AUTISM
SPECTRUM
DISORDER
DSM-V Criteria
• Criterion A: Persistent deficits in social communication and
interaction
• Can include social-emotional reciprocity, nonverbal communicative
behaviors, developing/maintaining relationships
• Criterion B: Restricted, repetitive patterns of behavior
• Repetitive motor movements (rocking), ecolalia, insistence on
sameness and a routine, highly restricted, fixated interests, unusual
interest in sensory aspects of the environment
• Symptoms must be present in early developmental period and
cannot be better explained by intellectual disability or global
developmental disability
• 3 levels of severity
• Viewed as a dimensional disorder
• Specifiers for each criterion
Secondary Features
• Intellectual disability
• Often large discrepancies in abilities in high functioning kids
• Motor disabilities
• Odd gait, clumsiness, walking on tiptoes
• Self-injury
• Inattention
• Disruptive behavior
• Catatonia
• Possible, not particularly common
• Most likely during adolescent years
Controversy
• DSM-IV included categories for Autism, Pervasive
Development Disorder NOS, High Functioning Autism,
and Asperger’s Syndrome
• Sevin et al (1995) studied 34 kids with autism and PDDNOS. Did not find discrete categories.
• Categories were collapsed into Autism Spectrum – PDDNOS, HFA, and AS now “on the spectrum”
• Concern about retaining diagnoses, receiving services,
stigma
Controversy
• Intent was NOT to remove anyone’s diagnosis
• Will actually help some higher functioning kids get services
• Everyone should convert to Autism Spectrum with
specifications if criteria used correctly
• DSM-IV included category for communication difficulty
• This is covered by DSM-V criteria A and B. Separate category was
not needed
DSM-V Schematic
Genetics
•
Unknown
Core Symptoms
• Social Deficits
• Restricted, repetitive
behaviors
Biological
Substrate
Secondary Symptoms
• Unknown
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Intellectual, motor disabilities
Self-injury
Inattention/Disruptive Behavior
Catatonia
Assessment – ADI-R
• Gold Standards are Autism Diagnostic Interview –
Revised (ADI-R) and Autism Diagnostic Observation
Scale (ADOS)
• ADI-R is semi-structured interview for caregivers
• 93 items, about 2 hours
• Based on DSM-IV criteria (Communication difficulties, social
reciprocity, restricted, repetitive behaviors)
• Chakrabarti and Fombonne (2001) found that interrater reliability
was excellent on those subscales
Assessment - ADOS
• Observational
• Can be used in nonverbal 2-year-olds – verbal adults and
all between
• 4 Modules:
• Pre-Verbal-Single Words
• Phrase speech
• Fluent Speech
• Activities for daily living, plans, hopes
Psychometric Issues in Diagnosis
• Low test-retest reliability on many instruments
• Little investigation of specificity or validity of screening
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measures
Lack sensitivity and specificity
Severity scores quantifying social deficits needed
Sometimes alternative thresholds are suggested for
research vs clinical diagnoses
Children of color or of less-educated parents less likely to
receive ASD diagnosis than Caucasian kids or kids with
well-educated parents (Mandell et al 2009)
Psychometric Issues in Diagnosis
• In a study of children with language disorder, both the ADOS and ADI-
R were administered to children
• Studied 21 children ages 6-9
• Correlation between instruments low (Bishop 2011)
• Χ^2 (4) = 1.86, p= .762
Social Problems
• Most universal, specific characteristic of ASD
• Consistent and replicated across studies
• Lack joint attention, theory of mind
• Cannot correctly assign motives, understand someone’s goals, difficulty
participating in spontaneous symbolic play
• Other groups show problems with theory of mind but may not show same
deficits in joint attention
• Down Syndrome, severe hearing impairment
• Pay proportionately less attention to people than objects
• Spend less time than TD kids doing something that shows intent
• Children are attached to mothers as much as age- and IQ-matched TD
kids (Rogers et al., 1991)
• Tend not to point, show objects – attention-sharing behaviors (Sigman et
al., 1986)
• Do not seem to recognize emotions (facial expression, gesture,
nonverbal vocalizations of emotion)
