Clinical Characteristics of High-Functioning Youth With ASD (2013)

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ReSEARCH ARTICLe

Clinical characteristics of
high-functioning youth with autism spectrum disorder
and anxiety
Danielle Ung1,2, Jeffrey J Wood3, Jill Ehrenreich-May4, Elysse B Arnold2, Cori Fujii3, Patricia Renno3,
Tanya K Murphy2,5, Adam B Lewin2,5, P Jane Mutch2,5 & Eric A Storch*1,2,5

Practice points
„„ Clinically significant anxiety is common in youth with autism spectrum disorder (ASD) and exacerbates the
severity of ASD core symptoms, in addition to family, school and social functioning.

„„ Anxiety in youth with ASD presents heterogeneously, differing in its nature, severity and associated
impairment.

„„ Distinguishing anxiety symptoms versus characteristics of ASD is necessary to appropriately treat the
respective symptom dimension.

„„ Given the heterogeneous presentation of anxiety in youth with ASD, tailoring treatment to patient
characteristics will likely enhance outcomes and intervention acceptability.

„„ When assessing anxiety in youth with ASD, clinicians should be aware of the potential for discrepancies
between child and parent reports of anxiety presence and severity due to reasons such as limited child insight,
cognitive and communication deficits, overlapping symptomology, and parents’ awareness of their children’s
internal states.

„„ In addition to anxiety, comorbid diagnoses (e.g., oppositional defiant disorder and ADHD) are common in
youth with ASD. Behavioral problems frequently occur in youth with ASD and can compromise treatment
efficacy.

„„ Research is needed to examine potential moderators of treatment outcome in anxious youth with ASD.

1
Department of Psychology, University of South Florida, 4202 East Fowler Avenue, PCD 4118G, Tampa, FL 33620-7200, USA
2
Department of Pediatrics, University of South Florida, 880 6th Street South, St Petersburg, FL 33701, USA
3
Departments of Education, Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, Moore Hall 3132A, 405 Hilgard
Avenue, Los Angeles, CA 90095-1521, USA
4
Department of Psychology, University of Miami, PO Box 248185, Coral Gables, FL 33124-0751, USA
5
Departments of Psychiatry & Behavioral Neuroscience, 3515 East Fletcher Avenue, Tampa, FL 33613, USA
*Author for correspondence: Tel.: +1 727 767 8230; Fax: +1 727 767 7786; [email protected] part of

10.2217/NPY.13.9 © 2013 Future Medicine Ltd Neuropsychiatry (2013) 3(2), 147–157 ISSN 1758-2008 147
ReSEARCH ARTICLe Ung, Wood, Ehrenreich-May et al.

SUMMARY Aim & methods: Clinical characteristics were examined in 108


high-functioning youth (children with a full IQ scale of at least 70) with an autism spectrum
disorder (ASD; aged 7–15 years) who were presenting for inclusion in one of four clinical
trials examining the efficacy of cognitive behavioral therapy in youth with ASD and anxiety.
Results: We present baseline characteristics of this cohort, including prevalence rates
of anxiety and comorbid disorders, and correlates of anxiety (e.g., comorbid diagnoses,
impairment, anxiety severity and mental health services received) as a function of age and
ASD diagnosis in treatment-seeking youth. Primary anxiety disorders were: 41.7% (n = 45)
social phobia, 25.9% (n = 28) generalized anxiety disorder, 15.7% (n = 17) separation anxiety
disorder, 12.0% (n = 13) obsessive–compulsive disorder and 4.6% (n = 5) specific phobia.
Overall, 91.6% of participants (n = 99) met criteria for two or more anxiety disorders. Parents
reported considerable functional impairment as measured by the Columbia Impairment
Scale and anxiety severity as measured by the Pediatric Anxiety Rating Scale; this did not
statistically differ as a function of ASD diagnosis or age. Anxiety severity, the number of
comorbid anxiety diagnoses and total comorbid diagnoses were directly associated with
parent-reported child impairment. Youth with ASD and anxiety present as a heterogeneous
cohort with significant impairments and complex diagnostic presentations. Conclusion:
These data provide information about the nature of anxiety in youth with ASD, which may
foster the development of tailored treatment protocols.

