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AnxietyinAutismSpectrumDisorder

AntonioHardan,MDStanfordUniversity

November,2017

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Disclosures

Source Advisory Board Consultant Grant Support

BioElectron X

Hoffmann Tech X

Q BioMed Inc. X

SFARI X

National Institutes of Health X

Roche X

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Outline

• Whatisanxiety?• ManifestationsofanxietyinASD• Anxietydisorders• Prevalencerates• Mechanisms• Treatment

– Generalapproaches– CBT– Pharmacology

• Conclusions

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WhatisAnxiety?

• AmericanPsychologicalAssociation:– Anxietyisanemotioncharacterizedbyfeelingsoftension,worriedthoughtsand

physicalchangeslikeincreasedbloodpressure.Peoplewithanxietydisordersusuallyhaverecurringintrusivethoughtsorconcerns.Theymayavoidcertainsituationsoutofworry.Theymayalsohavephysicalsymptomssuchassweating,trembling,dizzinessorarapidheartbeat.

• Threedomainsofanxiety– Cognitive:Difficultyconcentrating,mindgoingblank,impendingdoom…– Behavioral:Pacingandrestlessness,handwringing,oppositionalbehavior,

avoidance,inhibition…– Physiological:increaseinbloodpressure,rapidheartbeat,sweating,muscle

tension,easilyfatigued,sleepdisturbances…

• Adaptiveanxiety

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AnxietydisordersandASD

• Disordersthatsharefeaturesofexcessivefearandanxietyandrelatedbehavioraldisturbances.

• Fearistheemotionalresponsetorealorperceivedimminentthreat– Associatedwithsurgesofautonomicarousalnecessaryforfightorflight,thoughtsof

immediatedanger,andescapebehaviors

• Anxietyisanticipationoffuturethreat– Associatedwithmuscletensionandvigilanceinpreparationforfuturedangerand

developmentofavoidantbehaviors.

• InASD,anxietymaybemanifestedbyavoidance,elopement,distress,andtantrums.

• Effectofage,development,andlevelofcognitivefunctioning– Highfunctioningchildrenaremoreabletouselanguagetoexpressworriesandfears– Lowerfunctioningchildrenwillexpresssymptomsthroughbehaviors:

• Difficultyexpressingworries,interpretingphysiologicalsignalsandsortingemotions

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ExpressionofAnxietywithAge• Preschoolers:

– Crying,screaming,throwingobjects,self-harm,tantrums,withdrawal,hitting,kicking,hyperactivity,attentionseekingbehaviors…

– Repetitivebehaviors,repetitiveplay,echolalia,scripting…• Elementaryandmiddle-schoolagechildren:

– Resistancetotakeonnewtasks,repetitivequestioning,tantrums,aggressivebehaviors,arguing,withdrawal,rearrangingschedule,freezingbehavior,somaticcomplaints,selectivemutism,inhibition,hyperactivity,attentionseekingbehaviors…

• Adolescents:– Easilyoverwhelmedbyschooldemands,resistancetoschoolwork,somatic

complaints,schoolrefusal,increaseinsocialisolation,requiringmorere-assurance,emergenceorincreaseinmooddysregulation,aggressivebehavior,depressivesymptomatology,inhibition…

• Adults:– Difficultiesatthedayprogramoratwork,challengeswithtransitiontocollegeor

independentliving,inhibition,freezing…

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AnxietySymptomsandASD• SeparatinganxietyfromASD

– Socialavoidancevssocialanxiety– Separationanxietyfrommother:insistenceonsamenessvsseparationanxiety

• Additionalanxietydisorderdiagnosisisappropriate– “TobenotbetteraccountedforbytheASDitself”

• HowtothinkaboutanxietyinASD?• Co-morbiditymodel

– ASDandAnxietyDisordersaredistinct• AnxietydisordersinASDsameasgeneralpopulation

• Complicationmodel– ASDincreaseriskofanxiety

• Socialdisabilityriskofsocialanxiety• ConvergentModel

– AnxietyispartofASD• Insistenceonroutines,socialavoidance=anxiety

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AnxietyDisordersI

• GeneralizedAnxietyDisorder:– Excessiveanxietyandworryaboutavarietyoftopics,events,oractivities– verychallengingtocontrol– anxietyandworryareassociatedwithphysicalorcognitivesymptoms

• SeparationAnxietyDisorder:– Developmentallyinappropriateandexcessiveanxietyconcerningseparationfromhome

orfromthosetowhomtheindividualisattached– Distresswhenseparatedfromhomeorattachmentfigures– Worryaboutlosingorharmbefallingonmajorattachmentfigures– Nightmaresaboutseparationandphysicalsymptomswhenseparation

