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BMS3052_ > 34. Autism Spectrum Disorder > Flashcards

34. Autism Spectrum Disorder Flashcards

1
Q

Define

Autism Spectrum Disorder (ASD)

A

a developmental disorder that affects communication and behavior. Common symptoms include difficulty with communication, difficulty with social interactions, obsessive interests and repetitive behaviours

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2
Q

Define

DSM

A

the taxonomic and diagnostic tool published by the American Psychiatric Association

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3
Q

Define

ICD

A

the foundation for the identification of health trends and statistics globally, and the international standard for reporting diseases and health conditions.

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4
Q

Define

Brain derived neurotrophic factor (BDNF)

A

plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues.

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5
Q

Define

Purkinje cells

A

neurons in vertebrate animals located in the cerebellar cortex of the brain

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6
Q

Define

Theory of Mind

A

the ability to attribute mental states such as beliefs, intents, desires, emotions and knowledge, among others, to oneself and to others

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7
Q

Define

Discrete trial training

A

breakdown of complex skills by teaching each subskill in a series of highly-structured teaching trials, also known as early intensive behavioural intervention if delivered before 5 years of age

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8
Q

Define

Naturalistic interventions

A

embedding teaching into naturally occurring events e.g. play, mealtime, can address communicative functions and peer interactions

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9
Q

Define

Learning experiences

A

integration of ASD preschoolers with typically developing peers but with individualized curriculum to incorporate ASD’s idiosyncratic needs, promotion of social interactions and extensive parent training

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10
Q

Define

Early start Denver model

A

individualized interventions in consultation with caregiver, therapist, specialist and teaching occurs inside and outside family routines

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11
Q

Define

Construct validity

A

measure of how well the mechanism used to induce the disease phenotype reflects the currently understood disease etiology

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12
Q

Define

Face validity

A

measure of how well the model is able to replicate the disease phenotype

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13
Q

Define

Predictive validity

A

measure of how well an animal model can be used to predict unknown aspects of the disease

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14
Q

Definition

a developmental disorder that affects communication and behavior. Common symptoms include difficulty with communication, difficulty with social interactions, obsessive interests and repetitive behaviours

A

Autism Spectrum Disorder (ASD)

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15
Q

Definition

the taxonomic and diagnostic tool published by the American Psychiatric Association

A

DSM

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16
Q

Definition

the foundation for the identification of health trends and statistics globally, and the international standard for reporting diseases and health conditions.

A

ICD

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17
Q

Definition

plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues.

A

Brain derived neurotrophic factor (BDNF)

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18
Q

Definition

neurons in vertebrate animals located in the cerebellar cortex of the brain

A

Purkinje cells

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19
Q

Definition

the ability to attribute mental states such as beliefs, intents, desires, emotions and knowledge, among others, to oneself and to others

A

Theory of Mind

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20
Q

Definition

breakdown of complex skills by teaching each subskill in a series of highly-structured teaching trials, also known as early intensive behavioural intervention if delivered before 5 years of age

A

Discrete trial training

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21
Q

Definition

embedding teaching into naturally occurring events e.g. play, mealtime, can address communicative functions and peer interactions

A

Naturalistic interventions

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22
Q

Definition

integration of ASD preschoolers with typically developing peers but with individualized curriculum to incorporate ASD’s idiosyncratic needs, promotion of social interactions and extensive parent training

A

Learning experiences

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23
Q

Definition

individualized interventions in consultation with caregiver, therapist, specialist and teaching occurs inside and outside family routines

A

Early start Denver model

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24
Q

Definition

measure of how well the mechanism used to induce the disease phenotype reflects the currently understood disease etiology

