Download Overview of Autism Spectrum Disorder

Thank You
Autism Spectrum Disorders:
Overview of Clinical Features and
Clinical Services
• The children and families who support our clinical and research activities
• The Marcus Foundation
• The JB Whitehead and Woodruff Foundations
• The Children’s Healthcare of Atlanta Foundation
Marcus Autism Center 4th Annual Summer Symposium
on Autism Spectrum Disorder
• The Georgia Research Alliance
as well as
• The National Institute of Mental Health
• The National Institute of Child Health and Human Development
Ami Klin, PhD
Director, Marcus Autism Center, Children’s Healthcare of Atlanta
GRA Eminent Scholar Professor & Chief, Division of Autism, Department of Pediatrics, Emory University School of
Medicine
Emory Center for Translational Social Neuroscience
• The National Science Foundation
• The Simons Foundation
• The Autism Science Foundation
• Autism Speaks
• United Way
Marcus Autism Center
2
Marcus Autism Center at a glance
Marcus Autism Center
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Excellence
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CLINICAL
TRAINING
RESEARCH
ADVOCACY
The Science of Clinical Care
3
Web of Relationships =
PARTNERSHIPS
Children’s Sibley
Children’s Hughes Spalding
Children’s Chamblee
Georgia Tech Biomedical Engineering
Georgia Tech “Behavioral Imaging Solutions”
Georgia Tech several other projects
Emblematic!
Opportunities
Atlanta Speech School
National Black Church Initiative
Georgia Pathway to Language
Morehouse School of Medicine
Satcher Leadership Institute
GA Dep of Public Health
GA Dep of Education
GA Dep of Early Care & Learning
Social visual engagement: infants (0
to 36 months)
Emory Pediatrics
GI, Neonat
Emory Genetics
Emory Yerkes
Emory OB-GYN
Emory Rollins
Emory Nursing
Emory Psychiatry
UCSF
UCLA
Washington University
Albert Einstein, NY
Cornell
Drexel
Florida State University
Harvard
NICHD/Autism Speaks BSRC (> 20 sites)
Foundation for NIH group
Social vocal engagement: infants (0
to 36 months)
Georgia State, Economics
Georgia State, Neuroscience
Funding Partners
University Partners
Autism Center of Excellence
Treatment: infants & toddlers
(12 to 14 months)
NIH
NSF
HRSA
Marcus Foundation
/
Woodruff/Whitehead
Foundations
Georgia Research Alliance
Autism Speaks
Autism Science Foundation
Simons Foundation
United Way
Marcus Autism
m Center
5
Behavioral Neuroscience: infant rhesus monkeys
Challenges and Opportunities:
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Reducing Age of Diagnosis & Improving Access to Care
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Johnson & Myers, 2007; Dosreis et al., 2006; Heidgerken et al., 2005; Honigfeld et al., 2012; Shattuck et al., 2009; Mandell et al., 2005; 2009
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Marcus Autism Center
7
GENETIC
LIABILITY
MECHANISMS OF SOCIALIZATION
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BEHAVIORAL
SYMPTOMS
No Genetic
Determinism
First 2 years
of life
No Brain
Determinism
Born to
Socially Orient
Reciprocal
Social Interaction
Text
MH Johnson PhD
JE LeDoux PhD
Neuroplasticity
WHITE MATTER DEVELOPMENT
Jones et al. (2008). Arch Gen Psy, 65(8), 946-54; Klin et al. (2009). Nature, 459, 257-61; Jones & Klin
(2009). J Am Acad of Child Psy, 48(5): 471-3; Jones & Klin (2013). Nature, 504, 427-431; Klin et al. (2014).
Neurosci Biobehav Rev.
