Early Expression of Autism

Spectrum Disorders
What is autism? (2013)
• A developmental behaviorally-defined
syndrome/phenotype
– Impacts social skills & communication
– Associated with narrow, rigid, repetitive
behaviors
• NOT A “DISEASE” !
• Affects the immature, developing brain
Autism: Clinical Features

• Classic triad of symptoms:

– Impaired social interaction
– Impaired communication
– Presence of restricted interests
and activities
• Onset prior to 36 months

• Diagnosis often delayed

• Marked heterogeneity

• Developmental disorder
Leo Kanner
Age of Onset: Parental Perception

• Average age at first 25

concern:
20

– 15 months (SD=6.5)
15

Percent
• Primary concerns: 10

– Social difficulties
5

– Speech delays
0
0-2 3-4 5-6 7-8 9-10 11-12 13-14 15-16 17-18 19-20 21-22 23-24

• Why such a
Age (monhts)

variability? Chawarska, Paul, Klin et al., 2007, JADD.

 Patterns of Onset

• Early onset (1st year):

– “Inborn autistic disturbances of affective contact”
(Kanner, 1943)

• Later onset (2nd year):

– Regression (15-27% of cases) (Eisenberg & Kanner, 1955;
Dawson et al., 2006; Landa et al., 2007)

– Plateau (Ozonoff et al., 2008; Hansen et al., 2008)

Methodological Approaches to
Studying Emergence of Autism

• Retrospective studies of affected children

– Parental report
– Video diaries analysis

• Prospective studies of infant siblings at risk for ASD

– Recurrence risk for autism: 5-10%
– High risk for other developmental problems:
• Language or cognitive delays
• Broader Autism Phenotype, BAP
Autism in the First Year
Potential Areas of Dysfunction in
the 1st Year
1. Typical Development
– 0 to 3 months:
• Sensitivity to and preference for face-like stimuli and speech-like sound

– 3 to 6 months:
• Emergence of dyadic social interactions

– 6 to 9 months:
• Development of face processing skills (identity, affect, gender)
• Response to name
• Anticipatory social games

– 9 to 12 months:
• Social monitoring and imitation
• Social referencing
• Joint attention

2. Many skills affected in toddlers with ASD emerge

typically in the first year
Autism at 6 months?

• Reports of typical presentation at 6 months in children

with autism
– Eye contact and affective responses to mother (Young et al.,
2009)
– Social reciprocity and attention (Bryson et al., 2006; Zwaigenbaum
et al., 2005)
– Verbal and nonverbal skills (Landa et al., 2007)

• Emerging consensus that overt symptoms of ASD begin

to emerge between 6 and 12 months

• Possible factors responsible for these findings:

– Natural course of autism
– Limited sensitivity of existing behavioral methods
Emerging Symptoms of Autism at
12 months
• Limited response to name
– High specificity for ASD (89%)
– Low sensitivity (50%)

• Limited eye contact and use of

communicative gestures: pointing, showing

• Delays in language: limited range and

frequency of vocalizations

• Atypical behaviors: Spinning and intense visual

examination of objects
ASD in Toddlers
Abnormalities in Social Interaction

• Limited interest in people

• Limited of social reciprocity:

– Social smile
– Shared enjoyment
– Pleasure derived from interactions

• Unusual eye contact

• Limited affective range

• Limited joint attention skills

• Poor observational/imitative
learning

Chawarska, Klin & Volkmar (2008). Autism in Infants and Toddlers.

Communication

• Low frequency of communication

• Paucity of conventional and

descriptive gestures (nonverbal
communication)

• Limited goals of communication

(instrumental versus declarative)

• Stereotypical/idiosyncratic use of
language (e.g., echolalia, scripting)

• Use of other’s body to

communicate (hand-over-hand
gestures)
 Abnormalities in Play and Imagination
Development

 Exploratory: present but often

atypical

 Functional: may be spared but

atypical

 Pretend:
 Absent
 Present but atypical, non-
generative
Restricted Interests and Repetitive
Behaviors
• Seeking/avoiding specific visual
stimuli (lights, motion, touch)

• Seeking sensory input (jumping,

rocking, spinning)

• Interest in details of objects (e.g.,

wheels, dials)

• Hand and finger mannerisms

Exceptional Abilities

• John Longdon Down: Idiot Savant (1887)

• Savant skills in autism

– More frequent in males
– Prevalence 1-10% in autism, less prevalent
in other disorders

• Etiology: unknown Stephen Wiltshire

• Examples of savant skills:

– Exceptional memory
– Computational skills
– Artistic abilities
– Musical skills
Unusual Abilities in Toddlers

• Exceptional skills
– Interest in shapes, letters,
numbers
– Early recognition of signs
(“reading”)
– Good expressive vocabulary
– Great memory for movies, books

• Limited functionality such skills

– Isolated
– Repetitive & restrictive (e.g.,
labeling, scripting)
– Potentially transient
Diagnostic Assessment
Diagnostic Assessment Battery for Toddlers

