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

Opinion

San Angelo Autism ConferenceJune 2012

Autism Speaks and Others

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 Natl Acad Sci 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

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

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

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

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

• 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

Mitochondrial Disorder More Common Than Expected in ASD

Genetics• 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

2012- Half Sibling Study – parents equally sharing genetic info even tho males affected more. Washington University in Molecular Science.

???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

Sibling Studies• Ozonoff S,Iosif AM,Baguio F,Cook IC,Hill

MM,Hutman T,Rogers SJ,Rozga A,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

25 students at high risk and 25 with typical risk were studied6 month onset of differenceChanges in group were initially social communication

GI Recommendations to Medical Field• 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

More indicators that associated health issues will enter the intervention mix sleep, gut, eating, seizures, biochemical

Autism Speaks

Reseach: Ten Most Important Findings in Autism in 2009

April 15, 2010ESC 13Austin, Texas

Epidemiological Studies

– 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

Continue to increase

Impact PPCD

CDC on-going studies will likely produce yet another jump in incidence soon

CDC’s Autism and Developmental Disabilities Monitoring

• Dx 72 mo, Reliable at 24 mo.

• Do the math

Birth -3

ADOS-T

Programatic Comparison

< 30 mo.BlendedParent implementerDistance learning

ECI CollaborationOzonoff – 6 mo. onset

AAP Screen +ADOS-T +Intervention=New Opportunities

Genetic Explosion

• No consistent structural damage

• No strong transmitter evidence

• Minshew’s connectivity is strengthened

Wang, et al in NatureProcess moreFind more

Genetic Explosion

Weiss at Johns HopkinsSemaphorin 5ANeuronal development agent affects adheranceDispose of unused (plasticity and learning)

Subtypes and therapy General approach More research

Pharma and therapy

Resperidone alone and with therapyBetter results with therapy

We should expect continued employment

New attempts for pharma to get more research funding

2012 – First patent for medication to deal with Fragile X

Mouse Models

• Stanford and UT Dallas Medical – 9 studies pt to neurexin 1A• Mouse bred

around this gene• Stereotypies,

anxiety and social

Core elements/genes & models for Fragile X and tuberous sclerosis

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

Mitrochondrial Dysfunction and Autism

Hypotonia (low tone) Fatigue with activity Half also had

regressive autism and not specific to immunizations

Lethargic children with ASD anda dr. and lawyer for parents might get immunization fund money

Later Language DevelopmentLiterature 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

Specific Language Impairment and Autism

• 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 disorderDSM revision 2012 has diagnostic and medical implications: not currently educational issue.

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

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

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.

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

Recent: Possible Protein Marker

Protein marker found in some individuals. More research Genes are responsible for proteinsIf we know the function and we know the gene, the theory is we can fix the function.

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.

Earching