• PostTraumaticStressDisorder:– Traumaticevents;experienced,witnessed…– Re-experiencingthetrauma:nightmares,flashbacks,emotionaldistressafterreminders– Avoidanceoftrauma-relatedstimuli:thoughts,feelings,reminders– Negativethoughtsorfeelingsaboutoneselfortheworldafterthetrauma– Arousalandreactivityafterthetrauma:irritability,aggression,hypervigilence

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AnxietyDisordersII• SocialAnxietyDisorder(SocialPhobia):

– Fearoranxietyspecifictosocialsettings,inwhichapersonfeelsnoticed,observed,orscrutinized

– Typicallytheindividualwillfearthattheywilldisplaytheiranxietyandexperiencesocialrejection

– Socialinteractionwillconsistentlyprovokedistressleadingtoavoidanceorpainfullyandreluctantlyendured

– Thefearandanxietywillbegrosslydisproportionatetotheactualsituation• PanicDisorder:

– Recurrentunexpectedpanicattacks– Suddenperiodsofintensefearthatmayincludepalpitations,poundingheart,sweating,

shaking,shortnessofbreath,choking;andfeelingofimpendingdoom– Intenseworriesaboutwhenthenextattackwillhappen– Fearoravoidanceofplaceswherepanicattackshaveoccurredinthepast

• SpecificPhobia:– Fearoranxietyaboutaspecificobjectorsituation+avoidance– Animals,naturalenvironment(heights),situational(claustrophobia),needles…

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AnxietyDisordersIII• Obsessive-CompulsiveDisorder:

– Obsessions:• Recurrentandpersistentthoughts,impulses,orimagesthatareexperiencedasintrusiveandinappropriateandthatcausemarkedanxietyordistress

• Notsimplyexcessiveworriesaboutreal-lifeproblems• Attemptstoignoreorsuppresssuchthoughts,impulses,orimages,ortoneutralizethemwithsomeotherthoughtoraction

• Obsessionalthoughts,impulses,orimagesareaproductofhisorherownmind– Compulsions:

• Repetitivebehaviors(e.g.,handwashing,ordering,checking)ormentalacts(e.g.,praying,counting,repeatingwordssilently)thatthepersonfeelsdriventoperforminresponsetoanobsession,oraccordingtorulesthatmustbeappliedrigidly

• Aimedatpreventingorreducingdistressorpreventingsomedreadedeventorsituation

– SimilaritiesanddifferenceswithASD• UnspecifiedAnxietyDisorder

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Assessment and Treatment of Anxiety Disorders

Specific interventionsEffectiveness Anxiety Disorders Behavioral Symptoms

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Assessment and Treatment of Anxiety Symptoms

Lack of consistent effectiveness Non specific interventions Behavioral Symptoms

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Prevalence Rates• Range: 11-84% • 40% meet criteria for at least one anxiety disorder (meta-analysis)

– 5-32% in typically developing children • Higher prevalence of anxiety disorders than ID, language do., Down syndrome• High level of anxiety symptoms compared to TD based on parent- and self-

report• Symptoms exacerbate social deficits, impair daily living skills, negatively impact

relationships with peers, teachers, and family members• The most commonly reported: Specific Phobias, Social Anxiety Disorder, and

Generalized Anxiety Disorder• Challenges of assessing anxiety in ASD

– Psychiatric co-morbidity– Lack of a relevant, reliable, valid & practical measure of anxiety is a barrier to

assessing prevalence rates and effectiveness of interventions – Parent-rated Anxiety Scale for youth with ASD: PRAS-ASD (Larry Scahill, MSN, PhD)

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PsychiatricComorbidityinASDSimonoff etal.,2008

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PredispositiontoAnxiety• Patternofthinking:

– Centralcoherence:focusingonatreeinaforest– Narrowpatternofthinkingobservedinindividualswithanxietydisorders

• Social/communicationdeficits– Difficultiesunderstandingthesocialworldmaytriggeranxiety

• Languagedeficits• Abnormalsensoryprocessing:

– Leadtophysiologicsymptomsassociatedwithanxiety

• Feelingsarenotpredictableaswellasemotionalresponses• ER:Relyingonselfmonitoring,maindeficitinASD

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• Sample:– N=415– Meanage8.2+2.6y.– IQ:n=192>70