A

Construct validity

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25
# Definition measure of how well the model is able to replicate the disease phenotype
Face validity
26
# Definition measure of how well an animal model can be used to predict unknown aspects of the disease
Predictive validity
27
What is the estimated prevalence of ASD?
1 in 100 people worldwide
28
Which gender is ASD more prevalent in?
Boys (4:1)
29
By what age are the core symptoms of ASD usually detectable?
3 years old
30
What are the two core symptoms of ASD detectable in children before 3 years of age?
Persistent deficits in social communications Restricted and fixated interests
31
What are some behavioural symptoms of ASD?
Persistent deficits in social communications Restricted and fixated interests Anxiety Hyperactivity Agitation Impulsivity Aggressive behaviour
32
What are some functional symptoms of ASD?
Functional symptoms include sensory hypersensitivity, seizures and gastrointestinal disorders
33
What is the IQ range of ASD?
50 - 130+
34
What does the DSM require for an ASD diagnosis?
1. Persistent deficits in social communication/social interaction 2. Restricted, repetitive behaviours, interests and activities
35
What does the ICD require for an ASD diagnosis?
1. Abnormal development of receptive/expressive language 2. Impaired development of selective social attachments/reciprocal social interaction 3. Markedly restricted repertoire of activity and interest
36
What might we look at when using neuroimaging to diagnose ASD?
* Volumetric analysis – regional, cortical volume – thickness or surface area? * Connectivity – fibre tract measurements * Functional - fMRI, eye tracking
37
What might we look at when using plasma to diagnose ASD?
* Abnormal levels of brain derived neurotrophic factor (BDNF) in blood of ASD children? Increased/decreased levels have both been reported – “jury is still out” * Decreased night time production of melatonin –high rate of sleep disturbance? * Altered components of the metabolic (creatinine kinase, lactate dehydrogenase) and inflammatory (cytokine IL-1b, IL-4 levels) pathways
38
What is typical of a child with ASD's brain early in development?
It is larger than usual Decreased pruning Increased cortical thickness in parietal lobe Decreased GABA R expression Abnormal columnar structure in neocortex Hypermetabolism in the frontal regions
39
Why is the brain enlarged in early development for ASD children?
Increased number, size and myelin content of glial cells, increased neuronal dendrites and axons as a result of decreased pruning
40
Why does the increased brain volume disappear around age 6-8?
Abnormal slowness in brain growth
41
In older individuals with ASD, what is different about their brains?
Abnormalities in limbic structures in older individuals including hippocampus, amygdala and cingulate cortex – reduction in volume and smaller neurons that are more densely packed
42
How is the cerebellum effected by ASD?
Decreased volume, reduced number and size of Purkinje cells
43
What is typical of the brain regions and circuitry of ASD?
44
What is the heritablilty of ASD?
90%
45
What ASD susceptibility genes have been found?
Large number of ASD susceptibility genes identified including scaffold proteins SHANK2 & 3, adhesion molecules cadherins, GABA receptor subunits, voltage-gated calcium channel subunits, regulators of chromatin remodelling MSCP2, CHD8, proteins involved in synapse formation neurexins and neuroligins
46
What are the risk factors of ASD?
1. Infection/Immune dysfunction 2. Endocrine factors 3. Obstetric factors 4. Environmental factors
47
What infection/immune dysfunction factors contribute to ASD?
Cerebral spinal fluid of ASD children contains atypical levels of autoantibodies to neural antigens and inflammatory cytokines Maternal infection during the critical period of early neurodevelopment?
48
What endocrine factors contribute to ASD?
Maternal stress – intrauterine exposure to cortisol and thyroxine
49
What obstetric factors contribute to ASD?
Low birth weight, preterm/caesarean delivery, uterine bleeds?
50
What are the environmental factors that contribute to ASD?
Maternal exposure to prescription medication, illicit drugs, heavy metals (mercury), environmental toxins (pollution), cigarette smoke
51
What are the three theories of ASD?
1. Impeded plasticity 2. Excitation and inhibition dysregulation 3. Theory of mind
52
How does impeded plasticity explain ASD?
Abnormal regulation of cell division and apoptosis Early overgrowth of brain structures e.g. frontal cortex, amygdala and cerebellum Hyper- followed by hypo- neuronal connectivity
53
How does excitation and inhibition dysregulation explain ASD?
Imbalance of glutaminergic and GABAergic synapses ASD patients are susceptible to development of epileptic seizures
54
How is theory of mind related to ASD?
The capacity to understand subjective mental states including thoughts and desires is known as ToM ToM develops early in children without disabilities but is delayed in children with ASD
55
Which synapses are imbalanced in ASD?
Glutaminergic GABAergic
56
What is the role of oxytocin in pregnancy?
* Oxytocin is an important peptide hormone that participates in the induction of labour * During brain development, the GABAergic signals shift from “depolarization and excitation” to “hyperpolarization and inhibition” as a result of reduction in intracellular [Cl-]. At birth, OXY mediates a sudden short-lasting reduction in [Cl-], presumably to facilitate the shift which protects neurons from anoxic episodes
57
How is oxytocin involved in ASD?
* It is also a hormone that plays an important role in social behaviour * ASD children have lower baseline OXY levels * Intranasal OXY has been trialled as a therapy for the core symptom of ASD (doesn't work)
58
What are the interventional model behavioural treatments for ASD?
Discrete trail training Naturalistic interventions Learning experiences Early start Denver model
59
How is the skill-based model used to treat ASD?
Functional communication training, positive behaviour support, self management, speech generation
60
What are the most common pharmacological treatments for ASD?
Antipsychotics Stimulants Antihypertensives Antidepressants CNS depressants
61
What three attributes should a good animal possess?
Construct validity Face validity Predictive validity
62
What areas of ASD do animal models explore?
Neonatal lesions Maternal intervention Genetic models
63
What do neonatal lesion ASD animal studies explore?
* Amygdala – dysfunction in amygdala linked to ASD behaviours * Cerebellum – abnormalities (loss of Purkinje cells) detected in ASD patients * Medial prefrontal cortex – social deficits, overgrowth of mPFC pronounced in ASD patients
64
What do maternal intervention ASD animal studies explore?
* prenatal valproic acid exposure – mechanistically affect the epigenome at critical developmental stages * prenatal exposure to infection – Borna disease virus
65
What do genetic model ASD animal studies explore?
* BDNF overexpression – high seizure susceptibility, anxiety and depressive-like behaviour but no deficits in social behaviour * Fragile X mental retardation (FMR) 1 gene KO – decrease social interaction, increased repetitive behaviours, anxiety, hyperactivity, decrease spatial learning * GABARb3 subunit KO – seizure susceptibility, hyperactivity, stereotyped behaviour, learning and memory deficits, impaired social interaction * MeCP2 (transcriptional repressor) KO – increased anxiety, decreased motor coordination, impaired social interactions and learning and memory * Neuregulin (cell adhesion molecules) KO – mutations in NLGN3&4 associated with ASD * OXT, OXTR KO – oxytocin has key role in social interactions and recognition

BMS3052_ (12 decks)

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