UCSD AUTISM CENTER OF EXCELLENCE
School of Medicine, University of California, San Diego
SYNAPSES
Rampon et al., 2000
Turner et al., 2003
Greenough
and Chang, Review
CAPILLARY
PERFUSION
Black et al., 1987
Sirevaag et al., 1988
DENDRITIC BRANCHING
Volkmar&Greenoug
h, 1972
Greenough et al.,
1986
NEUROGENESIS
Kempermann et al, 1997
Brown et al., 2003
PLASTICITY
High
Low
Infancy
Childhood Adulthood
AGE
SUBJECTS
• 136 infants abandoned at birth in
Bucharest, Romania, and institutionalized
• 68 Foster Care (FCG)
• 68 Remained Institutionalized (IG)
• 72 Never Institutionalized (NIG) reared at Home
with Biological Parents
•DV
= Bailey Scale of Infant Development (Baseline,
30 & 42 mo) and WPPSI at 50 mo.
GROUP
Mean DQ
INSTITUTION (IG)- 42 mo
77.1
FOSTER CARE GROUP- 42 mo
85.6
NEVER INSTITUTIONALIZED (NIG) 42 mo
103.4
Foster Care DQ at 42 months BY AGE OF PLACEMENT
AGE AT PLACEMENT N
MEAND.Q
SD
0-18
14
94.9
11.9
18-24
16
89.0
11.3
24-30
22
80.1
13.3
30+
9
79.7
17.1
MIGHT NOT:
MIGHT:
Point at things
Talk or babble in a voice with an
unusual tone
Babble or talk back and forth with
another person
Display extreme sensory
sensitivities
Try to gain the attention of others
Play with toys in an unusual
manner
Show shared enjoyment
Smile in response to your smile
Display unusual body or hand movemen
Say their first word by 12-14 mo
Make good eye contact
Enjoy cuddling
Show objects to others
Respond to their name
Seem overly fussy or be difficult to
soothe
Carry around an objects for extended
periods of time. These items might seem
unusual or usual.
• Wetherby, Woods, Allen, Cleary, Dickinson, & Lord (2004)
• Landa, Holman, & Garrett-Mayer (2007)
Statistical Group Effects:
Specialized training often
• Werner,
Dawson,
Individual
levelOsterling,
uncertain& Dinno (2000)
required to detect red flags
• Luyster, Gotham, Guthrie, Coffing, Petrak, Pierce, Bishop, Esler, Hus, Oti,
Richler, Risi, & Lord (2009)
• Osterling & Dawson (1994)
• Osterling, Dawson, & Munson (2002)
• Vostanis,
Corbett,
Edwards, Gingell, Golding,
Unclear Smith,
how to
probe Sungum-Paliwal,
for
Red Flags usually obvious by 24Moore, & Williams (1998)
these behaviors in a medical
30months, what about younger?
setting
• Zwaigenbaum,
Bryson, Rogers, Roberts, Brian, & Szatmari (2005)
• Baron-Cohen, Cox, Baird, Swettenham, Nightingale,
Morgan, Drew, & Charman (1992)
The “Baby Sib” Approach
• Study autism from birth
• Need to study 100 babies
just to find 4 or 5 or 15
with an ASD
• Studies autism only in multiplex
families – are genetics different?
(Sebat et al., 2007)
95%
4-5%
(or 90%)
(or up to 15%)
Normal
ASD
(With up to 10% with language or social
problems)
Autism Observation Scale for Infants
✔ visual tracking
✔ eye contact
✔
attentional
disengagement
coordination of eye gaze and action
✔ imitation
affective responses
✔ social communicative
behaviors
sensory
motor behaviors
✔
✔ orienting to name
✔ social smiling
✔ behavioral reactivity
✔ social interest
Differences at 12 months
(7No
ADDifference
and 12 Spectrum
at 24 mo)
at 6 months
“There are no overall
differences in the
number of behavioral
markers observed at
6 months between
siblings
with an ADOS
classification
< Of ASD> at 24
months and other
infants.”
