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Research Article                                                                                                                                        Open Access

## Anxiety Disorders among Adolescents referred to General Psychiatry for Multiple Causes: Clinical Presentation, Prevalence, and Comorbidity

Susanne Olofsdotter 1* , Sofia Vadlin 1 , Karin Sonnby 1 , Tomas Furmark 2 , Kent W. Nilsson 1

1 Centre for Clinical Research, Västmanland County Hospital, Västerås, Sweden 2 Department of Psychology, Uppsala University, Sweden

*Corresponding author: susanne.olofsdotter@ltv.se

## Abstract

Background: Reports of anxiety disorder characteristics among youth in clinical settings typically include descriptions of patients who have been specifically referred for anxiety treatment. At odds with a large body of evidence which demonstrates these disorders to be most common among young people, prevalence studies in samples referred to general psychiatry for multiple causes are scarce and report highly discrepant estimates.

Methods: For this study and regardless of their presenting symptoms, 125 adolescents (57.6% girls) between the ages of 12 and 18 years who were consecutively referred to two child and adolescent general psychiatry clinics in Sweden were assessed for anxiety disorders and comorbidity using the Schedule for Affective Disorders and Schizophrenia for School-Age Children . Self-ratings of anxiety symptoms and difficulties with family, school, friends, sleep, and body aches were also obtained.

Results: At least one anxiety disorder was found in 46% of participants. Among anxious adolescents, homotypic comorbidity (concurrent anxiety) was observed in 43%, and heterotypic comorbidity (concurrent non-anxiety psychiatric disorders) was observed in 91%. No comorbidity was observed in 5%. Trauma, ache, and difficulties making friends were more common among anxious adolescents as compared with psychiatrically referred adolescents without anxiety.

Conclusions: The finding that only 21% of adolescents diagnosed with anxiety disorders were referred for anxiety further supports  the  routine  use  of  standardized  and  structured  instruments-irrespective  of  referral  cause-to  improve  both precision and detection rates in the clinical setting. Comprehensive assessments are of utmost importance to fully address the complexity of the symptoms in this patient group.

Keywords: anxiety disorders; adolescents; prevalence; comorbidity; general psychiatry

## Introduction

Anxiety affects  117  million  youths  worldwide;  it  is the sixth leading cause of disability, with the highest burden  (i.e.,  time  lived  with  the  condition)  among people who are 15 to 34 years old (1, 2). Early-onset anxiety  is  associated  with  adverse  short-  and  longterm social, academic, financial, and health outcomes, and it also predicts substance use disorders and adult anxiety (3-5). Early identification and treatment are critical to reduce the burden and to prevent negative life outcomes. However, anxiety is still  largely  unrecognized  in  primary  and  mental health care, and only a minority of affected children receives  treatment  (6-8).  Clinicians  and  decision makers  need  to  be  aware  of  the  presence  and deleterious  impact  of  childhood  anxiety.  However, there is a paucity of data regarding the prevalence and clinical  correlates  of  multiple  anxiety  disorders  in non-specialized psychiatric outpatient settings, where anxiety may not be a recognized or primary cause for the  seeking  of  help  (8,  9).  Only  three  prevalence studies of multiple anxiety disorders in non-anxietyspecialized  psychiatric  settings  have  been  reported, with  highly  discrepant  prevalence  rates  that  make adequate service planning and resource allocation for this setting and patient group difficult tasks (10-14).

Hammerness and colleagues (13) used the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) diagnostic interview (15) to examine the characteristics of seven non-obsessive-compulsive disorder  (OCD)  anxiety disorders  in  1375  psychiatrically  referred  children and  adolescents  in  North  America.  According  to diagnostic  criteria  presented  in  the Diagnostic  and Statistical  Manual  of  Mental  Disorders,  Third  Edition, Revised (DSM-III-R)  (16),  the  overall  prevalence  of anxiety was 57.7%, with a 53.8% homotypic comorbidity  (concurrent  anxiety  disorder)  rate  and higher  rates  of  depression,  bipolar  disorder,  and pervasive developmental disorder seen among anxious  youths  as  compared  with  youths  without anxiety. By contrast, a much lower prevalence rate of 5.7% was found for five non-OCD anxiety disorders in a Danish study of 13,241 psychiatrically referred youths that included data gathered from a national database of diagnoses from the International Statistical Classification of Diseases and Related Health Problems, 10th Revision [ICD-10]  (17).  Diagnoses  in  the  database were determined during clinical conferences using all available information collected via several unspecified  clinical  tools  rather  than  just  a  single instrument or interview (12). Moreover, homotypic comorbidity  was  found  in  only  2.8%  of  anxious youths, whereas heterotypic comorbidity (concurrent non-anxiety  psychiatric  disorder)  was  observed  in 42.9%. With the use of both data collection methods, six non-OCD anxiety disorders were investigated in 407 children between the ages of 7 and 13 years who were referred to child and adolescent psychiatric care in Norway (14). A prevalence of 32.7% of DSM-IV anxiety  disorders  was  found  when  the  K-SADS interview was used as compared with a rate of only 5% when data was collected from a patient register. On the basis of the K-SADS, homotypic comorbidity  was  observed  in  24.8%  of  anxietydisordered  children,  and  heterotypic  comorbidity was found in 70.7%.

The authors of the Danish and Norwegian studies suggested the limited use of standardized instruments in routine clinical practice as the main explanation for the low prevalence estimates derived from patient registers.

