Asking what causes autism is a little like asking what causes cancer.
Scientists have all but given up on finding one gene, virus or chemical that can explain it. The causes are almost certainly numerous and complex.
“If there was one single thing, we would have found it by now,” said Lisa Croen, a Kaiser Permanente epidemiologist who studies possible environmental causes of the brain disorder.
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Researchers have been more successful in ruling out popular theories — notably that autism is engendered by “refrigerator mothers” who failed to connect emotionally with their children or, more recently, that it results from vaccinations.
Studies of twins starting in the late 1970s established that autism has a strong genetic basis. If one twin has autism, researchers have found, the chances that the other does too depend largely on how much DNA they share. The odds are far higher — up to 90% — if the twins are identical.
Scientists have identified a few dozen gene variations more common in people with autism. Still, the genetic mechanisms of the disorder remain poorly understood. None of the variations identified thus far has been found in more than 1% of autism cases; none guarantees that a child will have autism; and roughly 80% of cases can't be linked to any of them.
In coming years, scientists expect to discover many more genes linked to autism, possibly hundreds. But they probably are not the sole culprit.
As in many medical conditions, the most likely scenario is that genes create a susceptibility, while environmental factors — which scientists broadly define to include such things as diet, drug use, radiation exposure and stress levels — act as triggers.
So far, the search for triggers has yielded little more than hypotheses.
Scientists say it's most likely that something damages a fetus in the first few months of development, when billions of neurons are being connected to form the hardware of the brain.
Some research suggests that the risk of autism rises with fetal exposure to the rubella virus and to two drugs — valproic acid, a mood stabilizer, and misoprostol, an ulcer medication sometimes used in illicit abortions. But that can't account for many cases because the exposures are extremely rare. The link to misoprostol emerged from a study of autistic children in Brazil who survived abortion attempts using the drug.
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The studies raise the possibility that other compounds, viruses or bacteria could have an effect.
“We know children are being exposed to a number of chemicals that didn't exist two decades ago,” said Dr. Philip Landrigan, a pediatrician and epidemiologist at Mount Sinai School of Medicine in New York.
Some studies provide tantalizing associations but don't point to clear causes.
Mothers of children with autism are more likely to have taken antidepressants known as selective seratonin reuptake inhibitors during pregnancy — and less likely to have taken prenatal vitamins — than the mothers of other children. Autism rates are higher in children living near freeways. In California, children conceived in the winter have a slightly higher risk of being diagnosed with autism than ones conceived in July. The risk of autism is also higher in children of older parents.
No study points to an environmental reason for the worldwide explosion in cases over the last two decades.
Given the slow pace of genetic change in large populations, genes can't account for the surge either.
That suggests the explanation for the boom lies mainly in social and cultural forces, notably a broader concept of autism and greater vigilance in looking for it.
About the series:
Rates of autism have exploded over the last 20 years. In exploring the phenomenon and its repercussions, Los Angeles Times staff writer Alan Zarembo interviewed dozens of clinicians, researchers, parents and educators and reviewed scores of scientific studies. Zarembo, along with Doug Smith and Sandra Poindexter of the Times data team, also analyzed autism rates and public spending on autism in California.