Autism Flashcards
1
Q
How is ASD defined?
A
- By deficits is 2 core domains (3 symptoms):
1. Atypical social behaviour
2. Disrupted verbal and non-verbal communication
3. Restrictive interests and repetitive behaviours - Onset before age of 3
2
Q
What does the DSM-V now do?
A
- Combines 3 prev separate but highly related diagnoses:
- Autistic disorder
- Asperger’s disorder
- Pervasive developmental disorder
3
Q
What kind of therapeutic actions are there?
A
- Therapy restricted to behavioural intervetion that can benefit if recieved early
- Only FDA app drugs, risperidone, which is effective in treating aggressive and repetitive behaviour and aripiprazole, which red irratability
- Drugs don’t treat core social deficit
4
Q
What are the signs of Autism?
A
- Inability to relate to children or adults
- Poor speech or lack of speech
- Inapp laughter or crying
- Oversensitive or undersensitive to sound
- Inapp playing with toys
- Diff dealing with changes in routine
- Oversens or undersens to touch
5
Q
What is the autism genetic landscape?
A
- Mendelian single gene, inherited
- Chromosome anomalies and CNVs
- De novo single gene mutations
- Majority unknown and/or multifactorial
6
Q
How do genes interact with development?
A
- Disorder of neuronal connectivity especially in cerebral cortex
- Prenatal neuronal migration and axonal pathfinding
- Postnatal dendritic development, synaptic pruning, neurogenesis
- Subtle diff in cerebral neuron columns
- Biological convergence of genes to pathways affecting synapse formation, neuronal activity and neuronal cell adhesion
7
Q
What are Neuroglins?
A
- Synaptic cell-adhesion molecules that bind with postsynaptic neuronal membranes
- Interact with either glutamate (NMDA rec - excitatory) or GABA receptors - (inhib) to maintain synaptic functions and excitatory/inhibitory balance
8
Q
What are Neurexins?
A
- Components of presynaptic neuronal membrane and their intracellular domain interacts with proteins involved in exocytosis
9
Q
Why are Neuroglin and Neurxin important?
A
- Mutations associated with ASD
10
Q
What is different about D2 receptors in ASD?
A
- D2 rec expression differences are evident in dorsal striatum in ASD
- Function is enhanced
- D2 coupled to decd cAMP signalling
11
Q
What is a de novo mutation?
(see pp)
A
- Mutation in the DAT gene associates dopamine dysfunction with ASD
- Removing DAT and also mutating DAT both increase behaviour
12
Q
How does 5-HT interact with ASD?
A
- Elevated whole blood serotonin (5-HT) levels (in platelets), termed hyperserotonemia
- Occurs in approx 25% of children with autism (also seen in OCD)
- Tryptophan depletion, which dec syn 5-HT, worsens irritability and rep behaviours
- Dec 5-HT2A receptor binding found in adults with Asperger’s and children with autism
- Alterations in SERT and MAO-A
- Genetic knock-out of SERT alters brain dev
- BUT SSRIs have little therapeutic benefit in ASD
13
Q
How does serotonin work in ASD?
A
- SERT specifically expressed in dorsal and median raphe neurons in midbrain
- Gene encoding serotonin transporter from solute carrier 6 (on chrom 17)
- Mutations can change serotonin transporter function and inc anxiety
14
Q
How is the gut-brain axis involved in ASD?
A
- Microbiota may contribute to the pathological symptoms seen in ASD
- Changes in gut microbiota composition and resultant altered gut-derived microbial products and neurotransmission can over activate immune system prod oxidative stress
15
Q
How does Dysbiosis work in ASD?
A
- Associated with increased permeability of GI, known as a ‘leaky gut’
