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

3/9/2018 Disclosures Siblings of Children with • I have nothing to disclose. 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 Overview • MIND Institute activities • Early detection of ASD in younger siblings MIND Institute Activities • Long-term outcomes of siblings of children with ASD – School-age – Adulthood • Questions 1

3/9/2018 Recent scientific achievements MIND Institute • Boys with ASD who experience regression • Founded by 6 families display increased brain size • Research and assessment • Folic acid taken preconception/prenatally clinic opened in 1998 can decrease ASD risk, especially in women who are poor metabolizers of folate • MIND Institute complex completed in 2003 • Animal models of neurodevelopmental disorders • MIND scientists currently • Early markers of, and effective early conducting 60+ funded research projects interventions for, ASD Autism Centers of Excellence Autism Centers of Excellence • PI: David Amaral, Ph.D. • S ite PI: Aubyn S tahmer, Ph.D. • Focus on 2 subgroups: • Adequate evidence that screening detects autism – ASD + anxiety: Identification, CBT+SSRI, neuroimaging and response to treatment • Harm from screening likely to be small – ASD + enlarged brains: Determine which brain • BUT…inadequate evidence of benefits systems are most affected; use induced (US PS TF) pluripotent stem cells to grow neurons and identify genetic alterations that may be related to – Lack of treatment studies in screen- enlarged brains detected cases – Overall limitations to treatment research 2

3/9/2018 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 Clinics Autism Centers of Excellence After Positive S creen or Provider Concerns: • Assessment and Diagnostic Clinic • Diagnostic report No cost No cost • Community referrals for treatment if not • Social Skills Training evaluation evaluation ASD Program for ASD • ADHD Program for If ASD: 1 year If ASD: 1 year • Early Start Denver Model intensive intensive Children and Adults • 20 hours/week, 1-on-1 treatment treatment • Parent coaching twice a month • Fragile X Research and Treatment Clinic Post-evaluations Post-evaluations • Recommendations for community • High-Risk Infant Follow-Up Clinic to chart progress to chart progress treatment after study treatment ends • Early Start Denver Model 3

3/9/2018 Education and Outreach • Centers for Excellence in Developmental Disabilities (CEDD) Early detection of ASD • Autism Research Training Program (ART P) • Leadership Education in Neurodevelopmental Disorders (LEND) • Developmental & Behavioral Pediatrics Early detection and diagnosis: Turning back the clock Why? • Infancy/early childhood: Ideal period in • Early identification  which to investigate phenomenology of early treatment  childhood disorders improved outcomes – Improve accurate, earlier detection • Decrease service utilization, economic – Identify critical time points/domains to be burden targeted by intervention/prevention efforts • Challenges: false – Investigate environmental/contextual and positives, unnecessary biological causal mechanisms treatment 4

3/9/2018 Early identification: How? Infant sibling design 6 9 12 15 18 24 36 School- Months Months Months Months Months Months Months age … Diagnostic Variety of eye tracking, outcomes behavioral, determined developmental, symptom measures Affected High-risk infant Low-risk infant Unaffected sibling sibling What can we learn from infant Recurrence risk siblings? • Recurrence risk • Previously thought to be 3-10% • Patterns of onset • More recently: 18.7% recurrence risk • Early behavioral and biological markers • Targets for intervention and prevention Ozonoff et al. (2011), Pediatrics 5

3/9/2018 Emergence of social communication Early behavioral markers of ASD behaviors Social Communication • Eye gaze • Vocalizations • Social smiles • Response to name Ozonoff et al. (2010), JAACAP Response to name Response to name • Names as social cues for orienting to 100% Response to • Low-Risk Non-ASD salient aspects of environment 90% name probe High-Risk Non-ASD 80% ASD from AOSI Percent receiving failing score • Diminished response to name consistently 70% Name called up • identified by 12 months via retrospective 60% to 2x per trial ** 50% or paper-pencil measures (2 trials) ** ** 40% * ** Failure = no • 30% • Little known regarding developmental response on any 20% trial progressions; direct assessment (vs. parent 10% report) 0% 6 9 12 15 18 24 Age (months) Miller et al. (2017), Journal of Pediatrics 6

3/9/2018 What about everyone else? Red flags for ASD in the first years • Broader autism phenotype; other • Lack of appropriate gaze • Decreased or absent use of pre-speech gestures developmental concerns Lack of warm, joyful • (waving, pointing, expressions with gaze showing) Lack of sharing enjoyment • No single words by 16 mos • or interests No two-word utterances • Lack of alternating to- • by 24 mos and-fro vocalizations with parents Repetitive movements or • posturing of body, arms, • Lack of response to name hands, or fingers Delayed onset of • Loss of language or social • babbling past 9 mo 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) Ozonoff et al. (2014), JAACAP School-age • 80% of younger siblings of children with ASD do not develop autism Long-term outcomes of • BUT… ～ 35% develop other, non-ASD siblings of children with ASD concerns by school-age 7

3/9/2018 School-age School-age/adolescence • Follow-up between 12-15 years ongoing 6-8 years 8-11 years (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? Miller et al. (2016), Autism Research Adulthood Adulthood 100% • 87 adult siblings (mean age: 39 years) 90% Unaffected • Previously evaluated and identified as BAP 80% “unaffected” or “broader autism phenotype” 70% 60% • Unaffected adult siblings: 50% – Average IQ, numeracy, literacy 40% – Functioning well in jobs, independence, social 30% relationships 20% • Adult siblings characterized by BAP: 10% 0% – Employment and social relationship levels low t s s s y d n s p m m m t l e i e o m h o o i h s t o t x y p t p n s n p A e o o m m m r l h – Elevated ASD traits and mental health problems p i t y y m a s y s t s D e l e D n n H r o d e C o D i s i e s O s A l o s s i l e k l e e s C r p r v p l / e o a e b d d n A o c c i s i d i n o s o e r f s h o i C p r E P Howlin et al. (2015), JADD Howlin et al. (2015), JADD 8

3/9/2018 Summary New: Early Risk Study T ypic ally • Much progress in early detection of ASD with AS D ADHD Developing 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 outcomes (e.g., ADHD) Low- AS D-Risk ADHD-Risk T D AS D ADHD Risk Heritability: ~0.9 Heritability: ~0.7-0.8 • More work needed on resilience and Currently enrolling! protective factors among siblings across the cmstanton@uc davis.edu | 916-703-0429 | www.bit.ly/EarlyRiskStudy lifespan Acknowledgments Early Risk and Infant Sibling Study Teams Funding Sources S ally Ozonoff, Ph.D. NIMH K99 MH106642 (Miller) NIMH R01 MH068398 (Ozonoff) Gregory S . Young, Ph.D. NIMH R01 MH109541 (Ozonoff) Ana-Maria Iosif, Ph.D. NICHD U54 HD079125 (Abbeduto) Devon Gangi, Ph.D. Monique Hill, M.A. Cady S tanton, M.S . Contact Alex Farquhar-Leic ester Meghan Miller, Ph.D. Alesha Hill Email: mrhmiller@ucdavis.edu Erika S olis Phone: 916-703-0217 S taff and researc h assistants Partic ipating families 9