Why Fever Helps Autism: A New Theory

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Bernard Bisson / Sygma / Corbis

A doctor treats an autistic child

The autism wars go on and on, and the debates go round and round. Is the number of afflicted kids climbing or are we just overdiagnosing the condition? If mercury in vaccines isn't the culprit (the metal has been removed from nearly all of them), then it must be environmental toxins. But if that's so, why aren't we all showing symptoms?

Too often, what's lost in all the finger-pointing over what's to blame for the problem is the salient question of how to fix it. A paper just published in the journal Brain Research Reviews is taking a stab at that, suggesting a brand-new strategy — one that focuses on a very particular part of the brain. (See pictures of a school for autistic students.)

The brain region that drew the attention of the authors is known as the locus coeruleus, a small knot of neurons located in the brain stem. Not a lot of high-order processing goes on so deep in the brain's basement, but the locus coeruleus does govern the release of the neurotransmitter noradrenaline, which is critical in triggering arousal or alarm, as in the famed fight-or-flight response. Arousal also plays a role in our ability to pay attention — you can't deal with the lion trying to eat you, after all, if you don't focus on it first. And attention, in turn, plays a critical role in such complex functions as responding to environmental cues and smoothly switching your concentration from one task to another. Those are abilities kids with autism lack. (Read a TIME cover story on autism and vaccines.)

Certainly, many other parts of the brain govern concentration and attention, but the locus coeruleus does one other thing too: it regulates fever. Generations of parents of autistic kids have reported that when their child runs a fever, the symptoms of autism seem to abate. When the fever goes down, the symptoms return. In 2007, a paper in the journal Pediatrics reported on that phenomenon and confirmed that, yes, the parents' observations are right. What no one had done before, at least not formally, was tie it to the locus coeruleus — that is, until Drs. Dominick Purpura and Mark Mehler of the Albert Einstein College of Medicine published the idea this week.

"It wasn't an experiment; it was more of a eureka moment," says Purpura. "We came to the conclusion that there could only be one system that would both ameliorate the effects of autism and govern fever."

It's not often that a mere flash of insight — as opposed to a formal, controlled study — commands much space in a medical journal, and Purpura and Mehler readily concede that a good deal of empiricism will have to be applied to their theory before it can become anything more than that. Still, they're convinced that the idea deserves attention. If the locus coeruleus is indeed malfunctioning in autism, the problem could involve hundreds or even thousands of genes. The researchers are careful to avoid the shooting war over what damaged those genes, suggesting that environment and toxic chemicals — but not vaccines — may have a role. They also, tellingly, think stress is involved.

Stress is thought to have a significant impact on the ability of the locus coeruleus to regulate noradrenaline properly, and Mehler and Purpura cite an improbable 2008 study published in the Journal of Autism and Developmental Disorders showing that mothers who lived through a hurricane during their pregnancy — particularly at the mid-gestational point — had a greater likelihood of giving birth to an autistic child than other women. "What would be involved here would be the mother's level of [the stress hormone] cortisol," says Purpura. "Between fetus and mother, the placenta acts as a very good barrier for maternal cortisol, except when the stress is extreme."

In theory, that blast of stress chemistry could alter the development of the fetal locus coeruleus, though Purpura is quick to point out that the study showing how cortisol can make it through the placenta was conducted in animals, not humans. Nonetheless, one day after their article in Brain Research Reviews was published, the journal Psychoneuroendocrinology published a study linking cortisol imbalance to Asperger's syndrome, a condition along the autism spectrum.

The question is, How can any of this be used to help autistic kids? Nobody recommends inducing fevers to kick-start the locus coeruleus, since that could lead to all manner of side effects and other ills. Instead, Mehler and Purpura believe the likeliest answer is in medications that target noradrenaline brain receptors. "First, we should look at the signaling pathways in the region of the brain involved," Purpura says. "Then we could look at treating the receptor sites with some kind of pharmacotherapy." For once, the step that's missing from a proposal is the one that involves shouting about what's to blame.

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