Restricted, Repetitive Behaviors
• Verbal and nonverbal repetitive, stereotyped behaviors
• More heterogeneous and context-dependent than social
deficits
• Including them on diagnostic instruments increases
specificity with little change in sensitivity
• One study showed only 9 of 2700 children with ASD
diagnosis did not show any RRB’s (Lord et al., 2012)
Restricted, Repetitive Behaviors
• Four subdomains:
• Motor stereotypies – lining things up, flipping things, step counting,
unusual responses to sensory input, rocking
• Some of these may be common in young children – clinicians must look at
the number and intensity of behaviors to discriminate TD from ASD
• Tend to emerge early in life but are somewhat malleable
• Most common subdomain
• Rituals and sameness – like Rain Man’s pancake Tuesday
• Prevalent in about 25% of ASD population
• Develop later than motor type, stable throughout life
• Circumscribed interests – highly fixated or unusual interests
• A particular movie, cartoon character, topic, the phone book, shoe size
• Self-injurious behavior – hand flapping, hitting
• Present in other disorders
• More common in ASD than general population
• Subdomains show different trajectories
Language Delay
• Language delay is not specific to ASD
• Delays in receptive language may be specific to ASD as
opposed to other communication disorders (Philofsky, Hepburn,
Hayes, Hageran, & Rogers 2004)
• Not yet connected to specific neurobiological problem
• Language (particularly receptive language) scores
correlate with IQ (specifically verbal) (Luyster et al., 2008)
Prevalence
• In 1990’s it was 1 per 2,000, including Asperger’s
Syndrome 1 per 1,000 (Tanguay 2000)
• Current prevalence rates around 1/150 to 1/100 for ASDs
(Croen et al., 2002, Rice, 2009)
• True increase in milder cases
• True increase of all case types
• More awareness
• Problems with diagnostic instruments
• Incorrect diagnoses
• Studies differ in screening methods, diagnostic instruments,
diagnostic criteria
• Diagnosed 4x as often in males than females
Diagnostic Criteria
• Projects using ICD-10 criteria show prevalence
around 1/2,000 (Autism) and 1/600 (Autism plus
other pervasive developmental disorders)
• Studies using less strict criteria show much
higher prevalence rates
• Bryson et al., 1988, 1/1,000 Used ABC (checklist)
• Sugiyama and Abe (1989) used DSM-III and noted
1/760
• Ehlers and Gillberg (1993) set of criteria specifically
designed to diagnose ASD found 1/143
Onset and Course
• Symptoms are usually noted first in months 12-24 of a
child’s life
• Delayed language, odd play patterns, lack of social interaction
• Pay attention to type, frequency, intensity of symptoms
• Can experience developmental plateaus or regression
• Rarely a severe regression after 2 years of normal development
• Onset must occur by age 3
• Individuals generally improve throughout lives
• Robust diagnosis
• Sensitivity of .82 and specificity of .87 (Volkmar et al 1994)
Common Comorbidities
• 70% of ASD individuals have one comorbid disorder, up to
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40% may have 2 or more (DSM-V)
Medical conditions such as epilepsy and sleep problems
somewhat common
Comorbid diagnoses of ADHD, anxiety and depressive
disorders, and developmental coordination disorder seen
First degree relatives have higher incidence of major
depression and social phobia than the rest of the
population (Bolton et al., 1998)
Relatives have 20% frequency of social phobia (Smalley et al.,
1995)
• 10 times higher than controls
• Over half (64%) had first episode before the birth of autistic child
Common Comorbidities?
• Posited that autism shared genetic cause and thus
comorbidities with:
• Fragile X (no more than 2-5% have FRA-X mutation,
Bailey et al., 1993)
• Tuberous sclerosis (mostly seen in autistic people with
severe deficits, Guiterrez et al., 1998)
• Celiac disease (Pavone et al., 1997 study of 120 people
with celiac disease showed none with diagnosis of
autism based on DSM-III, nor celiac disease in the 11
patients with autism)
Biological Contributions
?
Genetics
• Concordance rates in monozygotic versus dizygotic twins
range from 60-91% (MZ), 0-10% (DZ) (Folstein and Rutter, 1977,
Steffenburg et al., 1989, Bailey et al., 1995.)