In two recently conducted meta-analyses of community prevalence studies-one of which investigated mental disorders in children and adolescents  and  the  other  that  investigated  anxiety across all age groups-sources of prevalence variance were analyzed (2, 18). Sample representativeness, sample frame (e.g., schools, households), and diagnostic interviews (as contrasted with K-SADS) were the only significant moderators of prevalence and explained 88.9% of the variability in studies of mental disorders in youths. In prevalence studies of anxiety that  included age categories across the life span, significant moderators of prevalence estimates (with variance explained in parentheses) included the following: age (1%); conflict (e.g., war; 2%); economic status (e.g., low- or middle-income country; 2%); urbanicity (2%); diagnostic instrument used (2%); number of anxiety disorders  examined  (4%);  culture  (5%);  prevalence period  (9%);  and  gender  (25%).  More  research  is needed  to  determine  whether  the  moderators  that influence  anxiety  prevalence  variability  in  clinical studies are the same as those that influence community studies.

The major objective of the present study was to investigate anxiety prevalence and comorbidity patterns  among  adolescents  using  the  K-SADS diagnostic interview in a Scandinavian non-anxietyspecialized psychiatric setting. Thus, anxiety among psychiatrically referred adolescents was characterized in three ways: 1) by the prevalence of seven anxiety disorders: social anxiety disorder, generalized anxiety disorder, specific phobia, panic disorder, agoraphobia, separation anxiety disorder, and unspecified anxiety disorder; 2) by clinical presentation;  and  3)  by  patterns  of  comorbidity, including homotypic and heterotypic comorbidity.

## Methods

Setting and Enrollment of Participants

Patients who presented at two child and adolescent general psychiatric outpatient clinics in the county of Västmanland,  Sweden,  between  August  2011  and June 2013 were eligible for enrollment. These clinics provide services to children and adolescents 18 years old and younger who live within the catchment area (N = 37,494). There are no specialized anxiety clinics in  the  area.  Referrals  to  the  clinics  are  made  by parents,  primary  care  physicians,  social  services, school  health  services,  and  hospital  departments . Data from the clinics' patient administrative systems showed that, in 2010 (when procedures for diagnostic assessment did not include the systematic use  of  structured  interviews),  9.7%  of  all  admitted patients between the ages of 13 and 17 years (N = 1092) had received a diagnosis of anxiety. Patients were  eligible  if  they  met  the  age  criteria  (12  to  18 years old), regardless of their presenting symptoms. The  exclusion  criteria  were  inadequate  Swedishspeaking  skills  and  prior  diagnosis  of  intellectual developmental disorder. During the predefined recruitment  period,  which  totaled  63  weeks,  202 patients  were  found  to  be  eligible  for  inclusion, whereas 77 were excluded: 28 declined to participate, 45 were missed as eligible and therefore not scheduled for the diagnostic interview, and 4 did not show up for the diagnostic interview. There were no significant  differences  in  sex  or  age  between  the excluded and included patients. Clinical staff confirmed eligibility, checked for exclusion criteria, and obtained informed written consent to participate from  both  the  adolescents  and  their  parents.  The project was approved by the Regional Ethical Review Board in Uppsala.

## Measures

## Schedule for Affective Disorders and Schizophrenia for SchoolAge Children - Present and Lifetime Version, 2009

The  K-SADS  (15)  is  a  semi-structured  diagnostic interview designed to guide clinicians in the collection of evidence for 33 DSM-IV (19) psychiatric  disorders  in  children  and  adolescents between the ages of 6 and 17 years. It consists of a screening  interview;  symptom  severity  above  the threshold  determines  which  additional  diagnostic supplements should be completed. The K-SADS is widely  used  as  a  diagnostic  tool  and  reference standard in child and  adolescent  mental  health research (13, 20, 21).

## Spence Children's Anxiety Scale

Anxiety symptoms were measured using the Spence Children's Anxiety Scale (SCAS) (22), a 44-item (38 score-generating items and 6 positive filler items to reduce negative bias) Likert-type (0 = 'never;' 3 = 'always')  questionnaire  designed  to  assess  anxiety symptoms  in  children  and  adolescents.  The  SCAS provides  a  total  score  as  well  as  scores  on  six subscales: panic attacks and agoraphobia, separation anxiety,  physical  injury  fears,  social  phobia,  OCD, and  generalized  anxiety.  In  the  original  study  by Spence, the internal reliability coefficient for the total scale was 0.92, and it ranged from 0.60 to 0.82 for the subscales (22). In an evaluation of the psychometric properties of the Swedish translation of the SCAS, which  included  a  subgroup  of  the  current  study sample, Swedish clinical cutoff scores were obtained. Results showed an internal reliability  coefficient  of 0.94 for the total score and demonstrated the scale's ability  to  distinguish  between  adolescents  with  and without  an  anxiety  disorder  in  a  Swedish  nonanxiety-specific clinical setting (23).

## Functional impairment/negative life events

Self-reports of functional impairment and negative life  events were collected from adolescents during their initial visits through a routine intake questionnaire.  Items  were  related  to  problems  within  the family (any occurrence of child physical abuse in the family, violence between parents, or alcohol or drug problems in the family); difficulties in school (current need  for extra help or current failed courses);  interpersonal  difficulties  (school-related bullying or difficulty making new friends ); somatic concerns  (frequent  headache  or  stomachache  or pain in the neck, shoulders, back, or legs during the last three months); and sleep concerns (during the last  three  months).  On  the  basis  of  the  intake questionnaire,  nine  dichotomous  variables  were computed  and  organized  into  the  five  functional domains of family,  school,  interpersonal,  somatic, and sleep.

## Procedure

Clinical  staff  registered  each  patient's  demographic data, referral cause, and source and administered the SCAS as well as an intake questionnaire as part of a regular intake routine during each participant's first or second visit. A time was then scheduled for each patient to complete the K-SADS interview (median time between intake visit and interview, seven days; interquartile range, 15 days).

