Autism in 2011 Current Advancements & Future Directions

Autism in 2011Autism in 2011Current Current

Advancements & Advancements & Future DirectionsFuture Directions

Raphael Bernier, Ph.D.Raphael Bernier, Ph.D.Beau Reilly, Ph.D.Beau Reilly, Ph.D.

University of Washington Autism CenterUniversity of Washington Autism CenterJanuary 20January 20thth 2011 2011

Autism in 2011Autism in 2011OverviewOverview

EtiologyEtiology

NeuroscienceNeuroscience

DiagnosisDiagnosis

Early DetectionEarly Detection

InterventionIntervention

What We Know About What We Know About AutismAutism

Autism is a neurobiological disorder.

Autism is characterized by impairments in social communication and repetitive/restricted interests & behaviors.

Affects boys 3-4 more times than girls.

Autism is found in all social classes and in all racial/ethnic groups.

Autism might be better termed AUTISMS, not AUTISM.

There are no genetic or biological tests to diagnose autism.

Behaviorally based interventions are effective at improving outcomes.

Autism has a strong genetic component.

EtiologyEtiologyGenetic collaborations Genetic collaborations

Genotype leading the phenotypeGenotype leading the phenotype

Longitudinal environmental investigationsLongitudinal environmental investigations

EpigeneticsEpigenetics

Etiology: GeneticsEtiology: Genetics

We know the genetic cause in ~20% of individuals We know the genetic cause in ~20% of individuals diagnosed with ASD diagnosed with ASD

Result of known genetic disorder (e.g., Fragile X) or chromosomal abnormality (each only accounts for no more than ~1% of cases).

Two different theories: common variant vs rare variant models

These two different theories are not mutually exclusive

Simons Simplex Collection (SSC) is a core project and Simons Simplex Collection (SSC) is a core project and resource of the Simons Foundation Autism Research resource of the Simons Foundation Autism Research Initiative (SFARI). Initiative (SFARI).

Using identified “genomic hotspots,” we search for Copy Number Variations at specific locations in the genome.

We then explore in depth the outcome of that CNV on behavior.

One of the most common single One of the most common single genetic events is a deletion/duplication genetic events is a deletion/duplication of 16p11.2 (~1-2%)of 16p11.2 (~1-2%)

Simons Variation in Individuals Project Simons Variation in Individuals Project

(S-VIP)(S-VIP)

Etiology: Etiology: GeneticsGenetics

Etiology: Etiology: EnvironmentEnvironment

Identified Environmental Risk Factors:Identified Environmental Risk Factors:Birth complicationsBirth complicationsPaternal and Maternal agePaternal and Maternal ageExternal exposure of developing brain to: External exposure of developing brain to:

LeadLeadMethyl AlcoholMethyl Alcohol

Exposures in Early PregnancyExposures in Early PregnancyThalidomideThalidomideMisoprostol (Anti-Inflammatory Misoprostol (Anti-Inflammatory Medication)Medication)Maternal Rubella InfectionMaternal Rubella InfectionChlorpyrifos (Insectiside)Chlorpyrifos (Insectiside)

Childhood Autism Risk from Genetics & the Childhood Autism Risk from Genetics & the Environment (CHARGE) Study was launched in Environment (CHARGE) Study was launched in 2003 as a study of 1,000 to 2,000 children with 2003 as a study of 1,000 to 2,000 children with differing patterns of development. differing patterns of development.

Proximity to freeways and likelihood of AutismProximity to freeways and likelihood of Autism

Etiology: Etiology: EpigeneticsEpigeneticsThe study of factors that change the way genes express The study of factors that change the way genes express

themselves without changing the DNA itself.themselves without changing the DNA itself.

Valproate during pregnancyValproate during pregnancy

Maternal duplications on chromosome 15q11-13Maternal duplications on chromosome 15q11-13

EtiologyEtiologyGenetic collaborations Genetic collaborations

Genotype leading the phenotypeGenotype leading the phenotype

Longitudinal environmental investigationsLongitudinal environmental investigations

EpigeneticsEpigenetics

NeuroscienceNeuroscienceAutism is a neurodevelopmental disorder (based in the brain) marked by social communication impairments.

