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Peds 20171377
Peds 20171377
2 GORDON-LIPKIN et al
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ID was defined as a positive response TABLE 1 Subject Characteristics and Differences by the Presence or Absence of Comorbid ADHD
to the question, “Has [child name] Variable Total ASD ASD (−) ADHD ASD (+) ADHD P Effect
ever been diagnosed with intellectual (n = 3319) (n = 1816; 54.7%) (n = 1503; 45.3%) Size
disability (also known as mental
Demographic data
retardation)?” and/or an IQ score Age, y, mean (SD) 10.3 (3.08) 9.9 (3.06) 10.8 (3.0) <.001 0.30a
<70 on the question, “What was Boys, No. (%) 2753 (83.0) 1481 (81.6) 1272 (84.6) .019 0.04b
[child name]’s most recent IQ test White race, No. (%) 2894 (87.2) 1574 (86.7) 1320 (87.8) .348 NA
score?” Hispanic race and/ 254 (7.7) 150 (8.3) 104 (6.9) .150 NA
or ethnicity, No.
For the purposes of this study, (%)
children with autism spectrum Phenotypic data
disorder with parent-reported ID, No. (%) 649 (19.6) 381 (21.0) 268 (17.8) .023 0.04b
SRS total raw score, 112.60 (26.10) 110.04 (26.22) 115.70 (25.63) <.001 0.22a
attention-deficit/hyperactivity
mean (SD)
disorder are referred to as ASD Psychiatric
(+) ADHD, and children with comorbidities, No.
autism spectrum disorder without (%)
parent-reported attention-deficit/ Anxiety disorder 1025 (30.9) 345 (19.0) 680 (45.2) <.001 0.28b
Mood disorder 532 (16.0) 146 (8.0) 386 (25.7) <.001 0.24b
hyperactivity disorder are referred to
NA, not applicable.
as ASD (−) ADHD. a Cohen’s d.
the presence of anxiety or mood disorder only (school-aged: P = .041; independent of ADHD, which is
disorders with the presence or adolescent: P = .001). Neither sex, nor unsurprising given that the CAQ asks
absence of ADHD. The ASD (+) race, nor ethnicity were significant in if a child has ever been diagnosed
ADHD group had an increased risk of any of the GLM analyses. with these conditions, leading to an
reported anxiety disorder (adjusted inevitable cumulative diagnosis with
relative risk 2.20; 95% confidence time. Additionally, both groups follow
interval [CI] 1.97–2.46) and mood DISCUSSION the same trajectory as typically
disorder (adjusted relative risk 2.72; To our knowledge, this is the largest developing peers in that the onset
95% CI 2.28–3.24) compared with study in which researchers compare of symptoms consistent with mood
the ASD (−) ADHD group. Increasing comorbidities in individuals with ASD and anxiety disorders is most often
age was the most significant alone and ASD with ADHD. It is also seen in adolescence, which may
contributor for both anxiety disorder 1 of the largest in which researchers explain the higher prevalence of
and mood disorder (both P < .001), compare the clinical phenotypes these disorders in the older cohort. In
and the absence of report of ID was of these populations. We found an contrast, the relative risks of anxiety
a significant contributor for mood extremely high prevalence of parent- and mood disorders are greater in
disorder only (P < .001). Given the reported ADHD among children with the younger, school-aged children
association between increasing ASD, with ADHD affecting 45.2% of than in the older adolescents for
age and parent-reported ADHD, the children, which is commensurate those with ADHD compared with
we also analyzed relative risks by with previous studies that reveal those without ADHD. This suggests
age subgroups (school-aged and a 31% to 95% co-occurrence.28– 31
that ADHD may make children with
adolescent) to better appreciate Previous studies reveal that there ASD more vulnerable to an earlier
may be a genetic or symptom overlap onset of the symptoms of anxiety
a clinical practice perspective. As
of these disorders.3,32
Nonetheless, or mood disorders or more likely to
expected, we found an increased
this should not invalidate either exhibit detectable symptoms at an
prevalence of both anxiety disorder
diagnosis, especially when diagnosis- earlier age.
and mood disorder in the adolescent
group compared with the school- specific treatments are available.
