ARTICOLE

ARTICOLE
Articolul numarul 1.
Depression in Children and Adolescents with

Autism Spectrum Disorder
Melissa DeFilippis
Author information Article notes Copyright and License information Disclaimer
This article has been cited by other articles in PMC.
Abstract
Autism spectrum disorder (ASD) has a high rate of psychiatric comorbidity. The prevalence of
comorbid depression seems to correlate with higher functioning forms of ASD and increasing
age. Adolescence is a time when youth struggle with identity and interpersonal relationships, and
a diagnosis of ASD further complicates this process. Adolescents with ASD may be more aware
of the social communication deficits that come with the diagnosis than children with ASD, and it
is theorized that higher functioning adolescents may experience this more acutely. While this
may be true, the lack of reliable rating and diagnostic scales for depression in individuals with
ASD makes it difficult to accurately measure rates of depression among individuals with more
severe verbal deficits. While some research has focused on the prevalence of comorbid
depression in children and adolescents with ASD and on the associated risk factors, there is very
little evidence guiding treatment, including no empirical studies on psychopharmacology for
depression in this population. Available evidence exists only in psychosocial approaches to
treatment at this time and is mostly limited to adult studies. Current evidence will be presented in
this review, including prevalence rates of depression in youth with ASD, various risk and
protective factors, the use of diagnostic rating scales, and treatment studies. The lack of evidence
supporting various treatment approaches will be highlighted, including challenges specific to the
treatment of depression in ASD, which are not addressed in the current treatment studies in
typically developing youth with depression.
Keywords: autism spectrum disorder, depression, adolescents, prevalence, treatment
1. Introduction
Autism is a diagnosis that includes social communication deficits and restricted and repetitive
behavior, interests, or activities, which are severe enough to significantly impair functioning [1].
The prevalence of autism spectrum disorder (ASD) has increased significantly over the past few
decades, now affecting 1 in 59 children in the United States, based on recent Centers for Disease
Control data [2]. ASD also frequently includes associated behavioral symptoms and comorbid
psychiatric diagnoses, which can be as impairing as the core symptoms in some cases. It can be
difficult to distinguish associated symptoms of ASD from comorbid psychiatric diagnoses
(repetitive behaviors in ASD may be very similar to compulsions seen with obsessive-
compulsive disorder, for example), making it hard to measure true comorbidity in youth with
ASD. There is a relative lack in validated instruments for measuring comorbid psychiatric
illnesses in the ASD population; therefore, it is no surprise that prevalence estimates of
depression vary widely, from 2% to 30% [3]. Correctly identifying comorbid diagnoses in
children and adolescents with ASD is important in guiding clinicians toward more appropriate
and targeted treatment for these symptoms.
Depression is a fairly common diagnosis in youth, affecting about 12% of adolescents in the
general population [4]. Most youth with one episode of depression will experience a recurrence
of their symptoms at some point in adolescence or young adulthood [5]. Depression can include
isolation and interpersonal struggles, which may also be present in ASD, and there is always a
concern about suicidality in youth with depression. Individuals with ASD and depression may
experience an increase in obsessions and rituals or, by contrast, a complete loss of interest in
former preoccupations. Agitation, stereotypical behaviors, and self-injury may increase with
depression. In patients with significant deficits in verbal skills, clinicians may need to rely more
on vegetative signs, including decreased adaptive functioning skills and significant appetite and
sleep disturbances compared to baseline [6]. Reviewing research on the prevalence rates and risk
factors of depression in youth with ASD is important to help clinicians more accurately diagnose
depression in this population and provide appropriate interventions. More research is needed
examining efficacy and safety of treatment of depression in youth with ASD as current evidence
is lacking in this area, and most treatment decisions are extrapolated from research in depressed
youth with typical development [7].
2. Prevalence
Several studies examining prevalence of comorbid psychiatric symptoms and diagnoses in ASD
have shown increased rates of both when compared to the general population, though the rates
vary between studies. Accurately measuring the presence of depressive disorders in individuals
with ASD is further complicated by the lack of appropriate rating and diagnostic scales for this
population. In higher functioning youth with ASD, rating scales used in youth with typical
development may be considered, but questions focused on more subjective symptoms, such as
guilt and worthlessness, may be difficult for individuals with ASD and their parents to answer
correctly [8]. In lower functioning individuals with ASD, scales developed for use in individuals
with intellectual disability may be considered, such as the Reiss Scale [9] or the Disability
Assessment Schedule [10]. The Autism Comorbidity Interview—Present and Lifetime version
(ACI-PL) may be a more reliable measure in youth with ASD [11]. This scale includes questions
about increased agitation, self-injury, and temper outbursts as well as asking about baseline
functioning and measuring change from baseline. It also seeks to distinguish impairment from
comorbid psychiatric diagnoses from impairment from the core ASD symptoms.
A population-based study examined the prevalence of psychiatric disorders in 112 children and
adolescents (aged 10 to 14) with ASD [12]. About 70% of the youth had at least one comorbid
disorder and 41% had two or more comorbid disorders based on parent interview using the Child
and Adolescent Psychiatric Assessment (CAPA) [13]. The three-month point prevalence for
depressive symptoms in this sample was 1.4%. A study of comorbid psychiatric diagnoses in
ASD used the Autism Interactive Network database and included 4343 children and adolescents
with ASD, 11% of which had a parent-reported history of comorbid depression [14].
A study examined the prevalence of comorbid psychiatric disorders in 177 youth with ASD,
aged 3 to 18 years [15]. Using the Child Behavior Checklist, parents reported a 26% comorbidity
rate of significant affective symptoms in their children [16,17]. Teacher ratings were lower, with
only 6.2% rated at clinically significant ranges for affective symptoms, suggesting environmental
effects on symptom expression. Other studies have shown different trends in multi-informant
reports. One study examining comorbid psychiatric symptoms in 260 adolescents aged 11 to 17
years (including 43 with a diagnosis of Asperger syndrome or autism) showed higher rates of
depressive and anxiety symptoms in the youth with ASD (26% in ASD youth compared to 12%
in control group) [18]. Unlike the Kanne study, this one showed higher teacher-reported ratings
of symptoms when compared to parental reports.
A validity/reliability study of the Autism Comorbidity Interview—Present and Lifetime version

(a modification of the Kiddie Schedule for Affective Disorders and Schizophrenia—K-SADS)
showed high rates of comorbid psychiatric disorders in a sample of 109 youth with ASD (aged 5
to 17 years) [12,19,20]. In this sample, 10% met diagnostic criteria for major depressive
disorder, and 24% had subsyndromal depressive symptoms. A small study of 33 adolescents with
Asperger syndrome (aged 12 to 17 years) showed 9% scoring in the significant range for
depression on the Children’s Depression Inventory (CDI); however, 70% of the study
participants were already being treated with antidepressants [21,22]. Prevalence studies of
depression in youth with ASD are listed in Table 1.
Table 1
Prevalence Studies of Depression in Youth with autism spectrum disorder (ASD).
Number of Prevalence of
Study/Year Scale Used Comments
Participants Depression
Simonoff et 3 month point
112 CAPA
al., 2008 prevalence = 1.4%
Parent-reported
Rosenberg et community Autism Interactive
4343 11%
al., 2011 diagnoses of Network Database
depression
Kanne et al., 26%—parent-rated
177 CBCL
2009 6%—teacher-rated
26% (anxiety or
Hurtig et al.,
260 depressive CBCL
2009
symptoms)
Leyfer et al., 109 10%—MDD ACI-PL Scale designed
2006 24%— specifically for measuring
subsyndromal psychiatric comorbidity in
Number of Prevalence of
Study/Year Scale Used Comments
Participants Depression
depressive
ASD
symptoms
70% of participants
Barnhill et al.,
33 9% CDI already on antidepressant
2001
medication
A number of studies have compared prevalence rates of psychiatric disorders between youth with
ASD and either the general population or typically developing youth. A large population-based
longitudinal study included 6091 adolescents with and without ASD and examined the
association with depression over eight years [23]. Using the Short Mood and Feelings
Questionnaire (SMFQ) as the measure for depressive symptoms, adolescents with ASD had
higher average scores when compared to the general population at age 10 years, and scores
remained elevated in an upward trajectory until age 18 [24]. Depression at age 18 was associated
with social communication impairments and bullying. Youth with ASD showed higher rates of
depressive and anxiety symptoms than youth in the general population as measured by the
Revised Ontario Child Health Study (OCHS-R), a revision of the CBCL [25,26]. This study
included 59 children and adolescents with ASD and 1751 children from the community (general
population control), aged 9 to 14 years. In the ASD group, about 17% scored in the significant
rage on depression items compared to 3% in the general population.
A study of 70 adolescents, with mean age of 14, compared rates of depression in youth with
ASD (n = 35) and youth without ASD (n = 35) [27]. Depressive symptoms were measured using
the Centre for Epidemiological Studies Depression Scale—Children’s Version (CES-DC), and
the results showed significantly higher rates of depressive symptoms in the ASD group versus
the comparison group (66% and 40%, respectively) [28]. One study compared rates of depressive
symptoms between 30 youth with ASD, 30 typically developing (TD) youth with major
depressive disorder (MDD), and 35 typically developing youth without MDD, aged 7 to 17 years
[29]. Depressive symptoms were assessed using the CDI and the Children’s Depression Rating
Scale-Revised (CDRS-R) [30]. The ASD group showed significantly higher rates of depressive
symptoms when compared to the TD group and similar rates of depressive symptoms as the
MDD group. Depressive symptoms were associated with poorer global functioning in the ASD
group.
Comparisons between ASD and other disorders have also shown differences in rates of comorbid
psychiatric diagnoses and symptoms. A comparison study examined the difference in
psychopathology between children and adolescents with autism and intellectual disability (ID)
[31]. The ASD group had participants both with and without ID, but the ID group did not include
participants with ASD. This study included 962 youth, aged 4 to 18 years, and used parent-
reported symptoms on the Developmental Behavior Checklist (DBC-P) [32,33]. There were
significantly higher levels of psychopathology, including depressive symptoms, in the ASD
group when compared to the ID group. Higher scores on the depression scales were associated
with increased age and higher intelligence quotient (IQ). Comorbid depression is commonly seen
with other disorders, including disruptive behavior disorders. Youth with ASD were shown to
have similar rates of depressive symptoms as youth with conduct disorder (CD) in a small study
of 40 adolescents, aged 11 to 19 years [34].
3. Risk and Protective Factors

Youth with ASD and comorbid depression have a higher incidence of family history of
depression when compared to youth with ASD without comorbid depression, similar to research
in depressed youth without ASD [35]. Additionally, rates of depression are higher in first degree
relatives of individuals with ASD when compared to first degree relatives of individuals with
Down syndrome, when controlling for stress associated with raising a child with ASD [36].
Environmental stressors also play a role in the risk of depression in individuals with ASD, just as
they do in typically developing youth. Youth with ASD have reported increased negative life
events 12 months prior to the onset of depression when compared to controls [37]
Evidence shows risk of depression increases with increasing IQ and higher levels of functioning
as well as with increasing age in youth with ASD. A large study examined prevalence and risk
factors of anxiety and depression in 627 youth with autism, ages 1 to 17 years [38]; IQ ranged
from 16 to 146. The parent-rated Pediatric Behavior Scale (PBS) was used to measure rates of
anxiety and depressive symptoms in the study participants [39]. Prevalence of depressive
symptoms ranged from 22% to 72% across the age groups, with the highest rates seen in the
older groups. Along with age, the biggest predictors for depression in this study included
increased verbal IQ and increased maternal-rated ASD symptom severity, with the latter being
the single best predictor of both anxiety and depression.
A study of 1390 children and adolescents, including 350 with ASD, examined prevalence rates
of several symptoms in different groups of children and adolescents, including controls in the
general population and clinically referred youth with various psychiatric diagnoses, aged 6 to 16
years [40]. With regards to ASD and depression, the study showed higher rates of depressive
symptoms (54%) among youth with ASD and IQ ≥80 when compared to youth with ASD and IQ
<80 as measured by the PBS [39]. The study also found that youth with ASD and depression had
lower rates of suicidal ideation and suicide attempts when compared to typically developing
youth with depression. Though depression risk increases with age, evidence shows younger
children with ASD are still at risk of developing symptoms. A study of 101 children with ASD,
aged 4 to 9 years, showed a prevalence of depression that ranged from 6% (IQ < 70) to 19% (IQ
≥ 70) [41]. Though higher IQ was associated with a higher prevalence of depressive symptoms,
this finding did not reach statistical significance in this study. Anxiety symptoms, however, were
significantly associated with a higher IQ.
A study examined the effect of different coping strategies and level of social functioning on
depression in 120 male subjects (mean age 11), including 63 youth with ASD (IQ ≥ 80) and 57
youth with typical development [42]. When compared to the youth with typical development,
those in the ASD group who reported using avoidant strategies to manage stressful situations
reported fewer symptoms of depression on the CDI, suggesting a possible adaptive coping
strategy in this group. Poor social functioning was associated with increased symptoms of
depression [22].
The trajectory of depressive symptoms in youth with ASD has been studied with some mixed
results; however, all evidence supports higher rates of depression than in the general population
that remains into adulthood. One study showed improvements of depressive symptoms in youth
with ASD as they aged [43]. Other clinical trials, however, have shown symptoms of depression
either remaining elevated at similar rates or at increasing rates in older adolescents and young
adults with ASD [23,44]. Social communication deficits have been shown to be associated with
an increased risk of self-harm and suicidal ideation in youth [45]. This risk appears to be
independent of an ASD diagnosis, suggesting typically developing youth with social
communication deficits are also at an increased risk of suicidal thoughts and behaviors.
Depression in early adolescence appears to contribute somewhat to this risk, which highlights the
importance of early interventions for depression in children and adolescents. More research is
needed to better understand risk factors associated with suicidal thoughts and behaviors in youth
with ASD.
4. Treatment
Treatment for depression in youth with ASD tends to be guided by evidence from studies of
typically developing children and adolescents with depression. There is not much evidence to
help clinicians make treatment decisions, and there are no randomized, placebo-controlled trials
examining efficacy of antidepressants for the treatment of depression in youth with ASD [46].
Antidepressant treatment studies in youth with ASD have focused almost exclusively on the core
symptoms of autism, specifically repetitive behaviors. Randomized controlled trials have failed
to show efficacy of selective serotonin reuptake inhibitors (SSRIs) for repetitive behaviors in
youth with autism, and side effects have been a concern in these studies (specifically,
serotonergic activation effects) [47,48]. A small, 10-week, open-label study of escitalopram in 28
children and adolescents with ASD (aged 6 to 17 years) showed significant improvement in
symptoms of irritability but did not measure depressive symptoms specifically [49]. The youth in
the study experienced dose-related adverse effects of irritability and hyperactivity, and a quarter
could not tolerate doses above 10 mg. Responders tended to do so at lower doses of
escitalopram.
The lack of evidence supporting the use of SSRIs in children and adolescents with ASD is
concerning as these are the most commonly prescribed psychotropic medications in individuals
with ASD [50,51]. A study examining medication use in 286 adolescents and adults with ASD
(mean age 21) showed 33% of the study participants were prescribed antidepressants, rising to
43% by the end of the four-year study [52]. This was the most common psychotropic prescribed
to the individuals in the study. A Cochrane Review concluded that antidepressants should only
be used on a case-by-case basis for depression or obsessive-compulsive disorder in children with
autism, but the evidence does not really support its use, and there is significant evidence showing
potential harm in this patient population [53]. Clinicians should use their clinical judgment when
considering antidepressants for children and adolescents with ASD. If the decision to treat with
antidepressants is made, then clinicians should choose low doses to start, titrate slowly, and
carefully monitor for response and adverse effects.
Much of the evidence pertaining to psychosocial interventions, such as cognitive behavior

