Anxiety in Autism
Spectrum Disorders
Todd Levine MD, FAAP
Assistant Professor in Psychiatry and Human
Behavior
Brown Center for the Study of Children at Risk
Warren Alpert Medical School of Brown
University, Providence, RI
Disclosures
 No
financial relationships or conflicts of
interest
 Many
of these treatments are “off label”,
non-Food and Drug Administration
approved
Learning Objectives
 Investigate
the relationship between symptoms
of Autism Spectrum Disorders (ASDs) and
those of anxiety disorders
 Understand
common anxiety symptoms
assessed and treated in ASDs
 Understand
how mechanisms of arousal and
stress may differ in children with ASDs
Diagnostic Considerations
Core deficits in socialization and
communication can lead to difficulties
with:
Connecting
with one’s own feelings
and those of others
Interpretation of motivations behind
behaviors
Contextualizing behaviors
DSM-IV Considerations
Some diagnoses exclude/modify for Pervasive
Developmental Disorders:
 Social
Phobia (Social Anxiety Disorder)
 Separation Anxiety Disorder
 Selective Mutism
 Generalized Anxiety Disorder
 ADHD
 Pica
 Rumination Disorder
 Schizophrenia (Delusions/Hallucinations present)
 Schizoid Personality Disorder
 Schizotypal Personality Disorder
With this in Mind…

Children and adults with Autism Spectrum
Disorders (ASDs) are at higher risk for anxiety1,
depression2, and ADHD3

Psychiatric medications are likely to be prescribed
to those with ASDs4

Psychotherapies have been adapted for children
with ASDs and anxiety5
1Gillot
et al. Autism (2001), 2Ghaziuddin et al. J Autism Dev Disord. (2002),
Ghaziuddin et al. J Intellect Disabil Res (1998), 4Mandell et al. Pediatrics. 2008,
5Chalfant et al. J Autism Dev Disord (2007)
3
Possible Explanations
 Some
children with ASD may be overstimulated
due to a hyperactive nervous system1
 Children
with ASD may have difficulty with
emotional processing2
 Deficits
in socialization and communication
may cause vulnerability to anxiety and
depressive symptoms
1Hirstein
et al. Proc Biol Sci (2001) 2Losh and Capps. Dev Psyc (2006)
Other Factors in Anxiety in ASDs
 Intelligence?
 Social
Functioning Difficulties: May be
worsened by higher anxiety
 Sensory sensitivities
 Changes in routine
 Avoidance of non-preferred tasks
 Lack of expressive language
Eussen et al. Autism (2012), Lane et al. Am J Occup Ther (2012),
Ozsuvadjian et al. Autism (2012)
Psychotropic Prescribing in ASD
Martin et al. JAACAP. 1999
Psychotropic Prescribing in ASD




In a sample of 60,641 children with ASDs,
56% used at least 1 psychotropic medication
20% were prescribed 3 medications
concurrently
Use was common even in children aged 0 to
2 years (18%) and 3 to 5 years (32%)
Neuroleptic drugs were the most common
psychotropic class (31%), followed by
antidepressants (25%) and stimulants (22%)
Mandell et al. Pediatrics. 2008
Taking a Different Perspective
Obsessive Compulsive Disorder vs.
Repetitive Interests in ASDs
 Obsessions
are “recurrent and persistent
thoughts, impulses, or images that…cause
marked anxiety or distress” (DSM-IV)
 Compulsions are acts designed to counteract
those thoughts, impulses, or images
 Are either consistent with “restricted
repetitive and stereotyped patterns of
behavior, interests, and activities” in ASDs?
 “Insistence on Sameness” different from
anxiety in study. Gotham et al. Autism Research (2013)
When Does Generalized Anxiety
Occur in AS?
 Persistent
worries about scheduling can
occur in those with ASDs
 Generalized Anxiety (GAD) includes being
“keyed up”, sleep difficulties, and muscle
tension
 As in OCD, dysphoric thoughts and feelings
delineate problematic anxiety
Considering PTSD in AS
 Is
trauma processed differently in those with
ASD?
 The symptoms of hyperarousal and social
withdrawl can be difficult to delineate in
people with ASDs
 Is there a case for chronic trauma affecting
those with ASDs?
 Considerations for group therapy
Can Someone with AS be Socially
Anxious?
Excluded from Social Anxiety Disorder diagnosis
 Socially anxious people are fearful of humiliation
and opinions of others
 People with ASDs can be aware of these
factors
 Many with ASDs appear dysphoric or anxious in
groups of people, but is this anxiety?
 Cognitive behavior strategies have been applied

