Autism in 2011Current

Advancements & Future Directions

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

University of Washington Autism CenterJanuary 20th 2011

Autism in 2011Overview

Etiology

Neuroscience

Diagnosis

Early Detection

Intervention

What We Know About Autism

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.

EtiologyGenetic collaborations

Genotype leading the phenotype

Longitudinal environmental investigations

Epigenetics

Etiology: Genetics

We know the genetic cause in ~20% of individuals 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 resource of the Simons Foundation Autism Research 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 genetic events is a deletion/duplication of 16p11.2 (~1-2%)

Simons Variation in Individuals Project

(S-VIP)

Etiology: Genetics

Copy Number Variations

Genomic Hotspots

Chromosomes

Etiology: Environment

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

LeadMethyl Alcohol

Exposures in Early PregnancyThalidomideMisoprostol (Anti-Inflammatory Medication)Maternal Rubella InfectionChlorpyrifos (Insectiside)

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

Proximity to freeways and likelihood of Autism

Etiology: EpigeneticsThe study of factors that change the way genes express

themselves without changing the DNA itself.

Valproate during pregnancy

Maternal duplications on chromosome 15q11-13

Valproate taken during pregnancy

Inhibits histone deacetylase

Increased expression of multiple genes

Altered activations in Hippocampus

Greater risk for child with ASD

EtiologyGenetic collaborations

Genotype leading the phenotype

Longitudinal environmental investigations

Epigenetics

NeuroscienceAutism 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)

NeuroscienceKaiser et al. 2010 – Yale

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

Children with ASD

Unaffected siblings

Typically developing children

3 Kinds of brain activity

State

Trait

Compensatory

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)

DiagnosisAutism diagnosed by presence or absence of behaviors in 3 domains:

Social

Communication

Restricted/Repetitive Interests & Behaviors

Checklist of symptoms by experienced clinician

Diagnostic Criteria are changing

DiagnosisThree domains will now become two:

Social & Communicati

on Deficits

Fixated Interests & Repetitive Behaviors

Social Interaction

Communication

Stereotyped Interests

Autistic Disorder Autism Spectrum Disorder

Evidence for Change

Evidence for Change

1 2 3 4 5 6 7 8 9 10 110

20

40

60

80

100

120

Asperger'sPDD-NOSAutism

Site

Per

cent

age

Evidence for Change

Age (years)

detect - diagnose

intervene

0 1 2 3

deve

lopm

ent

(Adapted Schellenberg, 2008)

Early Detection

early detection

early intervention

better outcome?

Age (Years)

intervene

0 1 2 3

deve

lopm

ent

detect - diagnose

(Adapted Schellenberg, 2008)

Early Detection

Early DetectionUCSD

Eyler, Courchesne, & Pierce

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

Read stories inside machine while sleeping

Expect more use of this technology in 2011.

Interventions for Autism Spectrum Disorders

PSYCHO-EDUCATIONALStandardART THERAPYMUSIC THERAPYPLAY THERAPYOCCUPATIONAL THERAPYSPEECH THERAPYPROMPT SPEECH THERAPYPHYSICAL THERAPYBehavioral InterventionsEARLY START DENVER MODELPIVOTAL RESPONSE TRAININGDISCRETE TRIAL TRAININGSOCIAL STORIESSOCIAL SKILLS TRAININGSOCIAL GROUPSINTEGRATED PLAY THERAPYEducational and Integrated ServicesTEACCHDAILY LIFE THERAPYTechnology basedVIDEO MODELINGAlternative and Augmentative CommunicationVISUAL SCHEDULESPICTURE EXCHANGE COMMUNICATION SYSTEM (PECS)

COMPLEMENTARYAnimal basedCANINE COMPANIONDOLPHIN THERAPYHIPPO THERAPYTHERAPEUTIC HORSEBACK RIDINGSpirituality basedPRAYERENERGY HEALINGDiets and SupplementsDIETARY INTERVENTION (E.G. GLUTEN-FREE, CASEIN-FREE DIET (GFCF DIET); YEAST FREE; KETOGENIC)HOMEOPATHYIMMUNOTHERAPYVITAMIN THERAPYSECRETINMELATONINMedical ProceduresCHELATIONHYPERBARIC OXYGEN THERAPYELECTROCONVULSIVE THERAPYRelationship-based InterventionsFLOORTIMESON-RISE TREATMENTGENTLE TEACHINGHOLDING THERAPYRELATIONSHIP DEVELOPMENT INTERVENTIONPEER MENTORINGIntegrated InterventionsLINWOOD METHODSCERTS MODEL

COMPLEMENTARY ContinuedPhysiological InterventionsCHIROPRACTICCRANIO-SACRAL THERAPYACUPUNCTURE AND ACUPRESSUREYOGATHERAPEUTIC MASSAGEPATTERNING THERAPIESMILLER METHODAUDITORY INTEGRATION THERAPYRHYTHMIC ENTRAINMENT INTERVENTIONSAMONASSENSORY INTEGRATION THERAPYTOMATIS METHODVISION THERAPYIRLEN LENS SYSTEMBIOFEEDBACK AND NEUROFEEDBACKAQUATIC THERAPYTechnology basedASSISTIVE TECHNOLOGYTEACHTOWNFAST FORWORDONLINE COMMUNITIESAlternative and Augmentative CommunicationFACILITATED COMMUNICATIONRAPID PROMPTING

PSYCHO-PHARMACOLOGICALPHARMACOLOGICAL INTERVENTIONS: Including: Anti-convulsants; Anti-depressants; Anti-fungals; Anti-hypertensives; Anti-psychotics; Anxiolytics; Mood stabilizers; Sedatives; Stimulants; among others.

InterventionDawson et al. 2010: The Early Start Denver Model

First randomized, controlled trial of intervention for toddlers with autism

Developmental psychology & applied behavior analysis

Play-basedRelationship focused

Significant improvements

IQ Adaptive BehaviorAutism Severity

Intervention in 2011

Parent focused intervention

Intervention for at risk siblings (prevention)

Examination/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:

karalh@uw.edu

Or call toll-free:

1-800-994-9701