New evidence hints at mechanisms for ‘fever effect’

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Raising body temperature seems to alleviate seizures and other traits associated with two autism-linked genetic mutations in mice, according to unpublished research presented Sunday and Monday at Neuroscience 2022 in San Diego, California.

The findings hint at a mechanism that could account for anecdotal reports that some autistic children have temporary improvements in sociability and other behaviors during or after a fever. Although about 17 percent of autistic children showed this ‘fever effect’ in a 2017 study based on parent reports, far fewer did when the same team of researchers followed autistic children prospectively.

Extending the new animal findings to people requires caution, says Catherine Lord, professor of psychiatry and education at the University of California, Los Angeles, who led the prospective study.

“In our sample, we didn’t get any reports of changes in seizures in the kids we followed, but we didn’t have many of them, and the fevers were usually of short duration,” Lord says. “So I wouldn’t get too excited about these findings, but we certainly didn’t refute them. In our sample, the autistic kids were more affected by fever than the typical kids, but in only three kids did their behavior actually get better.”

Previous research in mice suggested the effect might stem from immune molecules, such as IL-17A, that act on the brain. But the new studies pour cold water on that idea: Raising the body temperature of mice or people with mutations in the SCN2A or IQSEC2 genes — associated with seizures, autism and intellectual disability — lessened the severity of some traits without inducing an immune response, suggesting that temperature itself may be responsible.

“I suspect that what these studies are really telling us is that there are really specific reasons that some kids get these effects,” says Andrew Zimmerman, clinical professor of pediatrics and neurology at UMass Chan Medical School in Worcester, Massachusetts, who was not involved in either study. If research could pinpoint which children might be affected, “starting out with a specific mutation and a clinical sign, and going from there,” he says, “I think we’re going to get a lot further faster.”