3rd Annual AAAP Symposium
September 13, 2014
Jan Harold D. Sia, M.D.
Developmental-Behavioral Pediatrics
Adoption & Foster Care
www.developmentalpediatricsmanila.weebly.com
Hospital Affiliations: Makati Medical Center, Manila Doctors Hospital
Outline
DSM-IV-TR and DSM-5
 Prevalence of symptoms
 Etiological evidence
 Symptom expression

 Neuropsychological/cognitive
 Behavioral
Impact of comorbid ASD & ADHD
 Efficacy of ADHD treatments in ASD
 Clinical pathway for evaluation and
treatment

Impairing attention deficits are not
improved by standard ASD treatments
(Deprey & Ozonoff, 2009)
 ADHD symptoms can often be
effectively improved with ADHD
treatments, including pharmacological
treatments (Handen, Johnson, Lubetsky
2000)

DSM-5

ASD & ADHD comorbid diagnoses
allowed
Prevalence of symptoms

High rate of ADHD symptoms in
individuals with ASD
 20 – 70% based on recent estimates
Prevalence of symptoms

Frazier, et al. 2001.
 Rate of ADHD did not differ significantly in
PDD and non-PDD children (83% vs 75%)
 Rate of PDD did not differ significantly in
ADHD and non-ADHD children (5% vs 3%)
Prevalence of symptoms

Carlsson, et al. 2013.
 33% had severe hyperactivity/ADHD
Prevalence of symptoms

Yoshida & Uchiyama. 2004.
 67.9% (36) met DSM-IV ADHD criteria
○ 20 – predominantly inattentive
○ 12 – combined type
○ 4 – predominantly hyperactive-impulsive
 ADHD by PDD subtype
○ Autistic Disorder – 57.6%
○ Asperger’s Disorder/PDD NOS – 85%
 ADHD by age
○ < 10 years – 78.8%
○ ≥ 11 years – 50%
Prevalence of symptoms

Sinzig, et al. 2009.
 53% had sufficient ADHD-symptoms to
warrant diagnosis based on DSM-IV
○ 46% - inattentive type
○ 32% - combined type
○ 22% - hyperactive/impulsive type
 ASD+: lower mean age (10.2y vs 13.3y),
lower IQ, took medications more often
Prevalence of symptoms

Ryden & Bejerot. 2008.
 37% - comorbid ADHD
○ 82% - inattentive subtype
Prevalence of symptoms summary
ADHD symptoms exist among
individuals with ASD, from preschool to
adulthood
 ADHD-Inattentive subtype is the most
common presentation
 Limitation – use of parental reports, selfreports
 Need for evidence from theoretical
domains and from neurobiological and
neuropsychological studies

Etiological evidence
ADHD symptoms are similar whether
occurring alone or comorbid with ASD
(Sinzig. 2009)
 Genetic studies

 High rate of ASD and ADHD in persons with
22q11 deletion syndrome (Niklasson, et al.
2009)
 Children with ADHD and their siblings have
higher levels of ASD symptoms compared to
typically developing children (Reiersen, et al
2007)
Symptom expression
Both ASD & ADHD are commonly
associated with deficits in executive control
and difficulty navigating social contexts
(Bühler, et al. 2011)
 Both are more common in males, have a
strong comorbidity with intellectual
disability, and are also associated with
other specific learning and developmental
difficulties (language, reading, and motor
problems). (Leitner. 2014)

Symptom expression

Nature of attention problems in ASD
may by qualitatively different from
attention problems in ADHD (Deprey &
Ozonoff 2009)
 ASD – hypervigilant attention & internal
distractibility
 ADHD – lack of focus & distractibility by
external stimuli
Symptom expression

Saulnier & Ventola. 2012
 In ASD, “inattention” to external stimuli may
be due to hyper-focused attention on an
object or topic of interest
 “Impulsive” behavior may be due to lack of
understanding of the social
inappropriateness of the behavior
Symptom expression

Similar high rates of delinquent,
aggressive, and other externalizing
behaviors for persons with ADHD
combined type or ADHD combined type
and PDD, but not for children with PDD
only (Matsushima, et al. 2008)
Symptom expression – Executive
function
ADHD – display difficulties on tasks
measuring inhibition and sustained
attention, while remaining relatively
unaffected on tasks measuring planning
or cognitive flexibility.
 ASD – appear to display preservation of
conscious inhibitory function, but with
quite severe problems in planning and
shifting attention.

