Autism Spectrum Disorder

Question 1

who first used the word autism?

Answer 1

Leo Kanner and Hans Asperger in 1940s

Question 2

what did autism describe when it was first used?

Answer 2

group of children with some recognizable traits such as preference for aloneness, insistence on sameness, and stereotyped behaviors.

Some of the children (under 3 years) also had remarkable capacity to memorize numbers or sing tunes.

Question 3

what two domains of functioning need to be impaired to get a diagnosis of ASD?

Answer 3

1. Persistent deficits in social communication and social interaction across multiple contexts
2. Restricted, repetitive patterns of behavior, interests, or activities,

Question 4

how does the DSM-V define mild vs severe severity for ASD?

Answer 4

mild: requires some support
severe: requires substantial support

Question 5

what are 3 deficits seen in the social domain of ASD?

Answer 5

social emotional reciprocity, nonverbal communicative behaviors used for social interaction, relationships

Question 6

what are 4 examples of restricted/repetitive patterns of behavior/interests/activities seen in ASD?

Answer 6

1. stereotyped or repetitive motor movements
2. insistence on sameness
3. restricted/fixated interests
4. hyper/ or hyporeactivity to sensory input

Question 7

for an ASD diagnosis, symptoms must be present in ______, must together ______ and cannot be better explained by _____.

Answer 7

early childhood; limit/impair everyday functioning; intellectual disability

Question 8

how are intellectual disability and ASD related?

Answer 8

ID and ASD frequently co-occur

For comorbid diagnoses of ASD and ID, social communication should be below that expected for general developmental level

Question 9

what is social (pragmatic) communication disorder?

Answer 9

Individuals who have marked deficits in social communication, but whose symptoms do not meet criteria for ASD

persistent difficulties in the social use of verbal and nonverbal communication

Question 10

currently, the prevalence of ASD is estimated to be as high as _____ and there are ___ times more males than females with autism.

Answer 10

1 in 44; 4x

Question 11

what are possible reasons for the rise in ASD prevalence?

Answer 11

better awareness and diagnosis or unidentified environmental risk factors are being discussed

Question 12

what are comorbid behavioural problems in ASD?

Answer 12

1. hyperactivity and attention abnormalities
2. anxiety
3. mental retardation

Question 13

explain the hyperactivity and attention abnormalities seen in ASD

Answer 13

ADHD-like symptoms such as hyperactivity, inattention, and impulsivity are frequent among individuals with PDD.

Verbal outbursts are also frequently observed: from tantrums, during which autistic children might slam doors or tip over tables or bang their head with their fists.

Question 14

(T/F): you can have both an ASD and ADHD diagnosis concurrently.

Answer 14

false: adhd is an exclusionary criterion for asd!

Question 15

explain anxiety in ASD

Answer 15

insistence on sameness and the repertoire of fixed behaviours and routines appear to have a relationship
with anxiety.

Features of anxiety problems in ASD overlap with social phobia, GAD and OCD.

It is suggested that individuals with autism do not have the coping skills to manage stress or the ability to cognitively appraise situations they may find anxiety provoking.

Question 16

what is the prevalence of anxiety disorders in ASD?

Answer 16

btw 47-84%

Question 17

about __% of asd children have avg to above avg intellectual ability

Answer 17

44%

Question 18

what are the main differentiating features btw autism and mental retardation?

Answer 18

(i) mentally retarded children usually relate to adults and other children in accordance with their mental age

(ii) there is little impairment of verbal communication in the mentally retarded

Question 19

what are neurological problems seen in ASD?

Answer 19

1. sensory integration abnormalities
2. seizures
3. fagile x syndrome
4. tuberous sclerosis
5. motor disturbance

Question 20

what sensory integration abnormalities are seen in asd?

Answer 20

Multimodal sensory abnormalities, including increased sensitivity to acoustic and tactile, stimuli are common.

Some ASD children are relatively
insensitive to extreme cold or pain.

Question 21

explain seizures in asd

Answer 21

25-30% ASD children experience epileptic seizures (Generalized tonic-clonic or partial seizures; frequency - weekly or less).

The seizures usually start from 8-10 years onwards.

