Autism and Related
Disorders:
CHLD 350a/PSYC350
Lecture I: An Introduction to Autism
Course Directors
Fred Volkmar MD
Ami Klin PhD
James McPartland PhD
Acknowledgements
• Support for the class this semester has
been provided by several Associates of
the Child Study Center.
• We are also grateful to our colleagues
and the various presenters in the
course
• For additional information on autism
and the Child Study Center please visit
• http://www.med.yale.edu/chldstdy/autism
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Conflicts of Interest
• Dr. Volkmar
– Various federal grants
– Book Royalties
– Journal Editor (Springer publishing)
• Dr. Klin
– Various federal and private foundation
grants
– Book Royalties
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Course information
• This semester
– We are filming for the web
• Logistics
– Tuesday 3:30 to 5 PM
– Starting next week in Ground floor conference
room
• Reading and additional materials will be
provided
– A Practical Guide to Autism (Volkmar & Wiesner,
Wiley, 2009) (general resource)
– Handbook of Autism (2005) – 2 volumes
(REFERENCE resource)
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Course Information
• Enrollment limited to 15-20 students
• We will discuss requirements, papers,
and so forth at end of time today
• History of course
– 25 years
– Seminar
– Field Placement
• Benhaven
• Chapel Haven
• Research or clinics at CSC
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Today’s presentation:
• Selective introduction
• Diagnostic Concepts
• History and Definitions
• Epidemiology
• Neurobiology and Genetics
• Social Development
• Psychological Functioning
– Learning, savants, circumscribed
interests
• Autism Program at Yale
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Autism before Kanner
• Improvements in infant mortality 
increased interest in child development
• Reports of ‘feral’ children
– May have had autism, Victor
– Reports of childhood ‘insanity’ (Maudsley,
1867) focused interest on childhood
disorders but led to confusion with
schizophrenia
• The terms childhood psychosis and
childhood schizophrenia became
synonymous
– (this continued until 1980)
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Leo Kanner: Early Infantile
Autism
• 1943
• Reported 11 children
• Two Essential Features
–
Autism
–
Resistance to change
•
Congenital in nature
•
Developmental Issues
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Kanner (1943) on autism
• The outstanding, “pathognomonic,”
fundamental disorder is in the
children’s inability to related
themselves in the ordinary way to
people and situations for the beginning
of life…. There is from the start an
extreme autistic aloneness that,
whenever possible, disregards,
ignores, shuts out anything that comes
into the child from the outside.
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Kanner – early confusion, lack of
consensus
• rate with higher SES 
– Implication: effects of experience
• no associated medical conditions
– Exclusion of ‘organic’ autism
• normal levels of intelligence
– Did well on some parts of IQ tests
– Poor ‘testability’
• not associated with schizophrenia
– Use of the word autism, broad views
of schizophrenia
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Diagnosis
• Early confusion with schizophrenia
– Work of Kolvin and Rutter
• DSM and ICD
• DSM-I and II
– Childhood schizophrenia
• DSM-III
– New category of disorder
– Monothetic definition
• DSM-III-R
– More detailed, polythetic definition
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Definition of Autism DSM-IV
• Criteria grouped in 3 areas (social/communicationplay, & restricted interests/activities/behaviors)
– Must have a total of at least 6
– At least 2 social, 1 from each of the other areas
• Onset before age 3 years based on delay/abnormal
functioning in
– Social interaction
– Language as used in social communication
– Symbolic or imaginative play
• Data show
– Good balance of Sensitivity and Specificity
– Good coverage of entire IQ Range
– Increased reliability for novice raters
• Convergence with ICD-10
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DSM-IV*
• Preparations
Reviews, data reanalyses
• Design
– International, multisite study
– Nearly 1000 cases, >100 raters
– Standard case ratings
– Data management/analysis
• Coordination with International System
(ICD-10)
*Diagnostic and Statistical Manual, 4th
edition (APA, 1994) Volkmar, et al. 1994
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Dimensional Assessment
instruments
• Many issues in instrument
development
– Instrument development, orientation
– Broad range of expression (age, IQ level)
– Reliability and validity
• Recent convergence with categorical
approaches
• Problem of the ‘gold’ standard
• Need for better and different
approaches for very young children
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Pervasive Developmental Disorders (PDDs)
(or Autism Spectrum Disorders – ASDs)*
• Official Name
Official Name
• Autistic Disorder
Childhood Autism,
Infantile autism,
Early infantile autism
• Rett’s Disorder
Rett’s Syndrome
• Childhood Disinegrative
Disorder
Heller’s Syndrome,
• Asperger’s Disorder
Asperger’s syndrome,
Disintegrative psychosis
Autistic psychopathy,
Autistic personality disorder
• Pervasive Developmental
Disorder Not Otherwise
Specified (PDD-NOS)
Atypical PDD,
Atypical personality,
Atypical autism
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Asperger - 1944
• Series of cases – all male
• Marked social problems
• Good cognitive/language skills
• Motor problems
• Circumscribed interests
• + Family Hx (esp. fathers)
• “Autistic Psychopathy”/ Autistic
personality disorder
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Asperger’s Current Status
• Issues
– Overlap other concepts
– Is this ‘high functioning’ autism
• Verbal Skills are STRENGTH
– Child ‘talks before he walks’ ‘words are
his lifeline’
– Implications for
• Mechanisms
• Intervention
• DSM-IV field trial Results
• Current Status
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Childhood Disintegrative
Disorder
• Rare condition, reports (1908) of
children who markedly regress
• Later onset than autism (3-10
years)
• Issues in understanding
‘regression’
– Differences in course and outcome
(worse than autism)
– ? Relation to genetic mechanisms
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Rett’s Disorder
• Andreas Rett (1966)
• Girls – unusual hand movements, early
development normal, head growth
slows, “autistic like” phase (preschool)
• Differences in outcome (very poor)
– Many associated problems
• Why include in DSM?