• Developmental tests: e.g., Mullen Scales of Early

Development

• Autism-specific delays and abnormalities: Autism

Diagnostic Observation Schedule –Toddler Version

• Communication: Communication and Symbolic Behaviors

Scale

• Adaptive skills: Vineland Adaptive Behaviors Schedules-II

• Medical and developmental history interview

• Genetic and neurological testing

Some Standardized Behavioral
Diagnostic Tests
• Childhood Autism Rating Scale – CARS
(Schopler et al., 1980)
• Autism Diagnostic Interview – ADI (Lord et al.,
1989)
• Autistic Diagnostic Observation Schedule –
ADOS (Lord et al., 1989)
• Modified Checklist for Autism in Toddlers --
M-CHAT (Robin et al., 1999)
• Etc.
Physical/neurologic features
None present in all cases or required for diagnosis
• Abnormal head growth curve
• Physical abnormalities/symptoms
• Motor findings
• Atypical sensory responses
• Sleep problems
• Language abnormalities
• Autistic-language regression
• Epilepsy
 Trajectory of brain growth in
ASD
(Courchesne et al, 2007)

Selectively affected
areas:
Frontal lobe
Temporal lobe
Cerebellum
Amygdala
Neuropathology
• 1980: 4 cases with severe MR: cerebellar +
other brain abnormalities (Williams et al.)
• 1985-2002: Cerebellum + limbic pathology
(Bauman and Kemper)
– No major brain anomalies/lesions
– Loss of Purkinje cells in cerebellar cortex, neurons in
deep cerebellar nuclei, inferior olive
– Stunted neurons in diencephalon, amygdala
– Pathology progressive in adults compared to
children?
• 1996: brainstem malformation in one case
(Rodier et al.)
– HOXA1 gene
– Thalidomide, valproate toxicity
Autism: Hippocampal Neurons
(Bauman & Kemper 1985-1994)

24
 Cortical minicolumns in cortical area 4
lamina III in autism vs control brain

Normal
control brain

Casanov
a ASD brain

2006
Stability of Early Clinical Diagnosis

• Short term stability (2nd year to 4 years) (Chawarska et al.,

2007; 2009)

– Very good for ASD diagnosis (80-90%)

– Changes expected within spectrum due to shifts in
number of symptoms and intensity

• Long term stability (2 to 4 to 9 years) (Lord et al., 2006)

– High stability of ASD diagnosis (90%)

– Shift from PDD-NOS to Autism Dx: ~20%
– Shift from Autism to PDD-NOS: ~10%
Stability of Clinical Diagnosis

Confirmatory Diagnosis at >3 yrs

N (%)

Provisional Diagnosis < 2 yrs Autism PDD-NOS Non-ASD Total

Autism 32 (74%) 11(26%) 0 (0%) 43

PDD-NOS 3 (16%) 15 (83%) 0 (0%) 18

Non-ASD 1 (4%) 2 (7%) 25 (89%) 28

Total 36 28 25 89

Chawarska, Klin, Paul, Macari, & Volkmar, 2009, JCPP

Eye-Tracking Studies of Face
Processing
• Scanning as active process of
seeking task-relevant
information

• Visual scanning is affected by:

– Perceptual factors (e.g.,
high contrast, motion, etc.)

– Semantic factors (e.g.,

familiarity with a specific
face, nature of the task)

– Individual characteristics
(e.g., age, disorders)

From: A.R. Yarbus, 1965

Face Scanning in Babies
Face Scanning and Recognition
Visual Paired Comparison Paradigm

Familiarization Test of recognition

Effect of Context on Face Scanning
in Infancy
Eyes Mouth
1

0.9 STATIC SMILING SPEAKING

0.8

0.7

0.6
% Time

0.5

0.4

0.3

0.2

0.1

0
3m 6m 9m 12m 3m 6m 9m 12m 3m 6m 9m 12m
Chronological Age
Atypical Face Processing in
Toddlers with ASD
Face Processing in Autism

• Deficits in face processing in older children and adults

– Face recognition
– Atypical face processing strategies (features over
configurations)
– Atypical brain activation pattern in response to
faces

• Developmental end-points versus developmental

process
Face Processing Abnormalities in
Toddles with ASD

• Limited attentional bias for faces

• Deficit in face recognition

• Restricted scanning of key features linked to less effective

encoding

• Face scanning pattern might become more abnormal with

age

• Next frontier:
– Primary or secondary impairments?
– Are other aspects of face processing affected as well?
 Early Expression of ASD
• Symptoms of social dysfunction are apparent in a
majority of cases by 24 months

• Early Autism Spectrum diagnosis is relatively stable

• High variability in the rate of progress reflected in

changes of diagnostic classification within spectrum,
IQ, and verbal ability

• Next frontier:
– ASD in the 1st year
– Parsing heterogeneity of syndrome expression
Goals of Intervention
• Stop looking for a cure
• Stop striving for ‘normality’
• Think adaptation, i.e., fixing, circumventing
• Consider the individual’s needs
• Tolerate socially acceptable differences
• Welcome the unique contributions of some
Where to go: biology
• Elucidate pathophysiology, i.e., what goes on
in the brain (neurotransmitters,
neuromodulators, epilepsy, etc…)
• Pathophysiology more likely to lead to new
drugs than genetics
• Elucidate basis of autistic regression
• Devise a rational treatment for autistic
regression
Where to go: genetics
• In the clinic:
– Limited referral based on family history &
phenotype
– Probability of a specific genetic diagnosis low
– Always discuss recurrence risk !
– Lack of prenatal diagnosis unless etiology
known
• For research (paid for by research
funds !)
– Strongly encourage enrollment in a funded
comprehensive study, but
Where to go: medical
interventions
• Discourage use of medical/dietary treatments
that have no reasonable rationale
• Urgent need to evaluate efficacy of medical
and educational interventions in well studied
subgroups of individuals