Psych 2AP3

Autism Spectrum – Week 4

History of Autism Category

1943 – Described by Leo Kanner (John Hopkins)

- “he seems to be self-satisfied. He has no apparent affection when petted. He does not observe
the fact that anyone comes or goes, and never seems glad to see father or mother or any
playmate. He seems almost to draw into his shell and live within himself”

1944 – Described by Hans Asperger

1943-1989 – 3,000 autism articles published
1990-2004 – 3,700 autism articles
2007 – 1,000 articles on autism
2008 – 1,300 articles on autism

Hughes (2009): nearly every conceivable problem that a child can have may be found in these
unfortunate children and nearly every conceivable etiology has been mentioned to account for this
serious disorder

DSM – 5 Diagnostic Criteria

Deficient social interaction, communication:
Deficits in social- emotional reciprocity:
- Lack of reciprocal conversation
- Reduced sharing of interests, emotions, affect
- Failure to initiate or respond to social interactions
Deficits in nonverbal communication:
- Poorly integrated verbal, nonverbal communication
- Abnormal eye contact or body language
- Deficient use and understanding of gestures
- Lack of facial expression and nonverbal communication
Deficits in developing, maintaining relationships:
- Difficulty adjusting behaviour to social context
- Difficulty sharing imaginative play, making friends
- Total absence of interest in peers

Restricted, repetitive patterns of behaviour:

- Stereotyped repetitive movements, speech, etc:
o Lining up toys
o Echolalia
o Idiosyncratic phrases
- Insistence on sameness of routines or rituals
- Fixated interests of unusual intensity or focus
- Hypo- , hyperreactivity to sensory input:
o Apparent indifference to pain, temperature
o Adverse response to specific sounds, textures, etc
o Excessive smelling, touching of objects
1
ASD
 o Fascination with lights, movement
DSM – 5 Diagnostic Criteria
- Symptoms present in early developmental period
- Symptoms cause “clinically significant impairment in social, occupational, or other important
areas of functioning”
- Symptoms not better explained by intellectual disability, or global developmental delay
- Specifications:
o With or without intellectual impairment
o With or without language impairment
o Associated with medical, genetic, environmental condition
o Associated with another mental, behavioural disorder
o With catatonia (lessening of movement)

Associated Features
- Intellectual and/or language impairment-
- Motor deficits:
o Unusual gait
o Clumsiness
- Self-injury
- Disruptive or challenging behaviours
- Prone to anxiety, depression (adolescents or adults)

Prevalence: Autism Spectrum Disorders

- Yeargin-llsopp et al (2003): 35/10,000
- CDC (2007) 67/10,000*
- Autism Ontario: 70/10,000
- CDC (2008): 113/10,000
- Nedsac (ON) (2012): 113/10,000*
- DSM-05 (2013): 100/10,000
- NHIS 3-17 (2016): 276/10,000
- CDC (2018) 168/10,000*

SE Ontario Prevalence of Autism Spectrum Disorders

2
ASD
Increased Prevalence
- Between 1966 – 1993: 5/10,000
- Between 1994 – 2004: 13/10,000
- California, 1987 – 1998 : 270% increase
Why the increase?
- Increased awareness of the disorder
- Earlier diagnosis
- Changes in diagnostic practice
- Diagnostic substitution
- Environmental toxins?

3
ASD
Epidemiology – General
- 4/5 times as common in boys than girls
- Highest male/female ratio in normal range of cognitive function
- Lowest male/female ratio in extreme low range of cognitive function
Epidemiology – Comorbidity
- 70% comorbid for one or more other disorders; 40% for two or more
- Intellectual disability 30-50%
- ADHD 30-40%
- Anxiety or phobic disorder 40%
o Social anxiety disorder 30%
- Oppositional defiant disorder 28%
Etiology – Psychological Processes
General Intellect:
- 40%+ have intellectual disability
- Language, abstract reasoning X
- Visuo-spatial processing ✓
- Attention to detail✓
- Rote memory✓

Savant abilities:
- Mathematics, especially rapid calculation
- Music
- Calendar calculations

Motor Development Problems

60% = dysdiadochokinesia- rapidly alternating movements
33% = problems with gait or balance
15% = abnormal muscle tone – muscles too tense
5% = abnormal reflexes
5% = abnormal motor coordination
o Impaired finger, heel tapping
o Slow or shuffling gait
o Rigidity, tremors, in arms

4
ASD
Theory of Mind
Deficit in understanding mental states
- States of knowledge or ignorance
- Pretense, deception, lying
- Jokes, irony, sarcasm
Criticisms of ToM in autism:
- Social impairment before precursors of ToM
- ToM & communication emerge independently
- ToM found in high functioning autism
- ToM deficits in intellectual disability

