Autism Flashcards
What are symptoms of autism?
- Neurological symptoms
- disturbed social interaction
- repetitive behavior
- impaired communication
- Non neurological comorbidities
- Sleep disorders
- Gastrointestinal problems (constipation, diarrhea, abdominal pain)
Greater incidence is found among boys (4:1)
What is the etiology of ASD?
Etiology remains unknown. Both genes + environment.
What medication is used for ASD?
No medication can improve the core signs of ASD
Specific medications can help control symptoms:
* Certain medications may be prescribed for hyperactivity
* Antipsychotic drugs are sometimes used to treat severe behavioral problems
* Antidepressants may be prescribed for anxiety
What is going on with the microbiome in ASD?
- Changed microbiome composition
- Impaired intestinal barrier
- Strong correlation between GI problems & ASD severity
- Mucosal and systemic inflammation
GI tract is crucial for what processes important for ASD?
- Neurogenesis
- Myelination
- Microglia
- Modifying susceptibility to and progression to brain disorders
What do studies thusfar show about the microbiome and ASD?
Several cohort studies: high heterogeneity (sample size, clinical issues, type of controls) & small sample size
Differences between ASD & control
Changed diversity in ASD
Differences in composition not consistent
What do antibiotics have to do with ASD?
Early life antibiotics (including during pregnancy) is associated with autism in mice & man
* confirmed in a Dutch & Swedish twin study
* preclinical study shows causality
However, there can also be improvement in children. In short: Modulation of the microbiome impacts the disease
Vulnerability in early life & its link to autism?
- Maternal infection during pregnancy: enhanced risk for neurodevelopmental disorders
- Medicine use during pregnancy: anti-depressive & anti-epileptic drugs and antibiotics are associated with autism
- Disturbed brain maturation and neurodevelopmental impairment found in preterm born infants with neonatal infection
In mouse model offspring: what happens after infection of the mother?
- Disturbed social behaviour & anxiety
- Changed microbiome
- Enhanced intestinal permeability
- Neuro- & systemic inflammation brain
What happens after autistic microbiome transplant in mice?
- The transplantation of gut microbiota derived from patients with ASD into germ-free mice led to autistic-like behavioral phenotypes in these mice and their offspring
What kind of acid has an association during pregnancy with ASD? What helps against it?
VPA
Prebiotic fibers enhanced the VPA-induced lack of sociability and cognition! Hooray
Also beneficial effect of intestinal barrier function loss, systemic inflammation.
Prebiotic fibers also enhanced the serotonergic system impairments in ASD pathology (serotonin levels are decreased)
- Postnatal prebiotic intervention normalized VPA-induced alterations in the offspring (immune and behavioural parameters)
True/false
True
- Specific dietary intervention that promote healthy gut microbiome might improve immune parameters and ultimately improve ASD detrimental behavioural outcomes.
True/false
True
- What kind of pre-clinical models can be used for the study of microbiota-gut-brain interactions in the context of ASD?
They can use hESCs’s = human embryonic stem cells, and make an in vitro ENS model
Can Human microbiota transplantation with stool samples from autistic patients exacerbate ASD-like phenotype in mouse models?
WT-mice: less explorative, but not core ASD behavioral symptoms
Second-trigger mice: do develop the full autistic behavioural phenotype.