• Variation in behavioral and cognitive deficits as great within
MZ pairs as between pairs
• These findings suggest that autism is highly heritable (broad cognitive
and social impairment)
• Different sets of genes do not act to produce different symptoms
Genetics
• Gender disparity led some researchers to wonder if ASD
linked to X chromosome
• Hallmayer et al (1996) found no major gene effect on X
chromosome causing autism
• International Molecular Genetic Study of Autism
Consortium (1998) found possible connections for regions
on chromosomes 7 and 16
• Significance is not yet known
• Found most often in those with severe language delays
Neuroligins and Neurexins
• Neuroligins and neurexins are the “building blocks” of
synapses
• Small percentage of those with ASD have mutations
which can cause neurexin deletions
• This affects synaptic formation and function
• May increase risk for developing ASD
Neuropharmacological Studies
• Cook and Leventhan (1996) noted that serotonin may be
involved in many of the symptoms of autism
• This is neither surprising nor particularly helpful
• One study found people with ASD have autoantibodies to
brain serotonin receptors (Todd and Ciaranello, 1985)
• Two studies failed to confirm findings
• People with ASD may have increased 5-HT on blood
platelets
Electroencephalography
• ASD people unlikely to show more EEG abnormalities
than the normal population
• This is nonspecific and not particularly helpful
Neuroimaging and Neuropathological
Studies
• General difficulty confirming neuroimaging findings
• Different measures used to correlate with brain function, generally
weak measures
• Future studies will probably add comparisons of ADHD or language
impairments to ASD
• Increased volume in amygdala, hippocampus, and limbic
system, decreased Purkinje cells
• We don’t know how high functioning these individuals were
• Harris et al. (2006) claimed to find abnormal patterns of activity
in the brains of those with ASD and claimed near-perfect
identification
• This has not been replicated
• Ongoing NIMH effort to form neurobiologically based
dimensions to help diagnose ASD, but no published data yet
Macroencephaly
• 14-30% of ASD people have increase in head
circumference (Fombonne et al., 1999)
• Developed in early/middle childhood (Lainhart et al), but this finding
relies on retrospective data
• Increase is in temporal, parietal, and occipital lobes (not frontal)
• Cause and effects of increase unknown
• Not correlated with IQ, verbal ability, seizure, other mental illness
Neuropsychological Patterns
• Compared to normal controls, ASD people have intact or
superior performance in attention, simple memory, simple
language, and visual-spatial domains
• Impaired in skilled motor tasks, complex memory,
complex language, and reasoning
• While interesting, not helpful in understanding much more
about autism than is already known
Neuropsychological patterns
• Executive functioning deficits
• Impairments in cognitive flexibility and set-shifting
• Nonspecific to autism
• May underlie theory of mind deficits
• Price et al., (1990) study of 2 individuals with
widespread frontal damage (early in developmental
process)
• Both showed severe impairment in role-taking, also
seen in ASD and is part of theory of mind
Neuropsychological Patterns
• 20 ASD, 19 Down’s Syndrome kids, 20 TD kids
• Two tasks:
• Delayed Non-Matching to Sample
• Rule-learning ability, visual recognition memory
• Amygdala and hippocampus
• Delayed Response
• Working memory and response inhibition
• Dorsolateral PFC
• Social and nonsocial stimuli task
Vaccines
Vaccines
• One study published in a medical journal concluded a link
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between vaccines (MMR) and autism
Article was fully retracted in 2010
Lead author Andrew Wakefield had many undeclared
conflicts of interest and manipulated some of his data
Found guilty of serious medical misconduct and no longer
allowed to practice medicine
Study has been disproved many times since its original
publication in 1998
Vaccines
• DeStefano et al (2013) evaluated 256 ASD kids and
752 TD kids matched on birth year and sex, ages 613
• Confirmed diagnoses via ADI-R and ADOS
• Study inclusion criteria required elevated scores on both
assessments and onset before 36 months
• Obtained vaccination histories,
• Looked at total antigen exposure, amount per day
• No significant differences
Environmental Factors
• Mouridsen et al. studied 328 children with autism,
“autism-like conditions,” or “borderline child
psychosis”
• Children with autism had greater incidence of births
in March or August
• Children with autistic-like conditions most often born
in May and November
• Essentially, this means nothing.
Environmental Factors
• Rutter 1998 study looked at institutionalized children in
Romania sent to the UK
• Experienced horrible living conditions
• 7/165 met criteria for autism based on a screening
questionnaire
• Severe social deprivation may lead to autistic-like social
and emotional difficulties
• Could less severe social deprivation interact with genes
to cause autism in some kids or worsen symptoms?
Treatment
Medication
• Tricyclics and SSRI’s seem to decrease hyperactivity,
anger, and compulsive behaviors (Gordon et al., 1993, Brodkin et al.,
1997)
• Neuroleptics may be effective in reducing hyperactivity,
impulsivity, aggressiveness (Potenza et al., 1999)
• (Obviously)
• Pharmacological interventions have a limited role
Medication
• Double-blind study of 40 kids, given placebo or
haloperidol
• Given semistructured interviews, rated by teachers on
Connors Parent-Teach Questionnaire
• While on haloperidol, kids showed significant decreases
in withdrawl, hyperacitvity, abnormal object relationships,
fidgetiness, negativeism, angry affect, and lability of affect
as compared to baseline or placebo
Therapy
• The key is early intervention!
