VC - Autism II & III Flashcards
What are the two views in the Spectrum vs. Overlap debate regarding the triad response?
Fractionable View: Triad components (social, verbal, repetitive) are distinct and independently expressed.
Integral View: Triad components are overlapping and inseparable traits.
What evidence supports the Fractionable View? (5)
Behavioral Studies:
- Social/verbal > verbal/repetitive > social/repetitive linkage observed. However, no significant linkage found among traits
- Normal individuals may show dysfunction in one triad aspect only.
- Autism traits often show partial fractionation e.g. traits like repetitive behavior often appear secondary to social or verbal dysfunction.
- Social bias in testing methods may obscure clearer separations between traits.
Genetic Studies:
- Twin studies suggest traits have genetic independence.
What are the specific brain regions associated with each component of the autism triad? (5)
Social Traits: Medial frontal cortex, temporoparietal junction, temporal sulcus/poles.
Verbal Traits: Voice-related cortical areas.
Repetitive Traits: Caudate putamen.
What does the Sally-Anne test assess?
Theory of mind – understanding others’ beliefs, desires, and intentions
How does the Sally-Anne test work? (4)
- Sally hides a marble in a basket and leaves.
- Anne moves the marble to a box.
- Question: “Where will Sally look for her marble?”
- Correct answer reflects understanding Sally’s false belief (basket). Incorrect answer suggests difficulty understanding others’ perspectives
What evidence suggests autism has a biological basis? (3)
- Changes in brain structure/function identified in imaging and post-mortem studies.
- EEGs in autistic individuals show unusual electrical activity, often linked with seizures (~30%).
- Abnormal brain size changes: slow neonatal and rapid postnatal growth.
What changes might be observed in different brain regions in autism? (4)
- Cell number increase or decrease
- Cell size changes
- Cell density increases
- Connectivity changes
Why do post-mortem studies have limitations?
They are influenced by a lifetime of experiences (e.g., treatments, medications) and variations in death circumstances.
What are the key stages of early brain development? (4)
- Progenitor cell division (asymmetrical).
- Neurogenesis (formation of new neurons).
- Migration (neurons move to their final positions).
- Cell death (elimination of excess neurons).
What are the later stages of brain development? (5)
- Neuronal differentiation (specialization).
- Neurite outgrowth (axons and dendrites form connections).
- Synapse formation. Retraction and shrinkage can also occur here
- Synapse maturation and stabilization.
- Synaptic pruning (refining connections)
How can these stages of brain development be disrupted in autism? (5)
- Abnormal neurogenesis
- Defective migration
- Impaired neuronal differentiation
- Excessive or reduced synapse formation
- Defective synaptic pruning
What genetic factors are linked to autism? (3)
- Mutations in specific genes.
- Chromosomal rearrangements.
- Polygenic inheritance (many genes with small effects).
What genetic research methods are used to study autism? (3)
- Linkage analysis
- Association studies
- Genome-wide association studies (GWAS)
What does GWAS identify in autism?
Single nucleotide polymorphisms (SNPs) associated with the disorder.
What is synaptopathy in the context of autism?
Abnormalities in the formation, function, or elimination of synapses
Give examples of genes involved in synaptic processes that are linked to autism? (3)
FMR1: Regulates protein synthesis at the synapse (linked to intellectual disability and autism).
NLGN3/NLGN4: Involved in synaptic adhesion and signaling.
What cellular processes do ASD-related genes influence? (7)
- Chromatin remodeling and gene regulation. (e.g. FMRP)
- Actin cytoskeleton dynamics.
- Synaptic scaffolding proteins.
- Receptors and transporters.
- Second-messenger systems.
- Cell adhesion molecules. (e.g. NLGN4 and NLGN3)
- Secreted proteins.
What role do neuroligins and neurexins play in the brain?
They are cell adhesion molecules critical for synapse formation and stabilisation. Disruptions in these proteins can lead to ASD
Where are neuroligins and neurexins located in the synapse?
Neurexins: presynaptic membrane
Neuroligins: postsynaptic membrane
What structural features are associated with neuroligins and neurexins? (3)
Neuroligins
- Share a fold similar to acetylcholinesterase (α/β-hydrolase fold).
Neurexins
- Built around LNS (Laminin-Neurexin-Sex Hormone-Binding Globulin) domains and EGF (Epidermal Growth Factor-like) repeats.
- Produce α-neurexins (long) and β-neurexins (short), both capable of protein-protein interactions.
How many genes encode neuroligins and neurexins and what are its key features? (7)
Neurexins:
- 4 genes
- Independent promoters enable transcription from distinct gene regions.
- Extensively spliced, creating thousands of isoforms for synaptic diversity.
Neuroligins:
- Humans: 5 genes; NLGN1–4X; NLGN4Y on Y chromosome
- Non-human mammals: 4 genes; NLGN1–4 distributed (no NLGN4Y)
- Extensively spliced
- Genetic complexity and redundancy make it difficult to replicate human neuroligin variants.
What happens to synapse numbers in neuroligin-deficient animal models?
Synapse numbers and structure are relatively normal, but synaptic function is disrupted.
How does neuroligin deficiency affect the brain stem in mouse models? (2)
- Normal synapse count, but reduced glutamate (excitatory) and GABA (inhibitory) transmitters.
- Ratio of inhibitory/excitatory transmission is reduced, with excitatory dominance.
Which neuroligin mutations are associated with autism?
Mutations in NLGN3 and NLGN4, particularly on the X chromosome
e.g. R451C mutation in NLGN3