Autism spectrum disorder (ASD), comprised generalized anxiety disorder (GAD; 15–35%)
of autistic disorder, Asperger’s syndrome and [4,13–16] . Anxiety in youth with ASD has been
pervasive developmental disorder not otherwise linked with increased difficulties across several
specified, is a chronic and debilitating neuro- domains including social reciprocity, behavior
psychiatric disorder affecting as many as one in problems, sleep disturbances, family conflict,
88 youth in the USA [1] . Characterized by social stereotyped behaviors and ASD symptomol-
and/or communication deficits and restricted ogy [8,13,17] . Some evidence suggests that the
interests/repetitive behaviors, affected individu- presentation, frequency and severity of anxiety
als can vary widely in the presentation and sever- symptoms in youth with ASD may differ as a
ity of core ASD symptoms and comorbid condi- function of age and ASD diagnosis. For example,
tions, and the degree to which autism symptoms older versus younger youth with ASD are more
and comorbid conditions impair family, school likely to report anxiety symptoms and be diag-
and social functioning [2] . Approximately 50% nosed with an anxiety disorder [4] . Youth with
of youth with ASD experience clinically signifi- Asperger’s syndrome and pervasive developmen-
cant anxiety that impairs functioning above and tal disorder not otherwise specified who are char-
beyond the impact of core ASD symptomology acterized as having higher adaptive functioning
[2–4] . In addition to the possibility of shared and fewer cognitive impairments may experience
pathophysiology of ASD and anxiety [5–8] , this greater anxiety than youth with autistic disor-
cohort may be particularly prone to experiencing der [18] . These youth may have greater levels of
clinically significant anxiety given findings that insight and interest in socially interacting with
youth with ASD experience heightened sensory others, but have difficulty with implementation,
sensitivity, difficulty understanding social cues leading to the development of social anxiety
and regulating emotions, and communication [14,19] . Poor pragmatic language use and deficits
deficits [9–12] . in verbal and nonverbal social reciprocity (e.g.,
Anxiety disorders are more prevalent in taking phrases or common sayings literally) may
youth with ASD than in typically developing also contribute to anxiety [19] . For example, these
children and have been associated with impair- youth may not be able to correctly interpret con-
ments above and beyond ASD symptomology versations directed towards them, which causes
[8,13] . Common comorbid anxiety disorders confusion and/or inter­personal problems, and
reported in children and adolescents with ASD leads to increased anxiety symptoms.
include obsessive–compulsive disorder (OCD; At present, the clinical characteristics associ-
17–37%), separation anxiety disorder (SAD; ated with anxiety in youth with ASD require
9–38%), specific phobia (26–57%), social pho- further exploration. In the present report, we
bia (13–40%), panic disorder (2–25%) and describe the phenomenology (i.e., gender, age,

148 Neuropsychiatry (2013) 3(2) future science group


Clinical characteristics of high-functioning youth with autism spectrum disorder & anxiety ReSEARCH ARTICLe

