Early childhood infection, genes, and male autism

Page 1 of 1 [ 1 post ] 

ASPartOfMe
Veteran
Veteran

User avatar

Joined: 25 Aug 2013
Age: 66
Gender: Male
Posts: 34,237
Location: Long Island, New York

18 Sep 2021, 7:35 am

Serious Infections Linked to Autism: Study

Quote:
While researchers have found plenty of gene variants that seem to increase the risk of an autism diagnosis, it’s not clear why some people carrying these mutations develop autism spectrum disorders and some do not. In a study published today (September 17) in Science Advances, researchers point to a potential answer: severe infections during early childhood. After an early immune challenge, male mice with a mutated copy of the tuberous sclerosis complex 2 (Tsc2) gene developed deficits in social behavior linked to changes in microglia, the immune cells of the brain. And an analysis of the hospital records of more than 3 million children showed that children, particularly boys, who were hospitalized for infections between ages 18 months and four years were more likely that healthy peers to receive a future autism spectrum disorder (ASD) diagnosis.

We have genetic models, and we have a lot of in utero exposure models and early life stress models, but it’s pretty rare that people are blending the two to find that gene [and] environment interaction,” says Audrey Brumback, a pediatric neurologist at the University of Texas at Austin Dell Medical School who was not involved in the work.

We knew that mutations predispose [people] for autism, but if you look in patients with genetic mutations, not everyone with that mutation has autism, and the question is why?” says neuroscientist Alcino Silva of University of California, Los Angeles (UCLA). One such type of mutation, linked to autism in about half of the people who carry the variants, are in the tuberous sclerosis complex 1 or 2 genes and can have a range of symptoms in addition to autism. Mice with a mutation in Tsc2 have some of the same symptoms, but until about a decade ago, the social deficits that can show up in people with the mutations had not been recreated in the mouse model. Then, in 2010, Silva’s group showed that challenging the immune systems of pregnant mice caused ASD-like behavior in their Tsc2 mutant offspring.

In the new study, Silva and colleagues further explore the interactions of genetics and environment, this time at later stages of development. They injected either an immune stimulant known as PolyI:C or saline into wildtype mice and Tsc2 heterozygotes at postnatal days 3, 7, and 14. After the mice reached adulthood, the researchers tested their social behaviors with the three-chamber social interaction test, in which mice are exposed to a chamber that’s empty on one side and contains a new mouse on the other. Twenty-four hours later, the chamber contains the now-familiar mouse on one side and a new mouse on the other side. All of the mice spent more time with the new mouse on the first day than on the empty side of the chamber. But only male Tsc2 heterozygotes who’d received the immune stimulant in early childhood spent equal time with the familiar mouse and the new mouse on the second day—instead of preferring the unfamiliar mouse, as the animals normally do—indicating that their social memory was impaired.

The team showed that early immune activation exacerbated the differences in vocalizations between wildtype mice and Tsc2 heterozygotes, and write in the paper that this “may parallel early ASD social communication deficits” seen in humans.

Then, the researchers analyzed gene expression in the brains of the adult mice and found that genes associated with microglia and interferon signaling were more active in male Tsc2 heterozygotes that received the immune stimulant, but not in any of the other mice. Using a drug to deplete the microglia in these mice reversed the defects in social behaviors, even after microglia reappeared months later.

The differences in the development of microglia in males and females may help explain the sex differences in the response to immune activation.

Finally, in what he calls “a Hail Mary,” Silva asked a friend, computational biologist Andrey Rzhetsky of the University of Chicago, to look at dataset of more than 3.5 million health insurance claims to see if there was any relationship between severe infections and autism in humans. “He comes back months later and says, ‘That’s the biggest association I’ve ever found in this dataset,’” says Silva. Male children, regardless of genetic status, who were hospitalized with infections between the ages of 18 months and four years were 40 percent more likely to be diagnosed with ASD later than were boys who weren’t hospitalized for infections, while for girls, hospitalization for infection at this age was associated with a 30 percent greater chance of ASD diagnosis. The difference for girls was not statistically significant, however.

“This paper has to be [understood] as proof that you need to vaccinate your kids,” since infectious diseases can not only be fatal, but can also raise the risk of ASD among children who survive, says coauthor Manuel López Aranda, a neuroscientist at UCLA.

So not getting vaccinated early on potentially increases the odds of being autistic. :lol:


_________________
Professionally Identified and joined WP August 26, 2013
DSM 5: Autism Spectrum Disorder, DSM IV: Aspergers Moderate Severity

“My autism is not a superpower. It also isn’t some kind of god-forsaken, endless fountain of suffering inflicted on my family. It’s just part of who I am as a person”. - Sara Luterman