## Diagnostic Procedure

Five  experienced  clinicians  (two  psychiatrists,  two psychologists, and one counselor) received extensive interview training by a K-SADS teacher before data collection. A free-marginal multirater kappa (24, 25) was  chosen  to  calculate  inter-rater  reliability.  This kappa statistic differs from Cohen's kappa in that it allows for multiple raters and is not dependent on marginal  distributions.  Calibration  meetings  were held monthly  throughout the study, and these involved  video  recordings  of  randomly  selected interviews.  The  average  inter-rater  reliability  and percent overall agreement (Po) during data collection was as follows: all diagnoses, 0.94 (Po = 0.97); any anxiety, 0.92 (Po = 0.96); separation anxiety, 0.83 (Po =  0.92);  social  phobia,  0.92  (Po  =  0.96);  specific phobia,  0.94  (Po  =  0.97);  OCD,  1.00  (Po  =  1.00); generalized  anxiety  disorder,  1.00  (Po  =  1.00);  and panic/agoraphobia, 0.94 (Po = 0.97).

Adolescents  and  their parents were  interviewed together. Interviewers determined the current presence of diagnoses on the basis of full DSM-IV criteria  and  information  collected  via  the  K-SADS only.  Diagnoses  were  not  classified  as  primary  or secondary. Anxiety disorders included in the analyses of  anxiety  prevalence  and  homotypic  comorbidity were social phobia (social anxiety), generalized anxiety disorder, specific phobia, separation anxiety disorder,  panic  disorder,  agoraphobia,  and  anxiety not otherwise specified (unspecified anxiety disorder). To harmonize with the chapter on anxiety disorders in the DSM-5 (26), the diagnoses of OCD and  post-traumatic  stress  disorder  were  excluded from the analysis of anxiety prevalence and homotypic comorbidity and included in the category of heterotypic comorbidity. If criteria for the DSMIV  diagnosis  of  panic  disorder  with  agoraphobia

(code 300.21) were fulfilled, both anxiety categories of  Panic  disorder  and  Agoraphobia  were  coded  as '1' (i.e., 'present') in the analysis of prevalence and homotypic  comorbidity.  All  non-anxiety  disorders were clustered into categories in accordance with the organizational structure of the DSM-5. An overview of the categories and organization of the K-SADSderived  DSM-IV diagnoses is presented  in  supplementary Table S1.

## Data Analysis

Statistical  analyses  were  conducted  with  the  use  of SPSS  22  software  running  on  the  Windows  7 operating  system.  Between-group  differences  were analyzed  with  independent t -tests  and  chi-squared tests. Binary logistic regression analyses were conducted to examine the variables associated with anxiety  and  comorbidity.  In  multivariate  models, separate for each covariate, we adjusted for sex and age.

TABLE 1. Anxiety prevalence and comorbidity among 125 psychiatrically referred adolescents

| Variables                    | All Participants (N = 125)   | Anxious (n = 58)      | Non-anxious (n = 67)   |  2 (df)              | p value               |
|------------------------------|------------------------------|-----------------------|------------------------|-----------------------|-----------------------|
|                              | Prevalence, %(95% CI)        | Prevalence, %(95% CI) | Prevalence, %(95% CI)  | Prevalence, %(95% CI) | Prevalence, %(95% CI) |
| Anxiety disorders            |                              |                       |                        |                       |                       |
| Any anxiety                  | 46.4 (37.9-55.1)             |                       |                        |                       |                       |
| Social anxiety               | 27.2 (20.2-35.6)             |                       |                        |                       |                       |
| Generalized anxiety          | 17.6 (11.9-25.2)             |                       |                        |                       |                       |
| Specific phobia              | 16.8 (11.3-24.3)             |                       |                        |                       |                       |
| Panic disorder               | 9.6 (5.6-16.0)               |                       |                        |                       |                       |
| Agoraphobia                  | 9.6 (5.6-16.0)               |                       |                        |                       |                       |
| Separation anxiety disorder  | 4.0 (1.7-9.0)                |                       |                        |                       |                       |
| Unspecified anxiety disorder | 1.6 (0.4-5.6)                |                       |                        |                       |                       |
| Comorbidity                  |                              |                       |                        |                       |                       |
| Homotypic                    |                              | 43.1 (31.2-55.9)      |                        |                       |                       |
| Without heterotypic          |                              | 3.4 (1.0-11.7)        |                        |                       |                       |
| No. of anxiety disorders:    |                              |                       |                        |                       |                       |
| 2                            |                              | 12.1 (6.0-22.9)       |                        |                       |                       |
| 3                            |                              | 20.7 (12.2-32.8)      |                        |                       |                       |
| 4                            |                              | 8.6 (3.7-18.6)        |                        |                       |                       |
| 5                            |                              | 1.7 (0.3-9.1)         |                        |                       |                       |
| Heterotypic                  |                              | 91.4 (81.4-96.3)      | 83.6 /72.9-90.6)*      | 1.7 (1)               | .193                  |
| Without homotypic            |                              | 51.7 (39.2-64.1)      |                        |                       |                       |
| Depressive                   | 44.8 (36.4-53.5)             | 53.4 (40.8-65.7)      | 37.3 (26.7-49.3)       | 3.3 (1)               | .070                  |
| Neurodevelopmental           | 56.0 (47.2-64.4)             | 51.7 (39.2-64.1)      | 59.7 (47.7-70.6)       | 0.8 (1)               | .370                  |
| Trauma                       | 9.6 (5.6-16.0)               | 15.5 (8.4-26.9)       | 4.5 (1.5-12.4)         | 4.4 (1)               | .037                  |
| Conduct                      | 14.4 (9.3-21.6)              | 13.8 (7.2-24.9)       | 14.9 (8.3-25.3)        | 0.0 (1)               | .857                  |
| Eating                       | 6.4 (3.3-12.1)               | 8.6 (3.7-18.6)        | 4.5 81.5-12.4)         | 0.9 (1)               | .470†                 |
| Obsessive                    | 7.2 (3.8-13.1)               | 6.9 (2.7-16.4)        | 7.5 3.2-16.3)          | 0.0 (1)               | 1.000†                |
| Psychotic                    | 3.2 (1.3-7.9)                | 3.4 (1.0-11.7)        | 3.0 (0.8-10.2)         | 0.0 (1)               | 1.000†                |
| Bipolar                      | 1.6 (0.4-5.6)                | 1.7 (0.3-9.1)         | 1.5 (0.3-8.0)          | 0.0 (1)               | 1.000†                |
| Substance                    | 1.6 (0.4-5.6)                | 0 (0.0-6.2)           | 3.0 (0.8-10.2)         | 1.8 (1)               | .499†                 |