The Elusive “Inner State”
 How
reliable/valid are self-reports in adults
and children with ASDs?
 Can parents tell us more about their kids
with ASDs than the kids?
 Can we look at more concrete, biological
markers of emotional response to help
understand psychiatric reporting?
 There are few psychiatric measures for those
with ASDs
The Study of Social Anxiety in
Asperger’s Disorder
 Compares
children ages 8-12 years old with
Asperger’s Disorder (AD, n=19) to those
without (n=12) during a social stressor
 Protocol involves parent and child reports of
anxiety (MASC and SPAI-C), child selfreport of anxiety during the events, and
measurement of psychophysiology:
 Salivary
cortisol reactivity
 Electrodermal reactivity (EDR)
 Heart rate variability, “vagal tone” (VT)
EDR
Vagal Tone
Participant Example #1
Participant Example #2
Who Has Asperger’s?
#1
#2
A Look at Cortisol Responses
0.25
0.2
0.15
0.1
0.05
0
Adjust
Pre-Stress
Post-Stress
Adjust
The envelope, please…
#1
#2
0.25
0.25
0.2
0.2
0.15
0.15
0.1
0.1
0.05
0.05
0
0
Adjust
Pre-Stress
Post-Stress
Adjust
Adjust
Pre-Stress
Post-Stress
Adjust
“Gas” and “Brake” Comparison
22
EDR
MicroOhms
20
18
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14
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Brief Summary of Study Results
 Children
with Asperger’s were twice as likely
to be cortisol non-responders than controls
(p=0.056)
 There were no between group differences on
EDR and VT across time
 EDR positively correlated with parent
reports of arousal on the MASC in controls,
but not the Asperger’s group
What’s Next?
Trends in Medication
Treatment Studies in AS/ASD
 Most
studies focus on specific behaviors
vs. diagnostic criteria
 Specific behavioral measures have been
created or modified for AS patients
 Successful strategies in “neurotypical”
children have been applied to children and
adults with AS and similar behaviors
Problem Behaviors Targeted by
Psychotropic Medications
 Hyperactivity
 Tantrums
 Lack
 Repetitive
of Attention
 Agitation
 Insomnia
 Aggression
 Self-injury
 Stereotypies
Behavior
 Compulsive Behavior
 Anxiety
 Hyperarousal
 Irritability
 Impulsivity
Side Effects of Psychotropic
Medications
 Hyperactivity
 Agitation
 Lack
 Repetitive
of Attention
 Agitation
 Insomnia
 Aggression
 Activation
Behavior
 Compulsive Behavior
 Hyperarousal
 Irritability
 Tics
Antidepressants
 Serotonin
Specific Re-uptake Inhibitors
(SSRIs) have evidence for use in children
and adolescents with anxiety and depression
 U.S. FDA Black Box warning spurned
controversy over use of SSRIs
 Applicability to AS behaviors has been
explored: repetitive behaviors and anxiety
 Recent research has changed previous
conceptions about SSRI use in ASDs
Sertraline for Perseverative Anxiety
 Based
on clinical experience
 Useful for overly-repetitive concerns or
“anti-Zen” states
 Low doses can work very well
 Don’t have to wait too long for results
 Low side effect profile
 Cheap
Citalopram for Repetitive Behaviors
King et al. (2009) Arch Gen Psychiatry
Risperidone for Irritability
McCracken et al. (2002) NEJM
Anxiolytics
 Family
includes benzodiazepines, and
antihistamines
 These medications can cause
disinhibition and irritability
 Sometimes used in conjunction with
antidepressants
 Sometimes used in children
Meds…The Ultimate Solution??
10 Minute Break
Video Examples of Anxiety in ASDs
What is RI-CART?
The Rhode Island Consortium for Autism Research and Treatment
RICART
My Home
Autism Spectrum Disorders Clinic
Child Psychiatry Consultation Service
Brown Center for the Study of Children
at Risk
Women and Infants’ Hospital
(401)274-1122 x 8935
tlevine@wihri.org