Face and Emotion Perception

- Sort faces by physical features not emotions
- ERP differences between familiar/unfamiliar objects, not faces (mother vs stranger)
- Different brain areas activated:
o Typicals: frontal lobes, amygdala, lateral fusiform gyrus
o Autism: superior temporal gyrus
- Why some autistic children in normal range?
o Only automatic processing of emotion disabled?
o Use alternative processes to decode faces and emotions?
Extreme Male Brain Theory
Systematisers:
- Identifying, understanding rules that govern a system
Empathizers:
- Recognizing and responding to the feelings of others
- Males are systematisers (weak on empathy)
- Females are empathizers (weak on systematizing)
- Autism = extreme male brain

Explains social disability in autism

- Lack of empathic understanding of others
Explains islets of special ability:
- Math, art, music all depend on systematizing
Explains ritualistic interests:
- Predictable, systematic behaviour

Assortive mating between systematisers:

- Parents of autistic children (POA) faster on embedded figures test than others
- POA more likely to have systematizing fathers (e.g engineers)
- Male/female brain activity different when empathizing or systematizing: POA show male pattern
- POA higher on self-reported autistic traits

Intense World Theory

- Strong response to sensory stimulation
- Valproic acid (VPA) and autism
- VPA moms = 10% ASD children
5
ASD
 - In utero VPA (rats):
o Brainstem damage
o Social withdrawal
o Hyper-reactivity to sensory stimuli
o More cortical cells
o More intra-, extra-cortical connections
- Brain has too many connections
- Brain hyper-reactive stimuli
- Individual withdraws to cope with chaos
o Social withdrawal= language decrement
o Repetition, stereotypy = controlling chaos
o Source of face perception problems
- Amygdala = rapid conditioning of fear
o Leads to fear of world & withdrawal

Empathy Imbalance Hypothesis

Cognitive versus emotional empathy:
- Cognitive (CE) = understanding others epistemic mental states (same as ToM)
- Emotional (EE) = feeling what others feel as a result of other’s emotions
Autism= high EE, deficient CE
Autistic symptoms= protection from intense empathic emotions
Empathy Imbalance Hypothesis
“ avoidance behaviour, obsessive interests, and insistence on routines may regulate the stress that
stems from living among people whose behaviour is difficult to comprehend but whose emotions are all
too readily sensed. Low CE ability may reduce the salience of social stimuli and render the social world
unpredictable and confusing. High EE sensitivity may compound this and act as a deterrent to attending
to the social world. In normal development, people can use CE to regulate and resolve their EE
responses’ people with autism may try to control and narrow their attention in an attempt to regulate
EE.”

Evidence for hypothesis:

- Children with autism show more facial affect than other children in empathy paradigm study
- Adults with autism show more facial EMG affect than other adults when shown expressions of
happiness, fear
- Children with autism show normal electrodermal response to pictures of distressed people;
often look away from such images
- Aspergers adults report high levels of distress to others’ suffering
- Data suggest eye contact with others ‘painful’ for people with autism

Empathy Imbalance Hypothesis

- What about high comorbidity with intellectual disability?
- What about language development and idiosyncratic language?
- What about face-processing deficits?
- What about early eye-tracking data and cuddling failure?

Theories of Autism
- Theory of Mind (TOM)
6
ASD
 - Intense world theory (IWT)
- Extreme male brain theory (EMB)
- Empathy imbalance hypothesis (EIB)
- Executive function Theory (EFT)
- Weak Central Coherence Theory

Major Deficits in Autism

- Social cognition
o Face recognition
o Emotion processing
- Language and communication
- Motor behaviour and coordination

Interpret Brain Differences with Caution

Findings inconsistent:
- Some studies find differences in a brain area, some do not
- Some studies find brain areas larger, some smaller
All differences seen as ASD deficits:
- If structure larger in ASD – see that as deficit
- If structure smaller in ASD – see that as deficit
Structures implicated in several disorders
Difference could be effect not cause

7
ASD
Structural/ Functional Abnormalities
Language areas:
- Reduced activity between areas during language processing
Amygdala:
- Fewer cells, fewer dendritic connections
- Or larger amygdalas?
- Less damping of amygdala activity by PFC
- Haar (2014) review finds no clear differences
Cerebellum:
- Fewer cells -fewer dendritic connections
- Abnormalities may be prenatal
- Haar (2014) review finds no smaller cerebellums

Prefrontal cortex:
- Fewer cells – fewer dendritic connections
- Lower blood flow and task-related activity
Temporal lobe & FFA:
- Fewer cells
- Abnormal FFA activity in face perception
- Some studies higher, some lower activity
Mirror neurons:
- Only fire for own activity, not for others
- 2010 studies find normal mirror neuron activity in autism

Structural/ Functional Abnormalities

- Reduced corpus callosum size
- High rate (33%) of seizure activity
o More frequent in females
- EEG abnormalities in 50%
- Brain volume, ventricle volume larger
o Mostly in infancy and early childhood
- Head circumference larger
- Excessive connections in frontal cortex; too few with rest of brain
- In infancy, excessive CSF on brain surface, esp over frontal lobes
- More variability in the location of internal brain networks
- Higher blood flow in frontal white matter, subcortical gray matter