*Presence of one or more non-anxiety psychiatric disorder

†Fisher's exact test, two-tailed

## Results

Description of Sample

The  study  group  consisted  of  125  consecutively referred  adolescents  (72  girls;  57.6%)  between  the ages  of  12  and  18  years  (mean,  15.7;  standard deviation, 1.5). The majority of the patients' parents were separated (60.8%). There were multiple causes for referral, as described by the referral source; the most common were symptoms of attentiondeficit/hyperactivity disorder (31.2%) and depression (29.6%). Problematic symptoms of anxiety were reported in 18.4% of patients at the time of referral. Among those referred for more than one cause (38 patients; 30.4%), the most frequent help- seeking  causes  were  symptoms  of  anxiety  (52.6%) and depression (52.6%).

The  total  number  of  diagnoses  per  participant ranged from 0 to 8 (median, 2; interquartile range, 1 to 3). The number of diagnoses was related to sex, with  girls  having  more  diagnoses  than  boys  (girls: mean, 2.8; standard deviation, 1.7; boys: mean, 1.8, standard  deviation,  1.3; t (123)  =  3.7; p <  .001). Eleven participants (8.8%) had no diagnoses.

## Prevalence of Anxiety Disorders

Fifty-eight adolescents (46.4%; 95%  confidence interval  [CI],  37.9  to  55.1;  62.5%  of  all  girls  and 24.5% of all boys) were diagnosed with at least one anxiety disorder, with a female-to-male ratio of 3.5:1. The prevalences of the individual anxiety disorders were  as  follows:  social  anxiety,  27.2%;  generalized anxiety, 17.6%; specific phobia, 16.8%; panic disorder, 9.6%; agoraphobia, 9.6%; separation anxiety disorder, 4.0%; and unspecified anxiety disorder,  1.6%.  Significant  associations  with  sexwith more girls meeting the criteria for diagnosiswere  found  for  all  anxiety  disorders,  except  for generalized anxiety and panic disorder. The prevalence of anxiety disorders is presented in Table 1.

TABLE 2. Demographic and clinical presentation characteristics of anxious versus non-anxious adolescents as defined by the Schedule for Affective Disorders and Schizophrenia for School-Age Children