H-J Park PhD
10
Research Enterprise at a glance
• • • UW
• ]
AX
• K
• • H
I
• Strategy for
Reseach Enterprise
• Q
Diagnosis
Concept
Psychopharmacology
Behavioral
Neuroscience
Animal
Models
Neurobiology
Genetics
Marcus Autism Center
11
Translational Opportunities
• High-throughput, low-cost,
deployment of universal
screening in the community
• Early detection, early
intervention, optimal
outcome
• Prevention or attenuation
of intellectual disability in
ASD
14
The next 10 years of genetics research
Molecular Genetics at Emory
Chris Gunter
Steve Warren
Mike Zwick
Jen Mulle
Peng Jin
David Cutler
Michael Gambello
ACE Network
Under-represented
populations
Marcus Autism Center
Marcus Autism Center
15
Ontogeny & Neural Basis of Social Visual Engagement
in Monkeys
16
Ontogeny & Neural Basis of Social Visual Engagement
in Monkeys
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Jocelyne Bachevalier, PhD
Xiao Ping Hu, PhD
Lisa Parr, PhD
17
In vivo diffusion MRI data
showing major white matter
pathways in a 2-week-old
rhesus macaque.
Jocelyne
Longchuan Li, PhD
Bachevalier, PhDMarcus Autism Center
Neurodevelopmental transitions underlying eye fixation in the first 6 months
of life and deviations thereof in infants and toddlers with Autism Spectrum Disorder
Sarah Shultz, Longchuan Li, Xiaoping Hu, Ami Klin, Warren Jones
Figure 2: Growth charts of eye fixation,
2-24 months, Typical (blue), ASD (red)
Figure 1: Video Stimuli
Figure 6: Example of Diffusion Tractography results, longitudinal, first 200 days of life
Community-Viable Solutions:
Figure 3: Differences in first 6 months of life
Figure 7: Example of graph-theoretic
analysis of resting-state functional brain
networks from an infant
Amy Wetherby, PhD
Figure 8: Method to test the association between two
sets of growth curves
Figure 4: Hypothesis for neurodevelopmental
transition underlying eye fixation
Figure 8: | Functional Data Analysis and
Functional Regression used to test association
between 2 sets of growth curves. Data in
example is from different study. A and B.
Lines plots of individual trajectories of
variables A and B; C and D. Smooth
estimates of the trajectories in A and B; E.
Association between growth curves is shown
as a functional regression surface. Color scale
at each point on the surface indicates the
correlation coefficient, r. Regression surface
indicates a significant positive association
between A and B; F. Bootstrap 95%
confidence intervals indicate that the
relationship is significant during the period
between 7.5 to 18.5 months (denoted by the
red vertical bars).
SOURCES
- Jones & Klin (2013). Nature, 504 (7480), 427-431.
- Klin, Shultz & Jones (2015). Neuroscience & Biobehavioral Reviews, 50, 189-203.
- NIMH grants P50-MH100029 and R21 MH105816
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Primary
Care
Physician
Family
Navigator for Early Intervention Providers
•
Navigator for Primary Care Physicians
•
Navigator for Families
•
Parent Engagement, Clinical Trials
•
Community Viable Treatments, Clinical Trials
•
Efficacy of Early Screening & Early Intervention
Jennifer Stapel-Wax, PsyD
United Way Partnerships
Figure 2: | Growth charts of eye fixation for typically
developing (TD, blue) and ASD (red) children.
Longitudinal change; between-group comparisons by
functional ANOVA. Thick lines indicate mean growth
curves, thin lines indicate 95% confidence intervals.
Top panel is per cent fixation; middle panel change in
fixation (first derivative); bottom panel plots F value
functions for between-group pointwise comparisons.
Significant differences are shaded in medium grey for
comparison of fixation data and light grey for
comparison of change-in-fixation data, with F ratio
critical value marked by an arrowhead on the y axis.
Figure 5: Behavior changes and hypothesized brain changes
•
• United Way new $ 1.875 m/3 yrs (Jennifer Stapel-Wax PI);
• NIH Multi-Site R01: Marcus, Cornell, Drexel, FSU (May 2014)
• Already work in Atlanta, several GA counties, as well as in FL, PA, TN
and NY
“Less than 20% of children with
Autism in the US are identified
before the age of 3 years”
Marcus Autism Center
20
Treatment Research: A Paradigm Shift
Treatment & neural underpinnings of food refusal
• From Emory+Children’s Seed Grant to
Program of Research
Model System at Yerkess
• Publication in high impact journal followed by
NIH + Autism Speaks grant submissions
• Paradigm Shift: From animal model at Yerkes
to clinical trial at Marcus
Shannon Gourley PhD
Human Clinical Trial
at Marcus
Early
Intervention
Provider
Larry Scahill, MSN, PhD
Will Sharp, PhD
•
First Randomized Controlled Trial of a manualized
behavioral intervention for feedign disorder
•
First investigation of a pharmacotherapy adjunct (Dcycloserine) for treatment of severe food aversion
•
First study of neural mechanisms underlying treatment
of severe food aversion.
