34. Autism Spectrum Disorder Flashcards
Define
Autism Spectrum Disorder (ASD)
a developmental disorder that affects communication and behavior. Common symptoms include difficulty with communication, difficulty with social interactions, obsessive interests and repetitive behaviours
Define
DSM
the taxonomic and diagnostic tool published by the American Psychiatric Association
Define
ICD
the foundation for the identification of health trends and statistics globally, and the international standard for reporting diseases and health conditions.
Define
Brain derived neurotrophic factor (BDNF)
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.
Define
Purkinje cells
neurons in vertebrate animals located in the cerebellar cortex of the brain
Define
Theory of Mind
the ability to attribute mental states such as beliefs, intents, desires, emotions and knowledge, among others, to oneself and to others
Define
Discrete trial training
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
Define
Naturalistic interventions
embedding teaching into naturally occurring events e.g. play, mealtime, can address communicative functions and peer interactions
Define
Learning experiences
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
Define
Early start Denver model
individualized interventions in consultation with caregiver, therapist, specialist and teaching occurs inside and outside family routines
Define
Construct validity
measure of how well the mechanism used to induce the disease phenotype reflects the currently understood disease etiology
Define
Face validity
measure of how well the model is able to replicate the disease phenotype
Define
Predictive validity
measure of how well an animal model can be used to predict unknown aspects of the disease
Definition
a developmental disorder that affects communication and behavior. Common symptoms include difficulty with communication, difficulty with social interactions, obsessive interests and repetitive behaviours
Autism Spectrum Disorder (ASD)
Definition
the taxonomic and diagnostic tool published by the American Psychiatric Association
DSM
Definition
the foundation for the identification of health trends and statistics globally, and the international standard for reporting diseases and health conditions.
ICD
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.
Brain derived neurotrophic factor (BDNF)
Definition
neurons in vertebrate animals located in the cerebellar cortex of the brain
Purkinje cells
Definition
the ability to attribute mental states such as beliefs, intents, desires, emotions and knowledge, among others, to oneself and to others
Theory of Mind
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
Discrete trial training
Definition
embedding teaching into naturally occurring events e.g. play, mealtime, can address communicative functions and peer interactions
Naturalistic interventions
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
Learning experiences
Definition
individualized interventions in consultation with caregiver, therapist, specialist and teaching occurs inside and outside family routines
Early start Denver model
Definition
measure of how well the mechanism used to induce the disease phenotype reflects the currently understood disease etiology
Construct validity
Definition
measure of how well the model is able to replicate the disease phenotype
Face validity
Definition
measure of how well an animal model can be used to predict unknown aspects of the disease
Predictive validity
What is the estimated prevalence of ASD?
1 in 100 people worldwide
Which gender is ASD more prevalent in?
Boys (4:1)
By what age are the core symptoms of ASD usually detectable?
3 years old
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
What are some behavioural symptoms of ASD?
Persistent deficits in social communications
Restricted and fixated interests
Anxiety
Hyperactivity
Agitation
Impulsivity
Aggressive behaviour
What are some functional symptoms of ASD?
Functional symptoms include sensory hypersensitivity, seizures and gastrointestinal disorders
What is the IQ range of ASD?
50 - 130+
What does the DSM require for an ASD diagnosis?
- Persistent deficits in social communication/social interaction
- Restricted, repetitive behaviours, interests and activities
What does the ICD require for an ASD diagnosis?
- Abnormal development of receptive/expressive language
- Impaired development of selective social attachments/reciprocal social interaction
- Markedly restricted repertoire of activity and interest
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
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
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
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
Why does the increased brain volume disappear around age 6-8?
Abnormal slowness in brain growth
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
How is the cerebellum effected by ASD?
Decreased volume, reduced number and size of Purkinje cells
What is typical of the brain regions and circuitry of ASD?
What is the heritablilty of ASD?
90%
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
What are the risk factors of ASD?
- Infection/Immune dysfunction
- Endocrine factors
- Obstetric factors
- Environmental factors
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?
What endocrine factors contribute to ASD?
Maternal stress – intrauterine exposure to cortisol and thyroxine
What obstetric factors contribute to ASD?
Low birth weight, preterm/caesarean delivery, uterine bleeds?
What are the environmental factors that contribute to ASD?
Maternal exposure to prescription medication, illicit drugs, heavy metals (mercury), environmental toxins (pollution), cigarette smoke
What are the three theories of ASD?
- Impeded plasticity
- Excitation and inhibition dysregulation
- Theory of mind
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
How does excitation and inhibition dysregulation explain ASD?
Imbalance of glutaminergic and GABAergic synapses
ASD patients are susceptible to development of epileptic seizures
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
Which synapses are imbalanced in ASD?
Glutaminergic
GABAergic
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
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)
What are the interventional model behavioural treatments for ASD?
Discrete trail training
Naturalistic interventions
Learning experiences
Early start Denver model
How is the skill-based model used to treat ASD?
Functional communication training, positive behaviour support, self management, speech generation
What are the most common pharmacological treatments for ASD?
Antipsychotics
Stimulants
Antihypertensives
Antidepressants
CNS depressants
What three attributes should a good animal possess?
Construct validity
Face validity
Predictive validity
What areas of ASD do animal models explore?
Neonatal lesions
Maternal intervention
Genetic models
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
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
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