therapy, is focused on treating either core symptoms of ASD, associated behavioral symptoms,
or anxiety [54]. A few studies have examined the efficacy of psychosocial interventions for
depression in individuals with ASD; however, most of these have been adult studies. One study
examined the efficacy of group cognitive behavioral therapy on symptoms of anxiety, stress, and
depression in 32 adolescents and young adults with ASD (aged 15 to 25 years) [55]. When
compared to the wait list control, individuals in the CBT group with symptoms of depression
pretreatment showed significant improvement in their depressive symptoms, as measured by the
Depression Anxiety Stress Scales (DASS) [56]. Studies in adults with ASD have shown
mindfulness-based therapy and social and vocational skills training to be effective for symptoms
of depression, but neither intervention has been studied as a treatment for depressive symptoms
in children or adolescents with ASD [57,58]. Evidence is still lacking in this area but
psychosocial interventions, such as cognitive behavior therapy, should be considered as
treatment options for youth with ASD and comorbid depression.
5. Conclusions
Depression is a fairly common comorbid diagnosis in children and adolescents with autism. It
may be harder to recognize in this patient population due to communication deficits, and
symptoms of depression may compound the interpersonal difficulties that youth with ASD
already experience. Accurate diagnosis may be difficult, especially in children and adolescents
with limited verbal skills. Reliance on parental-report and change from baseline behaviors is very
important in these cases. Current diagnostic scales may not be ideal for diagnosing depression in
youth with ASD, and scales developed specifically for youth with ASD, such as the ACI-PL,
may be more reliable in this patient population. Research examining the efficacy of various
treatments for depression in individuals with ASD is very limited, especially in children and
adolescents, and there are currently no randomized controlled trials examining the safety and
efficacy of treatments for depression in this population. Considering the rates of depression seen
in youth with ASD are higher than those observed in typically developing youth, the lack of
guidance for clinicians treating these patients is concerning. Additionally, evidence suggests
youth with ASD are at a higher risk of developing adverse effects with antidepressant
medications, and traditional psychosocial interventions need more study to determine whether
they are as effective in this population as in typically developing youth with depression.
Antidepressants continue to be the most commonly prescribed psychotropic medications for
patients with ASD despite concerns about side effects and lack of evidence supporting their use
in this patient population. Future research should focus on symptom expression in depressed
youth with ASD and how it may differ from typically developing youth. It should also focus on
establishing appropriate assessments for these symptoms and safe and effective treatments for
depression in this patient population.
References
1. American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. 5th
ed. American Psychiatric Publishing; Arlington, VA, USA: 2013. [Google Scholar]
2. Baio J., Wiggins L., Christensen D.L., Maenner M.J., Daniels J., Warren Z., Kurzius-Spencer
M., Zahorodny W., Robinson Rosenberg C., White T., et al. Prevalence of autism spectrum
disorder among children aged 8 years—Autism and developmental disabilities monitoring
network, 11 sites, United States, 2014. MMWR Surveill. Summ. 2018;67:1–23. doi:
10.15585/mmwr.ss6706a1. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
3. Matson J.L., Nebel-Schwalm M.S. Comorbid psychopathology with autism spectrum disorder
in children: An overview. Res Dev Disabil. 2007;28:341–352. doi: 10.1016/j.ridd.2005.12.004.
[PubMed] [CrossRef] [Google Scholar]
4. Merikangas K.R., He J., Burstein M., Swanson S.A., Avenevoli S., Cui L., Benjet C.,
Georgiades K., Swendsen J. Lifetime prevalence of mental disorders in US adolescents: Results
from the National Comorbidity Study-Adolescent Supplement (NCS-A) J. Am. Acad. Child
Adolesc. Psychiatry. 2010;49:980–989. doi: 10.1016/j.jaac.2010.05.017. [PMC free article]
5. Melvin G.A., Dudley A.L., Gordon M.S., Ford S., Taffe J., Tonge B.J. What happens to
depressed adolescents? A follow-up study into early adulthood. J. Affect. Disord. 2013;151:298–
305. doi: 10.1016/j.jad.2013.06.012. [PubMed] [CrossRef] [Google Scholar]
6. Ghaziuddin M., Ghaziuddin N., Greden J. Depression in persons with autism: Implications for
research and clinical care. J. Autism Dev. Disord. 2002;32:299–306. doi:
10.1023/A:1016330802348. [PubMed] [CrossRef] [Google Scholar]
7. Chandrasekhar T., Sikich L. Challenges in the diagnoses and treatment of depression in autism
spectrum disorders across the lifespan. Dialogues Clin. Neurosci. 2015;17:219–227. [PMC free
article] [PubMed] [Google Scholar]
8. Stewart M.E., Barnard L., Pearson J., Hasan R., O’Brien G. Presentation of depression in
autism and Asperger syndrome. Autism. 2006;10:103–116. doi: 10.1177/1362361306062013.
9. Reiss S. Reiss Scales for Children’s Dual Diagnosis: Mental Retardation and
Psychopathology. International Diagnostic Systems; Worthington, OH, USA: 1990. [Google
Scholar]
10. Holmes N., Shah A., Wing L. The disability assessment schedule: A brief screening device
for use with the mentally retarded. Psychol. Med. 1982;12:879–890. doi:
10.1017/S0033291700049175. [PubMed] [CrossRef] [Google Scholar]
11. Leyfer O.T., Folstein S.E., Bacalman S., Davis N.O., Dinh E., Morgan J., Tager-Flusberg H.,
Lainhart J.E. Comorbid psychiatric disorders in children with autism: Interview development and
rates of disorders. J. Autism Dev. Disord. 2006;36:849–861. doi: 10.1007/s10803-006-0123-0.
12. Simonoff E., Pickles A., Charman T., Chandler S., Loucas T., Baird G. Psychiatric disorders
in children with autism spectrum disorders: Prevalence, comorbidity, and associated factors in a
population-derived sample. J. Am. Acad. Child Adolesc. Psychiatry. 2008;47:921–929. doi:
10.1097/CHI.0b013e318179964f. [PubMed] [CrossRef] [Google Scholar]
13. Angold A., Costello E. A test-retest reliability study of child-reported psychiatric symptoms
and diagnoses using the Child and Adolescent Psychiatric Assessment (CAPA-C) Psychol. Med.
1995;25:755–762. doi: 10.1017/S0033291700034991. [PubMed] [CrossRef] [Google Scholar]
14. Rosenberg R.E., Kaufmann W.E., Law J.K., Law P.A. Parent report of community
psychiatric comorbid diagnoses in autism spectrum disorders. Autism Res. Treat. 2011;2011:10.
doi: 10.1155/2011/405849. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
15. Kanne S.M., Abbacchi A.M., Constantino J.N. Multi-informant ratings of psychiatric
symptom severity in children with autism spectrum disorders: The importance of environmental
context. J. Autism Dev. Disord. 2009;39:856–864. doi: 10.1007/s10803-009-0694-7. [PMC free
article] [PubMed] [CrossRef] [Google Scholar]
16. Achenbach T.M., Rescorla L.A. Manual for the ASEBA Preschool Forms & Profiles.
Research Center for Children, Youth & Families, University of Vermont; Burlington, VT, USA:
2001. [Google Scholar]
17. Achenbach T.M., Rescorla L.A. Manual for the ASEBA School-Age Forms & Profiles.
Research Center for Children, Youth & Families, University of Vermont; Burlington, VT, USA:
2001. [Google Scholar]
18. Hurtig T., Kuusikko S., Mattila M.L., Haapsamo H., Ebeling H., Jussila K., Joskitt L., Pauls
D., Moilanen I. Multi-informant reports of psychiatric symptoms among high-functioning
adolescents with Asperger syndrome or autism. Autism. 2009;13:583–598. doi:
10.1177/1362361309335719. [PubMed] [CrossRef] [Google Scholar]
19. Chambers W.J., Puig-Antich J., Hirsch M., Paez P., Ambrosini P.J., Tabrizi M.A., Davies M.
The assessment of affective disorders in children and adolescents by semistructured interview.
Test-retest reliability of the schedule for affective disorders and schizophrenia for school-age
children, present episode version. Arch. Gen. Psychiatry. 1985;42:696–702. doi:
10.1001/archpsyc.1985.01790300064008. [PubMed] [CrossRef] [Google Scholar]
20. Kaufman J., Birmaher B., Brent D., Rao U., Flynn C., Moreci P., Williamson D., Ryan N.
Schedule for affective disorders and schizophrenia for school-age children-present and lifetime
version (K-SADS-PL): Initial reliability and validity data. J. Am. Acad. Child Adolesc.
Psychiatry. 1997;36:980–988. doi: 10.1097/00004583-199707000-00021. [PubMed] [CrossRef]
[Google Scholar]
21. Barnhill G.P., Myles B.S. Attributional style and depression in adolescents with Asperger
Syndrome. J. Posit. Behav. Interv. 2001;3:175–182. doi: 10.1177/109830070100300305.
[CrossRef] [Google Scholar]
22. Kovacs M. Children’s Depression Inventory. Multi-Health Systems; North Tonawanda, NY,
USA: 1992. [Google Scholar]
23. Rai D., Culpin I., Heuvelman H., Magnusson C.M.K., Carpenter P., Jones H.J., Emond A.M.,
Zammit S., Golding J., Pearson R.M. Association of autistic traits with depression from
childhood to age 18 years. JAMA Psychiatry. 2018;75:835–843. doi:
10.1001/jamapsychiatry.2018.1323. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
24. Angold A., Erkanli A., Silberg J., Eaves L., Costello E.J. Depression scale scores in 8–17-
year-olds: Effects of age and gender. J. Child Psychol. Psychiatry. 2002;43:1052–1063. doi:
10.1111/1469-7610.00232. [PubMed] [CrossRef] [Google Scholar]
25. Kim J.A., Szatmari P., Bryson S.E., Streiner D.L., Wilson F.J. The prevalence of anxiety and
mood problems among children with autism and Asperger syndrome. Autism. 2000;4:117–132.
doi: 10.1177/1362361300004002002. [CrossRef] [Google Scholar]
26. Boyle M.H., Offord D.R., Racine Y., Fleming J.E., Szatmari P., Sanford M. Evaluation of the
revised Ontario child health study scales. J. Child Psychol. Psychiatry. 1993;34:189–213. doi:
10.1111/j.1469-7610.1993.tb00979.x. [PubMed] [CrossRef] [Google Scholar]
27. Whitehouse A.J., Durkin K., Jaquet E., Ziatas K. Friendship, loneliness and depression in
adolescents with Asperger’s syndrome. J. Adolesc. 2009;32:309–322. doi:
10.1016/j.adolescence.2008.03.004. [PubMed] [CrossRef] [Google Scholar]
28. Weissman M.M., Orvaschel H., Padian N. Children’s symptom and social functioning self-
report scales: Comparison of mothers’ and children’s reports. J. Nerv. Ment. Dis. 1980;168:736–
740. doi: 10.1097/00005053-198012000-00005. [PubMed] [CrossRef] [Google Scholar]
29. Mazzone L., Postorino V., De Peppo L., Fatta L., Lucarelli V., Reale L., Giovagnoli G.,
Vicari S. Mood symptoms in children and adolescents with autism spectrum disorders. Res. Dev.
Disabil. 2013;34:3699–3708. doi: 10.1016/j.ridd.2013.07.034. [PubMed] [CrossRef] [Google
Scholar]
30. Poznanski E.O., Mokros H.B. Children’s Depression Rating Scale, Revised (CDSR-R)
Western Psychological Services; Los Angeles, CA, USA: 1996. [Google Scholar]
31. Brereton A.V., Tonge B.J., Einfeld S.L. Psychopathology in children and adolescents with
autism compared to young people with intellectual disability. J. Autism Dev. Disord.
2006;36:863–870. doi: 10.1007/s10803-006-0125-y. [PubMed] [CrossRef] [Google Scholar]
32. Einfeld S.L., Tonge B.J. Manual for the Developmental Behaviour Checklist (DBC) Monash
University Centre for Developmental Psychiatry and School of Psychiatry, University of NSW;
Clayton, Australia: Melbourne, Australia: Sydney, Australia: 1992. [Google Scholar]
33. Enfeld S.L., Tonge B.J. The Developmental Behavior Checklist: The development and
validation of an instrument to assess behavioural and emotional disturbance in children and
adolescents with mental retardation. J. Autism Dev. Disord. 1995;25:81–104. doi:
10.1007/BF02178498. [PubMed] [CrossRef] [Google Scholar]
34. Green J., Gilchrist A., Burton D., Cox A. Social and psychiatric functioning in adolescents
with Asperger syndrome compared with conduct disorder. J. Autism Dev. Disord. 2000;30:279–
293. doi: 10.1023/A:1005523232106. [PubMed] [CrossRef] [Google Scholar]
35. Ghaziuddin M., Greden J. Depression in children with autism/pervasive developmental
disorders: A case-control family history study. J. Autism Dev. Disord. 1998;28:111–115. doi:
10.1023/A:1026036514719. [PubMed] [CrossRef] [Google Scholar]
36. Piven J., Palmer P. Psychiatric disorder and the broad autism phenotype: Evidence from a
family study of multiple-incidence autism families. Am. J. Psychiatry. 1999;156:557–563.
[PubMed] [Google Scholar]
37. Ghaziuddin M., Alessi N., Greden J. Life events and depression in children with pervasive
developmental disorders. J. Autism Dev. Disord. 1995;25:495–502. doi: 10.1007/BF02178296.
38. Mayes S.D., Calhoun S.L., Murray M.J., Zahid J. Variables associated with anxiety and
depression in children with autism. J. Dev. Phys. Disabil. 2011;23:325–337. doi:
10.1007/s10882-011-9231-7. [CrossRef] [Google Scholar]
39. Lindgren S.D., Koeppl G.K. Assessing child behavior problems in a medical setting:
Development of the Pediatric Behavior Scale. In: Prinz R.J., editor. Advances in Behavioral
Assessment of Children and Families. Volume 3. JAI Press; London, UK: 1987. pp. 57–90.
[Google Scholar]
40. Mayes S.D., Calhoun S.L., Murray M.J., Ahuja M., Smith L.A. Anxiety, depression, and
irritability in children with autism relative to other neuropsychiatric disorders and typical
development. Res. Autism Spectr. Disord. 2011;5:474–485. doi: 10.1016/j.rasd.2010.06.012.
41. Salazar F., Baird G., Chandler S., Tseng E., O’sullivan T., Howlin P., Pickles A., Simonoff
E. Co-occurring psychiatric disorders in preschool and elementary school-aged children with
autism spectrum disorder. J. Autism Dev. Disord. 2015;45:2283–2294. doi: 10.1007/s10803-
015-2361-5. [PubMed] [CrossRef] [Google Scholar]
42. Pouw L.B.C., Rieffe C., Stockmann L., Gadow K.D. The link between emotion regulation,
social functioning, and depression in boys with ASD. Res. Autism Spectr. Disord. 2013;7:549–
556. doi: 10.1016/j.rasd.2013.01.002. [CrossRef] [Google Scholar]
43. Gray K., Keating C., Taffe J., Brereton A., Einfeld S., Tonge B. Trajectory of behavior and
emotional problems in autism. Am. J. Dev. Disabil. 2012;117:121–133. doi: 10.1352/1944-7588-
117-2.121. [PubMed] [CrossRef] [Google Scholar]
44. Gotham K., Brunwasser S.M., Lord C. Depressive and anxiety symptom trajectories from
school-age through young adulthood in samples with autism spectrum disorder and
developmental delay. J. Am. Acad. Child Adolesc. Psychiatry. 2015;54:369–376. doi:
10.1016/j.jaac.2015.02.005. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
45. Culpin I., Mars B., Pearson R.M., Golding J., Heron J., Bubak I., Carpenter P., Magnusson
C., Gunnell D., Rai D. Autistic traits and suicidal thoughts, plans, and self-harm in late
adolescence: Population-based cohort study. J. Am. Acad. Child Adolesc. Psychiatry.
2018;57:313–320. doi: 10.1016/j.jaac.2018.01.023. [PMC free article] [PubMed] [CrossRef]
[Google Scholar]
46. Baribeau D.A., Anagnostou E. An update on medication management of behavioral disorders
in autism. Curr. Psychiatry Rep. 2014;16:437. doi: 10.1007/s11920-014-0437-0. [PubMed]
47. Autism Speaks . Autism Speaks Announces Results Reported for the Study of Fluoxetine in
Autism (SOFIA), First Industry-Sponsored Trial for the Autism Clinical Trials Network (ACTN)
Autism Speaks Inc.; New York, NY, USA: 2009. [Google Scholar]
48. King B.H., Hollander E., Sikich L., McCracken J.T., Scahill L., Bregman J.D., Donnelly
C.L., Anagnostou E., Dukes K., Sullivan L., et al. Lack of efficacy of citalopram in children with
autism spectrum disorders and high levels of repetitive behavior: Citalopram ineffective in
children with autism. Arch. Gen. Psychiatry. 2009;66:583–590. doi:
10.1001/archgenpsychiatry.2009.30. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
49. Owley T., Walton L., Salt J., Guter S., Winnega M., Lenthal B.L., Cook E.H. An open-label
trial of escitalopram in pervasive developmental disorders. J. Am. Acad. Child Adolesc.
Psychiatry. 2005;44:343–348. doi: 10.1097/01.chi.0000153229.80215.a0. [PubMed] [CrossRef]
[Google Scholar]
50. Spencer D., Marshall J., Post B., Kulakodiu M., Newschaffer C., Dennen T., Azocar F., Jain
A. Psychotropic medication use and polypharmacy in children with autism spectrum disorders.
Pediatrics. 2013;132:833–840. doi: 10.1542/peds.2012-3774. [PMC free article] [PubMed]
51. Martin A., Scahill L., Klin A., Volkmar F.R. Higher-functioning pervasive developmental
disorders: Rates and patterns of psychotropic drug use. J. Am. Acad. Child Adolesc. Psychiatry.
1999;38:923–931. doi: 10.1097/00004583-199907000-00024. [PubMed] [CrossRef] [Google
Scholar]
52. Esbensen A.J., Greenberg J.S., Seltzer M.M., Aman M.G. A longitudinal investigation of
psychotropic and non-psychotropic medication use among adolescents and adults with autism
spectrum disorders. J. Autism Dev. Disord. 2009;39:1339–1349. doi: 10.1007/s10803-009-0750-
3. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
53. Williams K., Brignell A., Randall M., Silove N., Hazell P. Selective serotonin reuptake
inhibitors (SSRIs) for autism spectrum disorders (ASD) Cochrane Database Syst. Rev. 2013;8
doi: 10.1002/14651858.CD004677.pub3. [PubMed] [CrossRef] [Google Scholar]
54. Danial J.T., Wood J.J. Cognitive behavioral therapy for children with autism: Review and
considerations for future research. J. Dev. Behav. Pediatr. 2013;34:702–715. doi:
10.1097/DBP.0b013e31829f676c. [PubMed] [CrossRef] [Google Scholar]
55. McGillivray J.A., Evert H.T. Group cognitive behavioural therapy program shows potential
in reducing symptoms of depression and stress among young people with ASD. J. Autism Dev.
Disord. 2014;44:2041–2051. doi: 10.1007/s10803-014-2087-9. [PubMed] [CrossRef] [Google
Scholar]
56. Lovibond S., Lovibond P. The structure of negative emotional states: Comparison of the
depression anxiety stress scales (DASS) with the beck depression and anxiety inventories.
Behav. Res. Ther. 1995;33:335–343. doi: 10.1016/0005-7967(94)00075-U. [PubMed]
57. Spek A.A., van Ham N.C., Nyklicek I. Minfulness-based therapy in adults with an autism
spectrum disorder: A randomized controlled trial. Res. Dev. Disabil. 2013;34:246–253. doi:
10.1016/j.ridd.2012.08.009. [PubMed] [CrossRef] [Google Scholar]
58. Hillier A.J., Fish T., Siegel J.H., Beversdorf D.Q. Social and vocational skills training
reduces self-reported anxiety and depression among young adults on the autism spectrum. J.
Dev. Phys. Disabil. 2011;23:267–276. doi: 10.1007/s10882-011-9226-4. [CrossRef] [Google
Scholar]
Characterization of Depression in Children

with Autism Spectrum Disorders
Katherine M. Magnuson, B.S. and John N. Constantino, M.D.
Author information Copyright and License information Disclaimer
The publisher's final edited version of this article is available at J Dev Behav Pediatr
See other articles in PMC that cite the published article.
Abstract
Depressive syndromes represent a disabling comorbidity for many children with autism spectrum
disorders (ASD), however the ascertainment of depression can be complicated by phenotypic
overlap between the two conditions, by ways in which autistic symptomatology can mask
cardinal features of depression, and by atypical manifestations of depression in children with
ASD. These issues have contributed to wide variation in the estimation of prevalence rates of
depression in individuals with ASD, and invoke the need for new approaches to the specific
detection of depression and other neuropsychiatric comorbidities that aggregate in children
affected by ASD. We review the scientific literature relevant to the occurrence of depression in
ASD, and consider important parameters of risk, including psychosocial factors such as insight
into affectation status, as well as biological factors such as the aggregation of depressive
syndromes in certain families affected by autism, which has suggested possible overlap in
genetic influences underlying the two conditions. Variability in the manifestations of depression
across environmental contexts provides important clues to intervention, and underscores the
potential importance of involving multiple informants in ascertaining depression in children and
adolescents with ASD. A practical strategy for evaluating the presence of depression in youth
with ASD is synthesized from the available data and discussed.
Keywords: Comorbidity, Internalizing Disorders, Pervasive Developmental Disorder, Asperger

Syndrome, Major Depressive Disorder
Introduction
Due in part to its chronic nature, the World Health Organization has recognized depression as the
single disease imposing the largest public health burden in the United States and the third largest
public health burden in the world.1 Depression not only affects the mental health of individuals,
but also imposes effects on physical health, which may further contribute to the maintenance of
depression.2 Major Depressive Disorder in adolescents is associated with decreased functioning
in adulthood, recurrence and an increased risk of death due to suicide.3, 4 Due both to the high
burden of disease and the treatable nature of depression, the US Preventive Services Task Force
(USPSTF) has recommended screening all adolescents for depression, provided that a framework
for accurate diagnosis, treatment and follow-up is in place.3 Although it might be assumed that
children and adolescents with autism spectrum disorders (ASD) might be relatively protected
from the development of depressive syndromes, there is accumulating evidence that this is not
the case. Given the seriousness of depression and inherent difficulties in ascertaining its presence
in children with autism spectrum disorders, a high degree of vigilance is warranted in the care of
children and adolescents with ASD, a population that is now believed to carry a significantly
heightened predisposition, not only to depression but to an array of other comorbid
neuropsychiatric conditions.5-8
Autism spectrum disorders often impose severe limitations on capacity for managing activities of
daily living,9 and quality of life has been shown to be significantly compromised for many
children and families affected by ASD.10 Prevalence rates have been increasing, and have most
recently been reported to be 1 in 91 children between the ages of 3 to 17 years as estimated by
the 2007 National Survey of Children's Health.11 Equally concerning is that autism spectrum
disorders are very frequently associated with a multitude of medical and psychiatric
comorbidities at rates higher than those of typically developing children.12 These comorbidities
range from gastrointestinal, neurologic, and endocrine abnormalities12, 13 to psychiatric
comorbidities such as mood disorders, anxiety, and ADHD.12, 14
As is true for youth unaffected by ASD, the occurrence of depression has specific, and at times
profound impact on functioning, however, in the context of ASD, it is not fully known how to
identify when a depressive syndrome is present.15 Identification of depressive states has
traditionally capitalized on subjective self-report information, which is difficult for many
children with ASD to provide.16, 17 Traditional measures of diagnosis have generally not been
tested for validity and reliability in ASD populations.18 Moreover, the presentation of depression
in children with ASD is often atypical, or at the least complicated by the social, cognitive, and
communicative impairments that characterize autism.7 Prevalence rates for depression in ASD
vary widely because of phenotypic overlap between the two conditions, the tendency for autistic
symptomatology to mask cardinal features of depression, and the fact that symptoms of
depression in children with ASD may be atypical.15, 19 Insight into one's own level of impairment
is known to be associated with depressive symptomatology,20, 21 but it is not clear if lack of
insight in severely affected children confers protection from depressive states, making it all the
more critical to develop better methods to ascertain depressive states in non-verbal autistic
children.
There has been only modest systematic evaluation of interventions for depression in children
with autism spectrum disorders, but enough to conclude that treatment may be effective when the
condition is identified. 5, 7, 8, 22, 23 The aggregation of depressive syndromes in certain families
affected by autism has suggested possible overlap in genetic influences underlying the two
conditions,24-27 but there is also evidence for substantial independence of their respective genetic
origins.28, 29
The goal of this review is to summarize pertinent information regarding the presentation and
identification of depressive states in ASD, and to consider important parameters of risk derived
from the existing data, including psychosocial factors such as insight into affectation status, as
well as biological factors such as inherited liability. For this review, we searched the National
Library of Medicine Pub Med database for all studies involving “depression” and either “autism
spectrum disorders” or “pervasive developmental disorder.”10, 18, 19, 21-23, 30-48 We synthesized the
results of these studies with literature on the development and diagnostic assessment of each
respective condition.
Presentation of Depression in Autism Spectrum Disorders

Manifestations of depressive symptoms vary as a function of age and therefore general level of
developmental maturation, 49 however commonalities across the life course include diminished
interest in activities, feelings of worthlessness or guilt, diminished ability to concentrate or make
decisions and recurrent thoughts of death.9 An allowance made by the DSM-IV-TR is the
substitution of irritability for depressed mood if necessary in diagnosing Major Depressive
Disorder in children.9, 49 A study of typically developing preschool-aged children found that
while irritability and sadness were the most sensitive predictors of depression (identified in 98%
of preschoolers), anhedonia was the most specific, apparent only in the depressed group.50
Younger children may present with somatic complaints and behavior problems and may
demonstrate a persistent engagement in activities or play with themes of death or suicide.50
Observation of activities is critical in the assessment of depression in very young children due to
limited verbal ability and tendency to express such thoughts through play, although even very
young children demonstrate neurovegetative signs and lack of brightening similar to depressed
adults.50 Adolescents more commonly display hypersomnia and have an increased risk for
suicide in comparison to preadolescents. In general, females more typically display changes in
appetite or weight, increased frequency of crying, and feelings of guilt or low self-esteem, while
males are more likely to endorse anhedonia, social withdrawal, and variation in mood or
energy.49
Given that many individuals with autism spectrum conditions have significant impairments in
communication, subjective states of sadness, hopelessness, or disinterest may be extremely
difficult to express. In such cases, identification and diagnosis of depression has largely relied on
outward behaviors or changes in mental state inferred from parent or caregiver observations.
Observable behaviors reported by caregivers and documented in the literature include an increase
in sadness, tearfulness, apathy, or an increasingly negative affect.5, 7, 15, 22, 34, 51 Additionally,
anhedonia, vegetative signs such as sleep and weight disturbances, or decline in performance /
regression of skills have been noted in youth with autism.15, 34, 38 Catatonic behavior has also been
reported.23
‘Theory of mind’ deficits associated with ASD can further complicate self-report of depressive
syndromes.18 Decreased ability or incapacity of innate self-reflection invoke reliance on alternate
signs or symptoms such as a decrease in self-care or an increase in self-injurious behavior (SIB)
as manifestations of an increasingly negative self-view.7, 46 SIB in the form of head banging or
self-hitting has been reported in children with autism. Theories of its causes include the need for
sensory stimulation or a response to stress, discomfort, or frustration.52 Preoccupation with
themes of death have also been noted in youth with ASD during periods of depression,8, 22, 53 and
case reports illustrate resolution of SIB after treatment of depression in individuals with autism
spectrum disorders.8, 34 In support of the theory that increasingly frequent SIB can be a proxy for
negative self-view when combined with other depressive signs or symptoms, SIB has also been
significantly associated with depression in persons with profound intellectual disabilities.51, 54
Atypical affective changes, such as increased aggression, irritability, agitation, and labile moods
may also be present in depressive states.15, 22, 34, 46 Overlap in symptomatology between depression
and autism spectrum disorders may challenge the clinician's ability to elicit whether classic signs
of depression are due to the primary diagnosis of ASD or to an actual comorbid psychiatric
condition.5, 7, 18 For instance, case reports and prospective studies discuss children with ASD and
depression demonstrating exacerbated compulsiveness or increased stereotypic behavior.7, 15, 22, 46
Both intensification of and decrease in autistic symptomatology have been reported with the
onset of depression. Intensification of autistic traits includes increases in ritualistic behavior or
obsessions, often coupled with irritability and hyperactivity. Less frequently associated with
depression but reported through anecdotal reports or case studies is the loss of interest in
repetitive behaviors and autistic preoccupations accompanying more social withdrawal and
decreased adaptive functioning.5, 7 No studies identified have specifically investigated the manner
in which autistic traits fluctuate with episodes of depression; however, many studies in the
literature demonstrate that deviation of autistic symptoms from baseline may indicate a
depressive episode.5, 18, 34, 51 Clinically, a change in behavior from baseline is an easily elicited
piece of information that can be of tremendous help in screening children with ASD for affective
disorders. A summary of traditional and ASD-specific signs and symptoms that may signify
depression in ASD-affected youth can be found in Table 1.
Table 1
The left column lists characteristics of depression seen in both children and adults. The asterisks
(*) indicate qualities that are unique to or more commonly observed in childhood depression.
The presentation of depression in children with autism spectrum disorders can be more
challenging to characterize and recognize. The right column lists additional characteristics that
have been described in ASD-affected children presumed to be affected by depression or
depressive symptomatology (ASD-affected children have been observed to exhibit signs or
symptoms from both the left and right columns).
Traditional signs and symptoms of Additional signs and symptoms that may be
depression including characteristics that present in ASD-affected children who are
may be seen in childhood depression experiencing depression
include:
 Depressed mood, sadness,  Aggression
tearfulness  Mood lability
 Irritability*  Hyperactivity
 Anhedonia  Decreased adaptive functioning or self-care
 Insomnia or hypersomnia  Regression of previously learned skills
 Psychomotor agitation or retardation  Increased compulsiveness
(behavioral problems*)  Fluctuations in autistic symptoms including
 Fatigue or loss of energy both increased stereotypic behavior and
 Social withdrawal decreased interest in
 Weight loss not associated with preoccupations/restricted interests
Traditional signs and symptoms of Additional signs and symptoms that may be
depression including characteristics that present in ASD-affected children who are
may be seen in childhood depression experiencing depression
include:
dieting / change in appetite  Self-injurious behavior
 Increased guilt or worthlessness  Catatonia
 Somatic complaints*  Overall marked change in behavior from
 Lack of brightening* baseline not otherwise specified by above
 Diminished ability to concentrate; characteristics
indecisiveness
 Recurrent thoughts of death or
suicidal ideation
 Play characterized by themes of
suicide or death*
Identifying Depression in ASD and Current Prevalence

To aid clinicians in determining the likelihood of depression in children with ASD, researchers
have attempted to estimate co-occurrence of the two conditions in the population. This has
proved to be a monumental challenge. Given the long list of complicating factors in identifying a
depressive episode, it is not surprising that while many studies have reported increased risk of
depression in children with ASD in comparison with typically developing children,5, 7, 12
prevalence rates of depression in autism have varied from 1.4%19 to 38%.15 A major obstacle has
been the lack of a gold standard assessment and measurement tool of psychiatric comorbidities
designed specifically for those with Autism Spectrum Disorders.7, 14, 15, 18 In lieu of such a tool,
clinicians have utilized semi-structured interviews and a variety of measures designed for either
the general or learning-disabled population.7, 15, 18
In an effort to address this issue, Leyfer and colleagues18 developed the Autism Comorbidity
Interview – Present and Lifetime Version (ACI-PL), a variation of the Kiddie Schedule for
Affective Disorders and Schizophrenia specifically modified for children with ASD. The
investigators studied 109 high functioning children and adolescents (5-17 years old) with ASD.
The mean IQ was 82.5 and the information was obtained via parent report. Validation consisted
of an analysis of diagnostic accuracy against community diagnosis of comorbid depression for
which the children actually had received clinical treatment; this revealed a sensitivity of 100%
and specificity of 83% - 93.7%. A critical aspect of this measurement system is that it
specifically seeks to establish the child's “best baseline” for qualitative and quantitative
comparison to presenting symptoms5, 7, 18, 53
Simonoff and colleagues19 conducted a standardized assessment of a population-based sample of

British children with ASD. DSM-IV diagnoses were made using the Child and Adolescent
Psychiatric Assessment – Parent Version (CAPA), a widely used measure, but one that has not
been modified specially for youth with ASD. They studied 112 children and adolescents (10 – 14
years old) with autism. The mean IQ was 72.7 and the information obtained via parent report.
The prevalence rate for major depressive episodes varied from 1.5% (Simonoff et al.) to 10%
(Leyfer et al.) in these studies, but both reported high rates of subsyndromal depressive
symptomatology (10.4% in the Simonoff et al. study and 14% in Leyfer et al.).
Across these studies, the disparity in prevalence was much more pronounced for depressive
symptomatology (1.5% - 10%) than for other comorbid psychiatric disorders.18, 19 Variation in
verbal ability or intellectual functioning in the respective samples could be responsible for this
specific discrepancy in depressive comorbidity, as could specific adaptation of the Leyfer
interview for ASD, operating to identify a higher number of cases in that study. This suggests
that a scale modified specifically for children with ASD, such as that designed by Leyfer and
colleagues, might more completely ascertain internalizing symptoms which are best elicited by
self-report in typically developing children.7, 14, 15, 18
Unfortunately, neither of these studies and no studies identified have sought to systematically
determine the prevalence of depression or sub-syndromic depression in lower functioning
autistic children with an IQ less than 70. Methods validated for this population would be
especially useful given the unique challenges that the symptoms of non-verbal ASD impose on
derivation of a diagnosis of depression.
Relationships Between Severity of ASD, Insight, Age, and IQ

to Depression in Youth with ASD
It has long been postulated that higher-functioning and more socially adjusted children with ASD
develop insight into their differences by virtue of their cognitive abilities, leading to more
negative self-perception and lower self-worth.5, 20 In support of this, Vickerstaff and colleagues21
found that higher cognitive abilities and greater insight into one's condition leads to a lower self-
perceived social competence and subsequently higher rates of depression. Similarly, Sterling and
colleagues found that depression in adults with autism spectrum disorders was associated with
higher cognitive ability, less social impairment, and older age.32 Taylor and Seltzer recently
showed that young adults with ASD without an intellectual disability were three times more
likely to have “no daytime activities” compared to adults with ASD who had an intellectual
disability, suggesting that inadequacy of current service systems to meet the needs of higher-
functioning youth might compound risk for the development of depressive syndromes.55 Finally,
Mazurek and Kanne found that youth with lower IQ and increased severity of ASD had fewer
symptoms of depression than did higher functioning youth with ASD. It is unknown to what
extent verbal ability, a characteristic generally associated with higher functioning youth with
ASD, influenced these disparities.47 Preliminary evidence has shown that the prevalence of
comorbid psychiatric problems was not a reflection of verbal ability when scored via parental
reports.47
Data regarding a significant relationship between age and depression has been less conclusive. It
is well known that in typically developing children the incidence of depression increases in
adolescence, and this has been postulated to occur in youth with autism spectrum disorders as
well.27 No study has directly compared rates of depression between children and adolescents
controlling for ASD severity, but several have suggested a lack of association between
prevalence and age,21, 43, 48 Vickerstaff et al. postulated that emotional age likely has more
influence than chronological age on the development of depression.21
While increased capacity for adaptive functioning has been associated with higher rates of
depression, it has also been theorized that increased severity of autism spectrum disorders may
itself be associated with greater vulnerability to stressors and thus psychopathology.37, 53, 56
Pearson et al. 37 found that children with autism had more severe symptoms of depression, social
withdraw and atypical behaviors than did children with Pervasive Developmental Disorder – Not
Otherwise Specified (PDD-NOS), although both groups had elevated rates of clinically
significant depressive syndromes. Interestingly, these results were unchanged when intelligence
was controlled for, leading the authors to suggest that diagnostic subgroups on the autism
spectrum might independently predict differing risks for the development of depression and other
psychiatric comorbidities.
It is unknown how constructs such as insight or self-awareness are best measured in children
with ASD. It is clinically observed that recognition of the condition and its social repercussions
has the potential to be depressogenic in and of itself.21, 41 It is unknown, however, whether those
who appear to lack such insight are protected from the development of depression.
Relationships Between Environment, Peer Relations, and

