The 20 Most Important Research Events in the Last Few Years Related to Autism – In My Opinion

1. The 20 Most Important Research Events in the Last Few Years Related to Autism – In My Opinion San Angelo Autism Conference June 2012 Autism Speaks and Others

2. Autism Screening/Language Development Oller DK, Niyogi P, Gray S, Richards JA, Gilkerson J, Xu D, Yapanel U, Warren SF. (2010) Automated vocal analysis of naturalistic recordings from children with autism, language delay, and typical development. Proc NatlAcadSci U S A. Jul 27;107(30):13354-9. Epub PMID: 20643944 1,486 all-day recordings, from 232 children with more than 3.1 million child vocalizations Distinguish vocalization patterns between au and nt Replicate Forming syllables best predictor Some distinction between au and general language delay

3. Joint Attention Training Successful Kasari C, Gulsrud AC, Wong C, Kwon S, Locke J. (2010) Randomized controlled caregiver mediated joint engagement intervention for toddlers with autism. J Autism Dev Disord. Sep;40(9):1045-56 Joint attention can be taught and instruction makes a difference Thirty-eight caregivers and their toddlers with autism who were 21-36 months of age were randomly assigned to either the treatment group or a waitlist control group – 8 wk intervention Maintained one year after treatment Random assigned – substantial number of subjects ECI intervention - parent directed - matches Tx. Model some what

4. Prematurity a Risk Factor 5 Studies followed preemies for several years Found that autism was one of several disorders found in the groups followed. Studies reviewed subjects from 4 to 14 and found a variety of issues with au being one of them Replication and additional information might lead to more information

5. Rhett Gene Causes Reduced Inhibition in Neurons Chao HT, Chen H, Samaco RC, Xue M, Chahrour M, Yoo J, Neul JL, Gong S, Lu HC, Heintz N, Ekker M, Rubenstein JL, Noebels JL, Rosenmund C, Zoghbi HY. (2010) Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature. Nov 11;468(7321):263-9. Found imbalance between substance that provides correct balance between excitation and inhibition. Mice models that ‘created’ and reversed Rhett’s Second wave of information that is drilling into genetics role in ASD. Rhett’s will be eliminated in DSM-V

6. Enhanced Imagining May Point to Another Screening Tool Ecker C, Marquand A, Mourão-Miranda J, Johnston P, Daly EM, Brammer MJ, Maltezos S, Murphy CM, Robertson D, Williams SC, Murphy DG. (2010) Describing the brain in autism in five dimensions--magnetic resonance imaging-assisted diagnosis of autism spectrum disorder using a multiparameter classification approach. J Neurosci. Aug 11;30(32):10612-23 Variety of differences MAY be predictor (Still the chicken or egg) If substantiated, may lead to additional tool for screening – medicine looking for proof This is relatively short procedure, but is more structure than function

7. Mitochondrial Disorder More Common Than Expected in ASD Giulivi C, Zhang YF, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, Tassone F, Pessah IN. (2010) Mitochondrial dysfunction in autism. JAMA. Dec 1;304(21):2389-96 Supports last years; studies and claims higher incidence Used less invasive technique Claims higher incidence Needs replication and substantiation May be subtype

8. Genetics 2012- Half Sibling Study – parents equally sharing genetic info even tho males affected more. Washington University in Molecular Science. Pinto D, Pagnamenta, etal. (2010)Functional impact of global rare copy number variation in autism spectrum disorders.Nature. Jul 15;466(7304):368-72 (CNVs) copy number variants, rare tiny insertions and deletions in the genome, which appear to disrupt more genes in individuals with autism than in the general population Some cause autism, some increase risk and some are not even found in parents. Does this mean we can reverse - time will tell along with lots of money and additional research If true, what is happening to cause increase CNV and the variants not found in parents - environment

10. ???Neurons from Skin Cells??? Three studies cited In 2010, researchers developed stem cells from living skin of individual with autism and caused them to form neurons using the DNA of a living person We can study what the DNA has made in the individual and study what is going on in a lab rather than the body Stem cells are self renewing and multifunctional – with the right information (proteins) they should be able to regenerate whatever. No need for fetus if this is true

11. Sibling Studies 25 students at high risk and 25 with typical risk were studied 6 month onset of difference Changes in group were initially social communication OzonoffS,IosifAM,BaguioF,CookIC,HillMM,HutmanT,RogersSJ,RozgaA,Sangha S, Sigman M, Steinfeld MB, Young GS. (2010) A prospective study of the emergence of early behavioral signs of autism.J Am Acad Child Adolesc Psychiatry. Mar;49(3):256-66.e1-2 Close careful observation of siblings of individuals with ASD Increased chances of additional autism in subsequent siblings once one is diagnosed Find au markers 6-12 months, such as looking, vocalizing, and smiling Also working on Infant ESDM Screening, diagnosis, intervention