Specific regions of the brain are structurally different or functioning differently from children with typical development

Social Brain Circuitry Implicated in ASD

Medial Prefrontal Cortex(Dawson et al, 1998)Medial Prefrontal Cortex(Dawson et al, 1998)

Superior Temporal Sulcus (Pelphrey &Carter, 2008)

Superior Temporal Sulcus (Pelphrey &Carter, 2008)

Mirror Neuron System(Dapretto et al, 2006)Mirror Neuron System(Dapretto et al, 2006)

Anterior Cingulate (Mundy, 2003)Anterior Cingulate (Mundy, 2003)

Amygdala(Baron-Cohen et al, 2000)Amygdala(Baron-Cohen et al, 2000)

Cerebellum(Courchesne, 1997Cerebellum(Courchesne, 1997

Hippocampus(Bauman & Kemper, 2005)Hippocampus(Bauman & Kemper, 2005)

Fusiform Gyrus(Schultz et al, 2000)Fusiform Gyrus(Schultz et al, 2000)

NeuroscienceNeuroscienceKaiser et al. 2010 – YaleKaiser et al. 2010 – Yale

Compared fMRI brain Compared fMRI brain responses to biological responses to biological motion using scrambled motion using scrambled and coherent point and coherent point light motionlight motion

Children with ASDChildren with ASD

Unaffected siblingsUnaffected siblings

Typically developing Typically developing childrenchildren

3 Kinds of brain activity3 Kinds of brain activityStateState

TraitTrait

CompensatoryCompensatory

Coherent

Scrambled

Video source http://www.psy.vanderbilt.edu/faculty/blake/BM/BioMot.html

Mirror Neuron System

Mirror neurons activate in response to the execution AND observation of actions.

Proposed to subserve action understanding, imitation, empathy, theory of mind, understanding of metaphor, even evolution of language.

Research suggests this system is impaired in autism.

(from Ramachandran & Oberman, 2006)

DiagnosisDiagnosisAutism diagnosed by presence or Autism diagnosed by presence or absence of behaviors in 3 domains: absence of behaviors in 3 domains:

SocialSocial

CommunicationCommunication

Restricted/Repetitive Interests & Restricted/Repetitive Interests & BehaviorsBehaviors

Checklist of symptoms by experienced Checklist of symptoms by experienced clinicianclinician

Diagnostic Criteria are changingDiagnostic Criteria are changing

DiagnosisDiagnosisThree domains will now become two: Three domains will now become two:

Autistic Disorder Autism Spectrum Disorder

Evidence for Change

Evidence for Change

Site

Per

cent

age

Evidence for Change

Age (years)

detect - diagnose

intervene

0 1 2 3

deve

lopm

ent

(Adapted Schellenberg, 2008)

Early DetectionEarly Detection

early detection

early intervention

better outcome?

Age (Years)

intervene

0 1 2 3

deve

lopm

ent

detect - diagnose

(Adapted Schellenberg, 2008)

Early DetectionEarly Detection

Early DetectionEarly DetectionUCSDUCSD

Eyler, Courchesne, & Eyler, Courchesne, & PiercePierce

Monitored brain activity Monitored brain activity of sleeping children with of sleeping children with ASD and typically ASD and typically developing controls developing controls during fMRI.during fMRI.

Read stories inside Read stories inside machine while sleepingmachine while sleeping

Expect more use of this Expect more use of this technology in 2011.technology in 2011.

Interventions for Autism Spectrum Disorders

InterventionInterventionDawson et al. 2010: The Dawson et al. 2010: The Early Start Denver ModelEarly Start Denver Model

First randomized, First randomized, controlled trial of controlled trial of intervention for toddlers intervention for toddlers with autismwith autism

Developmental Developmental psychology & applied psychology & applied behavior analysisbehavior analysis

Play-basedPlay-basedRelationship focusedRelationship focused

Significant Significant improvementsimprovements

IQIQ Adaptive BehaviorAdaptive BehaviorAutism SeverityAutism Severity

Intervention in Intervention in 20112011

Parent focused intervention

Intervention for at risk siblings (prevention)

Examination/evaluation of CAMExamination/evaluation of CAM

Use of technology in intervention

Further examination into cultural variables and influences on the factors of ASD

Diagnosis

Acceptance

Treatment

For more information about ongoing

studies:Visit the UWAC website:

http://depts.washington.edu/uwautism/

Email Kara Haney:

[email protected]

Or call toll-free:

1-800-994-9701