Self-Perception to Depression in Youth with ASD
Peers and the environment fundamentally shape an adolescent's self-perception and
understanding of the impact of ASD on day-to-day life.30 Many children and adolescents with
ASD recognize differences between themselves and their peers, and this recognition has been
correlated with higher levels of depressive symptoms.40 Youth with Asperger Syndrome who
perceived that they had the lowest group membership and social integration have been reported
to have elevated levels of depressive symptoms.31 It has been postulated that high-functioning
youth with ASD, in contrast to lower functioning youth with ASD, may be especially vulnerable
to depression due to their greater social and self-awareness and heightened interest in social
relationships.43, 57 Higher functioning adults with autism spectrum disorders who have been
shown to be more socially adept than their lower functioning peers also show an increased
incidence of depression.32 In a comprehensive, multi-rater study, Vickerstaff and colleagues21
examined variation in depressive symptomatology in autism as a function of self-perception,
insight, intelligence and age. In measurements of social competency, while the children overall
were rated by parents and teachers as less socially competent than their peers, it was only the
child's self-perceived social competence that was significantly associated with depressive
symptoms. Williamson and colleagues found that adolescents with Asperger Syndrome
perceived themselves to be less socially competent and to receive less peer approval. In this
study of adolescents, peer approval was predictive of depression, and both peer approval and
social competency were predictive of global self-worth scores.39
Abnormalities in emotion regulation have been postulated to have a substantial impact on mood
in autism spectrum disorders.56 While even commonplace life events can elicit intense affective
responses in youth with ASD,27 high-stress situations can be overtly overwhelming.30 Anxiety
has been shown to predispose typically developing individuals to depression, and its effects are
compounded in those who have difficulties in emotion regulation. 7, 56 For instance, in a recent
study one student with autism described a perceived-chaotic classroom environment as a place in
which “I'm upset every second, every second I've got tears in my eyes” (p. 38).30 Children and
adolescents with ASD also experience loneliness, and may be taught or advised that the
acquisition of friendships will assuage such feelings, but may be disinterested in peers or unable
to initiate or sustain friendships.58 In typically-developing children, loneliness is associated with
low self-esteem, higher levels of anxiety and can predispose to the development of depression.59
Whitehouse et al. studied the relationship between negative affect and quality of friendships in
adolescents with Asperger syndrome. In that study, adolescents with Asperger syndrome had
greater levels of loneliness and depressive symptomatology relative to their typically-developing
peers.33 A significant predictor of depression in this study was conflict and betrayal within
friendship. Mazurek and colleagues also studied the relationship between friendship and
depression. Analysis of the results revealed that ASD-affected children with more friendships of
poorer quality had the highest levels of anxiety and depression.41
Negative peer interactions have been shown to exert independent adverse effects on children
with high-functioning ASD who are very commonly bullied, teased or ostracized in educational
settings.30, 60, 61 Peer victimization and depressive symptomatology have been correlated, 42 and
observational reports document both social isolation and distress as direct consequences of being
bullied in the school environment.30 Interpersonal conflict with family members has also been
strongly associated with depressive symptomatology.43, 44 Both in family and educational
environments, assumptions about the cause of a child's deviant social behaviors (i.e. the premise
under which parents, educators, siblings, and peers are operating when interpreting those
behaviors) are critical in either buffering or intensifying the response of the environment to those
behaviors. There are remarkable anecdotes of positive change in interpersonal relationships and
behavior, for example, when the social network surrounding a child with ASD shifts from
viewing his/her behaviors as fundamentally “antisocial” in nature to fundamentally “asocial”.
This is particularly relevant for children with higher-functioning autistic syndromes who have
never been diagnosed, and for whom the assumption of caregivers over years of time has been
that the child is engaging in willful violations of social norms.62
Integrating multiple variables previously discussed, Barnhill described how higher functioning
children with ASD with higher IQ and increased level of functioning were more likely to
attribute social failure to lack of ability instead of chance. This perception resulted in an increase
in depressive symptoms.45 Such findings invoke the construct of learned helplessness as a factor
in the development of depression in this population. While no studies identified have empirically
assessed learned helplessness and depression in children with autism, case reports of depressive
symptomatology in conjunction with learned helplessness in persons with ASD have been
reported. As an adult female with Asperger syndrome reported: “When I am able to get people to
understand me, my view of life is positive, but when I am battling against the prejudice I feel
very low. This feeling comes from the powerlessness to change my situation in which I find
myself. … In formal situations this is not a major problem, but in informal ones it is a crushing
one” (p 233).56
Research has demonstrated that higher levels of autistic traits in college students are associated
with a more external locus of control, which contributes to the perception of helplessness.63 In
contrast when chances for success are maximized, increases in motivation and appropriate social
interactions are observed.64
Context-Specific Variation in Depressive Symptomatology in

ASD
Recent research has sought to evaluate autistic and depressive symptomatology in a variety of
environments with multiple informants to aid clinicians in diagnosing depression and to elucidate
other environmental factors that contribute to depression in ASD. As discussed above, the
diagnosis of depression is often complicated by its atypical presentation in youth with ASD. For
that reason, assessing rates and symptoms of depression in multiple environments can help to
clarify the presentation of depression and may reveal environments especially problematic for a
child. Other benefits of cross-context variation assessed via multiple raters include a more
accurate inference of the emotional state,65 a greater likelihood for diagnostic accuracy,66 and the
potential identification of a serious and stable problem.67 Furthermore, expanding on parental
report by drawing on the unique expertise and vantage point of teachers confers the advantage of
assimilating into the assessment process information from children in their natural social
environments and incorporating repeated observations over time from disparate observers.66
Despite these many benefits, a review of the recently published literature finds only a few studies
that have successfully used multi-rater assessment to determine how prevalence of depression in
ASD varies with the environment and rater. Vickerstaff et al.21 found the mean parental rating of
children's depressive symptomatology to be within the “clinically significant” range (via the
Behavior Assessment Scale for Children), but reported teachers' mean rating to be only in the
“at-risk” range. Similarly, Kanne and colleagues65 found that a higher percentage of parents
reported their children as having clinical level depressive symptomatology (26%) than did their
teachers (6%) when using the Achenbach System of Empirically Based Assessment.
Hurtig and colleagues recently expanded such multi-informant approaches by including input
from youth themselves, utilizing the Youth Self-Report; it is widely recognized from studies of
typically-developing youth that self-report is the most sensitive of all ascertainment strategies for
adolescent depression. Hurtig et al. found strong agreement between adolescents, teachers, and
parents on social problem scales, indicating awareness among all informants of such difficulties.
However, parents reported fewer problems in the internalizing problems subscale than did both
adolescents and their teachers. 68 Overall, results suggest that psychiatric symptoms in youth with
ASD may have distinct presentations across varying environments, and therefore interpretations
based upon a single source or environment may be incomplete, leading to inaccurate diagnoses.65
This has clear implications for any strategy to screen for or diagnose depression in ASD-affected
youth.
Genetic Contributions to Depression in ASD

Autism Spectrum Disorders are heavily influenced by genetic factors 69 and there is accumulating
evidence that genetic influence on ASD may overlap with that for other neuropsychiatric
conditions, including learning disorders, schizophrenia, epilepsy, ADHD, language disorders,
and tic disorders.69 The potential for genetic overlap between autism and depression has been
explored and is relevant to the ascertainment and identification of depression in this population.69
Depression and anxiety are observed commonly in family members of children affected by
autism; studies have found the rates of such conditions to be appreciably higher than the national
average.70 There is often a significant history of familial depression in children with ASD who
are diagnosed with depression,27, 71 as well as a higher prevalence of familial depression in
individuals with ASD compared to controls.72 In a large population-based case-control study, a
positive association was found between maternal depression and childhood autism.26
In an attempt to elucidate the possible nature of genetic overlap, twin studies have been
conducted. The possibility of genetic overlap between autistic traits and affective disorder traits
has been explored in at least four twin studies.28, 29, 73, 74 In a study by Constantino and colleagues28
sub-threshold autistic symptomatology as measured by the Social Responsiveness Scale was
largely attributable to unique genetic factors, and these factors were significantly independent of
the genetic influences on anxious/depressed symptomatology measured by the Child Behavioral
Checklist (CBCL); only social and attention problems as measured by the CBCL had significant
associations with autistic traits.
In a study of adolescent twins via self-report, Hoekstra and colleagues reported that social
problems related to depression and anxiety overlap with those observed in children with elevated
autistic traits. Their multivariate analysis also showed that approximately half of the genetic
variance in scores for autistic traits overlapped with those conferring susceptibility to other
behavioral problems.74 Autistic traits are known to be continuously distributed in the
population,72, 75 but it is important to note that it remains unknown whether the genetic influences
on sub-threshold or autistic-like traits are the same as the factors that cause ASD.75
In a multi-rater, population based twin study of 8 – 9 year old children, Hallett et al.29 found a
significant phenotypic association between autistic-like and internalizing traits such as
depressive symptoms, but only a modest level of genetic overlap. Non-shared environmental
influences were generally trait specific, while shared environmental influences contributed to
both autistic-like and internalizing traits, suggesting that co-occurrence may also be a
consequence of environmental factors.29 A follow-up longitudinal study by Hallett et al.73
supported this view, and demonstrated substantial reciprocal influence between autistic-like and
internalizing traits, implying that early autistic-like difficulties may have a pronounced impact on
later depression or anxiety, via the effects of stressful environments on individuals with autism-
related vulnerabilities.29, 73 In order to fully resolve the question of genetic overlap between
depression and autism spectrum disorders, studies in genetically-informative clinical populations
will be needed.72, 75
Synthesizing the Current State of Knowledge: a Testable

Strategy for Identifying Depression in Youth with ASD
Despite many unanswered questions regarding the interface between depression and ASD,
enough is now known to advance a more systematic approach to identification of ASD-affected
youth with or at risk for depressive syndromes. Figure 1 synthesizes the findings summarized in
this review into a model approach to diagnosis. The model considers both higher functioning
children with phrase speech and lower functioning children without verbal language. In an
attempt to address the unique signs and symptoms that a child on the autism spectrum may
present with, the model incorporates both classic features of depression and the atypical signs
and behavior changes indicative of depression in children with ASD that have been reported in
the scientific literature. It considers specific moderators and vulnerability factors as well as the
unique circumstances that may make insightful children with ASD especially vulnerable to the
negative consequences of stressful life events.
Figure 1
A proposed strategy for ascertainment and characterization of depressive syndromes in youth

with ASD. Such an algorithm is testable, and if proven, has the potential to be utilized at routine
well-child care visits or specialist visits.
Future Research
The complexities of identifying and characterizing depression in children with autism spectrum
disorders invoke the need for ongoing research. Emphasis should continue to be placed on
specifying the presentation of depression in autism. It will be necessary to further document the
atypical signs and symptoms of depression in this population, and it would be particularly useful
to identify how the pathognomonic behaviors of autistic syndromes may fluctuate with the onset
of a depressive episode. It will be important to clarify under what circumstances insight is
depressogenic in ASD and how risk for depression might be averted by timely implementation of
cognitive therapy over the course of development. Continued investigation into peer relations,
social awareness, and self-perception among youth with ASD will help identify interventions
that will assist such children with social skills, provide meaningful opportunities to learn and
contribute to the world around them, and help them construct and sustain a positive self-concept.
To these ends, use and further validation of the Autism Comorbidity Interview – Present and
Lifetime Version18 may facilitate progress, given that it was derived from an instrument
specifically designed to measure affective signs and symptoms of psychiatric comorbidities.
Utilizing such tools in a variety of environments with multiple raters will advance understanding
of the presentation of depression in ASD and help refine ascertainment strategies as presented in
Figure 1.
Finally, continued investigation into the overlap of causal influences on ASD and depression is
warranted. Prospective clinical studies examining pathways by which early autistic
symptomatology predicts depression later in life29 would be especially informative. Ultimately,
clearer characterization of depressive syndromes in autism will lead to better understanding of
their ontogeny, and will facilitate appropriate implementation of effective medical and
psychosocial interventions as early as possible in the course of their development.
Acknowledgments
This work was supported, in part, by a grant to Dr. Constantino from the National Institute of
Child Health and Human Development (HD-42541)
Contributor Information
Katherine M. Magnuson, Saint Louis University School of Medicine, St. Louis MO.
John N. Constantino, Departments of Psychiatry and Pediatrics, Washington University School

of Medicine, St. Louis MO.
Works Cited
1. Boerma J, Fat DM, Mathers C, Organization WH. The global burden of disease: 2004 Update.
Geneva: World Health Organization; 2008. [Google Scholar]
2. Keenan-Miller D, Hammen CL, Brennan PA. Health outcomes related to early adolescent
depression. J Adolesc Health. 2007 Sep;41(3):256–262. [PMC free article] [PubMed] [Google
Scholar]
3. Screening and treatment for major depressive disorder in children and adolescents: US
Preventive Services Task Force Recommendation Statement. Pediatrics. 2009 Apr;123(4):1223–
1228. [PubMed] [Google Scholar]
4. Williams SB, O'Connor EA, Eder M, Whitlock EP. Screening for child and adolescent
depression in primary care settings: a systematic evidence review for the US Preventive Services
Task Force. Pediatrics. 2009 Apr;123(4):e716–735. [PubMed] [Google Scholar]
5. Ghaziuddin M, Ghaziuddin N, Greden J. Depression in persons with autism: implications for
research and clinical care. J Autism Dev Disord. 2002 Aug;32(4):299–306. [PubMed] [Google
Scholar]
6. Howlin P. Psychiatric disturbances in adulthood. In: Howlin P, editor. Autism: Preparing for
Adulthood. London and New York: Routledge; 1997. pp. 229–235. [Google Scholar]
7. Stewart ME, Barnard L, Pearson J, Hasan R, O'Brien G. Presentation of depression in autism
and Asperger syndrome: a review. Autism. 2006 Jan;10(1):103–116. [PubMed] [Google Scholar]
8. Wachtel LE, Griffin M, Reti IM. Electroconvulsive therapy in a man with autism experiencing
severe depression, catatonia, and self-injury. J ECT. 2010 Mar;26(1):70–73. [PubMed] [Google
Scholar]
9. Association AP. Diagnostic and statistical manual of mental disorders: DSM-IV-TR.
Washington, DC: American Psychiatric Association; 2000. [Google Scholar]
10. Lee LC, Harrington RA, Louie BB, Newschaffer CJ. Children with autism: quality of life and
parental concerns. J Autism Dev Disord. 2008 Jul;38(6):1147–1160. [PubMed] [Google Scholar]
11. Kogan MD, Blumberg SJ, Schieve LA, et al. Prevalence of parent-reported diagnosis of
autism spectrum disorder among children in the US, 2007. Pediatrics. 2009 Nov;124(5):1395–
12. Gurney J, McPheeters M, Davis M. Parental report of health conditions and health care use
among children with and without autism: National survey of children's health. Arch Pediat
Adolesc Med. 2006 Aug;160(8):825–830. [PubMed] [Google Scholar]
13. Chen CY, Chen KH, Liu CY, Huang SL, Lin KM. Increased risks of congenital, neurologic,
and endocrine disorders associated with autism in preschool children: cognitive ability
differences. J Pediatr. 2009 Mar;154(3):345–350. 350 e341. [PubMed] [Google Scholar]
14. Matson JL, Nebel-Schwalm MS. Comorbid psychopathology with autism spectrum disorder
in children: an overview. Res Dev Disabil. 2007 Jul-Sep;28(4):341–352. [PubMed] [Google
Scholar]
15. Lainhart JE, Folstein SE. Affective disorders in people with autism: a review of published
cases. J Autism Dev Disord. 1994 Oct;24(5):587–601. [PubMed] [Google Scholar]
16. Baron-Cohen S, Leslie AM, Frith U. Does the autistic child have a “theory of mind”?
Cognition. 1985 Oct;21(1):37–46. [PubMed] [Google Scholar]
17. Tager-Flusberg H. Autistic children's talk about psychological states: deficits in the early
acquisition of a theory of mind. Child Dev. 1992 Feb;63(1):161–172. [PubMed] [Google
Scholar]
18. Leyfer OT, Folstein SE, Bacalman S, et al. Comorbid psychiatric disorders in children with
autism: interview development and rates of disorders. J Autism Dev Disord. 2006
Oct;36(7):849–861. [PubMed] [Google Scholar]
19. Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G. Psychiatric disorders in
children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a
population-derived sample. J Am Acad Child Adolesc Psychiatry. 2008 Aug;47(8):921–929.
20. Capps L, Sigman M, Yirmiya N. Self-competence and emotional understanding in high-
functioning children with autism. Dev Psychopathol. 1995 Dec;7(1):137–149. [Google Scholar]
21. Vickerstaff S, Heriot S, Wong M, Lopes A, Dossetor D. Intellectual ability, self-perceived
social competence, and depressive symptomatology in children with high-functioning autistic
spectrum disorders. J Autism Dev Disord. 2007 Oct;37(9):1647–1664. [PubMed] [Google
Scholar]
22. Perry DW, Marston GM, Hinder SA, Munden AC, Roy A. The phenomenology of depressive
illness in people with a learning disability and autism. Autism. 2001 Sep;5(3):265–275.
23. Takaoka K, Takata T. Catatonia in high-functioning autism spectrum disorders: case report
and review of literature. Psychol Rep. 2007 Dec;101(3 Pt 1):961–969. [PubMed] [Google
Scholar]
24. Bailey A, LeCouteur A, II G, et al. Autism as a strongly genetic disorder: evidence from a
British twin study. Psychol Med. 1995 Jan;25(1):63–77. [PubMed] [Google Scholar]
25. Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and
meta-analysis. Am J Psychiatry. 2000 Oct;157(10):1552–1562. [PubMed] [Google Scholar]
26. Daniels JL, Forssen U, Hultman CM, et al. Parental psychiatric disorders associated with
autism spectrum disorders in the offspring. Pediatrics. 2008 May;121(5):e1357–1362. [PubMed]
[Google Scholar]
27. Ghaziuddin M, Greden J. Depression in children with autism/pervasive developmental
disorders: a case-control family history study. J Autism Dev Disord. 1998 Apr;28(2):111–115.
28. Constantino JN, Hudziak JJ, Todd RD. Deficits in reciprocal social behavior in male twins:
evidence for a genetically independent domain of psychopathology. J Am Acad Child Adolesc
Psychiatry. 2003 Apr;42(4):458–467. [PubMed] [Google Scholar]
29. Hallett V, Ronald A, Happe F. Investigating the association between autistic-like and
internalizing traits in a community-based twin sample. J Am Acad Child Adolesc Psychiatry.
2009 Jun;48(6):618–627. [PubMed] [Google Scholar]
30. Humphrey N, Lewis S. ‘Make me normal’: the views and experiences of pupils on the
autistic spectrum in mainstream secondary schools. Autism. 2008 Jan;12(1):23–46. [PubMed]
[Google Scholar]
31. Hedley D, Young R. Social comparison processes and depressive symptoms in children and
adolescents with Asperger syndrome. Autism. 2006 Mar;10(2):139–153. [PubMed] [Google
Scholar]
32. Sterling L, Dawson G, Estes A, Greenson J. Characteristics associated with presence of
depressive symptoms in adults with autism spectrum disorder. J Autism Dev Disord. 2008
Jul;38(6):1011–1018. [PubMed] [Google Scholar]
33. Whitehouse AJ, Durkin K, Jaquet E, Ziatas K. Friendship, loneliness and depression in
adolescents with Asperger's Syndrome. J Adolesc. 2009 Apr;32(2):309–322. [PubMed] [Google
Scholar]
34. Pollard AJ, Prendergast M. Depressive pseudodementia in a child with autism. Dev Med
Child Neurol. 2004 Jul;46(7):485–489. [PubMed] [Google Scholar]
35. Meyer JA, Mundy PC, Van Hecke AV, Durocher JS. Social attribution processes and
comorbid psychiatric symptoms in children with Asperger syndrome. Autism. 2006
Jul;10(4):383–402. [PMC free article] [PubMed] [Google Scholar]
36. Tsuji H, Miyawaki D, Kawaguchi T, et al. Relationship of hypersensitivity to anxiety and
depression in children with high-functioning pervasive developmental disorders. Psychiatry Clin
Neurosci. 2009 Apr;63(2):195–201. [PubMed] [Google Scholar]
37. Pearson DA, Loveland KA, Lachar D, et al. A comparison of behavioral and emotional
functioning in children and adolescents with Autistic Disorder and PDD-NOS. Child
Neuropsychol. 2006 Aug;12(4-5):321–333. [PubMed] [Google Scholar]
38. Dominick KC, Davis NO, Lainhart J, Tager-Flusberg H, Folstein S. Atypical behaviors in
children with autism and children with a history of language impairment. Res Dev Disabil. 2007
Mar-Apr;28(2):145–162. [PubMed] [Google Scholar]
39. Williamson S, Craig J, Slinger R. Exploring the relationship between measures of self-
esteem and psychological adjustment among adolescents with Asperger syndrome. Autism. 2008
Jul;12(4):391–402. [PubMed] [Google Scholar]
40. Butzer B, Konstantareas M. Depression, temperament and their relationship to other
characteristics in children with Asperger's disorder. J Dev Disabil. 2003;10(1):67–72. [Google
Scholar]
41. Mazurek MO, Kanne SM. Friendship and Internalizing Symptoms Among Children and
Adolescents with ASD. J Autism Dev Disord. 2010 Apr 20; [PubMed] [Google Scholar]
42. Shtayermman O. Peer victimization in adolescents and young adults diagnosed with
Asperger's Syndrome: a link to depressive symptomatology, anxiety symptomatology and
suicidal ideation. Issues Compr Pediatr Nurs. 2007 Jul-Sep;30(3):87–107. [PubMed] [Google
Scholar]
43. Lopata C, Toomey JA, Fox JD, et al. Anxiety and depression in children with HFASDs:
symptom levels and source differences. J Abnorm Child Psychol. 2010 Aug;38(6):765–776.
44. Kelly AB, Garnett MS, Attwood T, Peterson C. Autism spectrum symptomatology in
children: the impact of family and peer relationships. J Abnorm Child Psychol. 2008
Oct;36(7):1069–1081. [PubMed] [Google Scholar]
45. Barnhill GP. Social Attributions and Depression in Adolescents with Asperger Syndrome.
Focus on Autism and Other Developmental Disabilities. 2001;16(1):46–53. [Google Scholar]
46. Skinner SR, Ng C, McDonald A, Walters T. A patient with autism and severe depression:
medical and ethical challenges for an adolescent medicine unit. Med J Aust. 2005 Oct
17;183(8):422–424. [PubMed] [Google Scholar]
47. Kim J, Szatmari P, Bryson S, Streiner D, Wilson F. The prevalence of anxiety and mood
problems among children with autism and Asperger syndrome. Autism. 2000 Jun;4(2):117–132.
[Google Scholar]
48. Gadow KD, Devincent C, Schneider J. Predictors of psychiatric symptoms in children with
an autism spectrum disorder. J Autism Dev Disord. 2008 Oct;38(9):1710–1720. [PubMed]
[Google Scholar]
49. Rao U, Chen LA. Characteristics, correlates, and outcomes of childhood and adolescent
depressive disorders. Dialogues Clin Neurosci. 2009;11(1):45–62. [PMC free article] [PubMed]
[Google Scholar]
50. Tandon M, Cardeli E, Luby J. Internalizing disorders in early childhood: a review of
depressive and anxiety disorders. Child Adolesc Psychiatr Clin N Am. 2009 Jul;18(3):593–610.
[PMC free article] [PubMed] [Google Scholar]
51. Janowsky DS, Davis JM. Diagnosis and treatment of depression in patients with mental
retardation. Curr Psychiatry Rep. 2005 Dec;7(6):421–428. [PubMed] [Google Scholar]
52. Minshawi NF. Behavioral assessment and treatment of self-injurious behavior in autism.
Child Adolesc Psychiatr Clin N Am. 2008 Oct;17(4):875–886. x. [PubMed] [Google Scholar]
53. Ghaziuddin M, Alessi N, Greden JF. Life events and depression in children with pervasive
developmental disorders. J Autism Dev Disord. 1995 Oct;25(5):495–502. [PubMed] [Google
Scholar]
54. Matson JL, Rush KS, Hamilton M, et al. Characteristics of depression as assessed by the
Diagnostic Assessment for the Severely Handicapped-II (DASH-II) Res Dev Disabil. 1999 Jul-
Aug;20(4):305–313. [PubMed] [Google Scholar]
55. Taylor JL, Seltzer MM. Employment and Post-Secondary Educational Activities for Young
Adults with Autism Spectrum Disorders During the Transition to Adulthood. J Autism Dev
Disord. 2010 Jul 17; [PMC free article] [PubMed] [Google Scholar]
56. Hill E, Berthoz S, Frith U. Brief report: cognitive processing of own emotions in individuals
with autistic spectrum disorder and in their relatives. J Autism Dev Disord. 2004 Apr;34(2):229–
57. Solomon M, Goodlin-Jones BL, Anders TF. A social adjustment enhancement intervention
for high functioning autism, Asperger's syndrome, and pervasive developmental disorder NOS. J
Autism Dev Disord. 2004 Dec;34(6):649–668. [PubMed] [Google Scholar]
58. Bauminger N, Shulman C, Agam G. Peer interaction and loneliness in high-functioning
children with autism. J Autism Dev Disord. 2003 Oct;33(5):489–507. [PubMed] [Google
Scholar]
59. Heinrich LM, Gullone E. The clinical significance of loneliness: a literature review. Clin
Psychol Rev. 2006 Oct;26(6):695–718. [PubMed] [Google Scholar]
60. Little L. Middle-class mothers' perceptions of peer and sibling victimization among children
with Asperger's syndrome and nonverbal learning disorders. Issues Compr Pediatr Nurs. 2002
Jan-Mar;25(1):43–57. [PubMed] [Google Scholar]
61. Brunstein Klomek A, Marrocco F, Kleinman M, Schonfeld IS, Gould MS. Bullying,
depression, and suicidality in adolescents. J Am Acad Child Adolesc Psychiatry. 2007
Jan;46(1):40–49. [PubMed] [Google Scholar]
62. Constantino JN. Social Impairment. In: Hollander K, Coyle, editors. Textbook of Autism
Spectrum Disorders. Arlington, VA: American Psychiatric Publishing, Inc.; 2010. [Google
Scholar]
63. Kanne SM, Christ SE, Reiersen AM. Psychiatric symptoms and psychosocial difficulties in
young adults with autistic traits. J Autism Dev Disord. 2009 Jun;39(6):827–833. [PubMed]
[Google Scholar]
64. Koegel RL, Mentis M. Motivation in childhood autism: can they or won't they? J Child
Psychol Psychiatry. 1985 Mar;26(2):185–191. [PubMed] [Google Scholar]
65. Kanne SM, Abbacchi AM, Constantino JN. Multi-informant ratings of psychiatric symptom
severity in children with autism spectrum disorders: the importance of environmental context. J
Autism Dev Disord. 2009 Jun;39(6):856–864. [PMC free article] [PubMed] [Google Scholar]
66. Constantino JN, Lavesser PD, Zhang Y, Abbacchi AM, Gray T, Todd RD. Rapid quantitative
assessment of autistic social impairment by classroom teachers. J Am Acad Child Adolesc
Psychiatry. 2007 Dec;46(12):1668–1676. [PubMed] [Google Scholar]
67. Kerr DC, Lunkenheimer ES, Olson SL. Assessment of child problem behaviors by multiple
informants: a longitudinal study from preschool to school entry. J Child Psychol Psychiatry.
2007 Oct;48(10):967–975. [PubMed] [Google Scholar]
68. Hurtig T, Kuusikko S, Mattila ML, et al. Multi-informant reports of psychiatric symptoms
among high-functioning adolescents with Asperger syndrome or autism. Autism. 2009
Nov;13(6):583–598. [PubMed] [Google Scholar]
69. Lichtenstein P, Carlstrom E, Rastam M, Gillberg C, Anckarsater H. The Genetics of Autism
Spectrum Disorders and Related Neuropsychiatric Disorders in Childhood. Am J Psychiatry.
2010 Aug 4; [PubMed] [Google Scholar]
70. Brimacombe M, Xue M, Parikh A. Familial risk factors in autism. J Child Neurol. 2007
May;22(5):593–597. [PubMed] [Google Scholar]
71. Mazefsky CA, Folstein SE, Lainhart JE. Overrepresentation of mood and anxiety disorders in
adults with autism and their first-degree relatives: what does it mean? Autism Res. 2008
Jun;1(3):193–197. [PMC free article] [PubMed] [Google Scholar]
72. Piven J, Palmer P. Psychiatric disorder and the broad autism phenotype: evidence from a
family study of multiple-incidence autism families. Am J Psychiatry. 1999 Apr;156(4):557–563.
73. Hallett V, Ronald A, Rijsdijk F, Happe F. Association of autistic-like and internalizing traits
during childhood: a longitudinal twin study. Am J Psychiatry. 2010 Jul;167(7):809–817.
74. Hoekstra RA, Bartels M, Hudziak JJ, Van Beijsterveldt TC, Boomsma DI. Genetic and
environmental covariation between autistic traits and behavioral problems. Twin Res Hum
Genet. 2007 Dec;10(6):853–860. [PubMed] [Google Scholar]
75. Constantino JN, Todd RD. Autistic traits in the general population: a twin study. Arch Gen
Psychiatry. 2003 May;60(5):524–530. [PubMed] [Google Scholar]
Anxiety and depression in adults with autism