• ChildhoodAnxietySensitivityIndex(CASI);26itemanxietyscale• Mostfrequentlyendorseditems(%) IQ>70IQ<70

– Actsrestlessoredgy 52 49– Moreanxiousinsocialsituationsthanmostchildren 56 50– Hasdifficultyfallingasleep 40 39– Extremelytenseorunabletorelax 29 31– Isoverlyfearfulofspecificobjects 30 42

• Anxiety Mean = 14.2 +/- 9.4 (range 0to50) – IQ<70:Mean = 12.4 +/- 7.94 – IQ>70:Mean = 16.5 +/- 10.26

• Anxietycorrelatedwithirritability(r=0.31,p<0.01)

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UnusualfearsinASD

Mayesetal.,2013

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Categoriesofunusualfears

Mayesetal.,2013

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Anxietysymptomstrajectories(Gothametal.,2015)

• Agerange:6-24years;ASD=109;non-ASDDD=56;Datacollectedevery3-6mo• Fgenderpredictedgreaterincreaseovertime;InternalizingsymptomsassociatedwithpoorER,lowerlifesatisfaction,greatersocialdifficultiesinearlyadulthood

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Parent-rated Anxiety Scale for youth with ASD (Larry Scahill, MSN, PhD)

• MeasuresofanxietyusedingeneralpediatricpopulationmaynotworkaswellinyouthwithASD

• Limitationsofseveralexistingscales:Spence,SCARED,AnxietyDiagnosticInterviewSchedule(ADIS),ChildhoodAnxietySensitivityIndex(CASI)…

• CASIinASD;N=415– Itemswith<5%responseinoverallsample:worriesaboutphysicalhealth,

nightmaresaboutseparationfromparents– Itemswith<5%ingroupIQ<70:worriesaboutbeinglefthomealoneorwith

sitter,moreanxiousinsocialsituationsthanmostchildren

• Anyanxietyscalecannotbeassumedthatithascontentvalidity(measureanxiety)ifpatientswerenotinvolvedininstrumentdevelopment

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PARS-ASDDevelopment• 3-siteNIMHgrant;PILarryScahill,MSN,PhD (EmoryUniversity);LucLecavalier,PhD(OhioStateUniversity);RobertSchultz,PhD(CHoP)

• Step1:SixfocusgroupswithparentsonthemanifestationsofanxietyinchildrenwithASD(generated600pagesoftranscripts)– Coveredtriggers(loudnoises,crowds,newsituations);observablebehaviors

(requestforreassurance,avoidancewithdistress);childcopingbehaviors(withdrawal,selfsoothingbehaviors,breakingincopingandemotionaloutburst)

– Generateitemsforaparent-ratedmeasure(focusgroupdata)

• Step2:Large-scaleonlinesurveyofadraftmeasure(Parentsof990youth)– Examinedistribution,factors,itemanalysistoprunethemeasure– Startedwith51items+CASI;Draft2:41items;Draft3:25items(onefactor)– Confirmatoryfactoranalysissupported25-itemsscale

• Step3:ClinicalassessmentsinaseriesofyouthwithASD– Testvalidityandreliabilityofrevisedparent-ratedscale

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Parent-ratedAnxietyScale-ASD(from25-item)

Instructions:Circlethenumberthatdescribesyourchild’sworriesandanxiety-relatedbehaviorsoverthepast2weeks.NONE=notpresent;MILD=Presentsometimes,notarealproblem;MODERATE=Oftenpresentandisaproblem;SEVERE=Veryfrequentandisamajorproblem.# None Mild Moderate Severe4. Uncomfortableinsocialsituations 0 1 2 3

5. Getsstuckonwhatmightgowrong

0 1 2 3

6. Consistentlyavoidscertainsituationsduetoanxiety

0 1 2 3

7. Onthelook-outforanychangeinroutine

0 1 2 3

8. Needsalotofreassurancethatthingswillworkout

0 1 2 3

9. Anxiousaboutupcomingevents 0 1 2 3

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Treatment:GeneralApproaches• Roleofparents:Evidenceofeffectivenessofparenttraining• Assesswhethertheseverityofanxietysymptomsisimpactingfunctioning• Questioning(areusureyouarefine?...),checking(doublecheckinghomework…),over-protectivebehaviors(winninggames…),avoidanceofstress,completingtasksforthechild(reductioninindependence),focusingontheanxiousbehavior– Somenegativeexperienceswillhelpwiththedevelopmentoftolerance

• Gentlepressure,progressivedesensitization,makingaccommodation• Encourageanxiogenic behaviorsandrewardappropriately(begenerousinitially)