| Variables                                   | All Participants (N = 125)   | Anxious (n = 58)   | Non- anxious (n = 67)   | t/  2 (df)   | p value   |
|---------------------------------------------|------------------------------|--------------------|-------------------------|---------------|-----------|
| Demographic data                            |                              |                    |                         |               |           |
| Sex                                         |                              |                    |                         |               |           |
| Female, n (%)                               | 72 (57.6)                    | 45 (77.6)          | 27 (40.3)               | 17.7 (1)      | <.001     |
| Age                                         |                              |                    |                         |               |           |
| Mean (SD)                                   | 15.7 (1.5)                   | 15.8 (1.4)         | 15.6 (1.5)              | 0.6 (123)     | .521      |
| Ethnicity                                   |                              |                    |                         |               |           |
| Swedish, n (%)                              | 122 (97.6)                   | 57 (98.3)          | 65 (97.0)               | 0.2 (1)       | 1.000 *   |
| Parents' marital status Divorced, n (%)     |                              |                    |                         |               |           |
|                                             | 76 (60.8)                    | 34 (58.6)          | 42 (62.7)               | 0.2 (1)       | .642      |
| Clinical presentation                       |                              |                    |                         |               |           |
| Referral source, n (%)                      |                              |                    |                         |               |           |
| Parent                                      | 44 (35.2)                    | 20 (34.5)          | 24 (35.8)               | 0.0 (1)       | .876      |
| Primary care                                | 32 (25.6)                    | 19 (32.8)          | 13 (19.4)               | 2.9 (1)       | .088      |
| School health services                      | 27 (21.6)                    | 9 (15.5)           | 18 (26.9)               | 2.4 (1)       | .124      |
| Hospital departments                        | 6 (4.8)                      | 4 (6.9)            | 2 (3.0)                 | 0.8 (1)       | .415 *    |
| Social services                             | 4 (3.2)                      | 1 (1.7)            | 3 (4.5)                 | 0.8 (1)       | .623 *    |
| Other                                       | 12 (9.6)                     | 5 (8.6)            | 7 (10.4)                | 0.1 (1)       | .729      |
| Referral cause, n (%)                       |                              |                    |                         |               |           |
| ADHD symptoms                               | 39 (31.2)                    | 11 (19.0)          | 28 (41.8)               | 7.5 (1)       | .006      |
| Depressive symptoms                         | 38 (30.4)                    | 23 (39.7)          | 15 (22.4)               | 4.4 (1)       | .036      |
| Anxiety symptoms                            | 23 (18.4)                    | 12 (20.7)          | 11 (16.4)               | 0.4 (1)       | .539      |
| Neurodevelopmental assessment               | 17 (13.6)                    | 10 (17.2)          | 7 (10.4)                | 1.2 (1)       | .269      |
| Self-harm, suicidal gestures                | 16 (12.8)                    | 9 (15.5)           | 7 (10.4)                | 0.7 (1)       | .398      |
| Autistic symptoms                           | 8 (6.4)                      | 3 (53.2)           | 5 (7.5)                 | 0.3 (1)       | .724 *    |
| Other causes                                | 20 (16.0)                    | 9 (15.5)           | 11 (16.4)               | 0.0 (1)       | .891      |
| Prior admission to a clinic, n (%)          | 37 (29.6)                    | 24 (41.4)          | 13 (19.4)               | 7.2 (1)       | .007      |
| Anxiety scores (SCAS)                       |                              |                    | 20.2                    |               |           |
| Mean (SD)                                   | 29.8 (19.1)                  | 40.2 (18.3)        | (14.2)                  | 6.7 (119)     | <.001     |
|  Diagnostic cutoff, n (%) †                | 44 (35.2)                    | 35 (60.3)          | 9 (14.3)                | 27.7 (1)      | <.001     |
|  Screening cutoff, n (%) ‡                 | 72 (57.6)                    | 52 (86.7)          | 20 (31.7)               | 42.0 (1)      | <.001     |
| Functional impairment/negative life events: |                              |                    |                         |               |           |
| Family, n (%)                               |                              |                    |                         |               |           |
| Child physical abuse §                      | 18 (14.4)                    | 11 (19.0)          | 7 (10.4)                | 1.8 (1)       | .176      |
| Violence between parents                    | 16 (12.8)                    | 9 (15.5)           | 7 (10.4)                | 0.7 (1)       | .398      |
| Alcohol/drug problems a                     | 28 (22.4)                    | 16 (27.6)          | 12 (17.9)               | 1.7 (1)       | .196      |
| School, n (%)                               |                              |                    |                         |               |           |
| Extra help/special class                    | 37 (29.6)                    | 17 (29.3)          | 20 (29.9)               | 0.2 (1)       | .639      |
| Failed course(s)                            | 80 (64.0)                    | 36 (62.1)          | 44 (65.7)               | 1.5 (1)       | .224      |
| Interpersonal, n (%)                        |                              |                    |                         |               |           |
| Bullied in school                           | 37 (29.6)                    | 22 (37.9)          | 15 (22.4)               | 3.6 (1)       | .058      |
| Difficulty making friends                   | 28 (22.4)                    | 21 (36.2)          | 7 (10.4)                | 11.9 (1)      | .001      |
| Somatic (pain), n (%)                       | 71 (56.8)                    | 46(79.3)           | 25 (37.3)               | 22.3 (1)      | <.001     |
| Sleep, n (%)                                | 55 (44.0)                    | 27 (46.6)          | 28 (41.8)               | 0.3 (1)       | .593      |
| No. of problems, mean (SD) b                | 3.0 (1.7)                    | 3.5 (1.7)          | 2.5 (1.6)               | 3.6 (123)     | <.001     |

## Clinical Presentation

There were no differences  between  K-SADSdefined  anxious  and  non-anxious  adolescents  in terms  of  age,  parents'  marital  status,  or  ethnicity. However, there was a significant sex difference, with a higher proportion of girls found among anxious as compared  with  non-anxious  adolescents  (  2 (1)  = 17.7; p <  .001).  Significant  differences  in  clinical presentation were found, with higher proportions of prior admission to the clinic (  2 (1) = 7.2; p = .007) and  symptoms  of  depression  as  the  referral  cause (  2 (1) = 4.4; p = .036) among anxious adolescents. Symptoms of attention-deficit/hyperactivity disorder  as  the  referral  cause  were  more  common among  non-anxious  adolescents  (  2 (1) =  7.5; p =  .006).  Anxious  adolescents  rated  themselves  as having  more  anxiety  symptoms  ( t (119)  =  6.7; p < .001) and more somatic and interpersonal problems, with higher proportions of frequent symptoms  of  pain  (  2 (1)  =  22.3; p <  0.001)  and difficulties making friends (  2 (1) = 11.9; p = .001) as compared with non-anxious adolescents. There were no  significant  differences  with  regard  to  referral source, family problems, school functioning, or sleep concerns. There was a tendency for a higher proportion of anxious than non-anxious adolescents to have experienced school-related bullying (  2 (1) = 3.6; p = .058). Table 2 shows the demographic and clinical  presentation  characteristics  of  anxious  and non-anxious adolescents.

## Associations between clinical presentation and anxiety disorders

For each covariate, separate binary logistic regression analyses, which were adjusted for age and sex, were performed for the total sample to examine associations between clinical presentation and anxiety disorders. A referral cause of anxiety symptoms was not related to any anxiety disorder. Only 21% of K-SADS-defined anxious adolescents were referred for symptoms of anxiety. The category of 'any anxiety' was associated with a referral that requested  a  neurodevelopmental  assessment  (odds ratio [OR], 4.2; 95% CI, 1.2 to 14.6; p = .023), selfreports of frequent body ache (OR, 4.3; 95% CI, 1.7 to 10.4; p = .001); and difficulties making new friends (OR, 4.5; 95% CI, 1.6 to 12.3; p = .004). Significant associations between generalized anxiety and clinical presentation were more frequently found than they were for the other anxiety disorders, with generalized anxiety being related to three variables: age (OR, 1.4; 95% CI, 1.0 to 2.1; p =  .047);  referral  source  (i.e., referral from a primary care physician; OR, 3.2; 95% CI, 1.2 to 8.7; p = .024); and self-reports of frequent body ache (OR, 5.6; 95% CI, 1.4 to 23.1; p = .016).

