[PPT] - Disclosures Siblings of Children with I have nothing to disclose. PowerPoint Presentation

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Siblings of Children with Autism

And Other Select Research Topics from the UC Davis MIND Institute UCSF Developmental Disabilities Symposium March 9, 2018 Meghan Miller, Ph.D. Assistant Professor UC Davis MIND Institute

I have nothing to disclose.

Disclosures

MIND Institute activities
Early detection of ASD in younger siblings
Long-term outcomes of siblings of

children with ASD

– School-age – Adulthood

Questions

Overview MIND Institute Activities

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Founded by 6 families
Research and assessment

clinic opened in 1998

MIND Institute complex

completed in 2003

MIND scientists currently

conducting 60+ funded research projects

MIND Institute

Boys with ASD who experience regression

display increased brain size

Folic acid taken preconception/prenatally

can decrease ASD risk, especially in women who are poor metabolizers of folate

Animal models of neurodevelopmental

disorders

Early markers of, and effective early

interventions for, ASD

Recent scientific achievements

PI: David Amaral, Ph.D.
Focus on 2 subgroups:

– ASD + anxiety: Identification, CBT+SSRI, neuroimaging and response to treatment – ASD + enlarged brains: Determine which brain systems are most affected; use induced pluripotent stem cells to grow neurons and identify genetic alterations that may be related to enlarged brains

Autism Centers of Excellence

S

ite PI: Aubyn S tahmer, Ph.D.

Adequate evidence that screening detects

autism

Harm from screening likely to be small
BUT…inadequate evidence of benefits

(US PS TF) – Lack of treatment studies in screen- detected cases – Overall limitations to treatment research

Autism Centers of Excellence

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Autism Centers of Excellence Autism Centers of Excellence

Universal, S tandardized, High-Fidelity S creening S creen ALL children at 18 month check-up S creen the S AME WAY for all using study procedures Avoid common errors Encourage ALL screen positive families to attend evaluation

Autism Centers of Excellence

After Positive S creen or Provider Concerns:

Diagnostic report
Community referrals for treatment if not

ASD

No cost evaluation No cost evaluation

Early Start Denver Model
20 hours/week, 1-on-1
Parent coaching twice a month

If ASD: 1 year intensive treatment If ASD: 1 year intensive treatment

Recommendations for community

treatment after study treatment ends

Post-evaluations to chart progress Post-evaluations to chart progress

Assessment and

Diagnostic Clinic

Social Skills Training

Program for ASD

ADHD Program for

Children and Adults

Fragile X Research and

Treatment Clinic

Clinics

High-Risk Infant Follow-Up Clinic
Early Start Denver Model

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Centers for Excellence in Developmental

Disabilities (CEDD)

Autism Research Training Program (ART P)
Leadership Education in

Neurodevelopmental Disorders (LEND)

Developmental & Behavioral Pediatrics

Education and Outreach Early detection of ASD

Early identification 

early treatment  improved outcomes

Decrease service

utilization, economic burden

Challenges: false

positives, unnecessary treatment

Early detection and diagnosis: Why?

Infancy/early childhood: Ideal period in

which to investigate phenomenology of childhood disorders

– Improve accurate, earlier detection – Identify critical time points/domains to be targeted by intervention/prevention efforts – Investigate environmental/contextual and biological causal mechanisms

Turning back the clock

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High-risk infant Low-risk infant Affected sibling Unaffected sibling

Early identification: How?

6 Months 9 Months 18 Months 24 Months 36 Months 12 Months 15 Months School- age

… Variety of eye tracking, behavioral, developmental, symptom measures Diagnostic

utcomes

determined

Infant sibling design

Recurrence risk
Patterns of onset
Early behavioral and biological markers
Targets for intervention and prevention

What can we learn from infant siblings?