1 Yr Well-Baby Check-Up Approach
• Fast
• Easy
• Investigates autism as
it occurs in the population
• Investigates the feasibility
of on-site screening and scoring
as pediatric standard of care
Pierce, Carter, Weinfeld, Desmond, Hazin, Gallagher, Bjork, in Review
CSBS DP Infant-Toddler Checklist
Wetherby
&Prizant, 2002
Social
Communication
Composite
Expressive
Speech
Composite
Symbolic
Composite
Dr. Robert Bjork, Dr. Michael Nelson, Dr. Cheryl Jennett
Dr. Dr. John Kafa, Dr. Douglas Wilson, Dr. Crystal De Freitas
Dr. Martin Gilboa, Dr. Patricia Juarez, Dr. George Madany,
Dr. Seven Brody, Dr. Ingrid Martinez-Andree, Dr. Irene Chang
Dr. Stephanie Powell, Dr. Adam Breslow, Dr. Patricia Pisinger
Dr. Isabel Baratta, Dr. Sheila Cason, Dr. Thomas Neglia
Dr. Stephen Balch, Dr. Randall Metsch, Dr. David Schmottlach
Dr. Sonja Brion, Dr. Anna Mendenhall, Dr. Nancy Clementino
Dr. Marshall Littman, Dr. Leslie McCormick, Dr. Sharon Sternfeld
Dr. Cara Cohen, Dr. Nicholas Tsoulos, Dr. Elena Fishman
Dr. Hilary Bowers, Dr. Albert Martinez, Dr. Genevieve Minka
Dr. Wendy Chacon, Dr. Leon Kelley, Dr. Victor Lipps, Dr. Jeffrey Selzer, Dr. Lynn Herring, Dr. Teresa
O’dea, Dr. Richard Walls, Dr. Vivian Tung, Dr. Christian Archambault, Dr. Veronique James, Dr.
Stuart Cohen, Dr. Nancy Shiau, Dr. Linda Smith, Dr. Tevor Henderson, Dr. Cheryl Morrell, Dr. Josef
Zwass, Dr. Lon Dubeye, Dr. Andrea Siano, Dr. Aida Martinez, Dr. Rachel Ireland, Dr. Louis Luevanos
Dr. Laurie Tyrrell, Dr. John Cella, Dr. Jill Gustafson, Dr. Rosemary Page, Dr. David Steele, Dr. Carlos
Quiros, Dr. Brian Chu, Dr. Kathleen Jones, Dr. James Moseman, Dr. Laurence Ashbacher, Dr.
Theresa Dailey, Dr. Frederick Frumin,Dr. Nicholas Levy, Dr. Julie Snyder Block, Dr. Lori Taylor, Dr.
Rosalind Dockweiler, Dr. Christine Wood, Dr. William Hitchcock, Dr. Robert Warner, Dr. Sheetal
Gandhi, Dr. Suzanne Mills, Dr. Mona Sobel, Dr. Craig Duck, Dr. James Hay, Dr. Georgine Jorgensen,
Dr. Richard Payne, Dr. James Quigley, Dr. Richard Buchta, Dr. Ann Marie Engfelt, Dr. Benjamin
Siegel, Dr. Lori Gould, Dr. Micelle Sanford Dr. Annie Kupelian, Dr. Paula Grayson, Dr. Raha Shaw,
Dr. Gary Chun, Dr. Matilda Remba, Dr. Janna Cataldo, Dr. Nicole Gorton, Dr. Bret Gerber, Dr. Denise
Brownlee, Dr. Stuart Rubenstein, Dr. Peggy Manuel, Dr. Veda Wu, Dr. Michael Berent, Dr.
GargiKubal, Dr. Norman Gollub, Dr. Teresa Hardisty, Dr. Jeanne Montal, Dr. Katrina Durkee, Dr.
Kamei Tolba, Dr. Carol Hart, Dr. Dennis Butler, Dr. Howard Mehl, Dr. Marta Awdykovych, Dr.
UmaNarayan, Dr. Richard McNeal, Dr. Marta Awdykovych Dr. Richard McNeal, Dr. Jennie Ou, Dr.
