Autism Spectrum Disorder Flashcards
who first used the word autism?
Leo Kanner and Hans Asperger in 1940s
what did autism describe when it was first used?
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.
what two domains of functioning need to be impaired to get a diagnosis of ASD?
- Persistent deficits in social communication and social interaction across multiple contexts
- Restricted, repetitive patterns of behavior, interests, or activities,
how does the DSM-V define mild vs severe severity for ASD?
mild: requires some support
severe: requires substantial support
what are 3 deficits seen in the social domain of ASD?
social emotional reciprocity, nonverbal communicative behaviors used for social interaction, relationships
what are 4 examples of restricted/repetitive patterns of behavior/interests/activities seen in ASD?
- stereotyped or repetitive motor movements
- insistence on sameness
- restricted/fixated interests
- hyper/ or hyporeactivity to sensory input
for an ASD diagnosis, symptoms must be present in ______, must together ______ and cannot be better explained by _____.
early childhood; limit/impair everyday functioning; intellectual disability
how are intellectual disability and ASD related?
ID and ASD frequently co-occur
For comorbid diagnoses of ASD and ID, social communication should be below that expected for general developmental level
what is social (pragmatic) communication disorder?
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
currently, the prevalence of ASD is estimated to be as high as _____ and there are ___ times more males than females with autism.
1 in 44; 4x
what are possible reasons for the rise in ASD prevalence?
better awareness and diagnosis or unidentified environmental risk factors are being discussed
what are comorbid behavioural problems in ASD?
- hyperactivity and attention abnormalities
- anxiety
- mental retardation
explain the hyperactivity and attention abnormalities seen in ASD
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.
(T/F): you can have both an ASD and ADHD diagnosis concurrently.
false: adhd is an exclusionary criterion for asd!
explain anxiety in ASD
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.
what is the prevalence of anxiety disorders in ASD?
btw 47-84%
about __% of asd children have avg to above avg intellectual ability
44%
what are the main differentiating features btw autism and mental retardation?
(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
what are neurological problems seen in ASD?
- sensory integration abnormalities
- seizures
- fagile x syndrome
- tuberous sclerosis
- motor disturbance
what sensory integration abnormalities are seen in asd?
Multimodal sensory abnormalities, including increased sensitivity to acoustic and tactile, stimuli are common.
Some ASD children are relatively
insensitive to extreme cold or pain.
explain seizures in asd
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
fragile X syndrome occurs in about ___% of people with asd
2-5%
explain tuberous sclerosis in asd
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
what motor disturbances are seen in asd?
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
the neurological problems in asd are taken as evidence to support ____
a biological/neural basis of asd
It is believed that certain cognitive deficits, especially those related with _________, underlie the social abnormalities in autism
social and emotional cues
what is the cognitive theory of asd?
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.
when is theory of mind present in normal children?
4yo
what is the ability to mentalize?
using and understanding the words such as “believe”, “know”, “wish”, “desire”, “intend”, and “pretend”.
a child with problems of theory of mind may assume that since he is happy, then others ____.
must be happy
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.
anxiety, ritualistic behaviour, inattention, and interest in objects
what evidence supports the involvement of genetic factors in asd?
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%.
what is the polygenic mode of inheritance of asd?
no one gene or variant either necessary or sufficient to express the phenotype.
the polygenic architecture of asd is significantly shared with what disorders?
schizophrenia, depression, intellectual disability
what are the genetics found from GWAS for asd?
- chromosomes 2q, 7q and 17q
- risk genes: x-lined genes (NLGN3-4), neurexin (NRXN1), postsynaptic density protein (SHANK3), contacting associated protein (CNTNAP2)
genes associated with asd are believed to cause an imbalance btw _______
excitatory-inhibitory NT in the brain
explain the neurexin-neuroligin-shank in asd
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.
what animal evidence do we have for neurexin-neuroligin-shank in asd?
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
what overlap btw genetic/environmental risk factors are seen in autism and schizophrenia?
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
(T/F): measles-mumps-rubella (MMR) vaccine causes autism
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.
what brain regions have been implicated in asd?
frontal cortex, amygdala, social brain circuit, cerebellum, brainstem nuclei, hippocampal formation
what are neuroanatomical abnormalities in asd?
- 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)
what are the neuroimmune abnormalities in asd?
(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
what are serotonin abnormalities in asd?
- children lack developmental peak of 5ht synthesis seen in 5yo
- reductions in 5-ht2a binding in cortex
- elevated levels of 5ht in platelets
where does the support for serotonin in autism come from?
studies that selective serotonin reuptake inhibitors (SSRIs) improve social behavior while decreasing aggressive and stereotyped behaviors in adults with autism.
how is glutamate altered in asd?
Excitatory glutamate receptors play a role in cortical development and some GluR genes have been shown to be associated with autism.
how is GABA altered in asd?
GABAergic pathways also play important roles during brain development, and reduction in the GABAergic receptor system has been shown in autism brain tissues.
how is DA altered in asd?
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.
what is OT?
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.
what are the brain functions of OT?
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.
explain the research on OT in animal research
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.
explain the human study of OT and social cues
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
explain the clinical trials assessing the efficacy of oxytocin in reducing asd symptoms
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.