spectrum disorder: a systematic review and
meta-analysis
Abstract
Adults with autism spectrum disorder (ASD) are thought to be at disproportionate risk of
developing mental health comorbidities, with anxiety and depression being considered most
prominent amongst these. Yet, no systematic review has been carried out to date to examine rates
of both anxiety and depression focusing specifically on adults with ASD. This systematic review
and meta-analysis examined the rates of anxiety and depression in adults with ASD and the
impact of factors such as assessment methods and presence of comorbid intellectual disability
(ID) diagnosis on estimated prevalence rates. Electronic database searches for studies published
between January 2000 and September 2017 identified a total of 35 studies, including 30 studies
measuring anxiety (n = 26 070; mean age = 30.9, s.d. = 6.2 years) and 29 studies measuring
depression (n = 26 117; mean age = 31.1, s.d. = 6.8 years). The pooled estimation of current and
lifetime prevalence for adults with ASD were 27% and 42% for any anxiety disorder, and 23%
and 37% for depressive disorder. Further analyses revealed that the use of questionnaire
measures and the presence of ID may significantly influence estimates of prevalence. The current
literature suffers from a high degree of heterogeneity in study method and an overreliance on
clinical samples. These results highlight the importance of community-based studies and the
identification and inclusion of well-characterized samples to reduce heterogeneity and bias in
estimates of prevalence for comorbidity in adults with ASD and other populations with complex
psychiatric presentations.
Footnotes
These authors contributed equally to this work.
Introduction
Our understanding of the social and mental health needs of individuals with an autism spectrum
disorder (ASD) across the lifespan has increased in recent years (Baxter et al., 2015), and there
has been increased emphasis on better understanding these in adults (Taylor and Seltzer, 2011;
Howlin, 2013; Moss et al., 2015, 2017). Adults with ASD are thought to be at heightened risk for
several co-occurring mental health conditions, with anxiety and depressive disorders being the
most prominent (Joshi et al., 2013). However, estimates of the rates of these co-occurring
disorders in adults with ASD vary considerably, with some studies reporting rates of anxiety or
depression as high as 70% (Charlot et al., 2008; Mazefsky et al., 2008), and others reporting
rates as low as <1% for depression (Buck et al., 2014), and 5% for anxiety (Tsakanikos et al.,
2011).
Given that ASD was, until recently, primarily considered a diagnosis of childhood, most research
to date has focused on the child and adolescent years. van Steensel and colleagues published a
meta-analysis of the prevalence of anxiety in young people with ASD aged <18 years of age (van
Steensel et al., 2011). Their results indicated that 39.6% of young people with ASD had at least
one anxiety disorder diagnosis, with specific phobias, obsessive-compulsive disorder (OCD) and
social anxiety being most commonly reported. Co-occurring depression in young people with
ASD has so far received less attention than anxiety, possibly due to lower prevalence estimates
in some studies. For instance, evidence from a population derived sample of children and
adolescents with ASD reported a 3-month point prevalence of any depressive disorder to be
1.4% compared with 41.9% for any anxiety disorder (Simonoff et al., 2008). In contrast, clinical
studies based on treatment seeking adults suggest that depression may indeed be common in
adults with ASD, with reported rates ranging from 20 to 35% (Mazefsky et al., 2008; Gotham et
al., 2015). In contrast, rates in the general population are reported to be around 7% for
depression, and between 1% and 12% for anxiety, depending on the specific diagnostic category
(Kessler et al., 2003, 2012).
There are several challenges to the use of meta-analytic methods with studies on the prevalence
of anxiety and depression in adults with ASD. Prominent amongst these are the lack of measures
available to assess mental health comorbidities in those with ASD, particularly in adulthood,
which are validated in ASD and non-ASD populations. This, along with variability in the
diagnostic assessment of ASD itself and a lack of community-based studies focusing on co-
occurring mental health presentations in individuals with ASD in adulthood means that there is
substantial heterogeneity in both the populations being assessed and the study designs and
methods/tools used to measure anxiety and depression. This is a potential caveat in the use of
meta-analytic techniques as it becomes very challenging to integrate and synthesize the literature
currently available. Nonetheless, describing these measurement differences enables us to
quantify the degree of heterogeneity in a robust way.
One important issue to consider when reviewing the available literature on mental health
comorbidities in those with ASD is the problem of diagnostic over-shadowing (Wood and
Gadow, 2010). This phenomenon has most often been discussed in relation to social phobia and
OCD, which are also the most commonly reported anxiety disorders in ASD (Ozsivadjian et al.,
2012; Kerns et al., 2014; Magiati et al., 2017). In the case of social phobia, it has been suggested
that the reduced social motivation or difficulties in social situations commonly observed in ASD
can appear behaviourally similar to the anxious avoidance of social situations which is
characteristic of social phobia. In addition, compulsive behaviours in OCD can appear similar in
presentation to restrictive and repetitive behaviours as observed in ASD, and indeed recent
evidence has suggested some neurobiological overlap (Carlisi et al., 2017). Similarly, social
disinterest and/or atypical social communication may be difficult to distinguish from
psychomotor symptoms of depression in those with ASD (Stewart et al., 2006; Chandrasekhar
and Sikich, 2015 ).
Another factor that adds to the complexity of determining the rates of anxiety and depressive
disorders in adults with ASD is the wide range of intellectual, verbal and adaptive functioning.
With regard to intellectual functioning, for example, it has been suggested that in clinical
samples approximately one-third of people with ASD have intellectual functioning in the
impaired range (Kim et al., 2011). Therefore, it is important to consider individuals’ functioning
when considering and interpreting findings from different studies of individuals with ASD with
and without intellectual disability (ID).
The aim of the current systematic review and meta-analysis was to examine the rates of anxiety
and depression in adults with ASD based on the literature currently available. To our knowledge,
previous systematic reviews have focused solely on depression rates, have considered both
children and adults together, or have included only a limited range of studies (i.e. Stewart et al.,
2006; Wigham et al., 2017). Therefore, a systematic review is now required that focuses on
adults, and examines both rates of depression and anxiety. Given our a-priori knowledge of a
lack of community-based prevalence studies in this area, we have opted to be inclusive in our
selection criteria. As discussed above, the current literature has been affected by a high degree of
between-study heterogeneity, both in terms of the clinical populations assessed, as well as the
study methodology and measures used to assess anxiety and depression. Therefore, as well as
providing the first, to our knowledge, meta-analysis of rates of anxiety and depression in adults
with ASD, we aimed to explore the potential impact of ASD diagnostic measures, measures of
comorbidity (i.e. clinical interviews v. questionnaire measures) and the role of ID on the
estimates reported.
Methods
Definition/operationalization of key constructs
In the current systematic review and meta-analysis, anxiety was defined as either clinically
significant/elevated symptoms of anxiety (defined as scores above clinical cut-offs on
questionnaires) or a clinical diagnosis of any specific anxiety disorder (including generalized
anxiety disorder; social phobia/social anxiety; specific phobia; separation anxiety;
panic/agoraphobia; post-traumatic stress disorder (PTSD); or OCD†1). Most studies present
panic disorder and agoraphobia as a single estimate, but in cases where they are presented
separately, the highest rate of the two was included. This was to reduce the chances of them
being double coded due to high comorbidity, given that most articles did not specify levels of
multiple comorbidities in their samples (Kessler et al., 2006).
For depression, we only included cases which were above recommended clinical cut-off scores
on validated questionnaires or where a professional/clinical diagnosis of major depression was
given. As an example, for the most commonly used questionnaire, the Beck Depression
Inventory (BDI; Beck, 1978), a cut-off score of ‘20’ or ‘24’, depending on the version, or at least
depression in the moderate range would be required. For all other questionnaires used, their
specific published cut-offs as applied by the original authors were used.
Information sources and search approach
We conducted a search of three electronic literature databases (PsycINFO, PubMed, and Web of
Science) selected to provide good coverage of both medical and psychology literature. The
search included publications from the start of the year 2000 and ran up until 30 September 2017.
The start date was selected based on the publication of the text revision of the DSM-IV, to
reduce the challenge of combining definitions from multiple diagnostic systems.
The search terms used were ( ‘autis*’ OR ‘Asperger*’ OR ‘Pervasive Developmental Disorder’);
AND (‘anxi*’ OR ‘anxiety disorder’ OR ‘anxious’) OR (‘comorbid* OR ‘psychiatric disorder’
OR ‘mental health’) OR (‘depress*’ OR ‘mood disorder’ OR ‘low mood’) AND (‘adults’ NOT
‘animal’).
Two earlier systematic reviews (Stewart et al., 2006; Wigham et al., 2017) and a narrative
review (Chandrasekhar and Sikich, 2015) on depression in adults with ASD were also examined;
and one additional citation (Crane et al., 2013) met our inclusion criteria and was included. We
identified no systematic reviews or meta-analyses focusing on the prevalence of anxiety in adults
with ASD. One review of comorbid Bipolar disorder was reviewed for depression related
literature, but no additional citations were identified (Vannucchi et al., 2014). A Preferred
Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) flowchart (Fig. 1) is
displayed as a summary of our search and review process (see Table 1 for inclusion and
exclusion criteria).
Fig. 1. Preferred reporting items for systematic reviews and meta-analysis (PRISMA) flowchart.
Table 1. Inclusion and exclusion criteria to be eligible for inclusion in the current systematic
review
Selecting studies for inclusion in the review
One author (MJH) initially screened titles and abstracts for eligibility and excluded those that
clearly did not meet criteria; following this, two authors (MJH & J-WL) reviewed all remaining
full-texts for eligibility. Disagreements were discussed and resolved on a case-by-case basis (see
Reliability).
Data extraction
We extracted the following information from each study: (a) sampling strategy; (b) descriptive
variables (e.g. age, gender); (c) tools used to diagnose ASD; (d) number of participants with an
ID in the sample; (e) tools used to assess anxiety/depression; (f) whether diagnostic
overshadowing/symptom overlap was considered in the study; and (g) current and lifetime
estimates of anxiety and depression.
As the primary interest of this meta-analysis is on current prevalence, all sensitivity analyses
were conducted on current estimates only. Three studies included both current and lifetime
estimates and both were used in their respective analyses (Joshi et al., 2013; Buck et al., 2014;
Gillberg et al., 2016).
Reliability
Selecting studies
There was good inter-rater reliability in study selection for inclusion in the review/ meta-analysis
(intra-class correlation = 0.72) and all disputes were resolved by referring to the
inclusion/exclusion criteria. On three occasions, the same dataset was used in data analyses in
three different publications, with different subsamples from the same study being analysed
(Tsakanikos et al., 2006, 2007, 2011). In this case, we included the most recent citation which
had the most participants. Reasons for exclusion included: no clinical cut-off/diagnostic
algorithm for anxiety/depression applied (n = 28); study did not measure anxiety/depression
(n = 25); minimum age of participants was <16 years (n = 11); non-ASD sample (n = 9); no
English translation was available (n = 8); not peer reviewed (n = 3), intervention study (n = 1),
review article (n = 1).
Data extraction
All data were extracted by the first author (MJH) and then a randomly selected sample of 25% of
the studies were checked for accuracy (J-WL), resulting in no disagreement.
Study sample
The final sample included 35 studies across both anxiety and depression, with 27 studies
measuring anxiety, 29 measuring depression, and 21 measuring both. Studies measuring anxiety
included a total of 26 070 participants (mean age = 30.9 years, s.d. = 6.2), and for depression
there were in total of 26 117 participants (mean age = 31.1 years, s.d. = 6.8; see Tables 2 and 3
for study characteristics and summary of main findings).
Table 2. Included studies assessing anxiety, study characteristics and prevalence rates of anxiety
ID, Intellectual Disability Disorder; Com, Recruited from a whole community or community
sampling strategy was used; Clin, Recruited through a clinical service; NT, Non-treatment
seeking and recruited through notices or databases, but not due to clinical contact; I, Structured
Interview, Q, Standardized Questionnaire, C, Clinical Records or not reported; ANY ANX, Any
Anxiety Disorder; SOC, Social Anxiety Disorder; OCD, Obsessive-compulsive Disorder; GAD,
Generalized Anxiety Disorder; PAN/AGO, Panic Disorder/Agoraphobia; SPH, Specific Phobia;
SEP, Separation Anxiety Disorder; PTSD, Post-traumatic Stress Disorder, NR, not reported.
Table 3. Included studies assessing depression, study characteristics and prevalence rates of
depression
ID, Intellectual Disability Disorder; Com, Recruited from a whole community or community
sampling strategy was used; Clin, Recruited through a clinical service; NT, Non-treatment
seeking and recruited through notices or databases, but not due to clinical contact; I, Structured
Interview, Q, Standardized Questionnaire, C, Clinical Records or not reported. NR, not reported.
For three studies where the age of the sub-sample of interest was not reported, the mean was
estimated based on the age of the overall sample (Morgan et al., 2003; Hermans et al., 2011;
Houghton et al., 2017). Seven of the 36 studies included in the meta-analysis included
adolescents in the sample (⩾16-years-old). Nine of the studies included had a sample that
included at least 50% of people with an ID and were included in the sub-analysis described
below (Morgan et al., 2003; McDermott et al., 2005; Charlot et al., 2008; Mazefsky et al., 2008;
Helverschou et al., 2009; Tsakanikos, et al. 2011; Hermans et al., 2012; Buck et al., 2014; Moss
et al., 2015).
Meta-analytic method
A random-effects meta-analysis with arcsine transformation was used to account for issues with
study weightings when estimating prevalence (Barendregt et al., 2013). Study heterogeneity was
assessed using the I 2 statistic, whereby a score of more than 50% indicates moderate, and a score
of 75% high levels of heterogeneity, respectively (Higgins and Thompson, 2002).
Subgroup analyses were conducted to investigate differences in rates reported in studies where
⩾50% of the sample had ID as compared with studies of participants without ID or with small
number of individuals with ID in the sample; assessment of ASD diagnoses (i.e. using Autism
Diagnostic Observation Schedule (ADOS)/Autism Diagnostic Interview (ADI)/other
standardized diagnostic assessment for ASD v. studies not reporting standardized diagnostic
procedures to confirm ASD diagnosis); and measurement of comorbidity (i.e. questionnaire v.
clinical interview). A table showing the range of measures used to assess anxiety and depression
and their psychometric properties can be seen online Supplementary Materials 2. It was also of
interest to investigate the impact of sample type (e.g. clinical v. community sampling). However,
as there were few studies that could clearly be defined as non-clinical, sampling was considered
under study quality.
The significance of differences in pooled estimates between subgroups was assessed via meta-
regression analyses. Study quality was assessed on two domains, selection bias and detection
bias, which were adapted for this meta-analysis from the Effective Public Health Practice Project
Quality Assessment Tool (Armijo-Olivo et al., 2012 ; see online Suppementary Material).
OpenMeta, a tool for running metafor package in R (Viechtbauer, 2010), was used to conduct the
meta-analysis (Wallace et al., 2012).
Results
Prevalence of anxiety disorders in adults with ASD
Any anxiety disorder

Meta-analytic pooling of the estimates yielded the prevalence of any current anxiety disorder as
27% (95% CI 17–37%; k (number of studies) = 13, n = 431/1444). Assessment of heterogeneity
indicated high levels of variance between studies included in the analysis (I 2 = 96%). A
subsequent analysis of the eight studies which were classified as measuring lifetime prevalence
indicated a prevalence of 42% (95% CI 35–50%; k = 8, n = 6634/25714, I 2 = 96%; see Table 4).
Table 4. Pooled estimates of current and lifetime anxiety and depression in adults with ASD
Social anxiety
Overall 12 studies reported on rates of social anxiety, together reporting an estimated current
prevalence of 29% and lifetime prevalence of 20% (current: 95% CI 18–40%, k = 9,
n = 200/1009, I 2 = 91%; lifetime: 95% CI 7–38%, k = 5, n = 75/322, I 2 = 91%).
OCD
Fifteen studies in total measured the rates of OCD with current prevalence estimate of 24% and a
lifetime prevalence of 22% (current: 95% CI 15–33%, k = 10, n = 265/1147, I 2 = 93%; lifetime:
95% CI 10–27%, n = 247/2063, k = 7, I 2 = 93%).
GAD
Seven studies reported current GAD prevalence of 18% and lifetime prevalence of 26% (current:
95% CI 10–26%, k = 4, n = 138/847, I 2 = 86%; lifetime: 95% CI 15–28%, k = 4, n = 63/272, I
2
= 74%).
Panic/agoraphobia
Eight studies in total reported an estimated current and lifetime prevalence of 15% and 18%,
respectively (current: 95% CI 8–23%, k = 4, n = 62/388, I 2 = 62%; lifetime: 95% CI 10–27%,
k = 4, n = 66/322, I 2 = 75%).
PTSD
PTSD was reported in five studies with a current prevalence of 1% and lifetime prevalence of
5% was found (current: 95% CI 0–5%, k = 3, n = 5/587, I 2 = 63%; lifetime: 95% CI 1–10%, n
studies = 3, n = 12/251, I 2 = 67%).
Specific phobia
A total of four studies reported on rates of specific phobia yielding an estimated current
prevalence of 6% and a lifetime prevalence of 31% (current: 95% CI 1–32%, k = 2, n = 13/537, I
2
= 97%; lifetime: 95% CI 10–66%, k = 3, n = 46/218, I 2 = 92%).
Separation anxiety
Current separation anxiety was reported by only one study as present in 3% of the sample
(n = 2/62), with a lifetime prevalence of 21% (13/62) (Joshi, et al., 2013).
Sub-group analyses: the role of clinical interview v. questionnaire measures, ASD

diagnostic tools and ID on current anxiety prevalence estimates
Use of clinical interview v. questionnaires to measure anxiety
When comparing studies which used a structured clinical interview v. questionnaires to assess
current rates of any anxiety disorder, we found no significant differences in prevalence estimates
(Clinical interview: k = 7; n = 275/786, estimated prevalence = 28%, 95% CI 19–39%, I 2 = 85%;
questionnaires: k = 4, n = 103/238, estimated prevalence = 31%, 95% CI 12–54%, I 2 = 91%).
However, all but one of the nine studies of current social anxiety used a structured diagnostic
interview, with this one study employing a questionnaire indicating a prevalence of 51% (Spain
et al., 2016) v. a pooled prevalence of 26% in the remaining studies (k = 8, n = 174/958, CI 16–
37%, I 2 = 90%).
Eight studies which assessed current OCD used clinical interviews resulting in a significantly
lower (β = 0.26, p = 0.03) estimated pooled prevalence of 19% v. 43% from the two studies
which used questionnaire measures and a reduced level of between study heterogeneity (Clinical
interview: k = 8, n = 215/1050, 95% CI 13–23%, I 2 = 79%; questionnaires: k = 2, n = 50/97,
95% CI 3–92%, I 2 = 97%).
Use of ASD diagnostic tools
Only 4/13 studies of current prevalence of any anxiety disorder used the ADOS and/or ADI to
confirm ASD diagnosis for inclusion into studies. The use of ADOS/ADI assessment lead to
slight, but non-significant, increases in the estimated pooled prevalence (ADOS/ADI studies:
k = 4, n = 223/603, estimated prevalence = 28%, 95% CI 15–43%, I 2 = 86%; non-ADOS/ADI
studies: k = 9, n = 208/841, estimated prevalence = 25%, 95% CI 13–37%, I 2 = 95%).
Similar results were found when looking at the 6/9 studies of current social anxiety (ADOS/ADI
studies: k = 6, n = 159/846, estimated prevalence = 33%, 95% CI 19–46%, I 2 = 92%; non-
ADOS/ADI studies: k = 3, n = 41/163, estimated prevalence = 21%, 95% CI 4–48%, I 2 = 93%)
and 5/10 studies of current OCD (ADOS/ADI: k = 5, n = 196/857, estimated prevalence = 24%,
95% CI 12–41%, I 2 = 95%; non-ADOS/ADI: k = 5, n = 69/290, estimated prevalence = 19%,
95% CI 14–31%, I 2 = 65%).
Presence of ID
Subgroup analysis of studies of current prevalence of anxiety disorder or clinically elevated

anxiety symptomatology of participants with or without associated ID revealed a somewhat
lower, but non-significant, pooled estimate of any anxiety disorder in adults with ASD and
associated ID (k = 6, n = 79/394, estimated prevalence = 20%, 95% CI 7–39%, I 2 = 93%)
compared with samples including only individuals with ASD without ID (k = 7, n = 352/1050,
estimated prevalence = 24%, 95% CI 19–43%, I 2 = 93%).
All nine studies of current social anxiety included only participants with ASD without an ID,
while only three of ten studies measuring OCD included primarily adults with ASD and ID,
resulting in no significant difference in pooled prevalence estimates (ID: k = 3, n = 55/177,
estimated prevalence = 24%, 95% CI 0.14–0.36, I 2 = 49%; non-ID: k = 7, n = 210/970,
estimated prevalence = 20%, 95% CI 0.10–0.34, I 2 = 93%).
Prevalence of depression in adults with ASD
Meta-analytic pooling of the estimates yielded a 23% prevalence of current co-morbid