ethnicity, frequency and type of anxiety disor- participants were between the ages of 7 and
ders, anxiety severity, functional impairment, 15 years, had a confirmed ASD diagnosis made
behavioral problems and mental health services by a certified rater through the Autism Diag-
received) of treatment-seeking youth with ASD nostic Interview-Revised and an observational
(conducted immediately prior to beginning measure (e.g., Autism Diagnostic Observation
treatment). We had three primary research Schedule and Childhood Autism Rating Scale),
questions. First, what is the frequency and type met DSM-IV diagnostic criteria for a primary
of primary anxiety disorder and comorbid dis- non-ASD diagnosis of an anxiety disorder (e.g.,
orders in high-functioning youth with ASD SAD, GAD, social phobia, panic disorder or
presenting for anxiety treatment? Second, what OCD) and had an IQ equal to or above 70. Par-
is the association between anxiety severity and ticipants were excluded if they met criteria for
functional impairment? Finally, what is the asso- bipolar disorder, schizophrenia or schizoaffective
ciation between comorbid anxiety diagnoses and disorder, endorsed clinically significant suicidal-
functional impairment, and does this vary by age ity or engaged in suicidal behaviors within the
and ASD diagnosis? last 6 months, had a significant and/or unsta-
There are several implications of this study. ble medical illness, initiated an antidepressant
First, rates of anxiety disorders and level of anxi- within 10–12 weeks preceding study enrollment
ety severity in anxious youth with ASD obtained or an antipsychotic within 6–8 weeks prior
in our study may provide an initial framework for to study enrollment, or made any changes in
evaluating anxiety in treatment-seeking cohorts established psychotropic medications (e.g., anti-
of youth with ASD and anxiety. Second, in the depressants and anxiolytics) within 6–8 weeks
same light, the results of this study may help to before study enrollment (6 weeks for antipsy-
highlight the clinical complexity of youth with chotic), or made any changes in alternative
ASD, which may help shape protocols to tar- medications that might have behavioral effects
get anxiety symptoms and impairment. Finally, within 4–6 weeks prior to the study baseline
this study will inform how impairment associ- assessment.
ated with anxiety and ASD symptoms can vary
according to age and ASD diagnoses, which may Independent evaluators
„„
help us to individualize treatment and increase Anxiety measures were administered by inde-
treatment efficacy. pendent evaluators who were blind to the
child’s eventual study treatment allocation.
Methods Independent evaluators were doctoral students
A total of 108 children and adolescents between in clinical psychology who were trained under
the ages of 7 and 15 years (mean: 10.95; stan- the supervision of licensed clinical psycho­
dard deviation [SD]: 2.07) were enrolled in one logists. Training included observations, video
of four randomized, controlled trials examin- training, inter-rater reliability checks and case
ing the efficacy of cognitive behavioral therapy conferences. Weekly supervisory meetings with
for anxiety in youth with ASD. All studies were a licensed clinical psychologist were held to
approved by the local institutional review board, discuss ratings.
parents consented and youth with ASD assented
to their participation in these studies. Partici- Clinician-administered measures
„„
pants were enrolled at two sites, the Universities Autism Diagnostic Interview-Revised
of South Florida (n = 86; FL, USA) and Cali- The Autism Diagnostic Interview-Revised [21] is
fornia, Los Angeles (n = 22; CA, USA), through a standardized semistructured clinical diagnos-
a variety of recruitment strategies, including tic interview for assessing ASD in children and
phone interviews and referrals. At the baseline adults based on the diagnostic criteria for autism
visit, independent evaluators queried parents and in the DSM-IV-TR [22] . The Autism Diagnostic
youth on a number of measures to establish clini- Interview-Revised focuses on behaviors in the
cian ratings. Upon completion of parent, child three content areas or domains: quality of social
and clinician questionnaires, participants were interaction (e.g., emotional sharing, social smil-
randomized to receive weekly cognitive behavior ing and responding to other children); commu-
therapy or to the control group [20] . nication and language (e.g., stereotyped utter-
Inclusion and exclusion criteria were largely ances and social use of language); and repetitive,
consistent across studies. In this report, restricted and stereotyped interests and behavior

future science group www.futuremedicine.com 149


ReSEARCH ARTICLe Ung, Wood, Ehrenreich-May et al.

(e.g., unusual preoccupations, and hand and to excellent [Ung D, Arnold EB, De Nadai AS et al. Inter-
finger mannerisms) [21] . rater reliability of the Anxiety Disorders Interview
Schedule for DSM-IV in high functioning youth with
Autism Diagnostic Observation autism spectrum disorder (2013), Submitted] .
Schedule – Module 3
The Autism Diagnostic Observation Schedule Clinical Global Impressions Scale – Severity
– Module 3 is a structured observation assess- The Clinical Global Impressions Scale – Sever-
ment used to elicit atypical language use, social ity (CGI-S) is a clinician-rated scale of global
interaction and stereotyped behaviors of individ- psycho­pathology severity rated on a 7-point Lik-
uals suspected of having ASD [23] . The Autism ert scale from 0 (no illness) to 6 (extremely severe)
Diagnostic Observation Schedule has demon- [29] . Clinicians rate the severity of a patient’s ill-
strated strong psychometric properties, includ- ness by comparison with their experiences with
ing test–retest reliability, inter-rater reliability other patients with the same illness. The CGI-S
and discriminant validity [23,24] . In this study, has been used as measures of global syndrome
a trained clinician administered the Autism severity, and treatment response and efficacy.
Diagnostic Observation Schedule to aid ASD
diagnosis. Pediatric Anxiety Rating Scale
The Pediatric Anxiety Rating Scale (PARS) [30] is
Anxiety Disorders Interview Schedule for the a 66-item clinician-rated scale assessing anxiety
DSM-IV – Parent & Child versions symptom presence and the associated severity in
The Anxiety Disorders Interview Schedule for children over the past week. Scores on the PARS
the DSM-IV – parent and child versions [25] is Severity Scale range from 0 to 30, with scores
a clinician-administered, structured interview greater than 13 consistent with clinically sig-
used to assess the presence, severity and level of nificant levels of anxiety [30] . Final PARS scores
interference of anxiety disorders and common are determined by the clinician after separate
disorders in youths based upon the criteria set interviews with the parent and child. The PARS
by the DSM-IV-TR [22] . Final diagnosis is deter- (five-item) total score was used for our estimate
mined by the clinician after separate interviews of anxiety severity. The five items included ques-
with the parent and child. Clinical diagnoses tions that addressed frequency and severity of
reflect endorsement of symptoms and a severity anxiety symptoms, avoidance caused by anxiety
rating (patient impairment/distress) of at least symptoms and level of interference in/outside of
4 on a 0–8 scale. The anxiety diagnosis with the home caused by anxiety symptoms. Clini-
the highest severity rating was labeled as the cians rated these questions on a 5-point Likert
primary anxiety diagnosis and all other anxiety scale from 0 (no symptoms) to 5 (extreme).
diagnoses were considered secondary. If two or
more anxiety diagnoses had the same highest Service Assessment for Children
severity rating, the clinician determined the & Adolescents
primary anxiety diagnosis based upon parent The Service Assessment for Children and Ado-
and child report, and their gestalt impression lescents is a standardized interview for parents,
regarding which disorder was more problematic. documenting the use of mental health services
Such a distinction between primary and second- including outpatient, inpatient and school based
ary diagnoses is essential because the primary [31] . Parents are asked if they have received assis-
diagnosis that is the most problematic for the tance for their child’s behavioral or emotional
youth and their family is often the target of problems, the type of assistance their child has
treatment and used to tailor treatment protocols received (e.g., assessment, individual therapy,
to meet the unique needs of the youth. More- group therapy or medication) and the number
over, the Anxiety Disorders Interview Schedule of hours spent using these services.
for the DSM-IV – parent and child versions has
demonstrated strong psychometric properties in Parent & patient report measures
„„
typically developing youth, including test–retest Child Behavior Checklist
reliability [26] , inter-rater reliability [27] and con- The Child Behavior Checklist is a parent-rated
current validity [28] . In a recent study conducted questionnaire consisting of 118 items that
in our clinic, inter-rater reliability of primary assesses the intensity and frequency of behavioral
diagnoses and secondary diagnoses were good and emotional problems exhibited by children

