AutismAutism

Virginia Beach Resort Hotel and Virginia Beach Resort Hotel and Conference Center Conference Center Virginia Beach, VA Virginia Beach, VA

7-19-117-19-11

Children’s Hospital of The King’s Daughters

CHKD

Earlier Diagnosis of AutismEarlier Diagnosis of Autism

John W Harrington MDJohn W Harrington MDAssociate Professor of PediatricsAssociate Professor of PediatricsEastern Virginia Medical SchoolEastern Virginia Medical School

Director of General Academic PediatricsDirector of General Academic PediatricsChildren’s Hospital of The King’s DaughtersChildren’s Hospital of The King’s Daughters

7-19-117-19-11

Brief OutlineBrief Outline

PrevalencePrevalenceNeurodevelopmental perspectiveNeurodevelopmental perspectiveGeneticsGeneticsScreening and DiagnosisScreening and DiagnosisDr. Hartmann segueDr. Hartmann segue

100

PREVALENCE

??

Maybe even higher

Pervasive Developmental DisordersPervasive Developmental DisordersDSM IVDSM IV

or or Autism Spectrum Autism Spectrum DisordersDisorders

1 in 1001 in 100Classic/Regressive Autism (0.2-Classic/Regressive Autism (0.2-

0.3/100)0.3/100)Asperger Disorder (0.1-0.2/100)Asperger Disorder (0.1-0.2/100)PDD – NOS (0.5-0.6/100)PDD – NOS (0.5-0.6/100)4:1 male to female (1:54 males)4:1 male to female (1:54 males)

PrevalencePrevalence Where do the numbers come Where do the numbers come

from?from?

HRSA and CDCHRSA and CDC

Kogan et al. Pediatrics November 2009

HRSA 1 in 100

Recent South Korean study on Recent South Korean study on prevalence of autismprevalence of autism

Able to do screening of all suspected Able to do screening of all suspected children with ADOS and ADIR in S. children with ADOS and ADIR in S. KoreaKorea

Reported rate at 2.4%- but this may Reported rate at 2.4%- but this may be a sampling bias (2.4 times higher)be a sampling bias (2.4 times higher)

Study had many problems, but does Study had many problems, but does highlight the importance of highlight the importance of screeningscreening and checking functioning and checking functioning

What does this mean for What does this mean for VA public schools?VA public schools?

If we use 1%If we use 1%

New Prevalence Rates New Prevalence Rates If 1% of all children in the US have an ASDIf 1% of all children in the US have an ASD

Total students in Total students in Virginia public Virginia public schools on schools on September 30, 2008September 30, 2008

1,236,5461,236,546

2008 Child Count 2008 Child Count students with Autistic students with Autistic Disorder receiving Disorder receiving special education special education services!services!

9,1369,136

Impact of New Prevalence Impact of New Prevalence Rates Rates

Projected number of Projected number of students with Autistic students with Autistic Disorders in VirginiaDisorders in Virginia

12,36512,365

Possible students Possible students not not identifiedidentified under under Autistic Disorder labelAutistic Disorder label Students receiving services Students receiving services under another label (Develop. under another label (Develop. Delay, OHI, etc)Delay, OHI, etc)Students not yet identified as Students not yet identified as having a disability and in the having a disability and in the general ed settinggeneral ed setting

3,2293,229

What drives diagnostic What drives diagnostic substitution?substitution?

Threshold for AutismThreshold for Autism

Significant Increase in DXSignificant Increase in DX

Autistic Spectrum DisorderAutistic Spectrum Disorderoror

Mental Retardation/Intellectual DisabilityMental Retardation/Intellectual Disability

Neurodevelopmental Neurodevelopmental perspective perspective

What is the brain doing and What is the brain doing and why and can this help us why and can this help us

diagnose earlier?diagnose earlier?

New FindingsNew Findings

Magnetoencephalography MEG Magnetoencephalography MEG showed children with ASD had a showed children with ASD had a 1/100 of a second delay in the brain 1/100 of a second delay in the brain response to sounds as compared to response to sounds as compared to controlscontrols

More variable in children with autism More variable in children with autism whereas normal children control whereas normal children control pitch betterpitch better

**Maybe a way to test children earlier through Maybe a way to test children earlier through some type of hearing testsome type of hearing test

Lip Lip motionmotion and and speech speech soundsound moremore interesting interesting to children to children with with autism autism than than eyeeye and and social social expressionexpression

Eye-tracking is abnormalEye-tracking is abnormal

With a split screen moving image With a split screen moving image upside down vs. upright. Children upside down vs. upright. Children with autism with autism no preference.no preference.

Mirror Neurons-Motor Neuron “Monkey see Monkey do

Understanding the intentions of others while watching their action is a fundamental building block of social behavior

Genetics and their Genetics and their interplay with the interplay with the

environment are the keyenvironment are the key

Genetic Predisposition

Environmental Factors

↑ paternal ageMultiple pregnancyPrematurityLow birth weightSSRI exposureOthers ???