Previously thought to be 3-10%
More recently: 18.7% recurrence risk

Recurrence risk

Ozonoff et al. (2011), Pediatrics

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Social Communication

Eye gaze
Vocalizations
Social smiles
Response to name

Early behavioral markers of ASD

Ozonoff et al. (2010), JAACAP

Emergence of social communication behaviors

Response to name

Names as social cues for orienting to

salient aspects of environment

Diminished response to name consistently

identified by 12 months via retrospective

r paper-pencil measures
Little known regarding developmental

progressions; direct assessment (vs. parent report)

Miller et al. (2017), Journal of Pediatrics 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 6 9 12 15 18 24 Percent receiving failing score Age (months) Low-Risk Non-ASD High-Risk Non-ASD ASD

* ** ** ** **

Response to name

Response to

name probe from AOSI

Name called up

to 2x per trial (2 trials)

Failure = no

response on any trial

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Lack of appropriate gaze
Lack of warm, joyful

expressions with gaze

Lack of sharing enjoyment
r interests
Lack of alternating to-

and-fro vocalizations with parents

Lack of response to name
Delayed onset of

babbling past 9 mo

Decreased or absent use
f pre-speech gestures

(waving, pointing, showing)

No single words by 16 mos
No two-word utterances

by 24 mos

Repetitive movements or

posturing of body, arms, hands, or fingers

Loss of language or social

skills at any age

(Dawson et al., 2000; Landa et al., 2013; Osterling & Dawson, 1994; Osterling et al., 2002; Ozonoff et al., 2008; Ozonoff et al., 2010; Ozonoff et al. 2011; Werner & Dawson, 2005; Werner et al., 2000; Zwaigenbaum et al., 2005)

Red flags for ASD in the first years

Broader autism phenotype; other

developmental concerns

Ozonoff et al. (2014), JAACAP

What about everyone else? Long-term outcomes of siblings of children with ASD School-age

80% of younger siblings of children with

ASD do not develop autism

BUT… ～35% develop other, non-ASD

concerns by school-age

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Miller et al. (2016), Autism Research

6-8 years 8-11 years

School-age School-age/adolescence

Follow-up between 12-15 years ongoing

(PI: Ozonoff)

– Psychopathology: ADHD, anxiety, mood – Academic functioning – Pragmatic language abilities – Attention, activity level, response inhibition – Peer relationships and social functioning

Key question: What factors early in life

predict non-ASD, non-TD outcomes?

Adulthood

87 adult siblings (mean age: 39 years)
Previously evaluated and identified as

“unaffected” or “broader autism phenotype”

Unaffected adult siblings:

– Average IQ, numeracy, literacy – Functioning well in jobs, independence, social relationships

Adult siblings characterized by BAP:

– Employment and social relationship levels low – Elevated ASD traits and mental health problems

Howlin et al. (2015), JADD

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% P r

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Unaffected BAP

Adulthood

Howlin et al. (2015), JADD

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Much progress in early detection of ASD with

clear implications for clinical practice

Longer-term outcomes of infant siblings now

coming into focus

– May help identify early predictors of range of later-diagnosed, atypical developmental

utcomes (e.g., ADHD)
More work needed on resilience and

protective factors among siblings across the lifespan

Summary New: Early Risk Study

AS D-Risk AS D ADHD-Risk ADHD

AS D ADHD

Low- Risk T D

T ypic ally Developing

Heritability: ~0.9 Heritability: ~0.7-0.8

Currently enrolling!

cmstanton@uc davis.edu | 916-703-0429 | www.bit.ly/EarlyRiskStudy

Early Risk and Infant Sibling Study Teams S ally Ozonoff, Ph.D. Gregory S . Young, Ph.D. Ana-Maria Iosif, Ph.D. Devon Gangi, Ph.D. Monique Hill, M.A. Cady S tanton, M.S . Alex Farquhar-Leic ester Alesha Hill Erika S

lis

S taff and researc h assistants Partic ipating families Funding Sources

NIMH K99 MH106642 (Miller) NIMH R01 MH068398 (Ozonoff) NIMH R01 MH109541 (Ozonoff) NICHD U54 HD079125 (Abbeduto)

Contact

Meghan Miller, Ph.D. Email: mrhmiller@ucdavis.edu Phone: 916-703-0217