by sex, age, other disorders and interaction of anxiety and non-anxiety disorders

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No anx.

173

Percentage of subjects with high-moderate impairment or distress Anx with any anxiety disorder and other non-anxiety disorders, No Anx with non-anxiety disorders and without anxiety disorders (anxiety symptoms could be present) c N of children with anxiety vs. N of children without anxiety. Significant Chi-square test differences: *p=.001; **p=.05; ***p=.01
b

Table 3 Functional impairment and distress in non-anxiety disorders in children with and without anxiety

Communitya

Anx.

in relation to the anxiety disorder than those that only had anxiety symptoms (or did not suffer any anxiety disorder) (Table 4). It is remarkable, however, that less than half of the cases that had anxiety disorders plus another disorder consulted professionals in relation to the anxiety disorder. The only exception to this was that of tic disorders, where 62% of the children that had tics plus an anxiety disorder consulted professionals about the anxiety disorder. Regarding consultation in relation to the non-anxiety disorder, for children with ODD the presence of anxiety was associated with seeking less frequently consultation in relation to that ODD in comparison with those that had ODD but no anxiety (Table 4). Children with anxiety disorders were those that received the most medication for the anxiety disorder. This occurred in less than 25% of the cases that had been diagnosed as having an anxiety. Regarding medication for the nonanxiety disorder, children with ADHD and children with tic disorders that also had anxiety disorders received a significantly lower percentage of medication for ADHD or tics. Having anxiety plus these disorders was related with less prescription of medication for ADHD or tics. However, the depressive children with anxiety (47.4%) were prescribed medication for depression more frequently than the depressive children without anxiety (29.2%). In the case of ADHD it may be that ADHD with anxiety is less medicated due to the inattentive subtype, where stimulants are less effective than for the combined subtype. This possibility was studied and it was found that there was no difference between the inattention subtype and the combined subtype and the combined or hyperactive subtypes in terms of medication (p=.364).

Non-anxiety disor. distressa

DICA impairment and distress questions

No anx. No anx. No anx. No anx. Anx. Anx. No anx. No anx. Anx. Anx.

Anxiety distressa

Anxiety impairmenta

Total (Mean)

Othersa

3.5 6.2 18.8 12.5 3.1 0 0 1.7 5.6 3.1

5.3 10.6 23.8 25.0 8.0 8.3** 14.3 7.3 9.1 9.5

32.2 41.9 65.6 56.3 23.8 27.1 13.6 33.0 20.7 38.9 34.4

32.7 40.9 61.9 43.8 22.0 16.7 14.3 0 43.6* 54.5 33.3

63.2** 66.8 86.3* 106** 62.4 65.2 65.5 68.3 50.6 57.8 55.0

55.5 61.5 68.1 76.3 54.4 70.0 58.6 36.0 55.4 59.1 50.0

65.0* 66.2* 60.0* 56.3* 75.4* 79.6* 82.6* 66.7 72.1* 52.6** 79.4*

14.5 16.0 17.8 6.3 30.2 16.7 14.3 40.0 11.1 20.0 7.1

41.5* 34.6* 28.6** 62.5* 42.8* 44.9 39.1 16.7 36.1* 21.4 44.1*

6.9 7.6 11.1 12.5 5.7 25.0 14.3 20.0 6.3 0 7.1

32.3 50.7 52.9 50.0 88.5 82.8 45.5** 36.4

Anx.

35.3 45.8 32.1 40.0 76.0 71.4 14.8 14.3

36.3 53.8 57.1 56.3 28.5 25.0 28.6 20.0 41.8* 27.3 23.8

Discussion The purpose of this study was to examine the comorbidity of anxiety, its consequences and its role in non-anxiety disorders. The results indicate that there is a specific association of homotypic comorbidity between anxiety disorders that is independent of the presence of other disorders, and that there is heterotypic comorbidity between anxiety and depressive disorders, ADHD, anorexia and tic disorders regardless of the presence of other disorders. The relationships between non-anxiety disorders are, in general, independent of anxiety. Anxiety only moderates the relationship between ADHD-CD and CD-enuresis. In the presence of other disorders, anxiety is associated with less reporting of difficulties at school, at home and in the community, but with the increase of the difficulties in social interaction and global functional impairment. The presence of an anxiety disorder does not modify distress or impairment associated to the non-anxiety disorder. It was

Homea

Anx. No anx. Anx.b

CAFAS

Schoola

Sample size: Nc

ADHD ODD CD Drugs MDD DD ANOR BUL ENU ENC Tics

N=123 vs. N=136 vs. N=35 vs. N=16 vs. N=138 vs. N=49 vs. N=23 vs. N=6 vs. N=61 vs. N=19 vs. N=34 vs.