Symptom expression

Additive effect?
 More impairment in daily functioning in
ASD+ADHD vs when they occur alone
(Goldstein & Schweback. 2004)
 Less severe symptoms of ASD+ADHD =
better social skills (Matson, et al. 2010)
 Combined ASD & ADHD was associated
with more severe ASD symptoms than
persons with ASD only (Ames & White.
2011)
Symptom expression

Additive effect?
 Individuals with ASD+ADHD had greater
impairments in verbal and spatial working
memory, response inhibition, and global
executive functioning than children with ASD
only or typically developing children (Yerys,
et al. 2009)
Etiology for co-occurrence?

Rommelse, et al. 2010
 The two are independent disorders occurring
together by association with a third independent
factor
 Alternatively, ASD & ADHD share a common
underlying etiology, a common genetic basis
○ Family and twin studies – about 50 – 72% of the
contributing genetic factors in both disorders show
overlap.
○ These shared genetic and neurobiological
underpinnings form an explanation why both
disorders occur so frequently within the same
patient and family.
Impact of comorbidity
There is preliminary evidence that when
ADHD is comorbid with ASD, the risk for
increased severity of psychosocial
problems increases (Gadow et al. 2004;
Yerys et al. 2009)
 Co-occurring symptoms are associated
with greater impairment than a single
diagnosis.

Impact of comorbidity
Children with ADHD and ASD experience
more difficulty in daily life as reported by
parents and teacher (Rao & Landa. 2013)
 These co-occurring conditions may be less
responsive to standard treatments for
either disorder.
 Children with comorbid ASD & ADHD show
lower cognitive functioning, more severe
social impairment, and greater delays in
adaptive functioning than children with
ASD-only as reported by their parents

Impact of comorbidity

St. Pourçain, et al. 2011.
 Autistic symptoms were more stable than
ADHD behaviors, which showed more
variability
Impact of comorbidity

St. Pourçain, et al. 2011.
 Trajectories for both traits were strongly, but
not reciprocally interlinked, such that the
majority of children with a persistent
hyperactive-inattentive symptomatology also
showed persistent social-communication
deficits, but not vice versa.
ADHD Treatments in ASD

General conclusions from clinical trials:
 IQ and gender are not a determinant of
stimulant efficacy
 Effect sizes for the ASD population are
somewhat smaller than the non-ASD
population
 Fewer individuals in the studies are
classified as ‘responders’ than in the nonASD population (preschool to adolescents)
 Side effects are more common in the ASD
population.
ADHD Treatments in ASD

Aman. 2008.
○ Stimulants – highly variable responses
(significant improvement through to more
problematic behavior), but would still be a
reasonable first choice for previously
untreated children with PDD and
uncomplicated ADHD
○ Noradrenergic reuptake inhibitor atomoxetine
ADHD Treatments in ASD

Aman. 2008.
 Evidence for positive effects:
○ Atypical antipsychotics – risperidone,
quetiapine, ziprasidone, aripiprazole
○ Alpha-2 adrenergic agonists – clonidine,
guanfacine
 Weak evidence for:
○ Antidepressants – TCA, SSRI
○ Anxiolytics – benzodiazepines
○ Antiepileptic mood stabilizers – divalproex
sodium, carbamazepine, topiramate
ADHD Treatments in ASD
Psychopharmacological treatment of
ADHD symptoms in individuals with
autism should be carefully considered.
 These individuals should not be treated
identically to those with ADHD only
(Gargaro. 2011).

ADHD Treatments in ASD

Psychosocial interventions ???
 No known psychosocial interventions that
target co-occurring ASD & ADHD (Davis &
Kollins 2012)
ADHD Treatments in ASD

Psychosocial interventions ???
 Similarities across approaches to treat both
disorders (Davis & Kollins 2012)
○ Use of conditioning procedures
○ Behaviorally oriented parenting intervention
but different conceptualization
 For ADHD, “parent training” typically involves
manual, group based programs designed to teach
parents strategies to manage the behaviors of their
children (eg, reduce impulsive behavior, increase
focus on tasks)
ADHD Treatments in ASD

Psychosocial interventions ???
 Similarities across approaches to treat both
disorders (Davis & Kollins 2012)
○ Behaviorally oriented parenting intervention
but different conceptualization
 For ASD, “parent education” places more emphasis
on individualized treatments that provide parents with
tools to promote child skills development (eg,
improve social engagement, increase communication
attempts).