Copy number variantsAnd SNP/mutations

Protective factors

PRODUCT

Genes and Autism before Genes and Autism before 20102010

90% identical twins affected 90% identical twins affected Sibling risk (Environmental/Genetic) Sibling risk (Environmental/Genetic)

2-10 % 2-10 % If 2 siblings= 8% to 25%If 2 siblings= 8% to 25%All siblings should be screened***All siblings should be screened***

Study by Hallmayer at Study by Hallmayer at Stanford Stanford

192 twins (identical 192 twins (identical and fraternal)and fraternal)

Type Type of of

twintwin

% % with with autisautis

mm

Male/Male/

FemalFemalee

IdentIdent 7777 malemale

IdentIdent 5050 femalefemale

FraterFraternn

3131 malemale

FraterFraternn

3636 femalefemale

•Only 30% determined byGenetics and 58% byEnvironment

OVERALL

Advancing GeneticsAdvancing Genetics

1990s-look at 500 base pairs and 23 1990s-look at 500 base pairs and 23 chromosomeschromosomes

2000s- look at 2-3,000 base pairs 2000s- look at 2-3,000 base pairs and deletions and duplicationsand deletions and duplications

2011- CGH arrays can now look at 7-2011- CGH arrays can now look at 7-9,000 base pairs, deletions, single 9,000 base pairs, deletions, single nucleotide polymorphisms, and copy nucleotide polymorphisms, and copy number variantsnumber variants

Figure 1.   Genetic variation may influence neurobiological endophenotypes (potential examples

shown), which predispose to neurodevelopmental and neuropsychiatric disease.

DSM VDSM Vor or Autistic DisordersAutistic Disorders

Aspergers

PDD-NOS/HFA

Classic/Regressive

NVLDADHD

Emotional Disorder

Schizophrenia

BipolarAnxiety Disorder

MR/DD

Seizures

Depression

Earliest Diagnosis?Earliest Diagnosis?

CAN AUTISM BE CAN AUTISM BE DIAGNOSED BEFORE AGE DIAGNOSED BEFORE AGE

6 MONTHS?6 MONTHS?

NOT YET CLINICALLY!NOT YET CLINICALLY!

Sally Ozonoff in CA (sibling study)Sally Ozonoff in CA (sibling study)No symptoms in 25 children before 6 No symptoms in 25 children before 6

months who later were diagnosed with months who later were diagnosed with autismautism

From 6-12 months gradual decline in From 6-12 months gradual decline in social responsivenesssocial responsiveness

Parental report in decline was wrong 83% Parental report in decline was wrong 83% of the timeof the time

Can’t really do parental screen before Can’t really do parental screen before age 1age 1

Average age of final diagnosis in Average age of final diagnosis in US for ASD in 2009US for ASD in 2009

3.1 years for classic autism (VA 5-6 3.1 years for classic autism (VA 5-6 yrs)yrs)

3.9 years for PDD-NOS (VA 6-7 years)3.9 years for PDD-NOS (VA 6-7 years)

7.2 years for Aspergers (VA 9 years)7.2 years for Aspergers (VA 9 years)

Autism Screening TestsAutism Screening Tests

Level 1 (primary care office)Level 1 (primary care office)

M-CHAT M-CHAT or modified checklist or modified checklist for autism in toddlersfor autism in toddlers

Sample questions from M-Sample questions from M-CHATCHAT

Does your child take an interest in Does your child take an interest in other children?other children?

Does your child ever bring objects Does your child ever bring objects over to you (parent) to show you over to you (parent) to show you something?something?

Does your child respond to his/her Does your child respond to his/her name when you call?name when you call?

***“protodeclarative pointing” and ***“protodeclarative pointing” and ‘hand guiding’‘hand guiding’

MCHATMCHAT

Sensitivity and Specificity variable by Sensitivity and Specificity variable by provider and by populationsprovider and by populations

Need to do regular developmental Need to do regular developmental screening and autism specific screening and autism specific screeningscreening

If the MCHAT is positive the screener If the MCHAT is positive the screener should do an MCHAT interview should do an MCHAT interview questionnaire. questionnaire.

www.m-chat.orgwww.m-chat.org

Higher level Autism TestingHigher level Autism Testing

Level 2 (EI, developmental, Level 2 (EI, developmental, neurodevelop, or autism diagnostic neurodevelop, or autism diagnostic clinic/center)clinic/center)ABC- Autism Behavioral ChecklistABC- Autism Behavioral ChecklistCARS- Childhood Autism Rating ScaleCARS- Childhood Autism Rating ScaleADOS-Autism Diagnostic ADOS-Autism Diagnostic

Observation ScaleObservation ScaleADIR-Autism Diagnostic Interview-ADIR-Autism Diagnostic Interview-

RevisedRevised

CasesCases

21 month old male with positive M-CHAT sees 21 month old male with positive M-CHAT sees speech therapist who does no formal testing, speech therapist who does no formal testing, but states child has eye-contact. She reports but states child has eye-contact. She reports unlikley autism. Child is later tested by unlikley autism. Child is later tested by psychologist who does ADOS and ADIR.psychologist who does ADOS and ADIR.

7 year old tested at age 5 by school 7 year old tested at age 5 by school psychologist who does less specific autism psychologist who does less specific autism screen that places child just outside autism screen that places child just outside autism range. Child tested with ADOS and ADIR by range. Child tested with ADOS and ADIR by Neurodevelopmentalist and Psychiatrist 2 Neurodevelopmentalist and Psychiatrist 2 years later, but school will not change OHI years later, but school will not change OHI classification to autism. classification to autism.