N=131 N=144 N=45 N=16 N=53 N=12 N=7 N=5 N=63 N=15 N=28

77.4 68.2 90.6 100 54.6 56.3 54.5 33.0 60.3 61.1 56.3

85.0 79.5** 97.6 93.8 56.0 83.3 42.9 60.0 80.0** 72.7 81.0

33.0 45.0 65.6 50.0 34.0 33.3 31.8 50.0 19.0 44.4 15.6

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Table 4 Percentages of consultation and medication about anxiety and non-anxiety disordersb Non-anxiety disorders Consultation about anxiety disorder Anx.c ADHD ODD CD Drugs MDD Dysthymia. Anorexia Bulimia Enuresis Encopresis Tics 35.8* 36.8* 37.1* 37.5 49.3* 44.9 43.5** 16.7 36.1* 15.8 61.8* No anx. 5.3 7.6 8.9 12.5 15.1 8.3 0 0 7.9 0 3.6 Consultation about non-anxiety disorder Anx. 50.5 55.1
a a

Medication about anxiety disorder Anx. 16.3* 14.7* 20.7* 18.8** 24.6* 18.4 13.0
a

Medication about non-anxiety disorder Anx. 18.8

a a a

No anx. 61.3 68.5**

a a

No anx. 1.5 2.8 2.2 0 5.7 8.3 0

a

No anx. 31.1**
a a a

55.0
a

46.7
a

47.4**
a a a

29.2
a a a

78.3 83.3 60.7 73.7 47.1

71.4 100 61.9 60.0 57.1

19.7*
a

0
a

13.1
a

11.1
a

23.5**

3.6

8.8

28.6**

Significant differences: *p=.001; **p=.05; ***p=.01 a Interview does not ask about this topic for this disorder b Percentages represent the number of consultation or medication in relation with the total number of subjects with anxiety or the total number of subjects without anxiety in each non-anxiety disorder c Anx with any anxiety disorder and other non-anxiety disorders, No Anx with non-anxiety disorders and without anxiety disorders (anxiety symptoms could be present)

also noted that comorbid anxiety had an impact on consultation and medication. The results for the frequency of anxiety disorders in Spanish children are in line with other studies of American (Verduin and Kendall 2003), German (Essau 2003) and Italian children (Masi et al. 1999). The same occurred in terms of sex, with higher rates of anxiety disorders in girls than in boys (Lewinsohn et al. 1998) and age, in that children that had SAD were younger and those that had SoPh were older (Westenberg et al. 2004). Anxiety disorders tend to co-occur and, when an anxiety disorder is present there is a need to explore the presence of other anxiety disorders. This is especially indicated when GAD or specific phobias are present. Extensive assessment of the presence of anxiety is also indicated in the case of depressive disorders, anorexia nervosa or tics. Considering the associations between non-anxiety disorders, anxiety is a modifier variable of the relationships between ADHD-CD, in the sense that if anxiety is present the risk of association between these disorders increases (the relationship between ADHD-CD was not significant if anxiety was absent). Multisite Multimodal Treatment Study results propose four subtypes of ADHD considering comorbidities: pure ADHD, ADHD+ANX, ADHD+ODD/CD and ADHD+ANX+ODD/ CD (Jensen et al. 2001). The present results indicate that in the ADHD+ANX+CD subtype proposed by these authors, anxiety is a moderating variable. The association between these three disorders, also reported by Newcorn et al. (2004), was related with more severe impairment at outcome. Essau et al. (2000) have reported that anxiety disorders cause significant impairment at school and in social