150 Neuropsychiatry (2013) 3(2) future science group


Clinical characteristics of high-functioning youth with autism spectrum disorder & anxiety ReSEARCH ARTICLe

within the past 6 months [32] . The Child Behavior Anxiety diagnoses, symptoms & comorbid
„„
Checklist produces nine clinical syndrome scales: conditions
withdrawn, anxious–depressed, social problems, The distribution of primary anxiety, secondary
thought problems, attention problems, delinquent anxiety and comorbid diagnoses are summarized
behavior, aggressive behavior, internalizing dys- in Table 1. Regarding primary anxiety diagnoses,
function and externalizing dysfunction. Each 41.7% (n = 45) presented with social phobia,
item is rated on a 3-point Likert scale: not at all 25.9% (n = 28) presented with GAD, 15.7%
(0), sometimes (1), all the time (2). (n = 17) presented with SAD, 12.0% (n = 13)
presented with OCD and 4.6% (n = 5) presented
Columbia Impairment Scale – Parent & Child with specific phobia. Overall, 91.6% (n = 99)
versions met criteria for two or more anxiety disorders.
The Columbia Impairment Scale (CIS) – Par- Of these, 28.3% (n = 28) had two anxiety disor-
ent (CIS-P) and Child (CIS-C) versions [33] are ders, 27.8% (n = 30) had three anxiety disorders
psychometrically sound 13-item parent-report and 38.0% (n = 41) had four or more anxiety
and child-report scales that assess impairment disorders.
in several domains of functioning, including In addition to meeting a diagnosis of an
school/work, social and home/family [34] . Each anxiety disorder, 75.0% (n = 81) met criteria
item is rated on a 4-point Likert scale that ranges for one or more comorbid nonanxiety disor-
from no problem (0) to a very bad problem (4). ders (i.e., oppositional defiant disorder, ADHD
The CIS total score was used for our estimates inattentive/hyperactivity/combined type,
of parent-reported child functional impairment. depressive disorders, selective mutism, sleep ter-
ror and enuresis). Of the most common comorbid
Data analysis
„„
Data were analyzed and reported through the
Table 1. Primary anxiety diagnoses, secondary anxiety diagnoses and other
use of frequencies, percentages, means, SDs,
DSM-IV comorbidities diagnostic summary.
correlations and one-way analysis of variance to
explore the association between ASD diagnosis Diagnosis type n %
and functional impairment. Through the use of Primary anxiety diagnosis
a computer program, hot deck imputation was Social phobia 45 41.67
used to address missing data [35] . This imputa- Generalized anxiety disorder 28 25.93
tion substitutes missing values using other sim- Separation anxiety disorder 17 15.74
ilar observations (i.e., variables) in the sample Obsessive–compulsive disorder 13 12.04
that are specified by the user. Specific phobia 5 4.63
Nonprimary anxiety diagnosis
Results
Specific phobia 61 56.48
Demographic characteristics
„„
Generalized anxiety disorder 53 49.07
The average age was 10.95 years (SD: 2.07;
Social phobia 51 47.22
range: 7–15 years). There were approximately
Obsessive–compulsive disorder 27 25.00
four-times more males (n = 86) than females
Separation anxiety disorder 23 21.30
(n = 22). The average age of the males was
Post-traumatic stress disorder 3 2.78
11.01 years (SD: 2.08) and the average age of
Panic disorder 2 1.85
the females was 10.82 years (SD: 2.02; p-value
Agoraphobia 1 0.93
not significant). The ethnic/racial distribution
Other DSM-IV diagnosis
was 84.3% (n = 91) Caucasian, 7.4% (n = 8)
Hispanic/Latino, 4.6% (n = 5) Asian and 3.7% ADHD combined type 37 34.26
(n = 4) other/mixed. Oppositional defiant disorder 32 29.63
ADHD inattentive type 31 28.70
ASD distribution
„„ Dysthymia 10 9.26
The ASD distribution was as follows: 42.6% ADHD hyperactivity type 7 6.48
(n = 46) were diagnosed with an autistic disor- Major depressive disorder 4 3.70
der, 32.4% (n = 35) were diagnosed with Asperg- Conduct disorder 3 2.78
er’s disorder and 25.0% (n = 27) were diagnosed Enuresis 3 2.78
with pervasive developmental disorder not Sleep terrors 3 2.78
otherwise specified. Selective mutism 1 0.93