Marcus Autism Center
22
Brief & Selective Overview of Autism Spectrum Disorders
Autism is ... in 1943 as in 2014
Leo Kanner
1894-1981
Autism
is ...
Autism Spectrum Disorders
TEST
Evolutionarily Highly Conserved and Developmentally Early
Emerging Mechanisms of Socialization
Normative social development:
Infants come into the world “pre-wired” for social engagement
• From the first days of life infants are profoundly sociable
• Human face and human voice are the most interesting stimuli in
the environment
• Early emergence of
• selective attention
• selective engagement
• social reciprocity
• attachments
• social-communication skills
• joint attention and social referencing skills
• “Theory of Mind”
• relationships
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Developmental Trajectories
Developing
expertise about
the
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Developing
expertise about
the
Physical World
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Social Attribution Task: narrative samples
Typically Developing Adolescent boy, age 13-9, FSIQ = 112
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Social Attribution Task: narrative samples
Adolescent boy with autism, age 14-9, FSIQ = 115
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Following Social Attention Cues
Following Social Attention Cues
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Following Social Attention Cues
Following Social Attention Cues
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Active ‘reading’ of social cues
•
•
•
•
•
•
Important for adjusting, predicting, ‘regrouping’
Eye contact / gaze
Facial and bodily gestures / posture
Prosodic cues (volume, inflection, rate)
‘Integrative’ cues
Practice in concrete situations (rehearsals, roletaking)
• Different settings – going from small therapeutic to
larger naturalistic (back and forth)
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• Topic selection
• Ways of marking topics shifts
• Background information (presupposition and
familiarity)
• Knowledge base of potential conversational
partners
• Repertoire of interests that can be discussed
• Conversational expectations (turn-taking, listening,
building on what is said)
• Pertinence, ‘quantity’, … (rules of pragmatics)
Self-monitoring in conversation:
Adjustments
• Style/register (e.g., more or less formal)
• Volume (e.g., in terms of social setting, proximity,
number of people, and background noise)
• Inflection modulation
• Rate, rhythm, and stress (e.g., emphasis, affective
communication)
• Awareness of self style
• The utilization of feedback (provided by others)
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What does it take to understand
a social situation?
OR HOW TO BUILD A SOCIAL SKILLS
TRAINING CURRICULUM
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Core Challenges aka Realities
• SOCIAL SKILLS: the intangibles, the unstructured, the novel, the
implicit, the intuitive, the “common sense”, the mentalistic
• COMMUNICATION SKILLS: the informal, the conversational,
the reciprocal, the ‘other-directed’, the polite, the ‘untrue’, the ‘chatty’
• ADAPTIVE SKILLS: grooming and self-care, domestic chores,
‘survival skills’, living in the community, functioning in bureaucracies,
groups
g
p and relationships,
p , legal
g concerns
• LEARNING SKILLS: rote & sequential, not conceptual &
integrative; learning ABOUT not learning HOW TO
• ORGANIZATIONAL SKILLS: repetitive schedules, ‘to do’ lists,
planning ahead, learning form feedback, adjusting to variants of
situations, recognizing novelty, knowing when and how to seek
assistance, breaking down big tasks into stepwise plans
• OBSTACLES TO ADAPTATION: anxiety, panic, fears and
phobias, depression and despondency, motivational issues, rigidities
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Autism Spectrum
Males (n = 20)
Normal Controls
Males (n = 20)
Right
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t maps of mean % signal change, p < .01
Masked for face-baseline & object-baseline at .05
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-Fusiform activation for Digimon characters
-Amygdala activation for Digimon characters
-Atypical specialization of ‘FFA’
-Emotional involvement and investment
in circumscribed interests
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Grelotti et al., 2005, Neuropsychologia
Exceptional drawing ability
Exceptional drawing ability
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Learning about autism from exceptional abilities
Learning about autism from exceptional abilities
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Learning about autism from exceptional abilities
TEST
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Learning Style
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• Circumscribed interest may be important pillar