The specific etiology behind the
aged group for both the ASD (+) Our primary study findings were relationships among these conditions
ADHD and ASD (−) ADHD groups; that children with both ASD and is unclear at this time. It is possible
however, there were higher relative ADHD are at an increased risk for that there is a genetic basis for an
risk ratios for the school-aged group being diagnosed with or treated for increased risk of multiple psychiatric
compared with the adolescent group anxiety and mood disorders when disorders, as has been found with
for both anxiety disorder and mood compared with those with ASD alone. ASD and ADHD.32 Alternatively, it
disorder. Within the age subgroups, These are supported by a 2011 study is possible that 1 syndrome is an
we also found the same pattern as in of adolescents in special education early manifestation of the other,
the full data set that increasing age that revealed increased rates of or the development of 1 syndrome
was the most significant contributor antidepressant and/or antianxiety increases the risk for the other. One
to the presence of both anxiety and medication use among children may also consider that children with
mood disorders (for both age groups with ASD and ADHD in comparison ADHD and ASD are at an increased
and both conditions: P < .001), with ASD only.33 Furthermore, the risk for behavioral problems,8,10
and
and absence of report of ID was a prevalence of reported anxiety and these behaviors may contribute to
significant contributor for mood mood disorders increases with age, anxiety or mood symptoms. This may
4 GORDON-LIPKIN et al
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also contribute to the differences were not assigned a diagnosis children with ASD and ADHD have
in SRS scores between the groups, because symptoms may overlap SRS scores ∼3 points higher than
which is discussed below. but were prescribed medication children with ASD who do not have
Referral bias may explain an for hyperactivity, anxiety, or mood ADHD.38 There is also evidence
increased risk for reported anxiety symptoms in the absence of a formal suggesting that children with ADHD
and mood disorders in children with diagnosis. With this in mind, our alone may have higher SRS scores
ASD and ADHD in comparison with rates of ADHD, anxiety, and mood than the normative population,39
ASD alone because practitioners who disorders may reflect the rate of suggesting that a behavioral overlap
diagnose ADHD may be more likely symptoms that are consistent with between ASD and other psychiatric
to also diagnose anxiety or mood these disorders rather than formal disorders exists. The clinical
disorders. However, this question diagnosis. Frequently still, diagnoses implication of a small increase in ASD
was addressed in a previous study of are not used until intervention is symptom severity in children with
the IAN registry,12 in which children needed, which suggests that our both ASD and ADHD is unclear. Six
with both ASD and ADHD were sample may be underidentifying points on the SRS may not translate
less likely to have a third diagnosis these comorbidities if the children to appreciable differences in an
than to not (odds ratio 0.1, 95% CI are not being medically treated. individual child’s outcome, but such
0.1–0.2), implying that referral bias is a difference may have a broader
Recognizing the increased risk
unlikely in this sample. Registration social or economic impact among
for psychiatric disorders in this
bias may also influence the findings this population. It is possible that the
population has implications
if parents of children with multiple SRS is not an adequately sensitive or
for clinical practice. This may
comorbidities are more likely to specific tool to assess ASD function in
be challenging in ASD because
participate in IAN. this setting, and additional studies of
symptoms of anxiety and mood
ASD symptomatology in the context
Evolving diagnostic criteria may also disorders may present differently
of ADHD are needed.
influence population-based studies. in these children than in typically
The Diagnostic and Statistical Manual developing children. Unfortunately, We also found a difference in the
of Mental Disorders, Fifth Edition,has information regarding how anxiety rates of ID among those children with
broadened the construct of autism and mood disorders were diagnosed ASD with and without ADHD. In our
toward a spectrum and narrowed and/or treated was not available cohort, those with ADHD had slightly
the diagnostic criteria for ASD, for this study. Further research is lower rates of ID. It may be that
although the definitions of ADHD needed to better understand how ADHD symptoms are more easily or
and mood disorders are similar mood and anxiety disorders present frequently detected in children with
to those outlined in the previous in both ASD and ADHD populations to normal intellect or that the genetic
edition. The evolution of definitions optimally assess and diagnose these phenotype associated with ASD and
and allowing the coexistence of disorders. Importantly, both anxiety ADHD is also associated with normal
multiple psychiatric diagnoses and mood disorder symptoms are intellect. Differential rates of ID
acknowledges and may affect medical treatable medical conditions through among those children with ASD with
recognition and treatment. The high psychotherapy35 and medication.36 and without ADHD may also be a
rates of comorbidity in this study Recognizing and treating the function of diagnostic overshadowing
may thus reflect changing practice symptoms can impact quality of (eg, ascribing inattention and/
with the evolution of the Diagnostic life37 and improve other short- and or impulsivity to ID rather than
and Statistical Manual of Mental long-term outcomes, with further ADHD). Researchers in future studies
Disorders. knowledge also being needed about examining this question may help
effective, evidence-based treatments clarify whether this association
Pharmacotherapy may also
for these comorbidities in ASD. is replicable and what its clinical
contribute to our findings because
implications may be.
ADHD, anxiety, and mood disorders We found that the presence of
all have treatments that are widely ADHD has a small association with The diagnosis of ASD has been
available and increasingly used greater ASD symptom severity, as validated in the IAN database with
in practice.34 Notably, IAN asks reflected in the SRS score, suggesting 98% accuracy,19,21
but similar
whether a child has ever been that children with increased ASD data are not available for the
diagnosed with or treated for these severity are either more likely to other diagnoses in this study.
comorbidities, acknowledging that be diagnosed with ADHD, or a dual Although performing standardized,
with the Diagnostic and Statistical diagnosis of ASD and ADHD impacts comprehensive psychiatric
Manual of Mental Disorders, Fourth ASD symptoms. Researchers in assessment is the gold standard
Edition, many children with ASD another study found similarly that for diagnosis, participant report
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: The Interactive Autism Network is funded by the Simons Foundation and the Patient-Centered Outcomes Research Institute.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
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