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Autism Spectrum Disorders (Genes (Aetiology) (Frith et al (2003) (Complex…
Autism Spectrum Disorders
Overview
History
Leo Kanner (1943)
Classic
First use of term infantile autism
Inability to relate to others
Poor use of lang
Excellent rote of memory
Perceptual sensitivites
Obsessive desire for sameness
New form of emotional disorder
Hans Asperger (1944)
Lack of empathy
Can't from friendships
One-sided conversations
Intense specialist interests
Clumsy
Little professors
Asperges > no longer used
Noticed cluster of characteristics to do with autism
Happe et al (2006)
No single cause for diverse symptoms defining autism
Behavioural fractionation of social impairment, communication difficulties + rigid/repetitive behaviours
Twin data = largely overlapping genes + cog level attempts for single explanation = failed
Cognition
Social Cognition Deficit
Theory of Mind ASD
ASD = poor ToM
Individuals can pass ToM task, but require verbal mental age of 9
Better lang can help
Different strategies used to help pass > still processing just in a different way
Pellicano (2010)
- poor FB, planning ability, set shifting + enhanced local processing (not universal profile)
Implicit ToM
Eye-tracking study suggested lack of spontaneous eye gaze towards expected box in ASD adults
Lack of automatic ToM processes?
Hard to interpret implicit tasks: do they measure ToM specifically, or domain general processes like violation of expectation, reaction to novelty
ASD seen to have no difference in the box they look at
Failure to orient to social stimuli early in life: reduced fixations to face/eyes, reduced preference for child directed speech
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Decreased participation in social interactions
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Poor joint attention/gaze following
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Poor understanding of social interaction/ToM, disruptions to lang learning/pragmatics
Early social deficits
from 12 months
Less likely to initiate joint attention through pointing, showing or gesturing
Limited gesture repertoire/use of gesture
Atypical use of gaze to regulate social interaction - also evident in children with other atypical outcomes
Reduced gaze to face and less social smiling
Causally related to later phenotype?
Usually emerging at similar point in time to other behavioural problems, not primary
Without another high-risk comparison group, no way of knowing if deficits are specific to ASD
More longitudinal studies needed - multiple links in chain
Lots of phenotypic heterogeneity - group means can mask sig within group variation
Early skill deficits reflect co-morbid deficits?
Weak Central Coherene
Focus on individual/local elects at expense of global/holistic meaning
Explains apparent skill at solving certain visuospatial tasks
Explain pragmatic lang impairments - need drive for coherence in order to integrate different pieces of information in context
3 Executive Dysfunction
Set of functions necessary for flexible, future-oriented behaviour
WM, Inhibitory control, Attention flexibility, Planning
E.g. Towers of Hanoi puzzle
Multiple deficits?
Together = better mapping than separate
Brunderson et al (2015)
Assessed large number of adolescents with ASD, their twins, + typical peers on number of different cog tasks
Multiple deficits associated with more severe symptom profile
ASD = atypical in more cog tasks
Pellicano et al (2006)
All three deficits predict group membership better than deficits in isolation
Sig group differences
Independent/domain general
Longitudinal
Measured EF, ToM, CC
Relationships between measures changed over time
Children with impaired ToM but intact EF, but never other way round
Against multiple deficit view
All measures strongly correlate with verbal IQ
No other measures of social behaviour
Geschwind (2011)
Combinations of abnormalities in lang, social cog, mental flexibility
Not signle disrder, neurodevelopmental syndrome
Susceptibility genes identified
ASD = etiologically heterogeneous + clues about pathophsiology
Behaviour
Diagnosis
DSM-IV: Pervasive Developmental Disorders
Different outcomes
Autistic disorder + Asperger syndrome > fall under broader term
Rhett syndrome
Childhood disintegrative disorder
PDD-NOS (pervasive developmental disorders not otherwise specified)
Diagnostic criteria
Triad > reciprocal social interaction, verbal/nonverbal communication, restricted + repetitive behaviour
Onset before 36 moths
Delayed lang acquisition (except Asperger Syndrome)
Perceptual Disturbances
DSM-5 (2013)
Autism spectrum disorder
Social Communication Disorder (similar social difficulties to Autism)
Subdivisions = not reliable so now two disorders
Diagnostic criteria
Diad > social communication and social interaction, restricted repertoire of interests/behaviour
S = social-emotional reciprocity, nonverbal communicative behaviours, developing/maintaining relationships
R = stereotyped behaviour, routines/rituals/rigidity, highly restricted/fixed interests, unusual sensory interests
Severity level important
Two domains of impairment
Social communication + interaction
Restricted, repetitive patters of behaviour, interests or activities
Level 1 - requiring support, Level 2 - requiring substantial support, Level 3 - requiring very substantial support
Clinical Specifiers
Prevalence + Demographics
1% of pop (compared to pre-1980s 4/10,000)
Increasing?