of self-identity
• Very important to take this very seriously
• Examples:
– Cul de sacs
– Gaining insight into people through mathematics (e.g.,
algebraic equations)
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From Early Childhood Autism, to Pervasive
Developmental Disorders, to Autism
Spectrum Disorders: Kanner & DSM ology
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Marcus Autism Center
114
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AKYA+<,+
• The importance of diagnostic labels
• The limitations of diagnostic labels
• The political science of nosology, and the scientific
politics of nosology: important considerations
• The concept of reliability
• The concept of validity
• Nosology: expecting too much
• The consequences of shifts in definitions: DSM-III,
DSM-III-R, DSM-IV, and DSM-V
KY:,/($/,8-/0,+&+$
– ASD vs ‘neurotypicality’ or non-ASD conditions valid
– Subtyping not reliable; better mediators: severity, language level or intelligence
– Best ASD + associated features
• 3 domains become 2
Social/Communication are inseparable
Language delays not specific to ASD: mediator
Better psychometric properties (better specificity; same sensitivity)
Examples across ages and levels of severity
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• Repetitive behaviors/narrow or fixated interests
–
–
–
–
Requiring 2 symptoms: improves specificity
Multiple sources of information
History thereof improves stability of diagnosis
Unusual sensory sensitivities included
– Present from infancy or early childhood but more likely to be detected upon social
demands
• Indices of severity
–
–
–
–
–
– Multiple criteria in DSM-IV, same symptom
– Data analyses (research on criteria) - SSC large sample
• DSM-5 vs. DSM-IV-TR
– 56 Studies published so far focused on DSM-5 (by 2013)
– ~ 10 studies comparing Se & Sp of DSM-5 relative to DSM-IV
DSM-5 definition of ASD
? (future, more quantitative)
Current instruments (ADOS, ADI)
Current parent reports/screeners (SRS)
Current measurements of ability (Vineland)
“Biomarkers”
DSM-5 definition of ASD
Social-Communication
Restricted, Repetitive Behaviors
• Persistent deficits in social communication and
social interaction across multiple contexts,
currently or by history: (all 3)
• R e s t r i c t e d , r e p e t i t i v e p a t t e r n s o f b e h a v i o r, i n t e r e s t s
or activities, current or by history: (2 of 4)
– Deficits in social emotional reciprocity
(from abnormal social approach
and failure of back-and-forth conversation; to reduced sharing of interests,
emotions; etc. )
– Deficits in nonverbal communicative behaviors
used for social
interaction (from poorly integrated verbal and nonverbal communication, to
abnormal eye contact, etc.)
to in making friends, absence of interest in peers, etc.)
L 8303&0,//AK
• Neurodevelopmental disorder
• Smaller number of symptoms
– Deficits in developing, maintaining, and understanding
r e l a t i o n s h i p s (from difficulties adjusting behavior to suit various social
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DSM-5 workgroup reasoning
• “ASD” for Autism, Asperger Syndrome, CDD, PDD-NOS
–
–
–
–
K
NU]]XO+K
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contexts
– Stereotyped or repetitive motor movements, use of objects, or
speech;
– Insistence on sameness, inflexible adherence to routines, or
ritualized patterns of verbal or nonverbal behavior;
– Highly restricted, fixated interests that are abnormal in
intensity or focus;
– Hyper- or hyporeactivity to sensory input or unusual interest
in sensory aspects of the environment;
DSM-5 definition of ASD
• Symptoms must be present in the early
d e v e l o p m e n t a l p e r i o d (may not be fully manifest until
social demands
exceed limited capacities, or may be masked by learned strategies in later life)
• Symptoms cause clinical significant impairment in
social, occupational, or other important area of
current functioning;
• Not better explained by intellectual developmental
d i s o r d e r o r g l o b a l d e v e l o p m e n t a l d e l a y (discrepancy between
social communication skills and intellectual ability)
• If child/individual met DSM-IV criteria for autistic
d i s o r d e r, A s p e r g e r ’ s , o r P D D - N O S ( w e l l - e s t a b l i s h e d ) ,
DSM-5 diagnosis of ASD applies;
• If marked deficits in social communication, but does not
meet criteria for ASD, evaluate for Social (Pragmatic)
C o m m u n i c a t i o n D i s o r d e r (i.e., no symptoms in the 2nd domain)
DSM-5 definition of
Social (Pragmatic) Communication Disorder
DSM-5 definition of ASD
• Specify
– if intellectual impairment
– if language impairment
– if associated with known medical or genetic condition
or environmental factor (additional code)
– if associated with another neurodevelopmental,
mental, or behavior disorder
– if catatonia (????!!!!!)