Up to 45% children show some form of EEG abnormalities

Question 22

fragile X syndrome occurs in about ___% of people with asd

Answer 22

2-5%

Question 23

explain tuberous sclerosis in asd

Answer 23

Tuberous sclerosis (swelling or benign tumors in brain and elsewhere) is
found in 3-4% of individuals with ASD.

Studies show that 20-40% individuals with tuberous sclerosis may meet the criteria of ASD diagnosis.

The risk of developing ASD appears greater when temporal lobe tubers and temporal lobe epilepsy and seizures

Question 24

what motor disturbances are seen in asd?

Answer 24

Problems in acquiring motor skills and motor dexterity are often present in children with ASD.

A study suggests that gait features for children with autism may be compatible with patients with cerebellar ataxia: specifically, greater difficulty walking along a straight line, and variable stride length and duration.

Children with autism were also less coordinated and rated as more variable and inconsistent (i.e. reduced smoothness) relative to the comparison group

Question 25

the neurological problems in asd are taken as evidence to support ____

Answer 25

a biological/neural basis of asd

Question 26

It is believed that certain cognitive deficits, especially those related with _________, underlie the social abnormalities in autism

Answer 26

social and emotional cues

Question 27

what is the cognitive theory of asd?

Answer 27

lack the ability to predict and explain the behaviour of other humans in terms of their mental states (theory of
mind or “mentalizing”)

Autistic children have difficulty understanding that people can have different beliefs including false-beliefs.

They have impairments in first and second order representations such as “I think he thinks” or “I think he thinks she thinks”.

In the absence of the knowledge of other peoples’ beliefs, feelings and attitudes, social relationship is difficult to form and maintain.

Question 28

when is theory of mind present in normal children?

Answer 28

4yo

Question 29

what is the ability to mentalize?

Answer 29

using and understanding the words such as “believe”, “know”, “wish”, “desire”, “intend”, and “pretend”.

Question 30

a child with problems of theory of mind may assume that since he is happy, then others ____.

Answer 30

must be happy

Question 31

Because pragmatic/socialization cues are difficult and autistic child does not understand what is going on around him/her, secondary problems such as _________ rather than people occur.

Answer 31

anxiety, ritualistic behaviour, inattention, and interest in objects

Question 32

what evidence supports the involvement of genetic factors in asd?

Answer 32

are affected by another disorder of known genetic cause: tuberous sclerosis, fragile X syndrome, Down syndrome and neurofibromatosis type 1.

Twin studies show a concordance rate of 36-95% in monozygotic twins and 10% in dizygotic twins for ‘broader autistic phenotype’.

The prevalence of autism in siblings of autistic individuals is about 2–6%.

Question 33

what is the polygenic mode of inheritance of asd?

Answer 33

no one gene or variant either necessary or sufficient to express the phenotype.

Question 34

the polygenic architecture of asd is significantly shared with what disorders?

Answer 34

schizophrenia, depression, intellectual disability

Question 35

what are the genetics found from GWAS for asd?

Answer 35

• chromosomes 2q, 7q and 17q
• risk genes: x-lined genes (NLGN3-4), neurexin (NRXN1), postsynaptic density protein (SHANK3), contacting associated protein (CNTNAP2)

Question 36

genes associated with asd are believed to cause an imbalance btw _______

Answer 36

excitatory-inhibitory NT in the brain

Question 37

explain the neurexin-neuroligin-shank in asd

Answer 37

make a complex with PSD95 at the excitatory glutamatergic synapses which stabilizes glutamate receptors to the postsynaptic membranes.

These genes thus modulate excitatory transmission in the CNS.

Question 38

what animal evidence do we have for neurexin-neuroligin-shank in asd?

Answer 38

Transgenic mouse models with alterations in NRXN1, NLGN3, SHANK3 and CNTNAP2 genes have been reported to display some behavioral
and neural phenotypes of ASD.

A recent study in macaque monkeys with embryonic CRISPR- mediated SHANK3 mutation showed that mutant monkeys display ASD-like behaviors such as stereotyped repetitive behaviors, reduced social behavior and longer latency to sleep

Question 39

what overlap btw genetic/environmental risk factors are seen in autism and schizophrenia?

Answer 39

Maternal infections during pregnancy
(bacterial or viral) have been reported to increase risk to ASD in the offspring.

Elevated risk of ASD was associated with infection in all trimesters.