Panic  disorder  was  related  to  a  referral  cause  of depressive symptoms (OR, 4.9; 95% CI, 1.3 to 18.7; p = .021), as was agoraphobia (OR, 6.9; 95% CI, 1.6 to 29.1; p = .009). Social anxiety and specific phobia were associated with difficulties making new friends (OR, 4.3; 95% CI, 1.7 to 11.1; p = .003 and OR, 3.8; 95% CI, 1.3 to 10.7; p = .012, respectively). Analyses of associations between self-rated anxiety symptoms showed that all anxiety categories, except separation anxiety and unspecified anxiety disorder, were related to the total SCAS scores (all ORs within the 95% CI of 1.0 to 1.1; all p values of <.02).

## Patterns of Comorbidity

Only  the  58  participants  who  had  been  diagnosed with anxiety disorders were included in the analyses of  comorbidity,  unless  otherwise  specified.  Three (5.2%) adolescents had no comorbidity (i.e., only one anxiety disorder).

## Homotypic comorbidity

Homotypic comorbidity was found in 25 adolescents (43.1%; 95%  CI, 31.2 to 55.9; see Table 1). Homotypic comorbidity without concurrent heterotypic  comorbidity  was  noted  in  two  anxietydisordered adolescents (3.4%). Age and sex were not significant predictors of total homotypic comorbidity among anxious adolescents, but sex was a significant predictor in the total sample, with more girls having additional anxiety disorders as compared with boys (OR, 7.3; 95% CI, 2.1 to 26.1; p = .002). The most frequent  overlaps  between  anxiety  disorders  were social  anxiety  with  concurrent  generalized  anxiety (20.7%) and social anxiety with concurrent specific phobia (20.7%). Six adolescents (10.3%) had both: social  anxiety  with  concurrent  generalized  anxiety and concurrent specific phobia. In the total sample, the diagnoses of social anxiety, generalized anxiety, specific phobia, panic disorder, and separation anxiety  disorder  were  significantly  associated  with the presence of additional anxiety. When analyses of homotypic  comorbidity  were  limited  to  anxious adolescents, significant associations remained for the diagnoses of generalized anxiety, specific phobia, and panic disorder. Self-rated symptoms of anxiety were also predictive of homotypic comorbidity, which was congruent with associations  between  K-SADSderived anxiety disorders and homotypic comorbidity.  In  the  total  sample  and  among  the anxiety-disordered adolescents, a total SCAS score at or above  a diagnostic cutoff was  a significant predictor of homotypic comorbidity, as were continuous measures of total anxiety symptoms and disorder-specific symptoms. Among referral causes, the only significant predictor of homotypic comorbidity was found in the total sample with the referral cause of autistic symptoms (OR, 9.6; 95% CI, 1.1 to 80.6; p =  .037).  Adjusted  ORs  for  the association between anxiety disorders, self-rated anxiety  symptoms, and homotypic comorbidity are presented separately for the total and anxious samples in Table 3.

TABLE 3. Adjusted odds ratios with 95% confidence intervals for the association between anxiety disorders, anxiety symptoms, and homotypic comorbidity

|                                                                 | Homotypic Comorbidity   | Homotypic Comorbidity   | Homotypic Comorbidity   | Homotypic Comorbidity   | Homotypic Comorbidity   | Homotypic Comorbidity   |
|-----------------------------------------------------------------|-------------------------|-------------------------|-------------------------|-------------------------|-------------------------|-------------------------|
| Covariates*                                                     | Total Sample (N = 125)  | Total Sample (N = 125)  | Total Sample (N = 125)  | Anxious Sample (n = 58) | Anxious Sample (n = 58) | Anxious Sample (n = 58) |
|                                                                 | OR                      | 95% CI                  | p value                 | OR                      | 95% CI                  | p value                 |
| Anxiety disorders                                               |                         |                         |                         |                         |                         |                         |
| Social anxiety                                                  | 11.560                  | 3.832-34.872            | <.001                   | 2.949                   | 0.909-9.573             | .072                    |
| Generalized anxiety                                             | 23.812                  | 6.429-88.187            | <.001                   | 7.226                   | 1.857-28.122            | .004                    |
| Specific phobia                                                 | 18.060                  | 5.492-59.392            | <.001                   | 6.148                   | 1.813-20.848            | .004                    |
| Panic disorder                                                  | 105.275                 | 9.313-1189.995          | <.001                   | 38.185                  | 3.437-                  | .003                    |
|                                                                 |                         |                         |                         |                         | 424.235                 |                         |
| Agoraphobia                                                     | +∞ †                    | -                       | -                       | +∞ †                    | -                       | -                       |
| Separation anxiety disorder                                     | 13.503                  | 1.337-136.390           | .027                    | 6.476                   | 0.611-68.663            | .121                    |
| Unspecified anxiety disorder                                    | -∞ †                    | -                       | -                       | -∞ †                    | -                       | -                       |
| Anxiety symptoms (Spence Children's Anxiety Scale, self-report) |                         |                         |                         |                         |                         |                         |
|  Diagnostic cutoff ‡                                           | 11.420                  | 3.336-39.094            | <.001                   | 5.664                   | 1.498-21.414            | .011                    |
|  Screening cutoff a                                            | 6.706                   | 1.402-32.075            | .017                    | 0.666                   | 0.085-5.188             | .698                    |
| Total score b                                                   | 1.073                   | 1.037-1.112             | <.001                   | 1.061                   | 1.017-1.106             | .006                    |
| Social anxiety b                                                | 1.327                   | 1.146-1.537             | <.001                   | 1.229                   | 1.032-1.463             | .021                    |
| Generalized anxiety disorder b                                  | 1.328                   | 1.144-1.542             | <.001                   | 1.212                   | 1.024-1.435             | .025                    |
| Physical injury fears (specific phobia) b                       | 1.187                   | 1.004-1.404             | .044                    | 1.134                   | 0.933-1.379             | .206                    |
| Panic/agoraphobia b                                             | 1.254                   | 1.123-1.401             | <.001                   | 1.173                   | 1.042-1.321             | .009                    |
| Separation anxiety b                                            | 1.338                   | 1.139-1.572             | <.001                   | 1.277                   | 1.056-1.543             | .011                    |

CI, Confidence interval; OR, odds ratio.

