Anxiety in Autism Anxiety in Autism Spectrum Spectrum DisordersDisorders

Todd Levine MD, FAAPTodd Levine MD, FAAPAssistant Professor in Psychiatry and Assistant Professor in Psychiatry and

Human BehaviorHuman BehaviorBrown Center for the Study of Brown Center for the Study of

Children at RiskChildren at RiskWarren Alpert Medical School of Warren Alpert Medical School of Brown University, Providence, RI Brown University, Providence, RI

DisclosuresDisclosuresNo financial relationships or No financial relationships or

conflicts of interest conflicts of interest

Many of these treatments are Many of these treatments are “off label”, non-Food and Drug “off label”, non-Food and Drug Administration approvedAdministration approved

Learning ObjectivesLearning Objectives Investigate the relationship between Investigate the relationship between

symptoms of Autism Spectrum symptoms of Autism Spectrum Disorders (ASDs) and those of anxiety Disorders (ASDs) and those of anxiety disordersdisorders

Understand common anxiety symptoms Understand common anxiety symptoms assessed and treated in ASDsassessed and treated in ASDs

Understand how mechanisms of Understand how mechanisms of arousal and stress may differ in arousal and stress may differ in children with ASDschildren with ASDs

Diagnostic Diagnostic ConsiderationsConsiderations

Connecting with one’s own Connecting with one’s own feelings and those of othersfeelings and those of others

Interpretation of motivations Interpretation of motivations behind behaviorsbehind behaviors

Contextualizing behaviorsContextualizing behaviors

Core deficits in socialization Core deficits in socialization and communication can lead and communication can lead to difficulties with:to difficulties with:

DSM-IV DSM-IV ConsiderationsConsiderations

Some diagnoses exclude/modify for Some diagnoses exclude/modify for Pervasive Developmental Disorders:Pervasive Developmental Disorders:

Social Phobia (Social Anxiety Disorder)Social Phobia (Social Anxiety Disorder) Separation Anxiety DisorderSeparation Anxiety Disorder Selective MutismSelective Mutism Generalized Anxiety DisorderGeneralized Anxiety Disorder ADHDADHD PicaPica Rumination DisorderRumination Disorder Schizophrenia (Delusions/Hallucinations Schizophrenia (Delusions/Hallucinations

present)present) Schizoid Personality DisorderSchizoid Personality Disorder Schizotypal Personality DisorderSchizotypal Personality Disorder

With this in Mind…With this in Mind… Children and adults with Autism Children and adults with Autism

Spectrum Disorders (ASDs) are at Spectrum Disorders (ASDs) are at higher risk for anxietyhigher risk for anxiety11, depression, depression22, , and ADHDand ADHD33

Psychiatric medications are likely to Psychiatric medications are likely to be prescribed to those with ASDsbe prescribed to those with ASDs44

Psychotherapies have been adapted Psychotherapies have been adapted for children with ASDs and anxietyfor children with ASDs and anxiety55

11Gillot et al. Gillot et al. Autism Autism (2001), (2001), 22Ghaziuddin et al. J Autism Dev

Disord. (2002), 3 Ghaziuddin et al. J Intellect Disabil Res (1998), 4Mandell et al. Mandell et al. Pediatrics. 2008,Pediatrics. 2008,55Chalfant et al.Chalfant et al. J Autism Dev Disord (2007)

Possible Possible ExplanationsExplanations

Some children with ASD may be Some children with ASD may be overstimulated due to a hyperactive overstimulated due to a hyperactive nervous systemnervous system11

Children with ASD may have difficulty Children with ASD may have difficulty with emotional processingwith emotional processing22

Deficits in socialization and Deficits in socialization and communication may cause communication may cause vulnerability to anxiety and depressive vulnerability to anxiety and depressive symptomssymptoms

11Hirstein et al. Proc Biol Sci (2001) Hirstein et al. Proc Biol Sci (2001) 22Losh and Capps. Dev Losh and Capps. Dev Psyc (2006)Psyc (2006)

Other Factors in Anxiety Other Factors in Anxiety in ASDsin ASDs

Intelligence?Intelligence? Social Functioning Difficulties: Social Functioning Difficulties:

May be worsened by higher May be worsened by higher anxietyanxiety

Sensory sensitivitiesSensory sensitivities Changes in routineChanges in routine Avoidance of non-preferred tasksAvoidance of non-preferred tasks Lack of expressive languageLack of expressive language

Eussen et al. Eussen et al. AutismAutism (2012), Lane et al. Am J Occup Ther (2012), Ozsuvadjian et al. Autism (2012)

Psychotropic Prescribing Psychotropic Prescribing in ASDin ASD

Martin et al. Martin et al. JAACAP.JAACAP. 1999 1999

Psychotropic Prescribing Psychotropic Prescribing in ASDin ASD

In a sample of 60,641 children with In a sample of 60,641 children with ASDs, 56% used at least 1 psychotropic ASDs, 56% used at least 1 psychotropic medicationmedication