Spectrum: broadening of diagnostic criteria
Awareness: practitioners, schools, parents
Heritability?
Environment
Baird et al (2006)
higher than previously recognised
better ascertainment, broadening diagnostic criteria, increased incidence
need to recognise needs of children
~ 30% experience regression of typical skills, lang
Male:Female, 4:1
Life long disorder > variability in presentation
16% = psychiatric disturbance in adulthood
IQ strong predictor of outcome
Comorbidity
Intellectual impairment (variable) 50-75%
Psychiatric disorder 70%
Lang impairment 30-75%
ADHD ~30%
Recent links with alexithymia - difficulties naming emotions/feelings
~ 15% = additional medical condition
Special talent or savant skill - only 1% in general pop
Assessment
Diagnosis based on multi-disciplinary assessment
Parent interview - developmental history 4-5 yrs
Direct behavioural obersavtion
Cognitive assessment = useful not diagnostic
Research gold standards
Autism Diagnostic Interview - parent interview
Autism Diagnostic Observation Schedule - Semi structured interview with child
Genes (Aetiology)
Important!!
Family risk: 10% of siblings affected (recurrence rate, community samples)
Twin studies: heritability estimates of 60-90%
Molecular genetics: evidence for multiple genes of small effect (no clear mapping 1-to-1)
Broader Autism Phenotype: 20-30% relatives social.cog abnormalities, don't necessarily meet ASD criteria
Environmental factors may also be important
Vaccines (MMR)
Refrigerator mothers
Facebook
Telephone mast
Pollutants, toxins, diet, low vitamin D in pregnancy
Obstetric factors just as likely to be consequence as cause
Frith et al (2003)
Complex disorder = heterogeneous > phenotypic + etiology
Genes + neurobiological mechanisms that underly behavioural symptoms + hampered by heterogeneity
Distinct subgroups based on neurocognitive profiles
Two kinds = lang profiles, cog profiles
Brain
Neurobiology
Enlarged head circumference
Normal at brith, but 10% larger at 3/4
Early overgrowth of neurons
Not good indication
Increased cell size and packing density
Good/robust indicator
Esp. in regions that sub-serve emotion/social behaviour + in cerebellum
Brain atypicality <-> atypical behaviour/cog
Abnormalities in synaptic pruning
Loosing connections - specialisation
Under pruning or over pruning
Thomas et al (2015)
Over pruning
Overly aggressive pruning in infacny/early childhood
Exaggeration of normal phase
Thats why 1st few months = typical + why sensory/motor go first
Reflect two different profiles
Poor neural connectivity
While matter abnormalities
Structural/functional MRI studies showing differences in ASD - cause or consequence? unique to ASD? small Ps + within group heterogeneity
Precursors
Rationale
Problem = stable diagnosis before 3 = tricky
Siblings of children ASD = greatly increased risk for developing disorder
Study infants from birth, before ASD is apparent
Infant-siblings design
Group infants at high risk (older sibling with ASD
Some later diagnosed
Some not meet criteria > broader phenotype/other difficulties, typical outcomes
Group of infants at low-risk (older typical deve siblings)
Compare groups on early behavioural + cog measures > precursors to later diagnosis
Studies of infant siblings at high genetic risk of ASD
Cortical suface
Hazlett et al (2017)
Expansion as early biomarker for later ASD diagnosis
Tested 106 infants high risk, 42 low risk
Hyper-expansion of cortical surface area between 5 and 12 months predicted ASD diagnosis age 2, but only 15 diagnosed
Early brain changes precede symptoms
Observed brain enlargement - retrospective circumference + longitudinal volumes
Imaging may identify changes before diagnosis
Elsabbagh + Johnson (2010)
Babies about autism
Rarely diagnosed before two > little known about early symptoms/causes
Determine earliest manifestations of condition > focus on infants at genetic risk for autism
Overt behavioural symptoms emerge around end of 1st year
However, lab brain function - differences in groups of infants at-risk compared with low risk controls during 1st year
Some = early differences - do not receive diagnosis
Search for earlly markers > infants at risk present persuasive model for gene enviro interactions leading to variable developmental pathway
Early signs = \/ response to name, difficulties in visual attention, impairments in joint attention, motor delays, delays in communication, 6 mnths > atypical EEG