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The quest for autism’s causes, and what it reveals about all of us

As alarm grew over autism prevalence at the turn of this century, there was much public talk of a growing “epidemic.” That language has since softened, and it is now clear that many autistic people were there all along, their condition unrecognized until relatively recently.

But what is the cause? The emerging narrative today is that there is no single cause — rather, multiple factors, roughly sorted into the categories of genetics and environment, work together in complex ways. Because of this complexity and the hundreds of gene variants that have been implicated, developing human brains may follow many possible paths to arrive at a place on the autism spectrum.

And this may help explain something true about autism: It varies greatly from one person to the next.

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As clinicians view it, autism involves communication deficits and formulaic, repetitive behaviors that present obstacles to establishing conventional relationships. The soft borders of that definition — where does communication difficulty cross over into communication deficit? — suggest blurred margins between people who are diagnosed with autism and those who approach, but never quite cross, the line into diagnostic territory.

Those who do have diagnoses display behaviors on a continuum of intensity. Their use of spoken language ranges from not speaking at all to being hyperverbal. They can have a unique interest in the finer details of window blinds or an intense but more socially tolerated fascination with dinosaurs. As with many human behaviors, each feature exists on a spectrum, and these spectra blend in a person to create what clinicians call autism.

By pinpointing risk-associated genes and uncovering their roles, studying the roots of autism also is providing new insights into the development of all human brains, autistic or not. Here is a taste of what we now know, and what we don’t, about autism’s causes — and what that search is teaching us about everybody’s neurology.

They know it when they see it

Despite the many and varied threads that may interweave to cause autism, the condition is largely identifiable. What clinicians are really saying when they diagnose autism, says James McPartland, a clinical psychologist at the Yale Child Study Center, is that they see a recognizable, if broadly defined, constellation of behaviors. “So really, there is something true about autism, and everyone who meets the diagnosis of autism shows these kinds of behaviors.”

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US rates of autism diagnoses have increased over the years, as shown in a graph. Numbers are averages of prevalence among 8-year-old children from several reporting sites of the CDC's Autism and Developmental Disabilities Monitoring Network. Not all sites reported in each year shown, and the ranges can be broad (for example, in 2000 the average was 6.7 per 1,000 children, but the range from different reporting sites was 4.5 to 9.9). At least part of the increase is due to heightened awareness and shifting diagnostic criteria.
US rates of autism diagnoses have increased over the years, as shown in this graph. Numbers are averages of prevalence among 8-year-old children from several reporting sites of the CDC’s Autism and Developmental Disabilities Monitoring Network. Not all sites reported in each year shown, and the ranges can be broad (for example, in 2000 the average was 6.7 per 1,000 children, but the range from different reporting sites was 4.5 to 9.9).  At least part of the increase is due to heightened awareness and shifting diagnostic criteria.

At the same time, the subtle differences in how each autistic person manifests the telltale features make it highly individual, says Pauline Chaste, a child psychiatrist at Inserm U 894, the Centre de Psychiatrie et Neurosciences, in Paris. “We describe a specific behavior that exists — that kind of social impairment and rigidity. You can have more or less of it, but it definitely exists.”

The more or less of autism could trace, in part, to the types of gene variants that contribute to it in a given person. Some of these variants have a big effect by themselves, while others make tiny contributions, and any autistic person could have their own unique mix of both. One thing seems clear: Though there may be something true about autism, as McPartland puts it, the existence of “one true autism gene” or even one gene for each autism feature is unlikely.

Instead, there will be patterns of gene combinations and the results they produce, says epidemiologist Elise Robinson of the Harvard T.H. Chan School of Public Health and an associate member of the Broad Institute. People who have both autism and intellectual disability, for example, tend to have more big-effect gene mutations than people with autism alone.

Facial communication

Looking for these contributing gene variants isn’t simply an exercise in scientific curiosity or in finding potential targets for drug treatments. Because most of these genes direct how human brains develop and nerve cells communicate, learning about how they lead to autism can also reveal a lot about how everyone’s brain works.

For example, a key autism trait is atypical social behaviors, such as, sometimes, not focusing on “social” facial features like the eyes. Although the tendency to look into another person’s eyes seems like something we might learn simply from being around other people, autism research has revealed that genes underlie the instinct.

In a 2017 study, the authors first showed that identical twins are similar in how they look at a video with social content, such as faces. When viewing the same video, the identical twin pairs shifted their eyes with the same timing and focused on the same things far more than did two non-identical siblings or unrelated children. The fact that almost all twin pairs shared this tendency suggests solid genetic underpinnings for the behavior.

Having established a strong genetic contribution to this trait, the investigators, from Emory University and the Marcus Autism Center in Georgia and Washington University in St. Louis, then showed that the tendency to look at the eye and mouth areas of a human face is decreased in autistic children. They concluded that while not all of the inclination to look at certain parts of a face is genetic, much of it is.


Knowable Magazine is an independent journalistic endeavor from Annual Reviews.

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