20% were prescribed 3 medications 20% were prescribed 3 medications concurrentlyconcurrently

Use was common even in children aged Use was common even in children aged 0 to 2 years (18%) and 3 to 5 years 0 to 2 years (18%) and 3 to 5 years (32%)(32%)

Neuroleptic drugs were the most Neuroleptic drugs were the most common psychotropic class (31%), common psychotropic class (31%), followed by antidepressants (25%) and followed by antidepressants (25%) and stimulants (22%)stimulants (22%)Mandell et al. Mandell et al. Pediatrics. 2008Pediatrics. 2008

Taking a Different Taking a Different PerspectivePerspective

Obsessive Compulsive Obsessive Compulsive Disorder vs. Repetitive Disorder vs. Repetitive

Interests in ASDsInterests in ASDs Obsessions are “recurrent and persistent Obsessions are “recurrent and persistent

thoughts, impulses, or images that…cause thoughts, impulses, or images that…cause marked anxiety or distress” (DSM-IV)marked anxiety or distress” (DSM-IV)

Compulsions are acts designed to Compulsions are acts designed to counteract those thoughts, impulses, or counteract those thoughts, impulses, or imagesimages

Are either consistent with “restricted Are either consistent with “restricted repetitive and stereotyped patterns of repetitive and stereotyped patterns of behavior, interests, and activities” in ASDs?behavior, interests, and activities” in ASDs?

““Insistence on Sameness” different from Insistence on Sameness” different from anxiety in study. anxiety in study. Gotham et al. Gotham et al. Autism Research Autism Research (2013)(2013)

When Does Generalized When Does Generalized Anxiety Occur in AS?Anxiety Occur in AS?

Persistent worries about Persistent worries about scheduling can occur in those scheduling can occur in those with ASDswith ASDs

Generalized Anxiety (GAD) Generalized Anxiety (GAD) includes being “keyed up”, sleep includes being “keyed up”, sleep difficulties, and muscle tensiondifficulties, and muscle tension

As in OCD, dysphoric thoughts As in OCD, dysphoric thoughts and feelings delineate and feelings delineate problematic anxietyproblematic anxiety

Considering PTSD in Considering PTSD in ASAS

Is trauma processed differently in Is trauma processed differently in those with ASD?those with ASD?

The symptoms of hyperarousal and The symptoms of hyperarousal and social withdrawl can be difficult to social withdrawl can be difficult to delineate in people with ASDsdelineate in people with ASDs

Is there a case for chronic trauma Is there a case for chronic trauma affecting those with ASDs?affecting those with ASDs?

Considerations for group therapyConsiderations for group therapy

Can Someone with AS be Can Someone with AS be Socially Anxious?Socially Anxious?

Excluded from Social Anxiety Disorder Excluded from Social Anxiety Disorder diagnosisdiagnosis

Socially anxious people are fearful of Socially anxious people are fearful of humiliation and opinions of othershumiliation and opinions of othersPeople with ASDs can be aware of these People with ASDs can be aware of these

factorsfactors Many with ASDs appear dysphoric or Many with ASDs appear dysphoric or

anxious in groups of people, but is this anxious in groups of people, but is this anxiety?anxiety?

Cognitive behavior strategies have been Cognitive behavior strategies have been appliedapplied

The Elusive “Inner State”The Elusive “Inner State”

How reliable/valid are self-reports How reliable/valid are self-reports in adults and children with ASDs?in adults and children with ASDs?

Can parents tell us more about Can parents tell us more about their kids with ASDs than the kids?their kids with ASDs than the kids?

Can we look at more concrete, Can we look at more concrete, biological markers of emotional biological markers of emotional response to help understand response to help understand psychiatric reporting?psychiatric reporting?

There are few psychiatric measures There are few psychiatric measures for those with ASDsfor those with ASDs

The Study of Social Anxiety The Study of Social Anxiety in Asperger’s Disorderin Asperger’s Disorder

Compares children ages 8-12 years Compares children ages 8-12 years old with Asperger’s Disorder (AD, old with Asperger’s Disorder (AD, n=19) to those without (n=12) n=19) to those without (n=12) during a social stressorduring a social stressor

Protocol involves parent and child Protocol involves parent and child reports of anxiety (MASC and SPAI-reports of anxiety (MASC and SPAI-C), child self-report of anxiety during C), child self-report of anxiety during the events, and measurement of the events, and measurement of psychophysiology:psychophysiology: Salivary cortisol reactivitySalivary cortisol reactivity Electrodermal reactivity (EDR)Electrodermal reactivity (EDR) Heart rate variability, “vagal tone” (VT)Heart rate variability, “vagal tone” (VT)

Vagal Tone

EDR

Participant Example #1Participant Example #1

Participant Example #2Participant Example #2

Who Has Asperger’s?Who Has Asperger’s?