Neurochemistry
Interest in dopaminergic systems:
- Role of dopamine in movement problems
- Dopamine-blocking agents in treatment
Serotonin:
- Elevated blood levels in 33% of autism patients
- Synthesis normally down by age 5; in autism, rises to 150% of normal adult level between ages 2
and 15 years

8
ASD
Autoimmune Factors and Autism
- Up to 25% of ASD associated with autoimmune attacks on fetal brain
- Saresella et al (2016): Compared proinflammatory cytokines in ASD, healthy siblings, healthy
controls
o More inflammatory cytokines in ASD than others
o Reduced production of anti-inflammatory cytokine in ASD
o Altered GI permeability in ASD and healthy sibs

Gut Microbiome and Autism

- High prevalence of GI problems in ASD children; GI problems more severe
- Adams et al (2011): compared GI flora and status in ASD controls
o GI symptoms strongly correlated with ASD severity
o Different levels of some strains of bacteria in ASD versus controls
- Several replications of these general results

Genes and Autism

- Most heritable psychiatric condition
- High concordance rates, heritability:
o MZ concordance = 65-75%
o DZ concordance = 3-10%
o H^2 estimates = 90%+ - gone down to 60% (2014), then 80% (2019)
- Associated with genetic conditions:
o Fragile X, PKU, congenital rubella
o Chromosome 15 duplication

Genes and Autism

- Variable expressivity:
o Susceptible to incomplete variants of autism
o Milder symptoms; atypical autism in co-twins
o Social/communication impairments in 20% of siblings
- Pleiotropy:
o Genes confer susceptibility to other disorders
o Parents:, anxiety, depression, substance abuse
- Etiologically, genetically heterogeneous:
o May have environmental and genetic causes
o Caused by different genes in different cases
o Polygenic etiology

Specific Genes
- Chromosomes 3,5,6,7,13,15,18,19,20
- CNV on chromosomes 2,3,7,15,16,22
- Overall, chromosomes 2,3,5,6,7,13,15,16,18,19,20,22
- Grofodatskaya (2010): genetic syndromes comorbid with ASD suggest epigenetics
- Paternal imprinting? Brain activated genes lead to neural overgrowth (vs undergrowth for
maternal-imprinted genes)

9
ASD
Genes vs “Junk”
- Human genome contains 20,000 genes
- Only 2% of human DNA codes for proteins (coding DNA; genes)
- Remaining human DNA is non-coding (“junk”) DNA
- Humans have fewer genes than many animals and plants

Functions of “junk” DNA

- Enhance or inhibit gene activity
- Produce non-coding RNA:
o Transfer RNA (tRNA)
o Ribosomal RNA (rRNA)
o Micro-RNA (miRNA)
- Prevent damage to DNA
- activate X chromosomes in females

Yuen et al (2016)
- multinational team does whole genome sequencing of 200 ASD individuals to locate de novo
mutations
o de novo mutations (DNM) = not present in parents genome, but present in sperm, egg
DNA, or arise early in fetal development
o looked in ‘junk’ DNA as well as coding
- Results:
o 76% of germline DNM came from father; because more frequent the older the father
o Clustered DMSs (w/I 20 kilobases of each other), majority from mother, and usually near
CNV’s with high mutations rates
o Between 16% and 22% of DNMs in non-coding (‘junk’) DNA

10
ASD
11
ASD
Environmental Risk Factors
- Maternal smoking in 1st trimester
- Caesarian delivery
- Baby small for gestational age
- Older fathers
- Mother exposed to heavy metals
- Mother exposed to pesticides
- Maternal diabetes, obesity
- Mother exposed to air pollution
- Prenatal German measles infection (rubella)
- Mother not born in Europe of N.A
o Lower immunity to viral infections?
- Summer conception (? At least in UK sample)

Treatment
Applied Behaviour Analysis
- Ivar Lovaas
- Shape and reward positive behaviours
- Extinguish undesirable behaviours
Teaching social skills
- Primarily for high-functioning cases
Pharmacotherapy:
- Tranquilizers ( neuroleptics)
- Antidepressants

Orinstein et al (2014):
- 8-21 yr-old ASD cases who met, or no longer met, ASD criteria. All high functioning. Compared
those with ASD, those without:
o Parents were concerned earlier
o Referred to specialists earlier
o Earlier, more intensive intervention
o More likely to receive ABA
o Less likely to receive medication

Treatment Outcomes
Anderson, Liang, & Lord (2014)
- Prospective study of 85 ASD kids from ages 2 through 19
- Intellectual disabilities at age 19 predictable from low IQ results (<70) at age 2
- 25% of those with IQ>70 at age 19, no longer had ASD at age 19. ( 10% of sample overall)
- Those recovered more likely to have received treatment

12
ASD