Howard Smart, Dr. NeethiRatnesar, Dr. Fujii, Dr. Mattson, Dr. Norman, Dr. Sauer, Dr. Gabriela
Mogrovejo, Dr. Julie Keeler, Dr. Liz Hourihan, Dr. Dania Lindenberg, Dr. Dori Mortimer, Dr. Marvin
Comprehensive Developmental Tracking
12 months
18 months
24months
30 months
36 months
Language
Language
Language
Cognitive
Cognitive
Cognitive
ADOS
ADOS
ADOS
Experimental
Experimental
Final Diagnosis:
ADI
Experimental
Private Consultation
Private Consultation
and test score review
and test score review
Private Consultation
TREATMENT if:
MA < CA
TREATMENT if:
MA < CA
And test score review
≈ Two hours per visit. Two visits per age point
Also Includes parent interview
Analyzing Patterns of Eye Gaze:
Predictors of Risk for an ASD?
Typical Infants are Socially Interested
9 MINUTE old
infants prefer faces
over non-face
patterns
Goren 1975, Replicated by Johnson
1991
3-4 Month old
infants prefer
happy to angry
sounds
Klin et al. 2002
Viewer with Autism
Viewer with Typical Dev
Am J Psychiatry 159:6, June 2002,
“ Results revealed that none of the 6-month old
infants previously identified as showing lower
rates of eye contact had any signs of autism at
outcome. “
138 Toddlers Age Range 12-43 Months
ASD
(28) Poor Calibration, Fussy, Technical issues, Looked away >
50% of trials
N
AGE
ADOS
MULLEN
Total
37
26 mo
16
68
(14-43 mo) (8-22)
53-101
DD
22
22 mo
(12-41 mo)
6
(0-7)
71
35-84
Typical
51
24 mo
(12-43 mo)
1.8
(0-7)
109
88-132
Pierce et al., (2010) Archives of General Psychiatry
WHAT TO LOOK FOR
1. PREFERENCE FOR SOCIAL IMAGES
14 months
15 months
16 months
Pierce et al., 2010
Sleep MRI
2-year old with autism:Before Surgery
2-Year old with autism: After Surgery
CUTE HAT
Why study LANGUAGE?
Vocabulary (words)
600
300
50
Birth 8 12
16
24
Age (mo)
11
8
36
Charman et al., 2003
IMPAIRED:
UNUSUAL FEATURES:
Pragmatics
Odd Inflection and Prosody
(Tager-Flusberg et al., 2005)
(usually monotone)
Phonology
Stereotyped speech
Syntax
Immediate and delayed echolalia
Semantics
Slide courtesy E. Redcay
Why study LATERALITY?
• Hemispheric specialization is crucial aspect of
language development
• Structural asymmetries in language areas
prenatal in origin
• In older children and adults, left hemisphere
predominance of language response, especially
in frontal and temporal cortex
• Greater right hemisphere involvement in
pragmatics
• Less known about normal development of
functional asymmetries or how this may go awry
in ASD
Brain Response to Speech During Sleep?
3 month old infant
From Dehaene-Lambertz et
al., (2002, Science)
Current Study
• Goals
– Extend prior work to include infants and toddlers with
subsequent confirmation of ASD
– Examine development of left-hemisphere
predominance of language response in typical
children and laterality abnormalities in ASD
• Participants
ASD (n=23)
Typical (n=20)
Mean Age in months
32.1
25.2
Age Range in months
14.5 - 47.6
13.2 - 45.3
18
11
Mullen Receptive Language Age in months
20.2
25.3
Mullen Receptive Visual Age in months
27.6
23.9
ADOS Score
13.3
1.9
Number of boys
Brain Response to a Bedtime Story in
Sleeping Infants and Toddlers
1.0
Effect
Size
(Eta2)
0.0
Typical
(n=20)
ASD
(n=23)
UCSD AUTISM CENTER OF EXCELLENCE
Exploration Patterns
Blood Based Immune Markers
Resting Functional Connectivity
Brain Response to Emotion Sounds
White Matter Profile
Language Profile
Patterns of Eye Gaze
Gene Expression
Cortical Thickness
Gene Association
Brain Growth Trajectory
Play Behavior
Thank You:
Sierra
www.autismsandiego.org
Eric Courchesne
Taran