depression diagnoses or moderate to severe clinically elevated depressive symptoms in adults
with ASD (k = 22, n = 400/1975; 95% CI 17–29%). Assessment of heterogeneity indicated high
levels of variance between studies included in the analysis (I 2 = 90%).
A subsequent analysis of the seven studies which were classified as measuring lifetime
prevalence of depression indicated a prevalence of 37% (k = 10, n = 4603/24384; 95% CI 27–
47%; I 2 = 98%).
Sub-group analyses: the role of clinical interview v. questionnaire measures, ASD
diagnostic tools and ID on current depression prevalence estimates
Use of clinical interview v. questionnaires to measure depression
When comparing studies which used a clinical interview v. questionnaires to assess depression,
we found a small, but non-significant, increase in prevalence estimates for studies using a
clinical interview rather than a questionnaire measure (Clinical interview: k = 11, n = 237/1182,
estimated prevalence = 27%, 95% CI 18–37%, I 2 = 92%; questionnaire: k = 8, n = 106/429,
estimated prevalence = 20%, 95% CI 11–33%, I 2 = 87%).
Use of ASD diagnostic measures
Only 6/19 studies of current prevalence used the ADOS and/or ADI to assess or confirm ASD in
their participants. This made little difference to prevalence estimates, but resulted in a
considerable drop in heterogeneity between studies (ADOS/ADI studies: k = 6, n = 170/878,
estimated prevalence = 22%, 95% CI 16–28%, I 2 = 66%; non-ADOS/ADI: k = 15,
n = 214/1047, estimated prevalence = 23%, 95% CI 14–34%, I 2 = 93%; p = 0.09).
Presence of ID
Subgroup analysis of studies of current prevalence of depression based on whether the sample
included participants with or without an ID revealed a significantly lower pooled estimate of
depression in those with ASD and ID (meta-regression: β = 0.12, p = 0.03), compared with
samples including only those without ID (ID: k = 6, n = 58/512, estimated prevalence = 14%,
95% CI 5–28%, I 2 = 92%; non-ID: k = 16, n = 326/1413, estimated prevalence = 26%, 95% CI
20–32%, I 2 = 83%).
Evaluating the quality of included studies
Our analysis of study quality revealed overall poor quality. Most prominent with regard to
prevalence is the reliance on clinic samples and little data available on how representative study
participants are of adults with ASD more generally. These results can be seen in online
Supplementary Materials 1 and indicate that there are few studies which have clearly taken
measures to reduce selection and detection bias.
Discussion
Summary of main findings
While it is widely accepted that adults with a diagnosis of ASD are at higher risk of experiencing
comorbid anxiety and depressive disorders, there has yet to be a systematic review and meta-
analysis to summarize the range of estimates of prevalence available in the literature (see also
Wigham et al., 2017). We found a pooled estimate of any current anxiety and depression of 27%
and 23%, respectively, in clinical studies, considerably higher than would be expected based on
estimates of 1–12% in the general population (Kessler et al., 2003, 2012). The rate of current
depression was consistent with the estimate of >20% reported by Wigham et al. (2017), which
examined a subset of the studies included in the present meta-analysis. The finding of somewhat
higher rates of anxiety compared with depression was also similar for pooled lifetime estimates
of any anxiety (42%) and depression (37%). Consistent with estimates from childhood (van
Steensel et al., 2011), we found that specific anxiety disorders, particularly social phobia and
OCD, were more commonly present in adults with ASD. However, our analyses of both
heterogeneity and study quality indicated high level of variance between studies, a wide range of
study methodologies and sample selection, all of which increase the likelihood of biases and
reduce our ability to make more firm estimates of prevalence from the studies currently
available.
Rates/prevalence of anxiety and depression in adults with ASD
The findings of the current study are consistent with meta-analyses of the prevalence of anxiety
in people with ASD aged 18 years and under (van Steensel et al., 2011; van Steensel and
Heeman, 2017). However, while the 2011 meta-analytic study suggested a current rate of any
anxiety disorder of around 39%, our pooled estimate of anxiety in adulthood appears lower at
27%. This may be explained by lower rates (when measured) of anxiety disorders more typically
associated with the childhood period such as separation anxiety (Bögels et al., 2013), and a
reduction in the estimated prevalence of specific phobias. It is notable, however, that compared
with the estimates by van Steensel and colleagues, we found a near 10% higher rate of both
social anxiety and OCD in adults. This could in part be accounted for by the fact that these
anxiety subtypes were assessed/reported more often in the literature included in the current meta-
analysis. It is also possible that these high rates could be at least partially due to diagnostic
overshadowing, which is a challenge with OCD and social anxiety as discussed earlier. In fact,
this was evident in our sub-group analysis comparing structured interviews and questionnaires,
with the later resulting in higher estimates of both OCD and social anxiety. This may suggest
that the process of eliciting a detailed description of the target behaviour, as is often the case
when conducting a diagnostic or a semi-structured interview and making a clinical judgement on
this may reduce the impact of diagnostic overshadowing. Similarly, this may account for the
higher heterogeneity of prevalence rates based on questionnaire measures v. structured
interviews. However, it is important to note that in both methods the heterogeneity remains high.
One a-priori aim of this systematic review and meta-analysis was to consider the possible impact
of diagnostic overshadowing on the estimated reported prevalence of anxiety and depression in
adults with ASD. Unfortunately, only four of the total of 36 studies included in this meta-
analysis considered diagnostic over-shadowing: two relied on clinical experience or trained
research staff who conducted the interviews in differentiating symptoms of anxiety and ASD
(Maddox and White, 2015; Capriola et al., 2016); one used a measure specifically designed to
assess comorbidity in ASD (Helverschou et al., 2008), and one removed all symptoms of OCD
which potentially overlapped with those of ASD from their diagnostic coding (Buck et al.,
2014). In the latter study, this resulted in the lifetime prevalence dropping from 36% to 22%,
suggesting that overlap between ASD and anxiety symptomatology and presentation does to
some extent impact the estimated reported prevalence and that caution should be exercised when
interpreting the results of the other studies and of this meta-analysis. From a clinical perspective,
this finding suggests that at the current time an overreliance on informant-based or self-report
questionnaire measures to assess mental health in ASD without the use of more detailed in depth
structured clinical interviews is not recommended. Rather, a detailed assessment focusing
explicitly on follow-up questions to clarify the nature of symptoms and to differentiate between
ASD and mental health symptomatology may be warranted in clinical settings, with checklists
used as supplementary or preliminary information. However, in research, this must be performed
in a transparently reproducible way, which so-called ‘clinical consensus’ methods often make
difficult.
In contrast to studies in children and adolescents with ASD (Simonoff et al., 2008; Salazar et al.,
2015) which report relatively low rates of depression, our current study found a high estimated
pooled prevalence of 22% in adults with ASD. This suggests that mood-related issues likely pose
significant difficulties for many adults with ASD. Moreover, these findings may also suggest a
developmental progression with depression becoming more prominent in adulthood.
Interestingly, our findings suggest the prevalence of depression was 10% lower in those with
compared with those without ID, suggests that current self-report measures may not be
adequately assessing symptoms of depression. This may be because of difficulties with
identifying and describing low mood, which may be further exacerbated by ID or difficulties
with the verbal articulation of the physiological, emotional, cognitive and behavioural
experiences of depression (Hassiotis and Turk, 2012).
Limitations
The results presented here must be considered in the context of several limitations. Due to the
high heterogeneity between the studies included, it is difficult to be certain how much our current
estimates reflect the true prevalence of anxiety and depression in adults with identified ASD. The
high heterogeneity, while making firm conclusions regarding prevalence difficult, is a realistic
presentation of the current literature on mental health comorbidities in ASD. Due to several
factors, including missing data from studies, we were unable to look at other factors that may
influence prevalence rates, such as age or gender ratio. For example, to explore whether rates of
depression increase with age or, as suggested in the non-ASD literature, that prevalence of
anxiety is higher in females than males (McLean et al., 2011). Future meta-analyses can
investigate the influence of these factors when more data from empirical studies become
available. Furthermore, there were several studies which we were unable to include due to not
being able to extrapolate a prevalence rate which may have influenced the accuracy of our
current estimates. In addition, due to the lack of studies which used information from multiple
informants, we were unable to evaluate the inter-rater reliability of diagnoses and reported
prevalence rates and the rates from studies using questionnaires mostly relied on self-report data.
Nevertheless, studies which did use measures completed by different informants (i.e. caregivers
v. self-report) suggested a reasonable overall level of agreement (Gotham et al., 2015; Maddox
and White, 2015), although the degree of agreement did vary between studies (Buck et al.,
2014). Furthermore, there were no community studies that included adults whose ASD had not
been recognized or who had not been in contact with clinical services, and therefore the samples
included in the current analysis may not fully represent adults with ASD in the whole population.
Accordingly, our findings should be of value in clinical practice settings but may be of more
limited value to our understanding of the relationship of ASD to other forms of mental health
disorders in the wider community.
Implications and recommendations for future research

The current analysis has identified several gaps in the literature. Future studies of prevalence
should use well defined and validated diagnostic assessments to both confirm the diagnosis of
ASD and to assess psychiatric comorbidity. We found no studies examining comorbidity in non-
clinical (i.e. community or general population) samples of adults with ASD. The development
and implementation of such studies should be a priority. In addition, the current literature does
not consider difficulties with alexithymia (difficulties with labelling emotions) which are
common in ASD (Bird et al., 2011). Variability in symptoms of alexithymia may influence the
reported levels of emotional symptoms and this should be considered in future studies. The use
of standardized and validated semi-structured, investigator rated ASD diagnostic tools, such as
the ADOS and ADI-R, in future prevalence studies may also help to reduce heterogeneity and
strengthen the characterisation of participants included in such studies. Despite the recognition of
possible diagnostic overshadowing, there is a dearth of research on validated assessments of
depression and anxiety in adults with ASD (Brugha et al., 2015). While across both child and
adult populations there have been efforts to validate some existing questionnaires (i.e. Zainal et
al., 2014; Magiati et al., 2017; Uljarevic et al., 2018) and to develop population-specific tools
(Bearss et al., 2016; Rodgers et al., 2016), more research in this area is still required concerning
assessment issues.
Conclusion and clinical implications

In conclusion, adults with a diagnosis of ASD experience high rates of comorbid anxiety and
depression. The exact prevalence is difficult to estimate precisely, given high levels of
heterogeneity between studies, but our results suggest rates significantly higher than one would
expect. Although it is possible that depression is underestimated, especially in the context of
ASD with ID, both anxiety and depression are prominent and common in adults with a diagnosis
of ASD. This suggests that in clinical settings a thorough assessment of the mental health of
individuals with ASD involving different methodologies and self-, in addition to other-
informant, measures are warranted. Provision for access to evidence-based psychological
interventions specifically adapted for this population is also important clinically (Russell et al.,
2017; Rodgers et al., 2018). As is to consider that due to the high rates of anxiety and depression
in this population, as yet unidentified and undiagnosed, individuals with ASD may be over-
represented in mental health services.
Note
1
We have included PTSD and OCD as they have a strong anxiety component and were
previously organized and conceptualized under anxiety disorders in DSM-IV-TR, when many of
the included studies took place.
† The notes appear after the main text.

References
Armijo-Olivo, S, Stiles, CR, Hagen, NA, Biondo, PD and Cummings, GG (2012) Assessment of
study quality for systematic reviews: a comparison of the Cochrane Collaboration Risk of Bias
Tool and the Effective Public Health Practice Project Quality Assessment Tool: Methodological
research. Journal of Evaluation in Clinical Practice 18, 12–18. CrossRef | Google Scholar |
PubMed
Ashwood, KL, Gillan, N, Horder, J, Hayward, H, Woodhouse, E, McEwen, FS, Findon, J,
Eklund, H, Spain, D, Wilson, CE, Cadman, T, Young, S, Stoencheva, V, Murphy, CM,
Robertson, D, Charman, T, Bolton, P, Glaser, K, Asherson, P, Simonoff, E and Murphy, DG
(2016) Predicting the diagnosis of autism in adults using the Autism-Spectrum Quotient (AQ)
questionnaire. Psychological Medicine 46, 1–10. CrossRef | Google Scholar
Barendregt, JJ, Doi, SA, Lee, YY, Norman, RE and Vos, T (2013) Meta-analysis of prevalence.
Journal of Epidemiology and Community Health 67, 974–978. CrossRef | Google Scholar
Baxter, AJ, Brugha, TS, Erskine, HE, Scheurer, RW, Vos, T and Scott, JG (2015) The
epidemiology and global burden of autism spectrum disorders. Psychological Medicine 45, 601–
613. CrossRef | Google Scholar | PubMed
Bearss, K, Taylor, CA, Aman, MG, Whittemore, R, Lecavalier, L, Miller, J, Pritchett, J, Green,
B and Scahill, L (2016) Using qualitative methods to guide scale development for anxiety in
youth with autism spectrum disorder. Autism 20, 663–672. CrossRef | Google Scholar | PubMed
Beck, AT (1978) Beck depression inventory. Depression 2006, 2–4. Google Scholar
Bejerot, S, Eriksson, JM and Mortberg, E (2014) Social anxiety in adult autism spectrum
disorder. Psychiatry Research 220, 705–707. CrossRef | Google Scholar | PubMed
Berthoz, S, Lalanne, C, Crane, L and Hill, EL (2013) Investigating emotional impairments in
adults with autism spectrum disorders and the broader autism phenotype. Psychiatry Research
208, 257–264. CrossRef | Google Scholar | PubMed
Bird, G, Press, C and Richardson, DC (2011) The role of alexithymia in reduced eye-fixation in
Autism Spectrum Conditions. Journal of Autism and Developmental Disorders 41, 1556–1564.
CrossRef | Google Scholar | PubMed
Bögels, SM, Knappe, S and Clark, LA (2013) Adult separation anxiety disorder in DSM-5.
Clinical Psychology Review 33, 663–674. CrossRef | Google Scholar | PubMed
Brugha, TS, Doos, L, Tempier, A, Einfeld, S and Howlin, P (2015) Outcome measures in
intervention trials for adults with autism spectrum disorders; a systematic review of assessments
of core autism features and associated emotional and behavioural problems. International Journal
of Methods in Psychiatric Research 24, 99–115. CrossRef | Google Scholar | PubMed
Buck, TR, Viskochil, J, Farley, M, Coon, H, McMahon, WM, Morgan, J and Bilder, DA (2014)
Psychiatric comorbidity and medication use in adults with autism spectrum disorder. Journal of
Autism and Developmental Disorders 44, 3063–3071. CrossRef | Google Scholar | PubMed
Capriola, NN, Maddox, BB and White, SW (2016) No offense intended: fear of negative
evaluation in adolescents and adults with autism spectrum disorder. Journal of Autism and
Developmental Disorders 47, 3803–3813. CrossRef | Google Scholar
Carlisi, CO, Norman, L, Murphy, CM, Christakou, A, Chantiluke, K, Giampietro, V, Simmons,
A, Brammer, M, Murphy, DG, Mataix-Cols, D, Rubia, K and Rubia, K (2017) Comparison of
neural substrates of temporal discounting between youth with autism spectrum disorder and with
obsessive-compulsive disorder. Psychological Medicine 47, 1–15. CrossRef | Google Scholar |
PubMed
Cederlund, M, Hagberg, B and Gillberg, C (2010) Asperger syndrome in adolescent and young
adult males. Interview, self- and parent assessment of social, emotional, and cognitive problems.
Research in Developmental Disabilities 31, 287–298. CrossRef | Google Scholar
Chandrasekhar, T and Sikich, L (2015) Challenges in the diagnosis and treatment of depression
in autism spectrum disorders across the lifespan. Dialogues in Clinical Neuroscience 17, 219–
227. Google Scholar | PubMed
Charlot, L, Deutsch, CK, Albert, A, Hunt, A, Connor, DF and McIlvane, WJJ (2008) Mood and
anxiety symptoms in psychiatric inpatients with autism spectrum disorder and depression.
Journal of Mental Health Research in Intellectual Disabilities 1, 238–253. CrossRef | Google
Scholar | PubMed
Crane, L, Goddard, L and Pring, L (2013) Autobiographical memory in adults with autism
spectrum disorder: the role of depressed mood, rumination, working memory and theory of mind.
Autism: the International Journal of Research and Practice 17, 205–219. CrossRef | Google
Scholar | PubMed
Croen, LA, Zerbo, O, Qian, Y, Massolo, ML, Rich, S, Sidney, S and Kripke, C (2015) The
health status of adults on the autism spectrum. Autism: the International Journal of Research and
Practice 19, 814–823. CrossRef | Google Scholar | PubMed
Ghaziuddin, M and Zafar, S (2008) Psychiatric comorbidity of adults with autism spectrum
disorders. Clinical Neuropsychiatry: Journal of Treatment Evaluation 5, 9–12. Google Scholar
Gillberg, IC, Helles, A, Billstedt, E and Gillberg, C (2016) Boys with asperger syndrome grow
up: psychiatric and neurodevelopmental disorders 20 years after initial diagnosis. Journal of
Gotham, K, Unruh, K and Lord, C (2015) Depression and its measurement in verbal adolescents
and adults with autism spectrum disorder. Autism: the International Journal of Research and
Practice 19, 491–504. CrossRef | Google Scholar | PubMed
Hassiotis, A and Turk, J (2012) Mental health needs in adolescents with intellectual disabilities:
cross-sectional survey of a service sample. Journal of Applied Research in Intellectual
Disabilities 25, 252–261. CrossRef | Google Scholar | PubMed
Hedley, D, Uljarevic, M, Wilmot, M, Richdale, A and Dissanayake, C (2017) Brief report: social
support, depression and suicidal ideation in adults with autism spectrum disorder. Journal of
Autism and Developmental Disorders 47:3669–3677. CrossRef | Google Scholar | PubMed
Helverschou, SB, Bakken, TL and Martinsen, H (2008) Identifying symptoms of psychiatric
disorders in people with autism and intellectual disability: an empirical conceptual analysis.
Mental Health Aspects of Developmental Disabilities 11, 107–115. Google Scholar
Helverschou, SB, Bakken, TL and Martinsen, H (2009) The psychopathology in autism checklist
(PAC): a pilot study. Research in Autism Spectrum Disorders 3, 179–195. CrossRef | Google
Scholar
Hermans, H, van der Pas, FH and Evenhuis, HM (2011) Instruments assessing anxiety in adults
with intellectual disabilities: a systematic review. Research in Developmental Disabilities 32,
861–870. CrossRef | Google Scholar | PubMed
Hermans, H, Jelluma, N, van der Pas, FH and Evenhuis, HM (2012) Feasibility, reliability and
validity of the Dutch translation of the anxiety, depression and mood scale in older adults with
intellectual disabilities. Research in Developmental Disabilities 33, 315–323. CrossRef | Google
Scholar | PubMed
Higgins, JPT and Thompson, SG (2002) Quantifying heterogeneity in a meta-analysis. Statistics
in Medicine 21, 1539–1558. CrossRef | Google Scholar | PubMed
Hill, E, Berthoz, S and Frith, U (2004) Brief report: cognitive processing of own emotions in
individuals with autistic spectrum disorder and in their relatives. Journal of Autism and
Developmental Disorders 34, 229–235. CrossRef | Google Scholar | PubMed
Hofvander, B, Delorme, R, Chaste, P, Nydén, A, Wentz, E, Ståhlberg, O, Herbrecht, E, Stopin,
A, Anckarsäter, H, Gillberg, C, Råstam, M and Leboyer, M (2009) Psychiatric and psychosocial
problems in adults with normal-intelligence autism spectrum disorders. BMC Psychiatry 9, 35.
Houghton, R, Ong, RC and Bolognani, F (2017) Psychiatric comorbidities and use of
psychotropic medications in people with autism spectrum disorder in the United States. Autism
Research, 10, 2037–2047. CrossRef | Google Scholar | PubMed
Howlin, P (2013) Social disadvantage and exclusion: adults with autism lag far behind in
employment prospects. Journal of the American Academy of Child & Adolescent Psychiatry 52,
Jones, L, Goddard, L, Hill, EL, Henry, LA and Crane, L (2014) Experiences of receiving a
diagnosis of autism spectrum disorder: a survey of adults in the United Kingdom. United States
Journal of Autism and Developmental Disorders 44, 3033–3044. CrossRef | Google Scholar |
PubMed
Joshi, G, Wozniak, J, Petty, C, Martelon, MK, Fried, R, Bolfek, A, Kotte, A, Stevens, J, Furtak,
SL, Bourgeois, M, Caruso, J, Caron, A and Biederman, J (2013) Psychiatric comorbidity and
functioning in a clinically referred population of adults with autism spectrum disorders: a
comparative study. Journal of Autism and Developmental Disorders 43, 1314–1325. CrossRef |
Google Scholar
Kerns, CM, Kendall, PC, Berry, L, Souders, MC, Franklin, ME, Schultz, RT, Miller, J and
Herrington, J (2014) Traditional and atypical presentations of anxiety in youth with autism
spectrum disorder. Journal of Autism and Developmental Disorders. 44, 2851–2861. CrossRef |
Google Scholar | PubMed
Kessler, RC, Berglund, P, Demler, O, Jin, R, Koretz, D, Merikangas, KR, Rush, AJ, Walters, EE
and Wang, PS (2003) The epidemiology of major depressive disorder. JAMA 289, 3095.
Kessler, RC, Chiu, WT, Jin, R, Ruscio, AM, Shear, K and Walters, EE (2006) The epidemiology
of panic attacks, panic disorder, and agoraphobia in the National Comorbidity Survey
Replication. Archives of General Psychiatry 63, 415–424. CrossRef | Google Scholar | PubMed
Kessler, RC, Petukhova, M, Sampson, NA, Zaslavsky, AM and Wittchen, HU (2012) Twelve-
month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the
United States. International Journal of Methods in Psychiatric Research 21, 169–184. CrossRef |
Ketelaars, C, Horwitz, E, Sytema, S, Bos, J, Wiersma, D, Minderaa, R and Hartman, CA (2008)
Brief report: adults with mild autism spectrum disorders (ASD): scores on the autism spectrum
quotient (AQ) and comorbid psychopathology. Journal of Autism and Developmental Disorders
Kim, YS, Leventhal, BL, Koh, Y-J, Fombonne, E, Laska, E, Lim, E-C, Cheon, K-A, Kim, S-J,
Kim, Y-K, Lee, H, Song, D-H and Grinker, RR (2011) Prevalence of autism spectrum disorders
in a total population sample. American Journal of Psychiatry 168, 904–912. CrossRef | Google
Scholar
Lai, MC, Lombardo, M V., Pasco, G, Ruigrok, AN V, Wheelwright, SJ, Sadek, SA, Chakrabarti,
B and Baron-Cohen, S (2011) A behavioral comparison of male and female adults with high
functioning autism spectrum conditions. PLoS ONE 6, p.e20835. CrossRef | Google Scholar |
PubMed
Lever, AG and Geurts, HM (2016) Psychiatric co-occurring symptoms and disorders in young,
middle-aged, and older adults with autism spectrum disorder. Journal of Autism and
Lugnegard, T, Hallerback, MU and Gillberg, C (2011) Psychiatric comorbidity in young adults
with a clinical diagnosis of Asperger syndrome. Research in Developmental Disabilities 32,
Maddox, BB and White, SW (2015) Comorbid social anxiety disorder in adults with autism
spectrum disorder. Journal of Autism and Developmental Disorders 45, 3949–3960. CrossRef |
Magiati, I, Lerh, JW, Hollocks, MJ, Uljarevic, M, Rodgers, J, Mcconachie, H, Ozsivadjian, A,
South, M, Van Hecke, A, Hardan, A, Libove, R, Leekam, S and Simonoff, E (2017) The
measurement properties of the spence children's anxiety scale-parent version in a large
international pooled sample of young people with autism spectrum disorder, 10 1–24. Google
Scholar
Mazefsky, CA, Folstein, SE and Lainhart, JE (2008) Overrepresentation of mood and anxiety
disorders in adults with autism and their first-degree relatives: what does it mean? Autism
Research 1, 193–197. CrossRef | Google Scholar | PubMed
McDermott, S, Moran, R, Platt, T, Issac, T, Wood, H and Dasari, S (2005) Depression in adults
with disabilities, in primary care. Disability and Rehabilitation 27, 117–123. CrossRef | Google
Scholar | PubMed
McLean, CP, Asnaani, A, Litz, BT and Hofmann, SG (2011) Gender differences in anxiety
disorders: prevalence, course of illness, comorbidity and burden of illness. Journal of Psychiatric
Research 45, 1027–1035. CrossRef | Google Scholar | PubMed
Morgan, CN, Roy, M and Chance, P (2003) Psychiatric comorbidity and medication use in
autism: a community survey. Psychiatric Bulletin 27, 378–381. CrossRef | Google Scholar
Moss, P, Howlin, P, Savage, S, Bolton, P and Rutter, M (2015) Self and informant reports of
mental health difficulties among adults with autism findings from a long-term follow-up study.
Scholar | PubMed
Moss, P, Mandy, W and Howlin, P (2017) Child and adult factors related to quality of life in
adults with autism. Journal of Autism and Developmental Disorders 47, 1–8. CrossRef | Google
Scholar | PubMed
Nylander, L, Holmqvist, M, Gustafson, L and Gillberg, C (2013) Attention-deficit/hyperactivity
disorder (ADHD) and autism spectrum disorder (ASD) in adult psychiatry. A 20-year register
study. Nordic Journal of Psychiatry 67, 344–350. CrossRef | Google Scholar | PubMed
Ozsivadjian, A, Knott, F and Magiati, I (2012) Parent and child perspectives on the nature of
anxiety in children and young people with autism spectrum disorders: a focus group study.
Scholar
Rodgers, J, Herrema, R, Honey, E and Freeston, M (2018) Towards a treatment for intolerance
of uncertainty for autistic adults: a single case experimental design study. Journal of autism and
developmental disorders, pp. 1–14. Google Scholar | PubMed
Rodgers, J, Wigham, S, McConachie, H, Freeston, M, Honey, E and Parr, JR (2016)
Development of the anxiety scale for children with autism spectrum disorder (ASC-ASD).
Autism Research 9, 1205–1215. CrossRef | Google Scholar
Roy, M, Prox-Vagedes, V, Ohlmeier, MD and Dillo, W (2015) Beyond childhood: psychiatric
comorbidities and social background of adults with asperger syndrome. Psychiatria Danubina 27,
50–59. Google Scholar | PubMed
Russell, A, Cooper, K, Barton, S, Ensum, I, Gaunt, D, Horwood, J, Ingham, B, Kessler, D,
Metcalfe, C, Parr, J and Rai, D (2017) Protocol for a feasibility study and randomised pilot trial
of a low-intensity psychological intervention for depression in adults with autism: the Autism
Depression Trial (ADEPT). BMJ open 7, p. e019545. Google Scholar
Russell, AJ, Murphy, CM, Wilson, E, Gillan, N, Brown, C, Robertson, DM, Craig, MC, Deeley,
Q, Zinkstok, J, Johnston, K, McAlonan, GM, Spain, D and Murphy, DG (2016) The mental
health of individuals referred for assessment of autism spectrum disorder in adulthood: a clinic
report. Autism: the International Journal of Research and Practice 20, 623–627. CrossRef |
Salazar, F, Baird, G, Chandler, S, Tseng, E, O'sullivan, T, Howlin, P, Pickles, A and Simonoff, E
(2015) Co-occurring psychiatric disorders in preschool and elementary school-aged children with
autism spectrum disorder. Journal of Autism and Developmental Disorders 45:2283–2294.
Simonoff, E, Pickles, A, Charman, T, Chandler, S, Loucas, T and Baird, G (2008) Psychiatric
disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated
factors in a population-derived sample. Journal of the American Academy of Child and
Adolescent Psychiatry 47, 921–929. CrossRef | Google Scholar
Spain, D, Happe, F, Johnston, P, Campbell, M, Sin, J, Daly, E, Ecker, C, Anson, M, Chaplin, E,
Glaser, K, Mendez, A, Lovell, K and Murphy, D (2016) Social anxiety in adult males with
autism spectrum disorders. Research in Autism Spectrum Disorders 32, 13–23. CrossRef |
Google Scholar
Sterling, L, Dawson, G, Estes, A and Greenson, J (2008) Characteristics associated with
presence of depressive symptoms in adults with autism spectrum disorder. Journal of Autism and
Stewart, ME, Barnard, L, Pearson, J, Hasan, R and O'Brien, G (2006) Presentation of depression
in autism and Asperger syndrome a review. Autism 10, 103–116. CrossRef | Google Scholar |
PubMed
Taylor, JL and Seltzer, MM (2011) Employment and post-secondary educational activities for
young adults with autism spectrum disorders during the transition to adulthood. Journal of
Tsakanikos, E, Costello, H, Holt, G, Bouras, N, Sturmey, P and Newton, T (2006)
Psychopathology in adults with autism and intellectual disability. United States Journal of
Tsakanikos, E, Sturmey, P, Costello, H, Holt, G and Bouras, N (2007) Referral trends in mental
health services for adults with intellectual disability and autism spectrum disorders. England
Autism: the International Journal of Research and Practice 11, 9–17. CrossRef | Google Scholar |
PubMed
Tsakanikos, E, Underwood, L, Kravariti, E, Bouras, N and McCarthy, J (2011) Gender
differences in co-morbid psychopathology and clinical management in adults with autism
spectrum disorders. Research in Autism Spectrum Disorders 5, 803–808. CrossRef | Google
Scholar
Uljarevic, M, Richdale, AL, McConachie, H, Hedley, D, Cai, RY, Merrick, H, Parr, JR and Le
Couteur, A (2018) The hospital anxiety and depression scale: factor structure and psychometric
properties in older adolescents and young adults with autism spectrum disorder. Autism
Research 11:258–269. CrossRef | Google Scholar
Vannucchi, G, Masi, G, Toni, C, Dell'Osso, L, Erfurth, A and Perugi, G (2014) Bipolar disorder
in adults with Asperger's Syndrome: a systematic review. Journal of Affective Disorders 168,
van Steensel, FJA and Heeman, EJ (2017) Anxiety levels in children with autism spectrum
disorder: a meta-analysis. Journal of Child and Family Studies 26, 1753–1767. CrossRef |
van Steensel, FJA, Bögels, SM and Perrin, S (2011) Anxiety disorders in children and
adolescents with autistic spectrum disorders: a meta-analysis. Clinical Child and Family
Psychology Review 14, 302–317. CrossRef | Google Scholar | PubMed
Viechtbauer, W (2010) Conducting meta-analyses in R with the metafor package. Journal of
Statistical Software 36, 1–48. CrossRef | Google Scholar
Wallace, BC, Dahabreh, IJ, Trikalinos, T a, Lau, J, Trow, P and Schmid, CH (2012) Closing the
gap between methodologists and end-users: r as a computational back-End. Journal of Statistical
Software 49, 1–15. CrossRef | Google Scholar
Wigham, S, Barton, S, Parr, JR and Rodgers, J (2017) A systematic review of the rates of
depression in children and adults With high-functioning autism spectrum disorder. Journal of
Mental Health Research in Intellectual Disabilities 10, 267–287. CrossRef | Google Scholar
Wood, JJ and Gadow, KD (2010) Exploring the nature and function of anxiety in youth with
autism spectrum disorders. Clinical Psychology: Science and Practice 17, 281–292. Google
Scholar
Zainal, H, Magiati, I, Tan, JWL, Sung, M, Fung, DSS and Howlin, P (2014) A preliminary
investigation of the Spence children's anxiety parent scale as a screening tool for anxiety in
young people with autism spectrum disorders. Journal of Autism and Developmental Disorders
Anxiety Disorders in Children and