• No more multi-axial system (of DSM-IV)
• Severity Levels of ASD
– Separate for Social Communication, and for Restricted, Repetitive
Behaviors
– Level 3: Requiring very substantial support
– Level 2: Requiring substantial support
– Level 3: Requiring support
DSM-5 definition of
Social (Pragmatic) Communication Disorder
• Onset: early developmental period
• Persistent difficulties in the social use of verbal and
nonverbal communication:
– Deficits in using communication for social purposes, such as
greeting and sharing information appropriate to social context
– Impairment of the ability to change communication to match
context or the needs of the listener (such as speaking
differently in, and adjusting to different contexts)
– Difficulties following rules for conversation and storytelling
(taking turns in conversation, rephrasing when misunderstood,
using verbal and nonverbal signals to regulate interaction)
– Difficulties understanding what is not explicitly stated (making
inferences) and nonliteral or ambiguous meanings of language
(metaphors, humors, irony)
• Deficits result in functional limitations in effective
communication, social relationships, academic
achievement, or occupational performance
(but deficits may not become
fully manifest until social communication demands exceed limited capacities)
• Symptoms not attributable to another medical or
neurological condition, low abilities in word
structure and grammar
• Symptoms not better explained by ASD, intellectual
d i s a b i l i t y, g l o b a l d e v e l o p m e n t a l d e l a y o r a n o t h e r
m e n t a l d i s o r d e r.
• “ R a r e < 4 y e a r s ” ; Va r i a b l e o u t c o m e
• Risks: family history of ASD, communication disorders,
s p e c i f i c l e a r n i n g d i s o r d e r.
• Is this a back door to “Broader Autism
Phenotype” (BAP) moved outside its original (ASD)
familial context?
• ASD without RRBs (current or by history!)
• Other rule outs: ADHD, Social Phobia, ID
Advocacy Groups’
position and concerns
• Misdiagnosis or underdiagnosis of people with
Asperger’s Disorder
• “Asperger’s” has meaning to individuals affected,
families, service providers, organizations,
communities, the general public
• Symptoms not comprehensive enough:
Less Discussed Complexities
• The dependency upon ADI-R and ADOS
•
– sensory atypicalities, anxieties, Executive Dysfunction, RH
learning difficulties - important for treatment/educational
programming
•
• Scales for measurement of ASD diagnostic criteria
not released yet -> Indices of Severity
•
•
– who administers these instruments
– reliability at the item level
– Doing away with the experienced clinician
Where are the challenges most felt
– Are these challenges captured by the instruments
– The need for real-life instrumentation
The “subthreshold” symptoms
– A “milder” social disability
– The real-life consequences of defining it as “mild”
Self-representation
The reality of community-based practices: the importance of
DSM
QUO VADIS
“diagnostic process” and DSM-5
• All encompassing definition: need for quantification and
individualization
• Need for “tests” that are both diagnostic and prescriptive
• Redefining autism/ASD for the biological sciences
(NIMH)
• What is “core” and what are “associated disabilities”
• Could these associated disabilities be significantly
attenuated if not prevented?
Thank you
Now you truly deserve to
go to lunch ...
Have a wonderful symposium!
It will be terrific!