Autism Flashcards
Diagnostic of ASD
two core domains: atypical social behaviour, and disrupted verbal/non-verbal communication. Also characterised by repetitive behaviours and restrictive interests. 30-50% have intellectual disability. Eye tracking movements and EEGs have been useful in diagnosis.
Neurobiology of ASD
Generally 20% larger head size. No common biomarkers, or neuropathology.
Genetics of ASD
15-20% genetic determinance. 3% from single inherited genes, 5% from chromosomal anomalies, and 5-10% de novo single gene mutation (not inherited from parents). 20% of siblings of autistic person develop ASD.
Multifactorial with several genes and developmental factors being linked to prevalence.
Large age differences between parents and increased maternal age is associated with higher prevalence in children.
Neurochemical proteins implicated in ASD
All below have been linked to ASD prevalence
Neurexins: presynaptic neuronal membrane component involved in exocytosis
neuroligins: cell-adhesion molecules that interact with postsynaptic neuronal membranes and NMDARs and GABARs there. Mutation associated with decreased GABA-mediated social interaction behaviours.
Neurotransmission in ASD
DAT: de novo mutation leading to DA dysfunction associated with ASD.
D2: Different expression in the dorsal striatum. Heightened expression in the caudate and putamen
Increased 5-HT in 25% of cases. Depletion of tyroptophan worsens repetitive and irritability behaviours.
SERT and MAO-A found to be altered. 14 long repeat polymorphism of SERT gene associated with anxiety-related traits and different brain structure also found to be involved in sociability.
Gut-Brain axis in ASD
microbiota will influence NT (e.g., 5-HT) production, and can activate immune response - increase oxidative stress.
Associated with increased gut permeability (“leaky-gut”). Cytokines will be able to be absorbed in the GIT - increased amounts in CNS.
Examples of NTs and signalling mediated by gut microbiota
All these seen in mouse models.
NA produced by E. coli, Bacillus spp
DA produced by Bacillus spp
5-HT produced by candida spp, E. coli, streptococcus spp
GABA produced by lactobacillus spp and lactobacillus rhamnosus
ACh produced by lactobacillus spp
oxytocin produced by lactobacillus reuteri
L reuteri increases social behaviour
Bifidobaterium longum upregulates BDNF - reduces anxiety/depression
bactericides fragilis improves anxiety, repetitive and communicative behaviours.
Bacteroides fragilis ameliorates ASD-related abnormalities in an offspring that underwent maternal immune activation