Adolescents with Autistic Spectrum
Disorders: A Meta-Analysis
 Francisca J. A. van Steensel,
 Susan M. Bögels &
 Sean Perrin
Clinical Child and Family Psychology Review volume 14, Article number: 302 (2011)
Abstract
There is considerable evidence that children and adolescents with autistic spectrum disorders
(ASD) are at increased risk of anxiety and anxiety disorders. However, it is less clear which of
the specific DSM-IV anxiety disorders occur most in this population. The present study used
meta-analytic techniques to help clarify this issue. A systematic review of the literature identified
31 studies involving 2,121 young people (aged <18 years) with ASD, and where the presence of
anxiety disorder was assessed using standardized questionnaires or diagnostic interviews. Across
studies, 39.6% of young people with ASD had at least one comorbid DSM-IV anxiety disorder,
the most frequent being specific phobia (29.8%) followed by OCD (17.4%) and social anxiety
disorder (16.6%). Associations were found between the specific anxiety disorders and ASD
subtype, age, IQ, and assessment method (questionnaire versus interview). Implications for the
identification and treatment of anxiety in young people with ASD are discussed.
Introduction
Autistic disorder, Asperger’s syndrome and pervasive developmental disorder not otherwise
specified (PDD-NOS) are characterized by varying degrees of impairment in communication and
reciprocal social interaction as well as stereotyped interests and behaviors (American Psychiatric
Association 2001). In addition to these core features of the autistic spectrum disorders (ASD),
the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR, APA 2001) identifies a
range of associated difficulties including cognitive and attentional deficits, behavioral symptoms,
disturbances of mood, and a lack of fear to real dangers and/or excessive fearfulness in response
to harmless objects. Indeed anxiety is viewed as sufficiently inherent to ASD that additional
diagnoses of certain conditions are required “to be not better accounted for by the ASD itself”
(i.e., separation anxiety disorder, social anxiety disorder, and generalized anxiety disorder).
Interestingly, no such requirements exist for obsessive–compulsive disorder, specific phobia,
panic disorder, or agoraphobia despite possible phenomenological overlap between the core
features of these conditions and the associated features of ASD. However, whether or not
comorbid symptoms of anxiety may be seen as part of the broader ASD-phenotype, such
comorbidity contributes to functional impairment over and above the functional deficits of ASD
with important implications for treatment and care of the young person (Matson and Nebel-
Schwalm 2007). In fact, several studies have already been conducted that examined the effect of
cognitive behavioral therapy (CBT) for the treatment of anxiety disorders in children with ASD
and found promising results (e.g., Sofronoff et al. 2005; Chalfant et al. 2007; Reaven et al.
2009). However, within this light, it is important to establish an estimate of the prevalence of
anxiety disorders in children with ASD and to explore the factors associated with these
prevalence rates.
Several investigations of the prevalence of anxiety disorders in young people with ASD have
been conducted (e.g., Leyfer et al. 2006; Simonoff et al. 2008). White et al. (2009) undertook a
systematic review of the literature and identified eleven studies involving 1,353 young people
(aged 6–18 years) with ASD where rates of anxiety were reported based on observation,
interview, or questionnaires. Significant heterogeneity was found across studies with rates of
clinically significant anxiety ranging between 11% and 84%. In addition, only two studies (De
Bruin et al. 2007; Simonoff et al. 2008) specifically reported rates for anxiety disorders (55 and
42%, respectively) based on a structured diagnostic interview. To date, only one other systematic
review of evidence for anxiety in children and adolescents with ASD has been undertaken.
MacNeil et al. (2009) identified 13 studies (largely overlapping with those selected by White et
al. 2009) where standardized measure of anxiety were administered. Again, rates for specific
anxiety disorders were not reported, and there was equally large variability across studies.
Since the publications of White et al. (2009) and MacNeil et al. (2009), ten additional studies
have been published where anxiety disorders were formally assessed. The primary aim of the
present study was to (meta-analytically) estimate the prevalence of each specific anxiety disorder
in children and adolescents with ASD by systematically reviewing all available studies reporting
on anxiety disorders in youth with ASD. In addition, as previous reviews suggest that the rates of
anxiety in this population may vary as a function of age, IQ, assessment method (interview
versus questionnaire), informant (parent versus child), and ASD subtype (MacNeil et al. 2009;
White et al. 2009), we explore the extent to which these factors “moderate” reported rates of
anxiety. To our knowledge, this is the first meta-analysis of anxiety disorders in young people
with ASD and the first to evaluate factors influencing the observed heterogeneity for rates of
anxiety reported in the literature.
Method
Literature Search
A systematic search of computerized databases (PsyInfo, Pubmed, Web of Science, ERIC) was
undertaken using the words “Autism,” “Asperger,” “Pervasive Development Disorder,” and
“PDD” in various combinations with the words “anxiety,” “anxiety disorder,” “anxious,”
“comorbid disorder,” “comorbidity,” “psychiatric disorder,” and “psychological disorder.” The
abstracts were reviewed by the first author for relevance. Abstracts were considered relevant if
they described their sample as having ASD and if they reported an anxiety measure. Next, the
reference sections for data-based papers not found by the computer search were checked. This
first search generated 86 studies including data-based studies, review papers and published
presentation/poster abstracts.
Selection of Studies
To be entered into the meta-analyses, the studies had to meet the following inclusion criteria: (1)
studies had to report on children with an ASD diagnosis; (2) the study was data-based and not a
review of the literature; (3) the study reported the number of subjects with a DSM-IV anxiety
disorder and/or the number of subjects falling above clinical cutoff for anxiety on a standardized
measure of anxiety; and (4) the mean age of the sample had to be less than 18 years. From the 86
studies identified by the initial search, a total of 31 were found to meet all four inclusion criteria
(see Table 1). Only two studies provided data on post-traumatic stress disorder, and these are not
listed in the table. De Bruin et al. (2007) found no cases of post-traumatic stress disorder in their
sample of 94 children with ASD, while Mehtar and Mukaddes (2011) found 17.4% of 69
children with ASD to be suffering from post-traumatic stress disorder.
Table 1 Studies selected for meta-analysis: Prevalence of anxiety disorders in children with
ASD
One study (Wozniak et al. 1997) reported the percentage of participants with two or more
anxiety disorders. A request for further information was made to the author, but it was no longer
possible for them to provide the percentage of at least one anxiety disorder. The study was
retained in the meta-analysis, and the rate for multiple anxiety disorders reported in the paper
was entered into the meta-analyses as if reflected a percentage of at least one comorbid anxiety
disorder. Also, the sample assessed by Gadow et al. (2004) was included in a later study by the
same group but with additional subjects and with different anxiety disorders (Gadow et al. 2005).
As both studies reported rates for social anxiety disorder, generalized anxiety disorder, and
separation anxiety disorder, only data from Gadow et al. (2005) for these conditions were used in
the meta-analysis. In the case of obsessive–compulsive disorder and specific phobia, data from
Gadow et al. (2004) were used because the data of those anxiety subtypes were not reported in
Gadow et al. (2005).
After contacting the author, data from one presentation abstract (Herguner and Motavalli 2009)
were found to display considerable overlap with the data from the published article of Mukaddes
et al. (2010), and this abstract was therefore excluded. The poster presentation of Loggins et al.
(2010) was included in the meta-analysis. Besides the two abstracts mentioned above, we did not
find other abstracts from presentations or posters that reported prevalence rates of anxiety in
children with ASD.
Assessment of ASD in the Selected Studies
No restrictions were made for inclusion or exclusion of studies in the meta-analysis concerning
the way that ASD diagnosis was established. The most common standardized measures,
however, that were used to confirm ASD diagnosis were the Autism Diagnostic Interview-
Revised (ADI-R; Lord et al. 1994) and the Autism Diagnostic Observation Schedule-Generic
(ADOS-G; Lord et al. 2000).
The ADI-R is a semi-structured interview with the caregiver(s) as informant(s) of a child’s
behavior and development. The behavioral items are grouped into three domains: (1) reciprocal
social interaction, (2) communication, and (3) restricted and repetitive behaviors (Lord et al.
1994). An algorithm is provided to establish a diagnosis of autism (i.e., all scores need to exceed
cutoffs of all categories). Reliability and validity is supported by the study of Lord et al. (1994).
The ADOS-G is a semi-structured assessment to observe behavior of children who are suspected
to have autism (Lord et al. 2000). The assessment contains four modules, and for each module,
separate diagnostic algorithms are provided. Classification is made based on scores that exceed
cutoffs in two domains: social behavior and communication (Lord et al. 2000). The inter-rater
reliability, internal consistency, and test–retest reliability as well as diagnostic validity of the
ADOS-G were found excellent (Lord et al. 2000).
Of the 31 selected studies, 14 studies (45.2%) used either the ADI-R and/or the ADOS to
confirm ASD diagnosis (see Table 2). In addition, five studies (16.1%) used a second rater to
either confirm ASD diagnosis or to establish inter-rater agreement of ASD diagnosis. The
minority of the selected studies (38.7%) did not use the ADI-R or ADOS nor a second rater to
confirm ASD diagnosis. However, inspection of previous case records and/or interviews
including developmental history was commonly used to verify ASD diagnosis in those studies.
Table 2 Assessment of ASD and anxiety in the selected studies
Assessment of Anxiety in the Selected Studies
For studies to be included in the meta-analysis, anxiety had to be measured either by a (semi-)
structured interview that assesses anxiety disorders or by a questionnaire that provided cutoff
scores for an indication whether anxiety levels were clinically relevant. An overview of the used
instruments to assess anxiety in children with ASD is displayed in Table 2. The rationale for
aggregating studies that assess anxiety by diagnostic interviews and studies that used screening
cutoffs of questionnaires was the following: (1) screening for anxiety disorders with
questionnaires has predictive value at least in typically developing children (e.g., Simon and
Bögels 2009), (2) questionnaires seem to have the ability to discriminate between anxiety-
disordered and non-anxiety-disordered children in typically developing populations with good
sensitivity and specificity (e.g., Beidel et al. 1996; Nauta et al. 2004; Bodden et al. 2009), and (3)
the sample size of the meta-analysis was too small to run analyses separately for interviews and
questionnaires. However, to overcome this latter issue, we added type of measurement method
(interview versus questionnaire) as a moderator to the analyses.
Of the selected studies, 13 studies (41.9%) used interviews to assess anxiety and 18 studies
(58.1%) used questionnaires. Only a few studies (Leyfer et al. 2006; Davis et al. 2011; Mazefsky
et al. 2011) have used an instrument specifically developed for the ASD population. The
instruments used in those studies were (1) the Autism Comorbidity Interview-Present and
Lifetime Version (ACI-PL), which is a modified version of the Kiddie Schedule for Affective
Disorders and Schizophrenia (K-SADS; Ambrosini 2000) and was used in the study of Leyfer et
al. (2006) and Mazefsky et al. (2011), and (2) the questionnaires used by Davis et al. (2011),
namely the Baby and Infant Screen for Children with aUtIsm Traits—Part 2 (BISCUIT-Part 2;
Matson et al. 2007) and the Autism Spectrum Disorders—Comorbidity for Children (ASD-CC;
Matson and González, 2007). In addition, some authors made specific adaptations to control for
possible confounding overlap between ASD and anxiety by excluding several items
(Sukhodolsky et al. 2008; Kuusikko et al. 2008) or training interviewers to distinguish anxiety
from ASD (Simonoff et al. 2008). However, most authors did not make any adaptations to either
the interview or the questionnaire used to assess anxiety in ASD. Other instruments that were
used to assess anxiety in children with ASD, and which are also commonly used to assess
anxiety (or psychopathology in general) in typically developing children, include the Diagnostic
Interview Schedule for Children (DISC; Shaffer et al. 1996), the Kiddie Schedule for Affective
Disorders and Schizophrenia (K-SADS; Ambrosini 2000), the Child Behavior CheckList
(CBCL; Achenbach 1991), the Spence Children’s Anxiety Scale (SCAS; Spence 1997), and the
Social Phobia and Anxiety Inventory for Children (SPAI-C; Beidel et al. 1998).
Coding
The prevalence of anxiety disorders in general included studies that reported a percentage of
subjects that met criteria for at least one anxiety disorder or studies that reported a percentage of
subjects meeting clinical cutoff for anxiety in general. Each study was reviewed, and we
calculated the percentage of children with ASD for the ASD subcategories as described in the
DSM-IV-TR (APA 2001), namely subjects with (1) autistic disorder, (2) Asperger’s syndrome,
and (3) PDD-NOS. Studies that reported children to have “autism” were included in the category
of children diagnosed with autistic disorder. Next, the prevalence rates (percentages) for anxiety
in general and the specific anxiety disorders (obsessive–compulsive disorder, separation anxiety
disorder, social anxiety disorder, generalized anxiety disorder, panic disorder, and agoraphobia)
were calculated. These percentages were then transformed into proportions by dividing by 100.
When multiple informants were used (e.g., rates of anxiety were reported separately for the child,
parent, and/or teacher), a weighted arithmetic average (based on the number of each informant)
of these rates was entered into the meta-analyses. In addition, the mean age, mean IQ,
measurement method (questionnaire or interview), and informant (parent versus child report)
were recorded from each study. Too little variance was found for informant (i.e., studies were
heavily dominated by parent reports), and this variable was dropped from all further analyses.
The first author coded all studies and then a second independent coder (with a Master of Science
in social studies) coded the same studies. Inter-rater agreement was excellent: all kappa and
interclass coefficients were above .90. Any disagreements between coders were discussed until
consensus was reached.
Normality, Outliers, and Publication Bias
When aggregating effect sizes across studies, it is important to take account of any departure
from normality for the resulting distribution of effects, to deal with statistical outliers, and
account for the general problem of publication bias (Lipsey and Wilson 2000). The
Kolmogorov–Smirnov test was used to test for the normality of distributions for each anxiety
disorder separately, and no violations were found. To test for statistical outliers, all proportions
of anxiety disorder subtypes were transformed into standardized Z scores. When the standardized
Z score falls outside the confidence interval bounded by −3.3 and +3.3, then the observation is
possibly an outlier (Tabachnick and Fidell 2001). No statistical outliers for anxiety in general or
for any of the specific anxiety disorders were identified using this method.
Publication bias refers to the observation that studies with (large) significant results are more
likely to be published than those with non-significant or small effects. Publication bias is
typically assessed via visual inspection of funnel plots (Munafò et al. 2004), tests of funnel plot
asymmetry (Egger et al. 1997), or rank correlation methods (Begg and Mazumdar 1994). The
validity of these methods, however, decreases when the number of studies under investigation is
small (Rothstein et al. 1996). In addition, heterogeneity in the aggregated dependent variables
(i.e., rates of the specific anxiety disorders) may lead to funnel plot asymmetry and false
positives for statistical tests assessing asymmetry (Sterne et al. 2000). We assumed that
publication was largely unrelated to the rate of anxiety disorders reported in the individual
studies as no variable was manipulated to achieve a specific rate and a null result is also of
theoretical value in this population (i.e., the findings are purely descriptive and were not tested to
be significant or not). Nevertheless, we examined publication bias for the 20 studies that reported
the prevalence of anxiety in general by statistically testing for funnel plot asymmetry with the
rank order correlation coefficient, the Egger’s regression method, and by adding the standard
error as a moderator to the random effect model. None of these methods for detecting publication
bias reached statistical significance (r = .068, p = .776; t = 1.407, p = .176; β = .147, p = .559).
Results
The first set of meta-analyses aimed to establish the mean effect size (proportions) for anxiety in
general and each of the anxiety disorders separately (obsessive–compulsive disorder, separation
anxiety disorder, generalized anxiety disorder, specific phobia, social anxiety disorder, panic
disorder, and agoraphobia) in the absence of any “moderators.” The SPSS macros from Lipsey
and Wilson were used for analyses, and both fixed and random effect models were computed for
each separate meta-analysis to examine whether the selected sample of studies contained
heterogeneity. Tests for homogeneity were conducted with Q statistics and tested at α = .05.
The second set of meta-analyses tested whether the rates of anxiety varied systematically across
studies owing to the proportion of subjects in each study with autistic disorder, Asperger’s
syndrome, and PDD-NOS; mean age; mean IQ; and whether questionnaires or interviews were
used to assess anxiety. Moderator analyses were carried out separately for studies reporting rates
for anxiety in general, specific phobia, social anxiety disorder, generalized anxiety disorder,
separation anxiety disorder, obsessive–compulsive disorder, and panic disorder. For
agoraphobia, the number of studies was too small (k = 5) to conduct moderator analysis reliably.
Moderator variables were entered separately in all analyses. If several moderators were
significant, those moderators were included simultaneously in the model to test for the
robustness of their effect.
Results of Meta-Analyses
Results of the first set of meta-analyses (without moderators) are presented in Table 3. The
column titled “Prevalence” includes the percentage (estimated) of subjects across studies who
were diagnosed with at least one anxiety disorder or have impairing levels of anxiety (ANX) and
each anxiety disorder: obsessive–compulsive disorder, social anxiety disorder, specific phobia,
generalized anxiety disorder, separation anxiety disorder, panic disorder, and agoraphobia. The
significance values associated with the fixed and random models indicate whether the
(estimated) prevalence is significantly different from zero. All homogeneity analyses yielded
significant results, indicating significant variability in rates of disorders across studies.
Table 3 Results of the meta-analyses for the prevalence of anxiety disorders in children
with ASD
Moderator Analyses
Results of the moderator analyses are presented in Table 4. On the left-hand side of the table are
listed anxiety in general (ANX), which refers to any anxiety disorder (diagnostic interview) or
clinically elevated anxiety (questionnaire), and each of the specific anxiety disorders (specific
phobia, obsessive–compulsive disorder, social anxiety disorder, generalized anxiety disorder,
separation anxiety disorder, and panic disorder), and on the right, the results for the different
moderators. The first column (Dir) indicates whether the moderator is associated with higher (+)
or lower (−) rates of anxiety, followed by the coefficients for each moderator variable (β), an
indication whether it was significant in the random (RM) or fixed effect (FM) model, and the
corresponding p value. Heterogeneity remained significant in all fixed effect models. We will
briefly give a summary of the results for each moderator.
Table 4 Results of the meta-analyses examining the effects of several moderators: their
direction (Dir), coefficient (β), and corresponding significance (p)
Method
Method of measurement (questionnaire versus interview) was found significant for anxiety in
general (ANX), and the specific anxiety disorders (social anxiety disorder, generalized anxiety
disorder, and separation anxiety disorder). The use of interviews was associated with higher
prevalence rates of anxiety in general, while for social anxiety disorder, the use of questionnaires
was associated with higher prevalence rates. In addition, studies that used questionnaires to
assess generalized anxiety disorder and separation anxiety disorder reported higher prevalence
rates of those disorders compared with studies that used interviews. The moderator “method”
remained significant when other moderators were included simultaneously, except for separation
anxiety disorder. In this case, the method was no longer found significant when mean age was
entered simultaneously.
Mean Age
The moderator mean age was found significant for anxiety in general (ANX), and for several
anxiety disorders: obsessive–compulsive disorder, generalized anxiety disorder, and separation
anxiety disorder. For anxiety in general and generalized anxiety disorder, it was found that
studies that reported a higher mean age also reported higher prevalence rates. However, for
obsessive–compulsive disorder and separation anxiety disorder, higher prevalence rates were
associated with studies that reported a lower mean age. In all these models, the moderator “mean
age” remained significant when multiple moderators were included.
IQ
IQ was found to have a significant moderating effect for rates of anxiety in general (ANX) and
for the following anxiety disorders: obsessive–compulsive disorder, social anxiety disorder, and
separation anxiety disorder. Studies that reported a lower mean IQ were associated with higher
prevalence rates of anxiety in general and social anxiety disorder. In contrast, studies that
reported a higher mean IQ were associated with higher prevalence rates of obsessive–compulsive
disorder and separation anxiety disorder. For anxiety in general (ANX) and social anxiety
disorder, this moderator remained significant when multiple moderators were included in the
model; however, for obsessive–compulsive disorder and separation anxiety disorder, the
moderating effect of IQ was no longer found significant when other moderators were included
simultaneously.
ASD Subtype
For anxiety in general (ANX), it was found that the moderators “AS” (proportion of subjects
with Asperger’s syndrome) and “PDD” (proportion of subjects with PDD-NOS) were significant
for explaining some of the heterogeneity across studies. Studies that included higher proportions
of subjects with Asperger’s syndrome reported lower prevalence rates of anxiety in general.
However, studies that included higher proportions of subjects with PDD-NOS were associated
with higher prevalence rates of anxiety in general. Furthermore, for all anxiety subtypes, at least
one ASD subtype moderator (“AD,” “AS,” and/or “PDD”) was found significant. Studies that
included higher proportions of subjects with autistic disorder were associated with higher
prevalence rates of specific phobia and obsessive–compulsive disorder, and lower prevalence
rates of generalized anxiety disorder. Studies that included higher proportions of subjects with
Asperger’s syndrome were associated with higher prevalence rates of generalized anxiety
disorder and lower prevalence rates of specific phobia, obsessive–compulsive disorder, social
anxiety disorder, and separation anxiety disorder. Finally, studies that included higher
proportions of subjects with PDD-NOS were associated with lower prevalence rates of
obsessive–compulsive disorder, but with higher prevalence rates of specific phobia, generalized
anxiety disorder, separation anxiety disorder, and panic disorder. For social anxiety disorder and
separation anxiety disorder, the significant effect of the ASD subtype moderators disappeared
when multiple moderators were included simultaneously. Also, the moderator “AS” (proportion
of subjects with Asperger’s syndrome) was no longer found significant in generalized anxiety
disorder, when multiple moderators (mean age and method of assessment) were simultaneously
included. In the other anxiety subtypes, the effects of the ASD subtype moderators remained
significant.
Discussion
The primary aim of the present study was to estimate the prevalence of (specific) anxiety
disorders in children and adolescents with ASD. The secondary aim was to evaluate whether the
observed variability in these rates were the result of ASD subtype, age, IQ, and method of
assessment (interview versus questionnaire). We now discuss the results of the meta-analysis and
the moderator effects and address the limitations and implications of the study.
Prevalence of Anxiety Disorders in Children with ASD