• A gene has recently been identified
(MECP2)
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PDD-NOS
• History of diagnostic concept
– Early interest in ‘autistic-like’ conditions
• By definition – definition is ‘negative’
– The child must have problems in the social area of the
type seen in autism and at least in one other area
• The relationship of PDD-NOS to autism
remains unclear
• There may be several subtypes of
PDD-NOS
• Most common disorder in group
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Epidemiology of autism
• See Fombonne (2005)
• Issues
– Study design
– Changes in definitions
– Sample Size/ case findings
• Smaller studies: higher rates
• Recent studies: higher rates
– Educational/ services issues
• “diagnostic substitution”
– PDD (broad) 1 in 150 or so
– Autism (1 in 800 to 1000)
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95% Confidence Intervals
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Epidemiology – Is the frequency
increasing?
• No question that more cases are being
identified but is there a ‘real’ increase?
• Issues:
– Changes in definition
– Better diagnosis at both ‘ends’ of the
spectrum
– More awareness of the condition
– Implications for service (diagnostic
substitution)
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Advances in Neurobiology
• Limitations of early research
– Unclear who was being studied
• In the 1970’s
– Validity of autism as a distinct category
was established
– Longitudinal studies:
• High rates of seizure disorder
– Family studies
• Significant genetic contribution to autism
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Onset of seizures in autism
Rates of first seizure (excluding febrile seizures)
From Volkmar and Wiesner (2009)
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Medical Conditions and Autism
• Historical perspective
• Swings of the pendulum
– Problems with case reports
– Strongest associations
• Fragile X, tuberous sclerosis
• Epilepsy
– Associations that now seem dubious
• Congenital Rubella
• PKU
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Neurobiological Findings
• High peripheral levels of serotonin
• High rates of seizure disorder
• Persistent primitive reflexes
• Increased head size (toddlers)
• Morphological changes in CNS
• Minicolumns, mirror neurons
• Fusiform gyrus and faces
• Placental abnormalities
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Autism and The Brain
•
Areas of Possible Difficulty
Functions
•
Prefrontal Cerebral Cortex
Social thinking
•
Hypothalamus
Attachment behaviors
•
Amygdala
Social orientation,
•
emotional learning
•
Fusiform Gyrus
Face recognition
•
Middle Temporal Gyrus
Recognition facial
•
•
Expression
Pulvinar
Emotional relevance
•
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Genetics of Autism
• Original impression
no genetics BUT
– Studies of MZ and
DZ twins reveal high
concordance for
autism AND a range
of other problems
100
90
80
70
60
Cog or Soc
Cog + Soc
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PDD
Autism
40
– 2-10% of sibs have
autism
• Implications: Likely
synergystic effects
of several genes
• Note nature of
increased risk for
sibs
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20
10
0
MZ Twins
DZ Twins
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Environmental Causes and
Autism
• Animal models
– Difficulty to produce to date
– Identification of genes will help
• Immunizations and Autism
• Environmental Toxins and Autism
– Heavy metals
– Drugs/other toxis
• Cluster cases
• On balance data for environmental
causes NOT robust (see Wing and
Potter, 2002)
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Outcome in autism
• Issues in research
– Howlin, 2005
• Differences in method, changes in
criteria
• In general trend has been towards
greater improvement
– Better adult outcome
– More individuals with language
– Higher levels of IQ
• Problems do remain
– Difficulties understanding ‘normal’ ‘cure’
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Treatment
• Historical perspectives
• NRC report
– Structured intensive intervention
– Commonalities (and differences) in
programs
– NOT every child gets better
– As a group improved/improving
outcomes
– Early intervention
• Pharmacological treatments
– Early efforts – major tranquilizers
– Newer studies
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