future science group www.futuremedicine.com 151


ReSEARCH ARTICLe Ung, Wood, Ehrenreich-May et al.

nonanxiety disorders diagnosed, 34.3% (n = 37) as measured by the CIS-P (r = 0.22; p < 0.05).
presented with ADHD combined type, 29.6% Number of comorbid anxiety diagnoses and total
(n = 32) presented with oppositional defiant dis- comorbid diagnoses were directly associated
order and 28.7% (n = 31) presented with ADHD with parent-reported child functional impair-
inattentive type. Of the participants who met ment (r = 0.26, p < 0.01; r = 0.48, p < 0.001,
criteria for a comorbid nonanxiety disorder, respectively).
28.7% (n = 31) met criteria for two nonanxiety
comorbid diagnoses, 5.6%(n = 6) met criteria for Obtained services & medication history
„„
three diagnoses and 1.9% (n = 2) met criteria for Overall, 82.4% of the parents (n = 89) in the
four or more diagnoses. sample reported receiving one or more mental
Table 2 summarizes parent- and child-reported health service for their child prior to presentation
measures (e.g., Child Behavior Checklist, CIS-P (mean: 1.95; SD: 1.42; range: 0–6) including
and CIS-C) and clinician-administered mea- individual treatment/therapy, psychiatric medi-
sures (i.e., CGI-S, Anxiety Disorders Interview cation management, or family treatment or edu-
Schedule for the DSM-IV – parent and child ver- cation. Approximately 62.9% (n = 68) received
sions, and PARS). Results revealed a PARS (five psychiatric services involving medication man-
item) mean score of 16.44 (n = 108; SD: 2.39), agement, 36.1% (n = 39) participated in indi-
corresponding to moderate anxiety severity, a vidual psychotherapy, 24.1% (n = 26) received
CGI-S mean score of 3.77 (n = 108; SD: 0.74), rehabilitative services (n = 19), 22.2% (n = 24)
corresponding to moderate to moderate-to- attended a special school or special classroom for
severe anxiety symptoms, a CIS-P mean score students with problems with behaviors or feel-
of 23.06 (n = 108; SD: 8.87), corresponding to ings, and 23.1% (n = 25) received counseling or
little-to-moderate functional impairment and a therapy in school. Of the youth who were tak-
CIS-C mean score of 14.47 (n = 106; SD: 9.13), ing medication (n = 68): 33.3% (n = 36) were
corresponding to little functional impairment. taking antidepressants, 20.4% (n = 22) were
Parents reported higher functional impairment taking antipsychotics, 10.2% (n = 11) were tak-
than their children on the CIS-P and CIS-C ing an antidepressant and antipsychotic, and
(mean: 22.94 vs 14.47; n = 106; t = 8.36; 20.4% (n = 22) were taking stimulants (the
p < 0.001). total exceeds 68 as some children were taking
Anxiety severity was directly associated with multiple medicines). There were no significant
parent-reported child functional impairment differences on anxiety severity associated with

Table 2. Sample clinical characteristics.