The results reveal substantial comorbidity for anxiety in children and adolescents with an autistic
spectrum disorder: nearly 40 percent were estimated to have clinically elevated levels of anxiety
or at least one anxiety disorder. The rate of anxiety observed here is consistent with previous
reviews of the ASD literature (e.g., White et al. 2009). In the present study, specific phobia was
most common at nearly 30%, followed by obsessive–compulsive disorder in 17%, social anxiety
disorder and agoraphobia in nearly 17%, generalized anxiety disorder in 15%, separation anxiety
disorder in nearly 9%, and panic disorder in nearly 2%. By way of comparison, anxiety disorders
in typically developing children are estimated to occur in 2.2–27% (Costello et al. 2005). In
addition, with the exception of panic disorder, the rates of the specific anxiety disorders observed
in children with an autistic spectrum disorder are more than two times higher than in typically
developing children (Costello et al. 2005), and higher than found in children seeking treatment
for ADHD (Gau et al. 2010) and learning difficulties (Dekker and Koot 2003).
Evidence of significant comorbidity between anxiety disorders and ASD was found in the
current meta-analysis. It is likely that the observed rates of comorbidity between anxiety and
ASD arise from diagnostic overlap and the use of measures of anxiety that were never developed
for use in ASD populations. However, the studies that used an ASD-specific measurement or
made certain adjustments (i.e., excluding particular items) reported prevalence rates of anxiety
disorders ranging from 31.5% to 50.0%, which are in accordance with our estimated prevalence
of nearly 40%. A related question that could be raised here is whether the studies measuring
anxiety in ASD are really assessing anxiety disorders and not just symptoms of ASD. Clearly,
there is diagnostic overlap between the anxiety subtypes and the criteria for ASD, especially
between ASD and OCD, and ASD and social anxiety disorder.
It may be that the core symptoms of ASD will be better distinguished from OCD by asking about
the target of the interests and routines and comparing it with those of children with OCD. Indeed,
Ruta and colleagues (Ruta et al. 2010) found different patterns of symptoms between the
children with Asperger’s syndrome and children with OCD. In addition, Baron-Cohen and
Wheelwright (1999) compared the obsessions of children with ASD and those with Tourette’s
syndrome. Parents rated the children with ASD to have more obsessions relating to folk physics
(e.g., machines, vehicles, computers) or television/audio and displayed fewer obsessions related
to folk psychology (e.g., imagination, gossip, beliefs, relationships). Parents of children with
Tourette’s syndrome reported obsessions relating to sensory phenomena (involuntary touching
and vocalizing).
With respect to the discrimination between symptoms of ASD and social anxiety disorder, one
discriminating factor may be that the behavioral and non-verbal abnormalities seen in both
disorders (e.g., social withdrawal, preference of being alone, and not speaking in social
situations, gaze avoidance, staring, and lack of emotional expression) will not be present in every
situation and will be strongly influenced by anxiety in individuals with social anxiety disorder,
whereas they probably vary less in ASD. Another distinctive factor may be that many subjects
with social anxiety disorder do have normal social skills and have the ability to use them
appropriately in social contexts, whereas subjects with ASD have qualitative impairments in
communication and social interaction early in life (APA 2001). Finally, a possible distinction is
that the interest in engaging in social situations may be different between the two groups (Bellini
2006), whereas individuals with social anxiety disorder generally have an interest in engaging in
social situations, this interest could be less in individuals with ASD.
Likely, such distinctions will not be found when comparing the total score of an anxiety
questionnaire to a certain cutoff. Therefore, we need questionnaires that tap the unique and
distinct features of anxiety in children with ASD as well as those that are more common to
young people with anxiety disorders and no ASD. Likewise, we need measures that do not rely
upon parent or child self-report to give an indication of anxiety, particularly for use with children
with more profoundly impaired verbal and communication abilities. Such measures might tap
autonomic arousal across baseline and (assumed) anxiety-provoking situations and computerized
tests of attentional bias to non-verbal threat cues. Ultimately, it is likely that a combination of
questionnaire and interview data, observed behavior/arousal, and multiple informants are
required to arrive at a best-guess diagnosis of anxiety disorder in young people with ASD.
Moderators
Method of Assessment
Method of assessment was found to influence the wide variability across studies that reported
anxiety prevalence rates in children with ASD. Anxiety disorders in general were most likely to
be diagnosed where the researchers used interview-based measures rather than questionnaires
(mostly parent report version). This may be explained by the goal of the anxiety assessment
(diagnosis versus descriptive). If the goal is diagnosis, one may be more likely to use diagnostic
interviews; however, if one’s goal is descriptive, a questionnaire would be more likely used. For
the specific anxiety disorder, generalized anxiety disorder, and social anxiety disorder, however,
questionnaires were associated with higher prevalence rates. An important issue here is to
distinguish anxiety disorders from anxiety symptoms and to discriminate anxiety symptoms from
ASD symptoms. Children with ASD will probably experience many symptoms of social anxiety
disorder and generalized anxiety disorder; however, they may not meet criteria for an anxiety
disorder because of the lack of interference with their daily activities or because those symptoms
are better accounted for by ASD. It is very likely that for this reason studies that used
questionnaires to assess (symptoms of) social anxiety disorder and generalized anxiety disorder
were found to report higher prevalence rates of those disorders compared with studies that used
interviews. This finding suggests that future research will need to employ multi-modal methods
for the assessment of anxiety to help disambiguate core ASD symptoms from those of comorbid
anxiety disorders.
Mean Age
In children with ASD, higher rates of anxiety in general were found in studies with a higher
mean age. Contradictory results of studies reporting on anxiety in ASD, however, have been
found for the relationship between age, anxiety, and ASD. Some studies (Kuusikko et al. 2008;
Lecavalier 2006) found older ASD children more likely to report anxiety, while others reported
no age differences (Ando and Yoshimura 1979; Pearson et al. 2006; Meyer et al. 2006;
Sukhodolsky et al. 2008; White and Roberson-Nay 2009). It is possible that the type of anxiety
disorder under study is an important issue here. For example, we found that studies with a higher
mean age also reported higher rates of generalized anxiety disorder and lower rates of separation
anxiety disorder. These findings are consistent with the results of studies examining anxiety
disorders in typically developing children, which found: (1) rates of anxiety disorders (generally)
increase with age (Ford et al.2003); (2) rates of generalized anxiety disorder (specifically)
increase with age (Frala et al. 2010; Tracey et al. 1997); and (3) rates of separation anxiety
disorder are associated with a lower mean age (Kearney et al. 2003; Last et al. 1992).
Interestingly and not consistent with studies that assess anxiety in typically developing children,
studies that included younger children with ASD reported higher prevalence rates of obsessive–
compulsive disorder than those that included older children with ASD. Obsessive–compulsive
disorder in typically developing children, however, tends to have a relatively late age onset
(Costello et al. 2005) and is found to increase with age (Ford et al. 2003). However, obsessive–
compulsive disorder and the restricted, repetitive behaviors observed in subjects with ASD share
much overlap in symptoms and therefore differentiation between the two disorders can be
extremely difficult. There is some evidence that younger children with ASD have more
restricted, repetitive behaviors compared with older children with ASD (Ebensen et al. 2008) and
that children with ASD “improve” in the ritualistic/repetitive behavior domain as they grow
older (Piven et al. 1996). These results would seem to support the present finding that a lower
mean age in the ASD sample was associated with higher rates of reported obsessive–compulsive
disorder. However, it is worth noting that (1) in the study of Piven et al. (1996), symptoms in the
social and communication domain decreased significantly more over time compared with the
symptoms in the ritualistic/repetitive domain; (2) other studies found no association between
severity scores of repetitive behavior and age (e.g., South et al. 2005); and (3) some studies
found no significant effect of time for the repetitive activities domain (e.g., Starr et al. 2003).
IQ
Across ASD subtypes, increased rates of anxiety disorders in general were associated with lower
IQ scores. This finding warrants further investigation as earlier studies point to both positive
(Sukhodolsky et al. 2008; Weisbrot et al. 2005; Witwer and Lecavalier 2010) and negative
correlations (White and Roberson-Nay 2009) between anxiety and IQ in this population. In post
hoc analyses, we found that IQ below versus above 70 did not moderate the relationship between
ASD and anxiety disorder, whereas having an IQ below the cross-study mean of 87 did. It is
possible that having an IQ between 70 and 87 and ASD increases the risk of anxiety disorders.
However, further research is needed as IQ was only significant in the fixed effect model. In
addition, the present study found that studies with a higher reported mean IQ were associated
with lower rates of social anxiety disorder. However, we note that this finding was significant
only in the fixed effect model, and only one study (Sukhodolsky et al. 2008) reported a mean IQ
less than 70. Nevertheless, it is possible that children with ASD and a (somewhat) lower IQ have
more difficulty adapting to social situations (as compared to those with high IQ who may be
more aware of social cues, have learnt how to behave in certain social situations, or may
compensate for their deficits). Further, they may notice that they are failing in this domain and
therefore become (socially) anxious. In partial support, Kristensen and Torgersen (2008) found
that in a population-based screening sample of typically developing children, those diagnosed
with social anxiety disorder, as compared to those having other disorders or no disorders, verbal
IQ was more reduced. However, whether a lower verbal IQ in typically developing children with
social anxiety disorder is also true of children with ASD remains unclear, and the present
findings of a relationship between IQ and anxiety in ASD has to be interpreted with caution.
ASD Subtype
There was some evidence that anxiety in general is more likely to be diagnosed in those with
PDD-NOS, followed by those with autistic disorder and Asperger’s syndrome. There was also
evidence of certain anxiety disorders being more strongly associated with one or more ASD
subtypes. The presence of autistic disorder was associated with higher rates of obsessive–
compulsive disorder and specific phobia, but with lower rates of generalized anxiety disorder,
while the presence of Asperger’s syndrome was associated with lower rates of specific phobia
and obsessive–compulsive disorder. Finally, the presence of PDD-NOS was associated with
higher rates of specific phobia, generalized anxiety disorder, and panic disorder, and with lower
rates of obsessive–compulsive disorder.
The few studies that have compared anxiety levels across ASD subtypes suggest that anxiety
varies with ASD severity: children with less severe ASD symptoms would endorse more anxiety
(MacNeil et al. 2009). A study of Weisbrot and colleagues suggests that children and adolescents
with Asperger’s syndrome have the highest anxiety levels followed by children with PDD-NOS
and autistic disorder, respectively (Weisbrot et al. 2005). However, there are also studies (Kim et
al. 2000; Pearson et al. 2006; Gadow et al. 2004; Sukhodolsky et al. 2008) that found no
differences in anxiety levels between ASD subtypes. Further, there is some evidence that the
kind of anxiety disorders may differ across ASD subtypes; however, results are inconclusive.
Muris and colleagues found children with PDD-NOS to be more likely to meet criteria for
specific phobia, separation anxiety disorder, and generalized anxiety disorder compared to
children with autistic disorder (Muris et al. 1998). In addition, Thede and Coolidge (2007)
reported generalized anxiety disorder to be more common in children with Asperger’s syndrome
as compared to children with high-functioning autism (HFA). It is possible that these
associations (found here and elsewhere) are confounded by overlapping phenomenology in ASD
and anxiety subtype. An example is the present finding that obsessive–compulsive disorder was
higher where a diagnosis of autistic disorder was made and lower in PDD-NOS. As subjects with
PDD-NOS are less likely to present with severely restricted, repetitive, and stereotyped patterns
of behavior (Szatmari et al. 1995; Buitelaar et al. 1999; Starr et al. 2003), the possibility of
“misdiagnosis” of obsessive–compulsive disorder in children across the ASD spectrum needs to
be considered.
Limitations
A limitation of the current meta-analytic study was the large heterogeneity found across the
meta-analyses. Heterogeneity can arise from a number of factors including methodological
differences between studies. An attempt was made to explain this heterogeneity, and we found
some significant moderator effects; however, heterogeneity remained significant across all fixed
models. One other possible moderator that could contribute to the large heterogeneity found in
this study, and which we have examined post-analytically, is publication year. We explored this
moderator to see whether cohort effects could have biased the results; however, this moderator
was not found significant. Further, a warrant is needed as many moderator effects were found
significant in the fixed effect models but not in the random effect models. These results should
therefore be interpreted with caution as effects found in the fixed effect model only allow for
inferences based on the studies included in the meta-analysis and limits the generalizability to
other (future) studies (see Hedges and Vevea 1998 for a detailed discussion).
Another limitation to generalization from the present findings was that few studies in the meta-
analyses included children with ASD and a low IQ (i.e., below 70). Thus, the rates of anxiety
observed here may under- or overestimate the true rate of anxiety in the larger population of
children with ASD. There are some tentative findings from the present meta-analyses that
suggest that anxiety disorders are more common among those with ASD and a lower IQ,
although this relationship varies as a function of ASD and anxiety subtype. Although a
significant moderating effect for IQ on rates of anxiety in ASD was only significant in the fixed
effect models, the present results suggest that further investigation of this relationship is
warranted.
A third limitation is that there were insufficient data to test whether informant moderated the
relationship between anxiety and ASD. Until now, researchers have relied heavily on parent
reports of anxiety by interviews and questionnaires that were not developed for use with the
ASD population. It is widely known that parents tend to underestimate the frequency of
internalizing symptoms in their own children (e.g., Muris et al. 1999; Cosi et al.2010) and that
child–parent agreement for internalizing problems is generally lower compared with the child–
parent agreement of externalizing problems (e.g., Achenbach et al.1987; Cantwell et al. 1997).
Future research studies will need to employ multiple informants (where possible) and examine
how anxiety varies across informants in terms of frequency, type, and severity.
Finally, large heterogeneity was found for the way anxiety in children with ASD was assessed
and whether anxiety was assessed by an instrument developed for or adapted to children with
ASD. Inspection of the studies showed that only a few studies used instruments developed for or
adapted to children with ASD, and the majority of the studies used instruments developed for
typically developing children. Research, however, has not yet established the validity and
reliability of those instruments in children with ASD, and therefore conclusions presented here
must be seen in this perspective.
Implications
Over the last 30 years, the definition of ASD has broadened and prevalence rates of ASD have
risen with estimates of 60 per 10,000 (Fombonne 2003). Although the prevalence of ASD may
not be as high as other disorders (such as anxiety or depression), ASD may have incurred
significantly higher health service use than other more prevalent disorders. For example, Mandell
et al. (2006) found that children with ASD had health care expenditures ten times higher than
those without ASD. It seems likely given the high rates of anxiety found in children with ASD
that this commonly occurring comorbid problem is a major contributor to health care usage in
this population. We know that anxiety disorders in typically developing children significantly
interfere with everyday functioning—particularly school attendance (DSM-IV; APA 2001),
negatively impact quality of life (Bastiaansen et al. 2004) and are associated with higher health
care usage and other social costs (Bodden et al. 2008). It is reasonable to assume that when
anxiety disorders occur in young people with ASD, they interact with the ASD such that
symptoms of both conditions are exacerbated. In light of the growing demand for evidenced-
based treatments (in a context of shrinking health expenditure), it is of major importance to
develop better (and more cost-effective) methods for assessing and treating anxiety disorders in
children with ASD.
A review of the studies revealed that the assessment of anxiety in children with ASD varies
enormously across studies with the majority using instruments that were developed to assess
anxiety in typically developing children. The current state of research has not yet examined the
validity and reliability of instruments used to assess anxiety in a typically developing population
for the ASD population. However, such research is heavily needed. To date, the authors are only
aware of one such study. Mazefsky et al. (2011) examined the sensitivity and specificity of self-
report questionnaires in adolescents with ASD and compared these self-reports with the outcome
of a parental diagnostic interview. Although conclusions are preliminary, the results suggest that
such measures may be less sensitive and specific when used in adolescents with ASD than in
similarly aged, typically developing adolescents. This may be because children with ASD
underreport (anxiety) symptoms (Russell and Sofronoff, 2005). On the other hand, comparing
results from self-report measures with parental diagnostic interviews may be problematic as child
and parent agreement for anxiety is generally low in typically developing children and the level
of agreement may be even less in children with ASD (e.g., children with ASD may lack
sufficient insight or emotion language to report accurately on their internalizing symptoms).
However, in the study of Mazefsky et al. (2011), it was also found that the results of the internal
reliability of the self-report questionnaire were as good, or better, than those of the
standardization samples and that of all self-report measures, the RCMAS (Revised Children’s
Manifest Anxiety Scale; Reynolds and Richmond 1985) showed the most promise (with rather
high specificity and positive predictive values). However, efforts are clearly needed to see
whether measures of anxiety designed for typically developing children need to be adapted for
the ASD populations and/or if alternative norms need to be established.
As discussed earlier, another issue concerning the assessment of anxiety in children with ASD is
whether anxiety symptoms can be distinguished from symptoms of ASD reliably. One overall
concern may be that measures intended to assess anxiety are merely assessing severity of autism.
Although we could not test this concern directly, it is found in this meta-analysis that children
with PDD-NOS have higher prevalence rates of anxiety disorders, suggesting that the less severe
ASD subtype (as compared to Asperger’s syndrome and autistic disorder) would have the
highest anxiety scores. This finding is rather contradictory to the concern that assessing anxiety
would be the same as assessing severity of ASD. In further support, treatment studies revealed
that the symptoms of anxiety, and anxiety disorders, in autism can be decreased (e.g., Sofronoff
et al. 2005; Chalfant et al. 2007; Reaven et al. 2009), while the core symptoms of autism are
found to be rather persistent (e.g. Billstedt et al. 2007). An examination of the selected studies
revealed that only a few studies tried to discriminate between symptoms of ASD and anxiety
symptoms and tried to overcome possible confounds by excluding particular items. However,
such an approach may also have disadvantages. First, use of anxiety measures adapted for the
ASD population will limit comparisons to typically developing children. However, we would
argue that it is of clinical value to determine how (if at all) anxiety symptoms and anxiety
disorders differ in topography (or impact) in children with ASD compared with typically
developing children, and the implication then for etiology and treatment. Regardless of how well
we fine-tune the measures, ambiguities may be unavoidable. For example, a positive answer to
the question “Do you have difficulty (and avoid) speaking in public?” may never clearly lead one
away from ASD to an additional diagnosis of social anxiety disorder. Regardless of whether the
additional disorder exists, the difficulty may still warrant intervention if it impairs the child’s
daily functioning.
It is worth returning to the usefulness of the DSM-IV (APA 2001) in distinguishing anxiety
disorders from ASD. The DSM states that social anxiety disorder, generalized anxiety disorder,
or separation anxiety disorder should be excluded if the symptoms of these conditions are better
accounted for by ASD. Does such a requirement lead to anxiety disorders being under-diagnosed
in children with ASD and leave the child less likely to be treated for what are otherwise very
treatable conditions in typically developing children? DSM-V (APA 2011) attempts to deal with
such issues at least with respect to social anxiety disorder; the proposed changes make an
additional diagnosis of social anxiety disorder in children with ASD more easy (Bögels et al.
2010). Similar changes to the criteria for the other anxiety disorders may be needed and would
certainly stimulate research in this area (and increase the likelihood of treatment for anxiety in
children with ASD). In support of such changes are studies that suggest that anxiety disorders
experienced by children with ASD are more similar than different in topography as those
experienced by typically developing children with anxiety disorders (Russell and Sofronoff
2005; Farrugia and Hudson, 2006). In addition, as found in this meta-analysis, they appear to
follow a similar developmentally sensitive course. We note as well a small but growing body of
evidence (e.g., Sofronoff et al. 2005; Chalfant et al. 2007; Reaven et al. 2009) that cognitive
behavioral therapy (CBT) as designed to improve anxiety in typically developing children has
moderate but positive effects on anxiety disorders in children with ASD. Such findings suggest
that greater allowance for the diagnosis of anxiety in ASD in DSM-V is warranted.
Finally, results from the present meta-analyses suggest that children with a particular ASD
subtype may be more likely to develop one type of anxiety disorder over another. While the ASD
subtypes are more similar than different, the severity of the communication, social interaction,
and stereotyped behaviors associated with the subtypes does vary, and this may lead the child
more toward one form of anxiety than another. Unfortunately, the severity of each domain of this
ASD triad (communication, social interaction, and stereotyped interests and behavior) is rarely
reported. Future studies should examine in greater detail whether the rates of particular anxiety
disorder vary as a function of the severity of the particular symptoms that make up the ASD
subtype. Such an approach would be consistent with changes discussed for the DSM-V wherein
ASD subtypes would no longer be distinguished (APA 2011).
References
References marked with an asterisk (*) indicate studies included in the meta-
analysis.
1. Achenbach, T. M. (1991). Manual for the child behavioral checklist/4–18 and 1991
profile. Burlington, VT: University of Vermont, Department of Psychiatry.
o Google Scholar
2. Achenbach, T. M., McConaughy, S. H., & Howell, C. T. (1987). Child/adolescent
behavioral and emotional problems: implications of cross-informant correlations for
situational specificity. Psychological Bulletin, 101, 213–232.
o PubMed
o Article
o Google Scholar
3. Ambrosini, P. J. (2000). Historical development and present status of the schedule for
affective disorders and schizophrenia for school-age children (K-SADS). Journal of
American Academy of Child Adolescent Psychiatry, 39, 49–58.
o Article
o Google Scholar
4. Association, American. Psychiatric. (2001). Diagnostic and Statistical Manual of Mental
Disorders (DSM-IV-TR). Washington, DC: American Psychiatric Association.
o Google Scholar
5. American Psychiatric Association. (2011). Diagnostic and Statistical Manual of Mental
Disorders DSM-5 Development proposed revisions anxiety disorders. Retrieved online at
January 26th 2011 from:
http://www.dsm5.org/ProposedRevisions/Pages/AnxietyDisorders.aspx.
6. *Ando, H., & Yoshimura, I. (1979). Effects of age on communication skill levels and
prevalence of maladaptive behaviors in autistic and mentally retarded children. Journal
of Autism and Developmental Disorders, 9, 83–93.
o PubMed
o Article
o Google Scholar
7. Baron-Cohen, S., & Wheelwright, S. (1999). ‘Obsessions’ in children with autism or
Asperger syndrome. British Journal of Psychiatry, 175, 484–490.
o PubMed
o Article
o Google Scholar
8. Bastiaansen, A., Koot, H. M., Ferdinand, R. F., & Verhulst, F. C. (2004). Quality of life
in children with psychiatric disorders: Self-, parent- and clinician report. Journal of the
American Academy of Child and Adolescent Psychiatry, 43, 221–230.
o PubMed
o Article
o Google Scholar
9. Begg, C. B., & Mazumdar, M. (1994). Operating characteristics of a rank correlation test
for publication bias. Biometrics, 50, 1088–1101.
o PubMed
o Article
o Google Scholar
10. Beidel, D. C., Turner, S. M., & Fink, C. M. (1996). Assessment of Childhood Social
Phobia: Construct, Convergent, and Discriminant Validity of the Social Phobia and
Anxiety Inventory for Children (SPAI-C). Psychological Assessment, 8, 235–240.
o Article
o Google Scholar
11. Beidel, D. C., Turner, S. M., & Morris, T. L. (1998). Social Phobia and anxiety inventory
for children (SPAI-C). User’s manual, North Tonawanda, NY: Multi-Health Systems Inc.
o Google Scholar
12. *Bellini, S. (2004). Social skill deficits and anxiety in high-functioning adolescents with
autism spectrum disorders. Focus on Autism and other Developmental Disabilities, 19(2),
78–86.
o Article
o Google Scholar
13. Bellini, S. (2006). The development of social anxiety in adolescents with autism
spectrum disorders. Focus on Autism and other Developmental Disabilities, 21, 138–145.
o Article
o Google Scholar
14. Billstedt, E., Gillberg, I. C., & Gillberg, C. (2007). Autism in adults: symptom patterns
and early childhood predictors. Use of the DISCO in a community sample followed from
childhood. Journal of Child Psychology and Psychiatry, 48, 1102–1110.
o PubMed
o Article
o Google Scholar
15. Bodden, D. H. M., Bögels, S. M., & Muris, P. (2009). The diagnostic utility of the Screen
for Child Anxiety Related Emotional Disorders-71(SCARED-71). Behaviour Research
and Therapy, 47, 418–425.
o PubMed
o Article
o Google Scholar
16. Bodden, D. H. M., Dirksen, C. D., Bögels, S. M., Nauta, M. H., de Haan, E., Ringrose, J.,
et al. (2008). Costs and Cost-Effectiveness of Family CBT versus Individual CBT in
Clinically Anxious Children. Clinical Child Psychology and Psychiatry, 13, 543–564.
o PubMed
o Article
o Google Scholar
17. Bögels, S. M., Alden, L., Beidel, D. C., Clark, L. A., Pine, D. S., Stein, M. B., et al.
(2010). Social Anxiety Disorder: Questions and Answers fort he DSM-V. Depression
and Anxiety, 27, 168–189.
o PubMed
o Article
o Google Scholar
18. *Bradley, E. A., Summers, J. A., Wood, H. L., & Bryson, S. E. (2004). Comparing rates
of psychiatric and behavior disorders in adolescents and young adults with severe
intellectual disability with and without autism. Journal of Autism and Developmental
Disorders, 34, 151–161.
o PubMed
o Article
o Google Scholar
19. *De Bruin, E. I., Ferdinand, R. F., Meester, S., De Nijs, P. F. A., & Verheij, F. (2007).
High rates of psychiatric co-morbidity in PDD-NOS. Journal of Autism and
Developmental Disorders, 37, 877–886.
o PubMed
o Article
o Google Scholar
20. Buitelaar, J. K., van der Gaag, R., Klin, A., & Volkmar, F. (1999). Exploring the
boundaries of pervasive developmental disorder not otherwise specified: Analyses of data
from the DSM-IV autistic disorder field trial. Journal of Autism and Developmental
Disorders, 29, 33–43.
o PubMed
o Article
o Google Scholar
21. Cantwell, D. P., Lewinsohn, P. M., Rohde, P., & Selley, J. R. (1997). Correspondence
Between Adolescent Report and Parent Report of Psychiatric Diagnostic Data. Journal of
the American Academy of Child and Adolescent Psychiatry, 36, 610–619.
o PubMed
o Article
o Google Scholar
22. Chalfant, A. M., Rapee, R., & Carroll, L. (2007). Treating anxiety disorders in children
with high functioning autism spectrum disorders; a controlled trial. Journal of autism
developmental disorders, 37, 1842–1857.
o Article
o Google Scholar
23. *Chung, S. Y., Luk, S. L., & Lee, P. W. H. (1990). A follow-up study of infantile autism
in Hong Kong. Journal of Autism and Developmental Disorders, 20, 221–232.
o PubMed
o Article
o Google Scholar
24. Cosi, S., Canals, J., Hernández-Martinez, C., & Vigil-Colet, A. (2010). Parent-child
agreement in SCARED and its relationship to anxiety symptoms. Journal of Anxiety
Disorders, 24, 129–133.
o PubMed
o Article
o Google Scholar
25. Costello, E. J., Egger, H. L., & Angold, A. (2005). The developmental epidemiology of
anxiety disorders: Phenomenology, prevalence, and comorbidity. Child and Adolescent
Psychiatric Clinics of North America, 14, 631–648.
o PubMed
o Article
o Google Scholar
26. *Davis, T. E., Hess, J. A., Moree, B. N., Fodstad, J. C., Dempsey, T., Jenskins, W. S., et
al. (2011). Anxiety symptoms across the lifespan in people diagnosed with Autistic
Disorder. Research in Autism Spectrum Disorders, 5, 112–118.
o Article
o Google Scholar
27. Dekker, M. C., & Koot, H. M. (2003). DSM-IV disorders in children with borderline to
moderate intellectual disability. I: Prevalence and impact. Journal of the American
Academy of Child and Adolescent Psychiatry, 42, 915–922.
o PubMed
o Article
o Google Scholar
28. *Demb, H. B., & Weintraub, A. G. (1989). A five-year follow-up of preschool children
diagnosed as having an atypical pervasive developmental disorder. Journal of
Developmental and Behavioral Pediatrics, 10, 292–298.
o PubMed
o Article
o Google Scholar
29. Ebensen, A. J., Seltzer, M. M., Lam, K. S. L., & Bodfish, J. W. (2008). Age-related
differences in restricted repetitive behaviors in autism spectrum disorders. Journal of
Autism and Developmental Disorders, 39, 57–66.
o Article
o Google Scholar
30. Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997). Bias in meta-analysis
detected by a simple, graphical test. British Medical Journal, 315, 629–634.
o PubMed
o Google Scholar
31. Farrugia, S., & Hudson, J. (2006). Anxiety in adolescents with Asperger Syndrome:
Negative thoughts, behavioral problems, and life interference. Focus on Autism and other
Developmental Disabilities, 21(1), 25–35.
o Article
o Google Scholar
32. Fombonne, E. (2003). The Prevalence of Autism. Journal of the American Medical
Association, 289, 87–89.
o PubMed
o Article
o Google Scholar
33. Ford, T., Goodman, R., & Meltzer, H. (2003). The British Child and Adolescent Mental
Health Survey 1999: The Prevalence of DSM-IV Disorders. Journal of American
Academic Child and Adolescent Psychiatry, 42, 1203–1211.
o Article
o Google Scholar
34. Frala, J. L., Leen-Feldner, E. W., Blumenthal, H., & Baretto, C. C. (2010). Relations
among perceived control over anxiety-related events, worry, and generalized anxiety
disorder in a sample of adolescents. Journal of Abnormal Child Psychology, 38, 237–247.
o PubMed
o Article
o Google Scholar
35. *Gadow, K. D., DeVincent, C. J., Pomeroy, J., & Azizian, A. (2004). Psychiatric
symptoms in preschool children with PDD and clinic and comparison samples. Journal
of Autism and Developmental Disorders, 34, 379–393.
o PubMed
o Article
o Google Scholar
36. *Gadow, K. D., DeVincent, C. J., Pomeroy, J., & Azizian, A. (2005). Comparison of
DSM-IV symptoms in elementary school-age children with PDD versus clinic and
community samples. Autism, 9, 392–415.
o PubMed
o Article
o Google Scholar
37. Gau, S. S.-F., Ni, H.-C., Shang, C.-Y., Soong, W.-T., Wu, Y.-Y., Lin, L.-Y., et al. (2010).
Psychiatric comorbidity among children and adolescents with and without persistent
attention-deficit hyperactivity disorder. Australian and New Zealand Journal of
Psychiatry, 44, 135–143.
o PubMed
o Article
o Google Scholar
38. *Gillot, A., Furniss, F., & Walter, A. (2001). Anxiety in high-functioning children with
autism. Autism, 5, 277–286.
o Article
o Google Scholar
39. *Green, J., Gilchrist, A., & Cox, A. (2000). Social and psychiatric functioning in
adolescents with Asperger syndrome compared with conduct disorder. Journal of Autism
and Developmental Disorders, 30, 279–293.
o PubMed
o Article
o Google Scholar
40. Hedges, L. V., & Vevea, J. L. (1998). Fixed- and Random-Effects Models in Meta-
Analysis. Psychological Methods, 3, 486–504.
o Article
o Google Scholar
41. Herguner, S., & Motavalli, N. (2009). Psychiatric comorbidity in children and
adolescents with high functioning autism. European Psychiatry, 24(Supplement 1), 795.
o Article
o Google Scholar
42. *Kanne, S. M., Abbacchi, A. M., & Constantino, J. N. (2009). Multi-informant ratings of
psychiatric symptom severity in children with autism spectrum disorders: The importance
of environmental context. Journal of Autism and Developmental Disorders, 39, 856–864.
o PubMed
o Article
o Google Scholar
43. Kearney, C. A., Sims, K. E., Pursell, C. R., & Tillotson, C. A. (2003). Separation anxiety
disorder in young children: A longitudinal and family analysis. Journal of Clinical Child
and Adolescent Psychology, 32, 593–598.
o PubMed
o Article
o Google Scholar
44. *Kim, J. A., Szatmari, P., Bryson, S. E., Streiner, D. L., & Wilson, F. J. (2000). The
prevalence of anxiety and mood problems among children with Autism and Asperger
Syndrome. Autism, 4, 117–132.
o Article
o Google Scholar
45. Kristensen, H., & Torgersen, S. (2008). Is social anxiety disorder in childhood associated
with developmental deficit/delay? European Child and Adolescent Psychiatry, 17, 99–
107.
o PubMed
o Article
o Google Scholar
46. *Kuusikko, S., Pollock-Wurman, R., Jussila, K., Carter, A. S., Mattila, M. L., Ebeling,
H., et al. (2008). Social anxiety in high-functioning children and adolescents with autism
and Asperger syndrome. Journal of Autism and Developmental Disorders, 38, 1697–
1709.
o PubMed
o Article
o Google Scholar
47. Last, C. G., Perrin, S., Hersen, M., & Kazdin, A. E. (1992). DSM-III-R anxiety disorders
in children: Sociodemographic and clinical characteristics. Journal of the American
o PubMed
o Article
o Google Scholar
48. Lecavalier, L. (2006). Behavioral and emotional problems in young people with
pervasive developmental disorders: Relative prevalence, effects of subject characteristics,
and empirical classification. Journal of Autism and Developmental Disorders, 36, 1101–
1114.
o PubMed
o Article
o Google Scholar
49. *Leyfer, O. T., Folstein, S. E., Bacalman, S., Davis, N. O., Dinh, E., Morgan, J., Tager-
Flusberg, H., & Lainhart, J. E. (2006). Comorbid psychiatric disorders in children with
autism: Interview development and rates of disorders. Journal of Autism and
o PubMed
o Article
o Google Scholar
50. Lipsey, M. W., & Wilson, D. B. (2000). In L. Bickman & D. J. Rog (Eds.), Practical
meta-analysis. Oaks: Sage.
o Google Scholar
51. *Loggins, K. S., Ivanisevic, M., Robins, D. L., & King, T. Z. (2010). Anxiety
Comorbidity in Children and Adolescents with Autism Spectrum Disorders. The Clinical
Neuropsychologist, 24, 557–645.
o Article
o Google Scholar
52. *Lopata, C., Toomey, J. A., Fox, J. D., Volker, M. A., Chow, S. Y., Thomeer, M. L., et
al. (2010). Anxiety and Depression in Children with HFASDs: Symptom Levels and
Source Differences. Journal of Abnormal Child Psychology, 38, 765–776.
o PubMed
o Article
o Google Scholar
53. Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Leventhal, B. L., DiLavore, P. C., et al.
(2000). Journal of Autism and Developmental Disorders, 30, 205–223.
o Google Scholar
54. Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism diagnostic interview–Revised: A
revised version of a diagnostic interview for caregivers of individuals with possible
pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24,
659–685.
o PubMed
o Article
o Google Scholar
55. MacNeil, B. M., Lopes, V. A., & Minnes, P. M. (2009). Anxiety in children and
adolescents with autism spectrum disorders. Research in Autism Spectrum Disorders, 3,
1–21.
o Article
o Google Scholar
56. Mandell, D. S., Cao, J., Ittenbach, R., & Pinto-Martin, J. (2006). Medicaid expenditures
for children with autistic spectrum disorders: 1994 to 1999. Journal of Autism and
o PubMed
o Article
o Google Scholar
57. Matson, J. L., Boisjoli, J., & Wilkins, J. (2007). The Baby and Infant Screen for Children
with aUtIsm Traits (BISCUIT). Baton Rouge, LA: Disability Consultants, LLC.
o Google Scholar
58. Matson, J. L., & González, M. L. (2007). Autism Spectrum Disorders–Comorbidity–
Child Version. Baton Rouge, LA: Disability Consultants, LLC.
o Google Scholar
59. Matson, J. L., & Nebel-Schwalm, M. S. (2007). Comorbid psychopathology with autism
spectrum disorder in children: An overview. Research in Developmental Disabilities, 28,
341–352.
o PubMed
o Article
o Google Scholar
60. *Mattila, M. L., Hurtig, T., Haapsamo, H., Jussila, K., Kuusikko-Gauffin, S., Kielinen,
M., et al. (2010). Comorbid Psychiatric Disorders associated with Asperger
Syndrome/High-functioning Autism: A Community- and Clinic-based study. Journal of
Autism and Developmental Disorders, 40, 1080–1093.
o PubMed
o Article
o Google Scholar
61. *Mazefsky, C. A., Kao, J., & Oswald, D. P. (2011). Preliminary evidence suggesting
caution in the use of psychiatric self-report measures with adolescents with high-
functioning autism spectrum disorders. Research in Autism Spectrum Disorders, 5, 164–
174.
o Article
o Google Scholar
62. Mehtar, M., & Mukaddes, N. M. (2011). Posttraumatic Stress Disorder in individuals
with diagnosis of Autistic Spectrum Disorders. Research in Autism Spectrum Disorders,
5, 539–546.
o Article
o Google Scholar
63. *Melfsen, S., Walitza, S., & Warnke, A. (2006). The extent of social anxiety in
combination with mental disorders. European Child and Adolescent Psychiatry, 15, 111–
117.
o PubMed
o Article
o Google Scholar
64. Meyer, J. A., Mundy, P. C., Van Hecke, A. V., & Durocher, J. S. (2006). Social
attribution processes and comorbid psychiatric symptoms in children with Asperger
syndrome. Autism, 10, 383–402.
o PubMed
o Article
o Google Scholar
65. *Mukaddes, N. M., & Fateh, R. (2010). High rates of psychiatric co-morbidity in
individuals with Asperger’s disorder. The World Journal of Biological Psychiatry, 11,
486–492.
o PubMed
o Article
o Google Scholar
66. *Mukaddes, N. M., Hergüner, S., & Tanidir, C. (2010). Psychiatric disorders in
individuals with high-functioning autism and Asperger’s disorder: Similarities and
differences. The World Journal of Biological Psychiatry, 11, 1–8.
o Article
o Google Scholar
67. Munafò, M. R., Clark, T. G., & Flint, J. (2004). Assessing publication bias in genetic
association studies: evidence from a recent meta-analysis. Psychiatry Research, 129, 39–
44.
o PubMed
o Article
o Google Scholar
68. Muris, P., Merckelbach, H., Brakel, A., van, & Mayer, B. (1999). The revised version of
the screen for child anxiety related emotional disorders (SCARED-R): Further evidence
for its reliability and validity. Anxiety, Stress, and Coping, 12, 411–425.
o PubMed
o Article
o Google Scholar
69. *Muris, P., Steerneman, P., Merckelbach, H., Holdrinet, I., & Meesters, C. (1998).
Comorbid anxiety symptoms in children with pervasive developmental disorders.
Journal of Anxiety Disorders, 12, 387–393.
o PubMed
o Article
o Google Scholar
70. Nauta, M. H., Scholing, A., Rapee, R. M., Abbott, M., Spence, S. H., & Waters, A.
(2004). A parent-report measure of children’s anxiety: psychometric properties and
comparison with child-report in a clinic and normal sample. Behaviour Research and
Therapy, 42, 813–839.
o PubMed
o Article
o Google Scholar
71. *Pearson, D. A., Loveland, K. A., Lachar, D., Lane, D. M., Reddoch, S. L., Mansour, R.,
et al. (2006). A comparison of behavioral and emotional functioning in children and
adolescents with autistic disorder and PDD-NOS. Child Neuropsychology, 12, 321–333.
o PubMed
o Article
o Google Scholar
72. *Pfeiffer, B., Kinnealey, M., Reed, C., & Herzberg, G. (2005). Sensory modulation and
affective disorders in children and adolescents with Asperger’s disorder. American
Journal of Occupational Therapy, 59, 335–345.
o PubMed
o Google Scholar
73. Piven, J., Harper, J., Palmer, P., & Arndt, A. (1996). Course of Behavioral Change in
Autism: A Retrospective Study of High-IQ Adolescents and Adults. Journal of the
American Academy of Child Adolescent Psychiatry, 35, 523–529.
o Article
o Google Scholar
74. Reaven, J. A., Blakeley-Smith, A., Nichols, S., Dasari, M., Flanigan, E., & Hepburn, S.
(2009). Cognitive-behavioral group treatment for anxiety symptoms in children with
high-functioning autism spectrum disorders: A pilot study. Focus on Autism and Other
Developmental Disabilities, 24, 27–37.
o Article
o Google Scholar
75. Reynolds, C. R., & Richmond, B. O. (1985). Revised children’s manifest anxiety scale
manual. Los Angeles: Western Psychological Services.
o Google Scholar
76. Rothstein, H. R., Sutton, A. J., & Borenstein, M. (1996). Publication Bias in Meta-
Analysis. Prevention, Assessment and Adjustments. West Sussex, England: Wiley.
o Google Scholar
77. Russell, E., & Sofronoff, K. (2005). Anxiety and social worries in children with Asperger
syndrome. Australian and New Zealand Journal of Psychiatry, 39, 633–638.
o PubMed
o Google Scholar
78. Ruta, L., Mugno, D., D’Arrigo, V., Vitiello, B., & Mazzone, L. (2010). Obsessive-
compulsive traits in children and adolescents with Asperger syndrome. European Child
and Adolescent Psychiatry, 19, 17–24.
o PubMed
o Article
o Google Scholar
79. Shaffer, D., Fisher, P., Dulcan, M. K., Davies, M., Piacentini, J., Schwab-Stone, M. E., et
al. (1996). The NIMH diagnostic interview schedule for children version 2.3. (DISC-2.3):
Description, acceptability, prevalence rates, and performance in the MECA study.
Journal of the American Academy of Child and Adolescent Psychiatry, 35, 865–877.
o PubMed
o Article
o Google Scholar
80. *Simonoff, E., Pickles, A., Charman, T., Chandler, S., Loucas, T., & Baird, G. (2008).
Psychiatric disorders in children with autism spectrum disorders: Prevalence,
comorbidity, and associated factors in a population-derived sample. Journal of the
American Academy of Child and Adolescent Psychiatry, 47(8), 921–929.
o PubMed
o Article
o Google Scholar
81. Simon, E., & Bögels, S. M. (2009). Screening for anxiety disorders in children.
European Child and Adolescent Psychiatry, 18, 625–634.
o PubMed
o Article
o Google Scholar
82. Sofronoff, K., Attwood, T., & Hinton, S. (2005). A randomised controlled trial of a CBT
intervention for anxiety in children with Asperger syndrome. Journal of Child
Psychology and Psychiatry, 46, 1152–1160.
o PubMed
o Article
o Google Scholar
83. South, M., Ozonoff, S., & McMahon, W. M. (2005). Repetitive behavior profiles in
Asperger Syndrome and high-functioning Autism. Journal of Autism and Developmental
Disorders, 35, 145–157.
o PubMed
o Article
o Google Scholar
84. Spence, S. H. (1997). Structure of Anxiety symptoms among children: A confirmatory
factor-analytic study. Journal of Abnormal Psychology, 106, 280–297.
o PubMed
o Article
o Google Scholar
85. Starr, E., Szatmari, P., Bryson, S., & Zwaigenbaum, L. (2003). Stability and change
among high-functioning children with pervasive developmental disorders: A 2-year
outcome study. Journal of Autism and Developmental Disorders, 33, 15–22.
o PubMed
o Article
o Google Scholar
86. Sterne, J. A. C., Gavaghan, D., & Egger, M. (2000). Publication and related bias in meta-
analysis: Power of statistical tests and prevalence in the literature. Journal of Clinical
Epidemiology, 53, 1119–1129.
o PubMed
o Article
o Google Scholar
87. *Sukhodolsky, D. G., Scahill, L., Gadow, K. D., Arnold, L. E., Aman, M. G., McDougle,
C. J., et al. (2008). Parent-rated anxiety symptoms in children with pervasive
developmental disorders: Frequency and association with core autism symptoms and
cognitive functioning. Journal of Abnormal Child Psychology, 36, 117–128.
o PubMed
o Article
o Google Scholar
88. Szatmari, P., Archer, L., Fisman, S., Streiner, D. L., & Wilson, F. (1995). Asperger’s
syndrome and autism: Differences in behavior, cognition and adaptive functioning.
Journal of the American Academy of Child and Adolescent Psychiatry, 34, 1662–1671.
o PubMed
o Article
o Google Scholar
89. Tabachnick, B. G., & Fidell, L. S. (2001). Using multivariate statistics. New York:
Harper & Row.
o Google Scholar
90. *Thede, L. L., & Coolidge, F. L. (2007). Psychological and neurobehavioral comparisons
of children with Asperger’s disorder versus high-functioning autism. Journal of Autism
and Developmental Disorders, 37, 847–854.
o PubMed
o Article
o Google Scholar
91. Tracey, S. A., Chorpita, B. F., Douban, J., & Barlow, D. H. (1997). Empirical evaluation
of DSM-IV generalized anxiety disorder criteria in children and adolescents. Journal of
Clinical Child Psychology, 26, 404–414.
o PubMed
o Article
o Google Scholar
92. Weisbrot, D. M., Gadow, K. D., DeVincent, C. J., & Pomeroy, J. (2005). The
presentation of anxiety in children with pervasive developmental disorders. Journal of
Child and Adolescent Psychopharmacology, 15, 477–496.
o PubMed
o Article
o Google Scholar
93. White, S. W., Oswald, D., Ollendick, T., & Scahill, L. (2009). Anxiety in children and
adolescents with autism spectrum disorders. Clinical Psychology Review, 29, 216–229.
o PubMed
o Article
o Google Scholar
94. *White, S. W., & Roberson-Nay, R. (2009). Anxiety, social deficits, and loneliness in
youth with autism spectrum disorders. Journal of Autism and Developmental Disorders,
39, 1006–1013.
o PubMed
o Article
o Google Scholar
95. *Witwer, A. N., & Lecavalier, L. (2010). Validity of Comorbid Psychiatric Disorders in
Youngsters with Autism Spectrum Disorders. Journal of Developmental and Physical
Disabilities, 22, 367–380.
o Article
o Google Scholar
96. *Wozniak, J., Biederman, J., Faraone, S. V., Frazier, J., Kim, J., Millstein, R., et al.
(1997). Mania in children with pervasive developmental disorder revisited. American
o Google Scholar
Affiliations
1. Research Institute of Child Development and Education, University of Amsterdam,