#1#1 #2#2

A Look at Cortisol A Look at Cortisol ResponsesResponses

0

0.05

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0.15

0.2

0.25

Adjust Pre-Stress Post-Stress Adjust

The envelope, please…The envelope, please…

0

0.05

0.1

0.15

0.2

0.25

Adjust Pre-Stress Post-Stress Adjust0

0.05

0.1

0.15

0.2

0.25

Adjust Pre-Stress Post-Stress Adjust

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““Gas” and “Brake” Gas” and “Brake” ComparisonComparison

10

12

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20

22

MicroOhms

HFA COMP

5

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COMP HFA

EDR

Vagal Tone

Brief Summary of Study Brief Summary of Study ResultsResults

Children with Asperger’s were twice Children with Asperger’s were twice as likely to be cortisol non-as likely to be cortisol non-responders than controls (p=0.056)responders than controls (p=0.056)

There were no between group There were no between group differences on EDR and VT across differences on EDR and VT across timetime

EDR positively correlated with parent EDR positively correlated with parent reports of arousal on the MASC in reports of arousal on the MASC in controls, but not the Asperger’s controls, but not the Asperger’s groupgroup

What’s Next?What’s Next?

Trends in Medication Trends in Medication Treatment Studies in Treatment Studies in

AS/ASDAS/ASDMost studies focus on specific Most studies focus on specific

behaviors vs. diagnostic criteriabehaviors vs. diagnostic criteriaSpecific behavioral measures have Specific behavioral measures have

been created or modified for AS been created or modified for AS patientspatients

Successful strategies in Successful strategies in “neurotypical” children have been “neurotypical” children have been applied to children and adults applied to children and adults with AS and similar behaviorswith AS and similar behaviors

Problem Behaviors Problem Behaviors Targeted by Psychotropic Targeted by Psychotropic

MedicationsMedications HyperactivityHyperactivity Lack of Lack of

AttentionAttention AgitationAgitation InsomniaInsomnia AggressionAggression Self-injurySelf-injury StereotypiesStereotypies

TantrumsTantrums Repetitive Repetitive

BehaviorBehavior Compulsive Compulsive

BehaviorBehavior AnxietyAnxiety HyperarousalHyperarousal IrritabilityIrritability ImpulsivityImpulsivity

Side Effects of Psychotropic Side Effects of Psychotropic MedicationsMedications

HyperactivityHyperactivity Lack of Lack of

AttentionAttention AgitationAgitation InsomniaInsomnia AggressionAggression ActivationActivation

AgitationAgitation Repetitive Repetitive

BehaviorBehavior Compulsive Compulsive

BehaviorBehavior HyperarousalHyperarousal IrritabilityIrritability TicsTics

AntidepressantsAntidepressants Serotonin Specific Re-uptake Serotonin Specific Re-uptake

Inhibitors (SSRIs) have evidence for Inhibitors (SSRIs) have evidence for use in children and adolescents with use in children and adolescents with anxiety and depressionanxiety and depression

U.S. FDA Black Box warning spurned U.S. FDA Black Box warning spurned controversy over use of SSRIscontroversy over use of SSRIs

Applicability to AS behaviors has been Applicability to AS behaviors has been explored: repetitive behaviors and explored: repetitive behaviors and anxietyanxiety

Recent research has changed previous Recent research has changed previous conceptions about SSRI use in ASDsconceptions about SSRI use in ASDs

Sertraline for Sertraline for Perseverative AnxietyPerseverative Anxiety

Based on clinical experienceBased on clinical experience Useful for overly-repetitive Useful for overly-repetitive

concerns or “anti-Zen” statesconcerns or “anti-Zen” states Low doses can work very wellLow doses can work very well Don’t have to wait too long for Don’t have to wait too long for

resultsresults Low side effect profileLow side effect profile CheapCheap

Citalopram for Repetitive Citalopram for Repetitive BehaviorsBehaviors

King et al. (2009) Arch Gen Psychiatry

Risperidone for Risperidone for IrritabilityIrritability

McCracken et al. (2002) NEJM

AnxiolyticsAnxiolyticsFamily includes Family includes

benzodiazepines, and benzodiazepines, and antihistaminesantihistamines

These medications can cause These medications can cause disinhibition and irritabilitydisinhibition and irritability

Sometimes used in conjunction Sometimes used in conjunction with antidepressantswith antidepressants

Sometimes used in childrenSometimes used in children

Meds…The Ultimate Meds…The Ultimate Solution??Solution??

10 Minute Break

Video Examples of Anxiety Video Examples of Anxiety in ASDsin ASDs

What is RI-CART?The Rhode Island Consortium for Autism Research

and Treatment

My HomeMy Home

Autism Spectrum Disorders Autism Spectrum Disorders ClinicClinic

Child Psychiatry Consultation Child Psychiatry Consultation ServiceService

Brown Center for the Study of Brown Center for the Study of Children at RiskChildren at Risk

Women and Infants’ HospitalWomen and Infants’ Hospital(401)274-1122 x 8935(401)274-1122 x 8935

tlevine@wihri.orgtlevine@wihri.org