12. GI Recommendations to Medical Field More indicators that associated health issues will enter the intervention mix Two studies cited While not clearly documented, there is consensus statement for pediatricians to evaluate GI with ASD What is going on How does it make autism worse Develop effective treatments Research, Funding, Research, Funding Same issue with Sensory Processing, but not a focus of Autism Speaks so not on the radar sleep, gut, eating, seizures, biochemical

13. Reseach: Ten Most Important Findings in Autism in 2009 Autism Speaks April 15, 2010 ESC 13 Austin, Texas

14. Epidemiological Studies Continue to increase Impact PPCD CDC on-going studies will likely produce yet another jump in incidence soon • Pediatrics - Incidence – 1/100 • Calif. 25% Changed diagnosis +environment+ maternal age -New is 1/88 and in Utah and New Jersey with boys 1/24

15. CDC’s Autism and Developmental Disabilities Monitoring ADOS-T Birth -3 Dx 72 mo, Reliable at 24 mo. Do the math

16. Programatic Comparison AAP Screen +ADOS-T +Intervention=New Opportunities < 30 mo. Blended Parent implementer Distance learning ECI Collaboration Ozonoff – 6 mo. onset

17. Genetic Explosion Wang, et al in Nature Process more Find more No consistent structural damage No strong transmitter evidence Minshew’s connectivity is strengthened

18. Genetic Explosion Weiss at Johns Hopkins Semaphorin 5A Neuronal development agent affects adherance Dispose of unused (plasticity and learning) Subtypes and therapy General approach More research

19. Pharma and therapy 2012 – First patent for medication to deal with Fragile X Resperidone alone and with therapy Better results with therapy We should expect continued employment New attempts for pharma to get more research funding

20. Mouse Models Core elements/genes & models for Fragile X and tuberous sclerosis • Stanford and UT Dallas Medical – 9 studies pt to neurexin 1A • Mouse bred around this gene • Stereotypies, anxiety and social

21. Mitochrondrial Dysfunction: Autistic Regression and Fever Mitochrondria = cellular energy production (metabolism) Closely tuned to environment Atlanta group is proposing a subpop of autism and mitorchrondrial disease

22. Mitrochondrial Dysfunction and Autism Lethargic children with ASD anda dr. and lawyer for parents might get immunization fund money Hypotonia (low tone) Fatigue with activity Half also had regressive autism and not specific to immunizations

23. Later Language Development Literature review: 167 instances of verbal language developing after 5 years of age Similarities: Language based interventions Traditional or naturalistic ABA during elementary Intensity from 30 min – 30 houirs/wk PECS, Computer Based Interventions, speech therapy NT track for development

24. Specific Language Impairment and Autism DSM revision 2012 has diagnostic and medical implications: not currently educational issue. UK study just beyond criteria for Au /deaf/general dvmp delay Onset of lang. loss was different -au dev early then lost, SLI dev later then lost Lang dev regressive NLD? Nonverbal language disorder

25. LEAP • Results gained in about 17 hours of intensive instruction per week (less than half of Lovaas study – effective and efficient) • LEAP on cutting edge • Fully inclusive setting for all children with ASD • Peers are strong element in all elements of instruction • Avoid the 1:1 adult driven instructional format

26. LEAP • Eight elements • Classroom organization and planning • Instructional strategies • Communication Issues • Social Issues • Behavior Issues • IEP and Measurement of Progress • Impact on children • Impact on adults

27. LEAP • General strategies used in most classrooms • PMII (peers are very important piece of the program • Errorless learning with associated elements (time delay, incidental teaching, etc) • Pivotal Response Training • Picture Exchange Communication System if needed • Communication Function Based FBAs with social behavior connection.

28. LEAP • Questions to answer • Do different children have different outcomes after two years of program • Is fidelity of implementation an issue in outcomes • Is baseline a predictor of final outcomes • Does the program have social validity

29. Recent: Possible Protein Marker Protein marker found in some individuals. More research Genes are responsible for proteins If we know the function and we know the gene, the theory is we can fix the function.

30. Cholesterol Models • 80 years of research from identifying cholesterol as a strong factor in heart attacks • To development of statins to reduce cholesterol buildup in the circulatory system. • It takes time – unfortunately it often takes generations.

36. Earching