Nieuwe Prinsengracht, 130 1018 VZ, Amsterdam, The Netherlands
o Francisca J. A. van Steensel
o & Susan M. Bögels
2. Biomedical Research Centre, King’s College London/Institute of Psychiatry (PO77), 16
DeCrespigny Park, London, SE5 8AF, UK
o Sean Perrin
van Steensel, F.J.A., Bögels, S.M. & Perrin, S. Anxiety Disorders in Children and Adolescents
with Autistic Spectrum Disorders: A Meta-Analysis. Clin Child Fam Psychol Rev 14, 302 (2011)
doi:10.1007/s10567-011-0097-0

ARTICOLE

Uploaded by

Copyright:

Available Formats

You might also like

ARTICOLE

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

ARTICOLE

Uploaded by

Copyright:

Available Formats

ARTICOLE

Depression in Children and Adolescents with

Keywords: autism spectrum disorder, depression, adolescents, prevalence, treatment

A validity/reliability study of the Autism Comorbidity Interview—Present and Lifetime version

Prevalence Studies of Depression in Youth with autism spectrum disorder (ASD).

3. Risk and Protective Factors

Much of the evidence pertaining to psychosocial interventions, such as cognitive behavior

Characterization of Depression in Children

Keywords: Comorbidity, Internalizing Disorders, Pervasive Developmental Disorder, Asperger

Presentation of Depression in Autism Spectrum Disorders

Identifying Depression in ASD and Current Prevalence

Simonoff and colleagues19 conducted a standardized assessment of a population-based sample of

Relationships Between Severity of ASD, Insight, Age, and IQ

Relationships Between Environment, Peer Relations, and

Context-Specific Variation in Depressive Symptomatology in

Genetic Contributions to Depression in ASD

Synthesizing the Current State of Knowledge: a Testable

A proposed strategy for ascertainment and characterization of depressive syndromes in youth

John N. Constantino, Departments of Psychiatry and Pediatrics, Washington University School

Anxiety and depression in adults with autism

Selecting studies for inclusion in the review

Any anxiety disorder

Sub-group analyses: the role of clinical interview v. questionnaire measures, ASD

Use of clinical interview v. questionnaires to measure anxiety

Use of ASD diagnostic tools

Subgroup analysis of studies of current prevalence of anxiety disorder or clinically elevated

Prevalence of depression in adults with ASD

Meta-analytic pooling of the estimates yielded a 23% prevalence of current co-morbid

Use of clinical interview v. questionnaires to measure depression

Use of ASD diagnostic measures

Evaluating the quality of included studies

Rates/prevalence of anxiety and depression in adults with ASD

Implications and recommendations for future research

Conclusion and clinical implications

† The notes appear after the main text.

Anxiety Disorders in Children and

Clinical Child and Family Psychology Review volume 14, Article number: 302 (2011)

Assessment of ASD in the Selected Studies

Table 2 Assessment of ASD and anxiety in the selected studies

Assessment of Anxiety in the Selected Studies

Normality, Outliers, and Publication Bias

Prevalence of Anxiety Disorders in Children with ASD

1. Research Institute of Child Development and Education, University of Amsterdam,

You might also like