activities. Differences found between groups with and without anxiety (in ODD, DD and enuresis) in the present study indicate that anxiety is associated with less impairment, as proposed by Jensen et al. (2001). Cognitive (fear, failure expectations,..), biological or behavioral (avoidance) components of anxiety can contribute to a lesser impairment in specific areas mitigating, for instance, the manifestations of ODD at school, resulting in a less severe picture. However, for the total score for CAFAS, children with comorbid anxiety had higher functional impairment. In relation to ADHD, Newcorn et al. (2004) concluded that comorbid anxiety was a strong predictor of a poor functional outcome in several domains and they argue that, in opposition to the idea that anxiety could play a protective role, the addition of anxiety can predict a more severe rather than less severe course. Along similar lines to data reported by other authors for anxiety in general, the presence of anxiety disorders plus other comorbid conditions tends to increase difficulties in social interaction (Essau et al. 2000; Messer and Beidel 1994; Newcorn et al. 2004). A decrease in social interaction, inhibition or fear, present in anxiety disorders, may explain social difficulties. The effects of comorbid anxiety on functioning may have major implications for the detection of both comorbid conditions and their intervention. The consequences on daily functioning can help draw the attention of other significant people to the existence of problems. If these consequences are attenuated, detection and diagnosis can be delayed or disregarded. The use of refined assessment diagnostic instruments may help to ensure that clinicians do not overlook all of the present conditions.

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Anxiety disorders with other comorbid conditions caused significantly more distress and more use of services than only anxiety in the community sample used in Essau (2003). In the present clinical sample, although anxiety was related to clinically significant distress, when other disorders were also present (comorbid) in less than half of the cases the anxiety motivated consultation of a professional, i.e. in the presence of comorbid disorders, anxiety remains invisible and is not a cause for concern to the point of seeking help. However, in general, there were no significant differences between comorbid cases in the way children seek help for their non-anxiety disorder. Only in the case of ODD the addition of anxiety was related with less consultation about the ODD. When ODD and anxiety are present together, it may be that anxiety attenuates the manifestations of ODD resulting in a less marked, less bothersome picture. Medication is not the treatment of choice for anxiety (Stock et al. 2001). In the sample studied, medication for anxiety was only prescribed in less than 25% of cases. However, anxiety comorbidity modified the rule of the medication of non-anxiety disorders. In comorbid cases there were two patterns of medication: one in which anxiety is related with higher frequency of medication of the nonanxiety disorder (the case of depression or enuresis) and another that is related with less frequency (the case of ADHD or tics). As a result, depression and enuresis are more medicated when there is comorbid anxiety, but ADHD and tics are less medicated when there is comorbid anxiety. Other authors have not found differences either in the medication exposure of ADHD as a function of comorbid anxiety (Newcorn et al. 2004), or in response to methylphenidate (Abikoff et al. 2005). So, the significantly lower medication treatment of ADHD with comorbid anxiety remains unexplained, which is even more so when ADHD+ANX presented significantly higher functional impairment than ADHD without anxiety. In the case of depression this result would be in accordance with recommended practice: when comorbid anxiety coexists with depression, treatment of depression needs to be prioritized (American Academy of Child and Adolescent Psychiatry 2007), but, as Ferdinand et al. (2005) have pointed out, it is rare for depression to occur without anxiety symptoms and, therefore, treatments should not only be directed at dealing with depression but also at dealing with the anxiety in accordance with its severity. This could be generalized to other associations. Clinicians should treat comorbidity when it occurs. A good diagnostic assessment would produce a clear picture of the whole psychopathology in order to decide upon the treatment strategy. The use of a broad clinical sample of children using the public health system with a reasonable number of subjects in each category of disorders, information about anxiety in a non Anglo-Saxon population, and the fact that analyses

were conducted while controlling for a wide number of potentially confounding variables, which has isolated the effect of the resultant relationships, are the unique contributions made by this research. Moreover, the measures combined information about multiple informants (parents and children) using rigorous interviews and diagnostic criteria. On the other hand, the use of a clinical sample could be a limitation, as clinical samples may be affected by a referral bias and by disproportionately high rates of comorbidity. However, the present study focused on the diagnostic difficulties of anxiety disorders in mental health primary care consultations when other disorders are present and, consequently, such a sample must be used. Findings are applicable to children referred to mental health services.
Acknowledgements This work was supported by grants DGICYT PM98-173 from the Ministry of Education and Culture and SEJ200501786 from the Ministry of Science and Technology, Spain.

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