Autism in 2011 Current Advancements & Future Directions

1. Autism in 2011Current Advancements & Future Directions Raphael Bernier, Ph.D. Beau Reilly, Ph.D. University of Washington Autism Center January 20th 2011

2. Autism in 2011 • Overview • Etiology • Neuroscience • Diagnosis • Early Detection • Intervention

3. 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.

4. Etiology • Genetic collaborations • Genotype leading the phenotype • Longitudinal environmental investigations • Epigenetics

5. 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).

6. Etiology: Genetics • 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)

7. Etiology: Environment • Identified Environmental Risk Factors: • Birth complications • Paternal and Maternal age • External exposure of developing brain to: • Lead • Methyl Alcohol • Exposures in Early Pregnancy • Thalidomide • Misoprostol (Anti-Inflammatory Medication) • Maternal Rubella Infection • Chlorpyrifos (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

8. Etiology: Epigenetics • The study of factors that change the way genes express themselves without changing the DNA itself. • Valproate during pregnancy • Maternal duplications on chromosome 15q11-13

9. Etiology • Genetic collaborations • Genotype leading the phenotype • Longitudinal environmental investigations • Epigenetics

10. Autism 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 Neuroscience

11. Social Brain Circuitry Implicated in ASD Anterior Cingulate (Mundy, 2003) Hippocampus (Bauman & Kemper, 2005) Superior Temporal Sulcus (Pelphrey & Carter, 2008) Medial Prefrontal Cortex (Dawson et al, 1998) FusiformGyrus (Schultz et al, 2000) Amygdala (Baron-Cohen et al, 2000) Mirror Neuron System (Dapretto et al, 2006) Cerebellum (Courchesne, 1997

12. Neuroscience • Kaiser 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

13. 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)

14. Diagnosis • Autism 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

15. Diagnosis Autism Spectrum Disorder Autistic Disorder Three domains will now become two:

16. Evidence for Change

17. Evidence for Change

18. Evidence for Change Percentage Site

19. Early Detection development intervene detect - diagnose 0 1 2 3 Age (years) (Adapted Schellenberg, 2008)

20. intervene Early Detection early detection development early intervention better outcome? detect - diagnose 0 1 2 3 Age (Years) (Adapted Schellenberg, 2008)

21. Early Detection • UCSD • 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.

22. Interventions for Autism Spectrum Disorders PSYCHO-EDUCATIONAL Standard ART THERAPY MUSIC THERAPY PLAY THERAPY OCCUPATIONAL THERAPY SPEECH THERAPY PROMPT SPEECH THERAPY PHYSICAL THERAPY Behavioral Interventions EARLY START DENVER MODEL PIVOTAL RESPONSE TRAINING DISCRETE TRIAL TRAINING SOCIAL STORIES SOCIAL SKILLS TRAINING SOCIAL GROUPS INTEGRATED PLAY THERAPY Educational and Integrated Services TEACCH DAILY LIFE THERAPY Technology based VIDEO MODELING Alternative and Augmentative Communication VISUAL SCHEDULES PICTURE EXCHANGE COMMUNICATION SYSTEM (PECS) COMPLEMENTARY Animal based CANINE COMPANION DOLPHIN THERAPY HIPPO THERAPY THERAPEUTIC HORSEBACK RIDING Spirituality based PRAYER ENERGY HEALING Diets and Supplements DIETARY INTERVENTION (E.G. GLUTEN-FREE, CASEIN-FREE DIET (GFCF DIET); YEAST FREE; KETOGENIC) HOMEOPATHY IMMUNOTHERAPY VITAMIN THERAPY SECRETIN MELATONIN Medical Procedures CHELATION HYPERBARIC OXYGEN THERAPY ELECTROCONVULSIVE THERAPY Relationship-based Interventions FLOORTIME SON-RISE TREATMENT GENTLE TEACHING HOLDING THERAPY RELATIONSHIP DEVELOPMENT INTERVENTION PEER MENTORING Integrated Interventions LINWOOD METHOD SCERTS MODEL COMPLEMENTARY Continued Physiological Interventions CHIROPRACTIC CRANIO-SACRAL THERAPY ACUPUNCTURE AND ACUPRESSURE YOGA THERAPEUTIC MASSAGE PATTERNING THERAPIES MILLER METHOD AUDITORY INTEGRATION THERAPY RHYTHMIC ENTRAINMENT INTERVENTION SAMONAS SENSORY INTEGRATION THERAPY TOMATIS METHOD VISION THERAPY IRLEN LENS SYSTEM BIOFEEDBACK AND NEUROFEEDBACK AQUATIC THERAPY Technology based ASSISTIVE TECHNOLOGY TEACHTOWN FAST FORWORD ONLINE COMMUNITIES Alternative and Augmentative Communication FACILITATED COMMUNICATION RAPID PROMPTING PSYCHO-PHARMACOLOGICAL PHARMACOLOGICAL INTERVENTIONS: Including: Anti-convulsants; Anti-depressants; Anti-fungals; Anti-hypertensives; Anti-psychotics; Anxiolytics; Mood stabilizers; Sedatives; Stimulants; among others.

23. Intervention • Dawson et al. 2010: The Early Start Denver Model • First randomized, controlled trial of intervention for toddlers with autism • Developmental psychology & applied behavior analysis • Play-based • Relationship focused • Significant improvements • IQ • Adaptive Behavior • Autism Severity

24. 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

25. 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