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:
Or call toll-free:
1-800-994-9701