Measure n Mean SD
Clinician report
PARS total score 108 16.44 2.39
CGI-severity 108 3.77 0.74
Highest ADIS CSR 108 5.67 0.85
Parent report
CIS-P 108 23.06 8.87
CIS-C 106 14.47 9.13
SACA 108 1.95 1.42
CBCL anxious/depressed (t-score) 108 71.33 8.72
CBCL withdraw (t-score) 108 66.94 8.63
CBCL somatic (t-score) 108 63.77 10.4
CBCL social (t-score) 108 70.63 9.19
CBCL thought (t-score) 108 70.56 8.29
CBCL attention (t-score) 108 72.44 11.54
CBCL rule breaking (t-score) 108 58.87 7.82
CBCL aggressive (t-score) 108 64.41 12.10
ADIS CSR: Anxiety Interview Schedule Clinician Severity Rating; CBCL: Child Behavior Checklist; CGI: Clinical Global Impressions;
CIS-C: Columbia Impairment Scale – Child Version; CIS-P: Columbia Impairment Scale – Parent Version; PARS: Pediatric Anxiety Rating
Scale; SACA: Service Assessment for Children and Adolescents; SD: Standard deviation.

152 Neuropsychiatry (2013) 3(2) future science group


Clinical characteristics of high-functioning youth with autism spectrum disorder & anxiety ReSEARCH ARTICLe

any psychiatric medication use (t[106] = 0.81; exclusion of children with OCD from one of
p = 0.42), antidepressant use (t[106] = 1.03; the studies, we carefully assessed OCD case-
p = 0.30), anti­psychotic use (t[106] = -0.62; ness to be consistent with the current diagnostic
p = 0.54) or stimulant use (t[106] = 1.82; system. It is relevant to note that the classifica-
p = 0.07). tion of primary and secondary diagnoses may
not translate well into the real world, where
Anxiety diagnoses, DSM-IV diagnoses,
„„ the clinician is faced with evaluating and treat-
anxiety severity & impairment ing a child with clinically significant anxiety
Age that may not fit into a clear diagnostic profile.
Age was dichotomized into childhood (ages Indeed, the high comorbidity rate suggests the
7–11 years) and early adolescence (ages presence of a common anxiety condition that
12–15 years). There were no significant differ- presents in multiple forms.
ences between participants aged 12–15 years Higher rates of comorbid psycho­pathology
(n = 46) and participants aged 7–11 years (n = 62) in youth with ASD may ref lect biological
for anxiety diagnoses (t[106] = 1.02; p = 0.31), underpinnings (e.g., neurological findings of
DSM-IV diagnoses (t[106] = 0.07; p = 0.95), amygdala abnormalities and serotonin neuro-
anxiety severity (t[106] = -1.30; p = 0.20) transmission abnormalities in youth with ASD
and functional impairment (t[106] = -0.49; and anxiety) [5–7] and/or may be the result of
p = 0.62). common characteristics found in youth with
ASD that increase the risk of developing clini-
ASD diagnoses cal anxiety and comorbid psychopathology
There were no statistically significant differences (e.g., heightened sensory sensitivity, difficulty
by ASD diagnosis found for anxiety diagnoses understanding social cues and regulating emo-
(F[2105] = 0.59; p = 0.55), comorbid diagno- tions and communication deficits) [9–12] . The
ses (F[2105] = 2.70; p = 0.07), anxiety sever- elevated incidence of anxiety disorders in this
ity (F[2105] = 0.77; p = 0.47) and functional treatment-seeking sample may also be indica-
impairment (F[2105] = 0.80; p = 0.45). tive of symptom overlap between diagnoses and
the difficulty teasing apart diagnoses in this
Discussion sample.
This study examined the clinical characteris- In addition to meeting criteria for an anxi-
tics associated with anxiety in high-functioning ety disorder, nearly 75% of participants met
youth with ASD. Multiple anxiety disorders criteria for one or more nonanxiety diagnoses
were common in this sample with over 90% (i.e., oppositional defiant disorder, ADHD
of the sample reporting two or more anxiety and depressive disorders), which is comparable
disorders. The most common primary anxi- with previous reports [13] . Notably, oppositional
ety diagnoses were social phobia (41.7%), defiant disorder and symptoms consistent with
GAD (25.9%), SAD (16.6%), OCD (12.0%; ADHD were prevalent (29.6 and 63%, respec-
diagnostic criteria for one of the clinical trials tively). One possible explanation is that deficits
excluded OCD as a primary diagnosis, conse- inherent in ASD symptomology may increase
quently, rates of primary diagnoses may not be the risk of behavior problems. For example,
representative of this population) and specific social and cognitive deficits may lead to diffi-
phobia (4.6%). By comparison, with clinical culty with emotion regulation when frustrated
studies that have investigated anxiety in youth or distressed [11] . Anxiety symptoms may also
with ASD [20] and typically developing youth manifest themselves as oppositional behaviors
[36,37] , similar rates of individual anxiety disor- (e.g., temper tantrums and aggression) in efforts
ders and comorbid diagnoses were found. For to avoid anxiogenic triggers [38] . This interplay
example, in a clinical study investigating anxi- among anxiety and disruptive behavior in youth
ety in youth with ASD, Wood and colleagues with ASD may complicate diagnosis and treat-
reported that 87.5% of their sample had a diag- ment course. For example, an anxious youth
nosis of social phobia that is comparable with with ASD who is oppositional may refuse to
88.9% of our sample that had a diagnosis of participate in therapy sessions because he/she
social phobia [20] . Rates of OCD were modest does not feel that a problem exists and does not
in this sample compared with other anxiety understand the need for intervention. It may
disorders. In addition to being a result of the be necessary to target comorbid conditions