*Each multivariate model included a single covariate adjusted for age and sex.

+∞ † Diagnosis was only present without homotypic comorbidity; -∞ † Diagnosis was only present without homotypic comorbidity; ‡Total score of 33 or more (23);  a Total score of 22 or more (23);  b Continuous scores.

## Heterotypic comorbidity

Categories of K-SADS-derived heterotypic comorbid diagnoses are presented as supplementary material (see Table S1). Heterotypic comorbidity was found in 53 anxiety-disordered adolescents (91.4%; 95%  CI,  81.4  to  96.3).  Heterotypic  comorbidity without concurrent homotypic  comorbidity was found in 30 adolescents (51.7%). Logistic regression analyses showed that no specific anxiety disorder was significantly associated with increased odds of overall heterotypic  comorbidity.  In  separate  multivariate models,  adjusted  for  age  and  sex,  single  anxiety disorders  were  used  as  independent  variables,  in logistic  regression  analyses  of  associations  between the  four  most  frequent  heterotypic  categories  and individual anxiety disorders. Significant relationships between three heterotypic categories and four anxiety  disorders  were  observed:  trauma  disorders and panic disorder (OR, 8.6; 95% CI, 1.6 to 46.1; p = .012); trauma disorders and social anxiety (OR, 0.1; 95% CI, 0.1 to 0.6; p = .011); depressive disorders and generalized anxiety (OR, 4.1; 95% CI, 1.2 to 13.9; p =  .024);  and conduct disorders and agoraphobia (OR, 5.7;  95%  CI,  1.1  to  29.9; p =  .040).  Overall, significantly higher rates of trauma-related disorders were observed among adolescents with anxiety than in those without (15.5% vs. 4.5%; p = .037). There were no other significant differences in heterotypic comorbid  categories  between  anxious  and  nonanxious adolescents. Heterotypic comorbidity in the total  sample  and  separately  for  anxious  and  nonanxious adolescents is presented in Table 1.

## Discussion

This  study  examined  the  characteristics  of  seven anxiety disorders in a sample of 125 adolescents who were consecutively referred to psychiatric outpatient clinics  for  multiple  causes.  At  least  one  anxiety disorder  was  found  in  46.4%  of  adolescents,  with girls  diagnosed  more  than  three  times  more  often than boys. The most frequent anxiety disorder was social  anxiety  (27.2%),  whereas  the  least  frequent were separation anxiety (4.0%) and unspecified anxiety disorder (1.6%). Conspicuous differences in clinical presentation  between  anxious  and  nonanxious adolescents were higher levels of self-rated anxiety symptoms,  higher proportions of prior admission, and more frequent reporting of depression as the referral cause. As compared with psychiatrically referred adolescents without anxiety, anxious  adolescents  reported  more  symptoms  of pain and  difficulties making  friends. Nearly all adolescents who were diagnosed with anxiety disorders had concurrent disorders, with heterotypic comorbidity being twice as common as homotypic comorbidity.

To  the  best  of  our  knowledge,  there  are  no comparable reports involving the use of a diagnostic interview to investigate the specific characteristics of multiple  anxiety  disorders  among  adolescents  with multiple referral causes in a non-specialized psychiatric setting. Previous studies of youths referred specifically for anxiety treatment have found differences in clinical characteristics between children and adolescents with regard to prevalence rates, especially for separation anxiety disorder (which is uncommon  among adolescents) and symptom  severity  (which  has  been  found  to  be significantly  higher  among  adolescents)  (27,  28). Thus,  relating  the  findings  of  the  current  study  to three  previously  reported  studies  of  prevalence  in non-specialized  psychiatry  is  curtailed,  because  the other studies all included either combined samples of children  and  adolescents  or  only  younger  children (12-14). With this limitation in mind, the prevalence of any anxiety disorder observed in this study is more akin to the estimates of 57.7% reported by Hammerness and colleagues in the United States (13) and  32.7%  reported  by  Hansen  and  colleagues  in Norway (14) rather than to the rate of 5.7% reported by  Esbjørn  and  colleagues  in  Denmark  (12).  This must  be  viewed  in  relation  to  the  methodological similarities and differences of these studies. Similarities included the setting and the inclusion of participants irrespective of referral cause. Dissimilarities in the current study as compared with previous studies were as follows: 1) a higher proportion  of  girls;  2)  the  age  range  (i.e.,  only adolescents);  and  3)  the  categories  and  number  of studied anxiety disorders. The low-prevalence Danish  study  differs  from  both  the  current  study, North American and Norwegian studies in the same way: it used ICD-10 criteria, as well as unstandardized  diagnostic  assessments.  However, not even the 95% CI (37.9 to 55.1%) surrounding the observed  prevalence  of  any  anxiety  in  the  current study  included  the  reported  estimates  from  the United  States  and  Norway,  although  the  same  KSADS  diagnostic  interview  was  used.  It  is  worth noting that the described between-study differences listed  previously  are  analogous  to  some  of  the findings reported by Baxter and colleagues in their meta-analysis of sources of anxiety prevalence variability  in  community  studies  (18).  Specifically, Baxter and colleagues found that sex explained 25% of the variance and that there was no effect of the diagnostic instrument after the number of disorders was considered. This observation suggests that anxiety  prevalence  variability  in  community  and clinical  studies  may  be  influenced  by  the  same moderators, although further research is needed to understand their specific impact on child and adolescent psychiatry.