• This means developing specific measures is crucially
important
• Two types
• Traditional behavior learning (ABA)
• Focus is on adult control and child compliance, uses
positive reinforcement
• Social-pragmatic teaching (child-centered therapy,
incidental teaching)
• Focuses mainly on social skills
• Focus of therapy is on increasing independence and
quality of life
Applied Behavior Analysis
• Gold standard
• Based on behaviorism
• Uses positive reinforcement to decrease maladaptive and
unwanted behaviors, increase adaptive behaviors
• Uses negative reinforcement/negative punishment when necessary
(rarely)
• Treatment can begin when children are as young as 3
• In severe cases, focus is on compliance
• Intensive (20-40 hours/week), one-on-one format
• Targets a wide range of skills
• Includes parents (and important others when possible –
siblings, teachers, etc.)
ABA Effect Size Metrics
• Meta-Analysis of 22 studies (Virués-Ortega 2010)
• Different outcome reported: full-scale IQ (18 studies),
nonverbal IQ (9), receptive language (10), expressive
language (9), language composite (5), adaptive behaviorcommunication (10), adaptive behavior – daily living skills
(10), adaptive behavior – socialization (10), adaptive
behavior – motor skills (3), overall composite adaptive
behavior (14)
• Mean age ranged from 22.6-66.3 months
• Some studies included PDD-NOS
ABA
• ABA positively impacted:
• IQ – 1.19 no evidence of effect from intensity/duration
• Nonverbal IQ – 0.67
• Receptive language – 1.48
• Expressive language – 1.47
• General language skills – 1.07
• Communication – 1.45
• Daily living skills – 0.62
• Socialization - 0.68
• Motor skills – 0.71
• Adaptive behavior (composite score) – 1.09
• ABA leads to long-term medium to high positive effect sizes
for adaptive behaviors
• Social support (siblings) moderate response (Hastings, 2003)
CBT
• CBT has been modified for ASD kids presenting with
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anxiety
Goal is to remediate social skills in the hopes that this will
translate to decreased anxiety
Random assignment to 16 sessions of CBT or 3-month
waitlist
CBT model emphasized adaptive behavior, parental
training, school consultation
78% of CBT group had reductions in anxiety on Clinical
Global Impressions-Improvement scale compared to 8.7%
of waitlist
CBT did not reduce self-reports of anxiety
Virtual Interactive Environments
• Used for teaching social skills, theory of mind
• Practical situations, such as taking the bus, going to the
grocery store
• Some studies use robots (can play games with kids)
• Interactions (eye gaze, tough, contact time) increase
• Not yet known if this generalizes to real life
Complimentary and Alternative Medicine Therapies
(Mostly pseudoscience)
• Auditory integration Training
• Facilitated communication
• Nonverbal/severely handicapped people are
suddenly writing emotional, grammatically correct
messages
• This is due to the facilitator (Bomba et al 1996)
• Viamin B6 and Magnesium
• 30% of children showed improvement in
Martineau (1998) study.
• Other studies show no improvement
• Changes in nutrition
• All are ineffective
Genetics
Some combination of:
• Neurexin and
neuroligin abnormality
• Chromosome 16
abnormality
• Chromosome 7
inversion
Genetics
Some combination of:
• Neurexin and
neuroligin
abnormality
• Chromosome 16
abnormality
• Chromosome 7
inversion
Genetics
Some combination of:
• Neurexin and
neuroligin
abnormality
• Chromosome 16
abnormality
• Chromosome 7
inversion
Therapy
•
Core
Features
ABA
• Social
difficulties
• Restricted,
repetitive
behaviors
Biological
Substrate
Some combination of:
• Enlarged amygdala,
hippocampus
• Abnormal fusiform gyrus
• Macroencephaly
• Decreased Purkinje cells
• Increased 5-HT
Biological
Substrate
Some combination of:
• Enlarged amygdala,
hippocampus
• Abnormal fusiform gyrus
• Macroencephaly
• Decreased Purkinje cells
• Increased 5-HT
Medication
• SSRI’s
• Antipsychotics
Secondary
Features
Environment
• Abuse
• Social support
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•
•
Intellectual
disability
Inattention
Motor
problems
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