future science group www.futuremedicine.com 153


ReSEARCH ARTICLe Ung, Wood, Ehrenreich-May et al.

prior to or in conjunction with the treatment Conclusion


of anxiety symptoms to maximize treatment Youth with ASD and anxiety present as a hetero­
adherence and efficacy [39] . For example, treat- geneous population with significant levels of
ing ADHD symptoms or oppositionality prior functional and social impairment. The pres-
to anxiety may increase a youth’s ability to focus ent data highlight the complexity of comorbid
and engage in treatment more effectively. psychopathology and associated impairments
The presence of an anxiety disorder and in youth with ASD seeking anxiety treatment.
comorbid DSM-IV diagnoses was directly asso- To date, treatment options for anxiety in ASD
ciated with functional impairment. Youth who are limited, although improving. Although anti-
had greater ASD symptomology and youth who depressants are widely used in youth with ASD
had greater anxiety severity were reported to [44] , there are few corresponding efficacy data. By
have greater levels of functional impairment, contrast, cognitive behavioral therapy has shown
which is consistent with previous findings [8] . promising results [20,45] , and is safe and accept-
In addition to the burden and stress associated able to families. To date, it is unclear which and
with ASD symptomology [40] , an additional for whom intervention approaches work best.
diagnosis of an anxiety disorder may increase Consequently, individualized treatment based
the overall degree of impairment experienced on clinical characteristics of the youth with
by the child [8, 41] . Our findings suggest that ASD (e.g., ASD severity, anxiety severity, level
the number and severity of anxiety disorders of impairment, level of insight and motivation)
in youth with ASD is associated with increased may result in greater treatment adherence and
risk of child impairment. Consequently, by efficacy [11,19] .
targeting and treating anxiety in youth with
ASD, associated impairments may significantly Future perspective
decrease and improve quality of life. Youth with ASD are frequently diagnosed with
Consistent with previous findings [8] , anxiety anxiety disorders, causing great concern for clini-
presentation did not differ as a function of age cians and parents. There are a number of ways for
or ASD diagnosis, suggesting that these factors the field to move forward. First, knowledge about
may not play a significant role in determining how anxiety symptoms differ as a function of
anxiety severity and functional impairment. It varying clinical characteristics may inform treat-
would be of interest for future research to exam- ment aims and intervention specificity, thereby
ine how anxiety may differentially present as a increasing treatment efficacy. In this study, age
function of other possible moderating factors and ASD diagnosis did not moderate anxiety
such as intelligence, level of social relations and severity. Future research is needed to explore
comorbidity [8,42,43] . other clinical characteristics and how they may
Some limitations to the present study should moderate anxiety severity (e.g., social relations,
be noted. First, our study reported prevalence intelligence and ASD severity). Second, attention
rates of youth with ASD who were seeking treat- should be given to differentiating anxiety symp-
ment for anxiety at one of two clinical sites. toms from ASD symptoms to inform treatment
Consequently, rates of anxiety diagnoses should protocols and assist in targeting specific areas
not be taken as representative of the greater of impairment. For example, although previous
population of youth with high-functioning findings have shown that serotonin reuptake
ASD, but rather as a sample of anxious youth inhibitors decrease obsessive–compulsive symp-
seeking treatment via clinical research studies at toms in youth with ASD [46–48] , King et al. found
academic specialty clinics. Second, our sample that citalopram did not significantly decrease
consisted largely of Caucasian males, limit- repetitive behaviors in youth with ASD, which
ing the generalizability of our results. Third, may be because repetitive behaviors fundamen-
all diagnoses were based solely on structured tally differ from obsessive–compulsive symptoms
interviews without individual evaluations by [49] . This study highlights the need for the cre-
expert clinicians (despite senior clinician over- ation of or refinement of existing assessment tools
seeing the results/recordings of diagnostic inter- to differentiate anxiety symptoms from ASD
views). Consequently, the subtle differentiation symptoms. Third, future research is needed to
between psychiatric disorders with similar/over- understand how anxiety and comorbid disor-
lapping symptoms may have been missed and ders may interfere or hinder therapy for youth
more subject to parent/child bias. with ASD. Treating these psychiatric comorbid

