anxiety in autism spectrum disorder - amazon web...
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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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Questions?