As can be expected in a general psychiatric sample that  includes  patients  with  multiple  referral  causes, total comorbidity among anxiety-disordered adolescents  was  very  high,  with  only  5%  being diagnosed  with  one  single  anxiety  disorder  and  no other concurrent disorders. Overall homotypic comorbidity was in line with the findings reported by Hammerness  and  colleagues  in  the  United  States (13),  with  most  anxiety  disorders  associated  with additional diagnoses of anxiety. Although comorbidity  estimates  reported  by  Esbjørn  and colleagues  in  Denmark  (12)  and  by  Hansen  and colleagues  in  Norway  (14)  were  markedly  lower  as compared  with  the  findings  of  the  current  study, observations of heterotypic comorbidity as the more prevalent type were similar. Moreover, the percentage point ( pp ) differences between homotypic and heterotypic comorbidity in those studies (40 pp and 46 pp ) were similar to the difference observed in the  current  study  (48 pp ),  which  implies  that  this comorbidity  pattern  is  a  clinical  characteristic  that can  be  expected  among  anxious  youths  in  nonanxiety-specialized  psychiatric  settings.  The  more frequently  observed  heterotypic  comorbidity  could also  be  a  possible  explanation  for  the  low  anxiety prevalence estimates observed in patient registers in Denmark  and  Norway  and  in  the  current  study clinics before data collection, if in fact the heterotypic comorbidity was the primary cause for the seeking of help and diagnostic procedures inadequately assessed the presence of concurrent disorders.

As has been seen in other studies, self-ratings of family,  interpersonal,  school,  sleep,  and  somatic functioning  among  anxious  adolescents  revealed problems in all areas. Few significant differences in domain function were found between anxious and non-anxious adolescents, but the frequency and cooccurrence of the inquired problems with anxiety still warrant noting. However, although a high proportion of anxious adolescents rated themselves as  having  functional  impairment  or  difficulties  in multiple areas, the impairment of these adolescents cannot be attributed to anxiety specifically because the  intake  questionnaire  was  designed  to  measure overall functioning, regardless of presenting symptoms.  Nonetheless,  the  clinical  correlates  of anxiety  disorders  observed  in  this  study  have  been associated with more chronicity and negative outcomes, and they call attention to the necessity of comprehensive assessment and proficient treatment planning to fully attend to the complexity of symptoms in this patient group (5, 29-33).

Finally, in line with the findings of the Norwegian study  (14),  we  determined  that  a  referral  cause  of anxiety  was  an  inadequate  method  for  identifying adolescents with anxiety, because it yielded a sensitivity of only 21 %.

## Strengths

There  are  several  indicators  of  the  validity  and generalizability  of  the  current  investigation.  First, participants were consecutively included irrespective of  referral  cause  or  presenting  symptoms.  Second, the diagnostic assessments were based on a standardized interview, thereby increasing both diagnostic precision and detection. Third, data collection was conducted in a non-anxietyspecialized setting and is thus likely to be generalizable to standard clinical care settings. Fourth,  the  proportion  of  girls  observed  in  the current sample (58%) was similar to the proportion observed  in  referrals  to  the  clinics  during  the  6month  period  that  followed  the  end  of  the  study (63%).

## Limitations

Several  limitations  of  the  current  study  should  be acknowledged.  Only  13  boys  met  the  diagnostic criteria  for  an  anxiety  disorder,  thus  precluding analyses of sex differences beyond the prevalence of any anxiety disorder. A majority of parents did not report their educational level  or  socioeconomic status, which precluded the analysis of these demographics  in  relation  to  anxiety. Whereas  the administration  of  the  K-SADS  typically  involves separate  interviews,  adolescents  and  parents  were interviewed together in the current study, which may have  had  an  effect  on  the  inclination  of  both informants to describe psychiatric symptoms. Moreover, diagnoses were based only on information collected during the K-SADS interview; interviewers were unaware of the results of questionnaires completed at intake or other additional information sources. This diagnostic procedure requires patients to be able to adequately recognize and verbalize their feelings and  behaviors, but these skills can  be impaired in psychiatrically referred youths for various reasons.

## Clinical Significance

For the detection of anxiety disorders  among adolescents referred to non-anxiety-specialized child and adolescent psychiatry, the findings of this study provide  further  evidence  for  the  referral  cause  of anxiety being an inadequate method, with detection rates ranging from only 21% for any anxiety to 50% for the diagnosis of unspecified anxiety. Thus, this study provides further support for the routine use of standardized and structured instruments to improve both the precision and detection rates of anxiety in this setting. This study also adds important information about clinical presentation and comorbidity patterns, and it underscores the importance  of  comprehensive  assessment  to  fully address  the  complexity  of  the  symptoms  in  this patient group.

## Role of Funding Source

This research was supported by the Swedish Research Council, the Swedish Brain Foundation, the Swedish  Alcohol  Monopoly  Research  Council,  the Swedish Council for Working Life and Social Research, the Uppsala and Örebro Regional Research Council, the Fredrik and Ingrid Thurings Foundation,  the  County  Council  of  Västmanland, the König-Söderströmska Foundation, the Swedish Psychiatric Foundation, and the Svenska Spel Research Foundation. The funding sources had no further role in study design; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the paper for publication.

## Conflict of Interest

The  authors  declare  that  they  have  no  potential conflicts  of  interest  with  respect  to  the  research, authorship, or publication of this article.

## Acknowledgments

The authors would like to thank all of the adolescents, parents, and staff at the mental health service clinics for their participation in and contributions to this study

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## Supplementary file

TABLE S1. Categories of diagnoses from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, among 125 adolescents as derived from the Schedule for Affective Disorders and Schizophrenia for School-Age Children.