• Ignorenon-bravebehavior• Acknowledgefeelingsofanxietyandstress;normalizemistakes• Modelingandselfrevelation• Roleplayandreversal

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Treatment:GeneralApproachesII• Discussinggoalsandinvolvetheindividualinthespecifictreatmentprogramdevelopment

• Increaseyourtoleranceofnon-functionalbehaviorsandRRB• Relaxzonewithcalmingactivities• Manageacademicexpectations:Don’tbefooled

– Breaksfromclassroomwork:scheduledorondemands– Provideinformationvisually

• Bepatient• Don’tworkalone:relyingonyourtreatmentteam(therapists,PhD,MD,BCBA,teachers…)andsupportnetwork

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Treatment:GeneralApproachesIII

• Treatmentofspecificpsychiatricdisorders• Balancebetweenbehavioral/cognitive/psychosocialandpsychopharmacologicalinterventions– StartwithCBTfirstforhighfunctioning

• Notallornothingresponse• Oneinterventionatatime• Assessmentofcomplementaryandalternativetreatment• Re-challenge

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Cognitive-Behavior Therapy for Anxiety in ASD

• CBTisawell-establishedinterventionforanxietyinTDchildren• Targets:

– Anxiogenic cognitivefactors:distortions– Behavioralfactors(e.g.,avoidance,rituals…)

• Psychoeducationandrelaxationtechniques• Emotionregulationandcognitiverestructuring• Creationoffearhierarchy• Exposureandresponseprevention:Repeatedandgradualexposure• Short-termduration,upto16sessions• Parentsinvolvedintreatment• CBTforanxietyadaptedforhigh-functioningyouthwithASD:

– Limitedlanguageandcognitiveabilities:Usevisualaids,writtenworksheets,innovativeassignments…

– Difficultieswithlearning:multiplesteps,role-play,positivereinforcement,repetition– Limitedgeneralization:Increasefrequencyofpracticing,adaptedhomework,rewardsystems– Socialdeficits:Includingsocialstories

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CBTforanxietyinhigher-functioningASD(Sukhodolsky etal,2013)

MainFindings:

• 8randomizedcontrolledstudiesofCBTforanxietywerelocated.

• CBTwassuperiortowaitlistonparentandclinician-ratedanxiety.

• Effectsizes:– Parentsratings:1.19

– Clinicianratings:1.21

– Childreports:0.68

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• 14studies;551HFA;83%males;7-17years• Intervention:60-120minlastingfrom6to32weeks;M=14.8weeks• Self-reportandparentsquestionnaires

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AnxietyinASDandID• Singlesubjectstudies• Specificfears– injections,doctors,dentists• Sensoryhypersensitivity• Behavioralapproaches:

– Systematicdesensitization– Reinforcement– Modeling– Prompting

• NoRCT

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Only4StudiesIdentified(Vasaetal.,2014)

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Medication Use Patterns in Autism• Survey of Families in Autism Society of North Carolina 1538 respondents

(Langworthy-Lam et al, 2002): – Antidepressants: 22%– Antipsychotics: 17%; Stimulants: 14%; Antiepileptic drugs: 13%– Supplements: 6%– Any med: 54%

• Psychotropic Medication Use Among Medicaid-Enrolled Children with ASD (Mandell et al., 2008):– 56% at least 1 psychotropic with 20% of 3 or more– Antipsychotics: 31%– Antidepressants: 25%– Stimulants: 22%

Schubart etal.2014

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• RCTofbuspirone,5HT1Aserotoninpartialagonist,targetingcorefeatures• ASD(2-6years);N=166;placebo/2.5mg/5mg;24weeks• NodifferenceonAutismDiagnosticObservationSchedule(ADOS)compositetotalcorescore;effectonADOSrestrictedrepetitivebehaviors(RRB)scorewith2.5mgbutnot5mg

• Decreaseintheanxietycompositescore(irritability,ABC-I)andmooddysregulation withthe2.5mgandplacebo,butnotwith5mgdose

• Overallwelltolerated

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Summary and Future Directions:

• Summary: – Cognitive-behavioral therapy is useful for

anxiety in children with ASD– Medications, specifically SSRIs, are

probably effective– Regular re-evaluation of treatment – No simple recipes– Family role

• Future directions: – Treatment protocols for lower functioning

individuals– Identification of behaviorally- and/or

biologically-defined subgroups– Combination of treatments Isurewishtherewasaformula

forpickingtherighttreatment

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