Beyond Genes: Looking at What Causes Autism

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Findings from two new studies indicate that non-genetic factors play a surprisingly large role in determining autism risk.

Non-genetic factors play an unexpectedly large role in determining autism risk, according to findings from two new studies which run contrary to popular assumptions about the condition’s cause.

A study by researchers at Stanford University School of Medicine compared cases of autism in identical and fraternal twins, and found that fraternal twins exhibit unusually high rates of autism, while a Kaiser Permanente study found that exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants in early pregnancy may modestly increase the risk of autism spectrum disorders.

In both cases, investigators concluded that factors other than genetics may be triggering the disease.

From prior studies of shared autism in twins, researchers had estimated that 90% of autism risk was attributable to genes and only 10% to non-genetic environmental factors. But the new study—the largest ever of twins in which at least one in each pair has autism—found that genes account for 38% of autism risk, with environmental factors explaining the remaining 62%.

“It took me a bit by surprise that the heritability of autism was so much lower than previous studies calculated,” said Joachim Hallmayer, MD, lead of the study on twins, which is published in the July 4 issue of Archives of General Psychiatry. “Our work suggests that the role of environmental factors has been underestimated.”

The findings also indicate that researchers “should be studying “both generic and environmental factors, as well as how they interact with each other,” Hallmayer added. “We need to explore areas of environmental risk that are shared by both twin individuals and impact the development of the child.”

Although the study does not identify specific environmental factors, they could include any non-genetic factors that influence autism risk, including infection, exposure to chemicals, and air pollution, among others.

Another factor that should be further explored as a possible trigger is prenatal exposure to SSRIs, according to another study, published in the same issue of Archives on General Psychiatry.

A population-based, case-control study of 1805 children found that those whose mothers were treated with SSRI antidepressants during the year before delivery exhibited a two-fold increased risk of autism spectrum disorders (ASDs).

The strongest effect was associated with first trimester treatment, according to researchers, who found that in utero exposure to antidepressant medications was reported in 6.7% of cases and 3.3% of controls. After adjusting for maternal age, race/ethnicity, education, and child's birth weight, gender, birth year, and facility of birth, mothers of children subsequently diagnosed with ASD were twice as likely to have at least 1 antidepressant prescription in the year prior to delivery of the study child, and more than 3 times as likely to have a prescription in the first trimester of pregnancy.

“Our results suggest a possible, albeit small, risk to the unborn child associated with in utero exposure to SSRIs, but this possible risk must be balanced with risk to the mother of untreated mental health disorders,” said Lisa Croen, PhD, of the Kaiser Permanente Division of Research, noting that further studies are needed to replicate and extend these findings.

The finding that autism risk is strongly influenced by environmental factors should alert scientists to the need to study risk factors they haven't been considering, the researchers noted.

"Scientists need to look for environmental factors," said Linda Lotspeich, MD, of the Stanford Autism Center at Packard Children's Hospital. "But that doesn't take away the fact that autism also has a genetic component and is still caused by unknown genes."

For more on this topic:

  • Closely Spaced Pregnancies Boost Autism Risk
  • To Rebuild Trust in Vaccines, Educate Parents
  • Non-genetic Factors Play Surprisingly Large Role in Determining Autism (Stanford University School of Medicine)
  • Exposure to Antidepressants in Early Pregnancy May Increase the Risk of Autism Spectrum Disorders (Kaiser Permanente)

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