Infections were associated with greater risk of ASD with intellectual disability than for ASD without intellectual disability.

obstetric complications, intrauterine exposure to the teratogenic drugs valproate and thalidomide, and heavy metal (mercury, lead) poisoning in pre or perinatal periods has also been linked to autism

Question 40

(T/F): measles-mumps-rubella (MMR) vaccine causes autism

Answer 40

false: disproved by many studies

Additives such as thimerosal that contain small amounts of mercury compounds were blamed.

Today, this additive is not used in the US, with the exception of some flu vaccines.

Further, epidemiological studies in countries with excellent health registers do not support a link between MMR vaccine and autism.

Question 41

what brain regions have been implicated in asd?

Answer 41

frontal cortex, amygdala, social brain circuit, cerebellum, brainstem nuclei, hippocampal formation

Question 42

what are neuroanatomical abnormalities in asd?

Answer 42

• decrease in brain volume in adolescence
• early brain overgrowth until early-late childhood (5-12% larger in autistic infants)
• hyper expansion of cortical surface btw 6-12 mo preceded brain volume overgrowth seen btw 12-24 mo (due to over proliferation of cortical progenitor cells)

Question 43

what are the neuroimmune abnormalities in asd?

Answer 43

(similar to schizophrenia)

• increased expression of pro-inflammatory cytokines in the brain and in plasma samples of 2-5yo
• increased microglial nb or activation profile in brains
• decrease in microglial-mediated synaptic pruning

Question 44

what are serotonin abnormalities in asd?

Answer 44

• children lack developmental peak of 5ht synthesis seen in 5yo
• reductions in 5-ht2a binding in cortex
• elevated levels of 5ht in platelets

Question 45

where does the support for serotonin in autism come from?

Answer 45

studies that selective serotonin reuptake inhibitors (SSRIs) improve social behavior while decreasing aggressive and stereotyped behaviors in adults with autism.

Question 46

how is glutamate altered in asd?

Answer 46

Excitatory glutamate receptors play a role in cortical development and some GluR genes have been shown to be associated with autism.

Question 47

how is GABA altered in asd?

Answer 47

GABAergic pathways also play important roles during brain development, and reduction in the GABAergic receptor system has been shown in autism brain tissues.

Question 48

how is DA altered in asd?

Answer 48

Increased CSF HVA in autism has been
reported.

Atypical antipsychotic drug risperidone, at relatively low doses, is quite effective in reducing aggression, self-injury and tantrums.

Question 49

what is OT?

Answer 49

nine amino acid peptide that is produced mostly in the hypothalamus in both sexes.

Reproductive role of oxytocin is in stimulating uterine contractions in labor and induction of milk production.

Question 50

what are the brain functions of OT?

Answer 50

Brain functions of oxytocin are suggested by the presence of oxytocin receptors in brain regions associated with emotional and social behaviors (e.g., amygdala).

An important function of oxytocin is described in the processing of social cues, social attachment and bonding.

Question 51

explain the research on OT in animal research

Answer 51

Studies show high levels of oxytocin receptor in the nucleus accumbens in prairie voles, compared to the
promiscuous montane voles, which may contribute to the monogamous social structure in this species.

A role of oxytocin in social behaviour is also revealed in oxytocin knock-out mice.

These mice fail to recognize familiar conspecifics after repeated social exposures, despite normal olfactory and spatial learning abilities.

OT treatment fully restored social recognition in the mutant mice.

Question 52

explain the human study of OT and social cues

Answer 52

oxytocin makes people more sensitive to social cues.

Administration of oxytocin (through intranasal route) increases trust and cooperation, and boosts social perceptiveness, such as increased eye contact, emotional recognition from facial expression

Question 53

explain the clinical trials assessing the efficacy of oxytocin in reducing asd symptoms

Answer 53

Using a single dose of oxytocin nasal spray, a small clinical trial in 16 autistic boys (12-19 years) showed a modest effect of oxytocin in improving performance on the RMET task.

Another study in young ASD cases (8-16 yrs) showed that a single intranasal oxytocin enhanced activity in brain reward circuit as well as brain regions
supporting social attention and social cognition during processing of social cues (eyes) vs non-social cues (vehicles).

However, no improvement in task performance noted.