154 Neuropsychiatry (2013) 3(2) future science group


Clinical characteristics of high-functioning youth with autism spectrum disorder & anxiety ReSEARCH ARTICLe

conditions prior to treatment entry for anxiety Speaker’s Bureau and Scientific Advisory Board for the
diagnoses may increase treatment efficacy by International OCD Foundation. J Ehrenreich-May receives
allowing clinicians to focus their attention on the grant funding from the NIH. JJ Wood receives grant fund-
presenting problems rather than diverting their ing from the NIH. AB Lewin receives grant funding from
attention to problematic comorbid conditions. the University of South Florida Research Council, NIH,
Finally, although empirical data exist for the effi- Agency for Healthcare Research and Quality, CDC,
cacious treatment of anxiety in youth with ASD, National Alliance for Research on Schizophrenia and
efforts to disseminate these treatments have been Affective Disorders, Joseph Drown Foundation and
lacking. Consequently, future research is needed International OCD Foundation. AB Lewin is a consultant
to investigate how efficacious treatment for youth for Prophase Inc. and has received speaker’s honorariums
with ASD and anxiety can be disseminated to from the Tourettes Syndrome Association. TK Murphy has
the population, and practiced among healthcare received research support in the past 3 years from NIH,
providers. Forest Laboratories, Janssen Pharmaceuticals, International
OCD Foundation, Tourette Syndrome Association, All
Acknowledgements Children’s Hospital Research Foundation, CDC, Shire,
The authors would like to acknowledge the contributions Transcept Pharmaceuticals Inc., and National Alliance for
of K Berkman, L Brauer, A Parks and M Toufexis. They Research on Schizophrenia and Affective Disorders. TK
would also like to thank each participating family. Murphy is on the Medical Advisory Board for Tourette
Syndrome Association and Scientific Advisory Board for
Financial & competing interests disclosure International OCD Foundation. TK Murphy receives text-
These studies were supported by grants awarded to EA Storch book honorarium from Lawrence Erlbaum, and research
from the NIH (1R34HD065274-01), All Children support from the Maurice and Thelma Rothman Endowed
Hospital Research Foundation and the University of South Chair. The authors have no other relevant affiliations or
Florida (FL, USA) Internal Grants Program, and grants financial involvement with any organization or entity with
to JJ Wood and J Ehrenreich-May from the NIH a financial interest in or financial conflict with the subject
(5R34HD065274-02). EA Storch has received grant fund- matter or materials discussed in the manuscript apart from
ing in the last 3 years from the NIH, All Children’s Hospital those disclosed.
Research Foundation, CDC, Agency for Healthcare No writing assistance was utilized in the production of
Research and Quality, National Alliance for Research on this manuscript.
Schizophrenia and Affective Disorders, International OCD
Foundation, Tourette Syndrome Association, Janssen Ethical conduct of research
Pharmaceuticals and Foundation for Research on The authors state that they have obtained appropriate insti­
Prader–Willi Syndrome. EA Storch receives textbook hono- tutional review board approval or have followed the princi­
rarium from Springer publishers, American Psychological ples outlined in the Declaration of Helsinki for all human
Association and Lawrence Erlbaum. EA Storch has been an or animal experimental investigations. In addition, for
educational consultant for Rogers Memorial Hospital, a investi­gations involving human subjects, informed consent
consultant for Prophase Inc. and CroNos Inc., and is on the has been obtained from the participants involved.

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