Flashcards in Autism Deck (48):
what are the three core deficits in autism?
1. social and emotional
2. language and communication
3. flexibility of thoughts (imagination)
what are the difficulties in social and emotional deficit of autism?
2. managing unstructured parts of the day
3. working in a team (cooperatively)
what are the difficulties in language and communication deficit of autism?
1. learning and memory of verbal information
2. difficulty in understanding
2a. jokes and sarcasm
2b. social language
2d. body language, facial expression and gesture
what are the difficulties in imagination deficit of autism?
1. coping with routine changes
3. generalisation - across differentiations situations
what are the clinical hallmarks of autism?
1. three core deficits of ASD
2. enlarged TBV at 12-24m
3. increased surface area in 6-12m
What is Asperger’s syndrome ?
- it is described as Autistic Psychopathy with high language subject but poor social skills
- genetically transmitted
how is Asperger's syndrome different from other types of autism?
- due to extreme ability in some areas (e.g. high language skills)
- also called pervasive development disorder (PDD) or high functioning autism
Identify at least three specific genes associated with Autism
CHD8, SHANK3, MECP2 – involved at the synapses
NRX1, NLG1, MLG4, CYFIP1, SHANK2, SHANK3, CNTNAP2
what are the biological function of the autism associated genes?
1. CHD8 - regulates different sets of genes associated with autism via direct or indirect mechanism
2. SHANK3 – reduced expression leads to excitatory synapse dysfunction
3. MECP2 – dysregulation in MECP2 expression, responsible for regulation neuronal genes
environmental factors play a role in the aetiology of autism
genetics and env factors play a role in aetiology of ASD
what are the environmental factors influencing the aetiology of ASD?
1. Parental age
2. birth complications
3. vit D deficiency
4. family history
what brain growth abnormalities have been associated with ASD?
2. frontal and temporal lobe
5. glial - few too active
1. cerebellum - small no. of purkinje cells
there is homogeneity in ASD
B. False, there is heterogeneity
what is the autism spectrum?
it is the classification of autism type based on the intellectual abilities ranging from learning disabilities (autism) to extreme abilities in some areas (PDD)
is blood test available for diagnosing psychiatric illness like ASD?
how are psychiatric illness diagnosed?
According to the Diagnostic Statistical Manual of Mental Disorders (DSM-5)
why is DSM used to diagnose psychiatric illness?
offers common language and standard criteria for the classification of mental disorders
how is autism clinically diagnosed?
1. no definite medical test
2. clinical team uses -
2c. specific checklist used
3. must rule out
3b. hearing impairment
3c. behaviour disorders
3d. eccentric habits
what are the heterogeneity and comorbidities of ASD?
2. developmental and coordination disorder
3. anxiety disorder
4. depressive disorder
5. specific learning disabilities
7. sleep problems
8. GI problems
in which gender is autism more prevalent and by how much?
- more prevalent in male
- ratio 4:1 (male:female)
what are the differences in presentation of ASD in male and females?
1. ASD diagnosed later in females (some evidence)
2. fewer restricted and repetitive and external behaviour problems in females
what is the extreme male brain theory proposed by Simon Baron- Cohen?
1. he proposed that ASD arises from hypermasculinisation of brain
2. due to the testosterone secreted by fetal testes
what are the causes of neurodevelopmental disorders?
1. genetic mutations >90%
2. immune dysfunction
4. metabolic disorders
6. teratogenic substances
In Autism, 90% is genetic and 10% is non genetic
what are the factors affecting the normal brain development to ASD or SZ?
2. polygenic variation
3. environmental insults
4. stochastic (random) factors
what is the concordance rate for ASD in identical/monozygotic and non-identical/fraternal/dizygotic twins?
identical/monozygotic - 80-95%
non-identical/fraternal/dizygotic twins - 5-20%
these syndromes are more prevalent in boys or girls?
1. Fragile X syndrome
2. Rett syndrome
3. Sporadic causes
1. Fragile X syndrome - boys
2. Rett syndrome - girls
3. Sporadic causes - boys
in which gene do you get mutation for Fragile X and Rest syndrome?
1. Fragile X - FMR1
2. Rett - MECP2
they are both single rate variant with strong effect
how prevalent is Fragile X and Rest syndrome?
1. Fragile X ~10%
2. Rett ~5%
what are the problems in moving from genes to new therapies?
1. heterogenous phenotype - of ASD
2. mutations - in hundreds of genes associated with increased ASD risk
3. function of the genes - a better understanding of those genes function and impact on neuronal circuits is essential to develop rational treatment strategies
how have mouse model of humans mutations helped?
helped to identify specific molecular pathways which are linked to alterations in circuit function and cognitive/social behaviour
what are the advantages of mouse model in ASD?
1. homologs of human genes exist + conservation specific relevant circuits e.g. corticosterone striatal
2. practical, genetically tractable, cost effective. Most ASD phenotype expressed in mouse models
3. well established phenotypic batteries for core ASD phenotype
4. accessibility to multiple levels e.g. cellular, molecular, circuit and behavioural
what are the limitations of mouse models for ASD?
1. evolutionary distance + poor modelling of conserved circuits
2. some internal phenotypes observed in humans like language ability cannot be measured in mice models
3. confounding of ASD core phenotype by commodities like anxiety, fear learning defects etc. Therefore, multiple tests required for meaningful interpretation
4. invertebrates and other vertebrates like zebra fish have higher throughput studies
name one mouse model, its characteristics and what is has taught us about ASD
- mouse model - dup 15q11-q13
- characterised by impaired social interaction, decreased social communication, behavioural inflexibility, altered serotonergic signalling and increased spine dynamics
- helped us to identify specific molecular pathways which are linked to alteration in circuit function and cognitive/social behaviour
what is the public misperception about autism?
1. vaccine like MMR cause autism
2. the use of organic food will reduce/prevent autism
what is evidence of environmental factors ASD?
1. twin studies show 40% variance in ASD might be due to environmental factors
what is the role of epigenetic in ASD?
1. rate of methylation differs between foetal and developmental state in different regions of brain
2. epigenetics changes associated with neuronal activity in dissociated hippocampal cultures
what are the characterstics of rett syndrome?
1. brain region affected
2. more prevalent in male/females
3. caused by mutation of
1. grey matter
3. MECP2 (X-chromosome)
where is MECP2 expressed and what is its function ?
- expressed in neurones
- regulates the expression of neuronal genes
how does MECP2 mutation result in rett syndrome?
MECP2 binds to the methylated DNA thus silencing the expression
why is epigenetics essential in normal functioning of CNS?
it is involved in neuronal differentiation and development, specially;
1. neuronal plasticity
2. synaptic transmission
3. memory formation and storage
4. reinforcement/reward pathways in addiction
name three disease epigenetics plays a role?
1. rett syndrome
2. fragile X syndrome
3. 15q11-13 duplication
what are epigenome targets for drug discovery for ASD?
1. writers - HATs, HMTs
2. readers - chromodomain, bromodomain
3. erasers - HDACs
what are the two graphical models of ASD?
1. multiple threshold model
2. multiple liability model
explain the multiple threshold model
- based on genetic liability
explain the multiple liability model
- based on total liability, includes genetic variation, environment, biological factors
explain the trajectory brain growth in ASD
- the brain undergoes precocious growth during early post natal life followed by deceleration age-related growth
- the early natal age is characterised by overgrowth, arrested growth at middle age and possible degeneration. at older age in ASD individuals