The picture that is emerging on the
comorbidity of ASD & ADHD is one of
common neurodevelopmental pathways,
overlapping symptoms, and co-occurring
disorders (Lindblad, Gillberg, & Fernell,
2011; Samyn, Roeyers, & Bijttebier,
2011).
Mahajan R, et al. Pediatrics. 2012.
Pathway 1: Symptom Evaluation

Key points
 Accurate ASD diagnosis should be made
using existing ASD diagnostic guidelines
(including language and cognitive testing)
 Educational, speech & language, and
behavioral supports should be optimized
 ADHD-focused clinical interview if ADHD
symptoms continue despite initial steps;
supplemented by ADHD-focused
questionnaires (Conners Scale, Vanderbilt)
Pathway 1: Symptom Evaluation

Key points
 Need for information from school, home and




community
Systemic medical evaluation to rule out any
undiagnosed medical problem that may
contribute to the ADHD symptoms
Optimize medical, mental health, and
educational/behavioral interventions
Reevaluate to assess need for medication trial
Simultaneous evaluation and treatment across
multiple steps
Pathway 2: Medication Choice

Key points
 Methylphenidate preparations are generally
the first choice
○ Preferable to start with short-acting
formulation to gauge side effects
Pathway 2: Medication Choice

Key points
 2nd line medications
○ Amphetamine salts
○ Atomoxetine
○ Alpha-2 adrenergic agonists: Clonidine,
Guanfacine
○ Atypical antipsychotics: Risperidone,
Aripiprazole
 Most evidence for efficacy in the context of irritability
and aggression
Clinical practice

Involve the family in the decision-making
process to discuss:
 Evidence
 Target symptoms that may improve and when to
expect improvement
 Potential side effects or adverse events
 Explore beliefs and values about medication for
ADHD symptoms

More than 1 clinic visit/appointment may be
necessary to discuss pros and cons of a
given treatment plan
Clinical practice

Careful documentation and analysis of
this potential overlap between ASD and
ADHD should be a mandatory
component in assessment. (Geurts, et
al. 2008)
Five-year view
There may be an increase in the research
base on the comorbid state
 Future research based on the framework
adopted by Biederman et al (1991)

 The comorbid disorders are the expression
of phenotypic variability of the same DSM-5
disorder
 Each disorder is a separate DSM-5 disorder
 ADHD and ASD possess common
vulnerabilities
Five-year view

Future research based on framework
adopted by Biederman et al (1991)
 The comorbid ADHD and ASD state represents
a homogeneous subgroup with the ADHD (or
ASD) population
 One condition is a developmental precursor
to the other condition
 One disorder increases the risk for the
second disorder
Five-year view

Other research topics
 Assessment strategies
 Treatment with mixed amphetamine salts
 Treatment using combined behavioral and
medication management
 Focus on family level variables (eg,
parenting efficacy, parenting stress, parent
mental health, etc.) as either independent or
dependent variables.
Final thought….

This new attitude will not only allow for
more efficient clinical management of
these children, but will also clear the
way for a more precise scientific
understanding of the overlap of these
two disorders. (Leitner. 2014)
Summary
A majority of children with ASD have
significant symptoms of ADHD but not
all children with ASD have these
symptoms
 Family and twin studies suggest a
common genetic etiology for both
disorders
 ADHD and ASD are associated with
executive dysfunction but in different
domains

Summary
There is evidence for using MPH in
treating ADHD in ASD
 Dual diagnosis may be essential to
implementation of effective treatments.
(Holtmann, et al. 2007)

References
Matson JL. Rieske RD, Williams LW. The relationship between autism spectrum disorders
and attention-deficit/hyperactivity disorders: an overview. Res Dev Disabil. 2013;34.
Gargaro BA, Rinehart NJ, Bradshaw JL, Tonge BJ, Sheppard DM. Autism and ADHD: how
far have we come in the comorbidity debate? Neuroscience and Biobehavioral Reviews.
2011; 35.
Sinzig J, Walter D, Doepfner M. Attention-deficit/hyperactivity disorder in chidlren with
autism spectrum disorder: symptom or syndrome? Journal of Attention Disorders. 2009.
Leitner Y. The co-occurrence of autism and attention-deficit hyperactivity disorder in children
– what do we know? Frontiers in Human Neuroscience. 2014; 8.
Davis NO & Kollins SH. Treatment of co-occurring attention-deficit/hyperactivity disorder and
autism spectrum disorder. Neurotherapeutics. 2012; 9.
Antshel KM, Zhang-James Y, Faraone SV. The comorbidity of ADHD and autism spectrum
disorder. Expert Rev. Neurother. 2013; 13(10).
Mahajan R, et al. Clinical practice pathways for evaluation and medication choice for
attention-deficit/hyperactivity disorder symptoms in autism spectrum disorders. Pediatrics.
2012; 130(Supp 2).