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UCSF, Stanford autism study shows surprises

By
July 5, 2011 |

By Erin Allday

Environmental factors play a more important role in causing autism than previously assumed and, surprisingly, an even larger role than genetics, according to a new study out of UC San Francisco and Stanford that could force a dramatic swing in the focus of research into the developmental disorder.

The study, published in Monday’s issue of the Archives of General Psychiatry, looked at 192 pairs of twins in California and, using a mathematical model, found that genetics account for about 38 percent of the risk of autism, and environmental factors account for about 62 percent.

Previous twin studies had suggested that autism was highly inheritable, with genetics accounting for roughly 90 percent of all cases worldwide. As such, much recent research into autism has focused on tracking down the genes and unlocking the complex genetic codes that are associated with autism.

“We’re not trying to say there isn’t a genetic component — quite the opposite. But for most individuals with autism spectrum disorder, it’s not simply a genetic cause,” said Neil Risch, director of the UCSF Institute for Human Genetics, who designed the study.

Autism doctors and patient advocates said the study, which probably will be followed up with similar studies of twins and other siblings, could have a significant impact on research into the disorder.

Earlier beliefs

For decades in the mid-20th century, autism was linked mostly to environmental factors — specifically, poor parenting, with much of the blame falling on mothers. As rates of autism skyrocketed in the ’80s and ’90s — it’s now thought to affect as many as 1 percent of U.S. children — scientists and patient advocates shifted away from blaming families.

Research has focused on obvious genetic factors for the past 10 or 15 years. Now, scientists said, they hope to broaden the study and look at how genetics and environmental influences work together to cause autism.

“We’ve known that genetics played a huge role. The surprise was that the environmental factors have been underestimated,” said Clara Lajonchere, vice president of clinical programs for Autism Speaks, a patient advocacy group that participated in and helped fund the new twin study.

“Families are going to really hold researchers more accountable now,” Lajonchere said. “A lot of parents view genetics as a long-term solution. They are going to want to know how we can accelerate the pace of research such that we can find answers now.”

Twin studies often are used to distinguish between environmental and genetic influences on medical disorders. Identical twins share nearly 100 percent of their genes, and fraternal twins share about half of their genes. In both cases the siblings’ early developmental environment — both in the womb and after birth — are very similar.

Several small twin studies in the past decade looked at how common it was for twin siblings to share an autism diagnosis, and results of those studies placed genetics as the primary cause of autism. But some scientists believe that those studies weren’t large enough to note the differences in shared diagnoses rates between identical and fraternal twins.

Diverse study

The new study is the largest, and the most diverse, to look at twins. Of the 192 pairs of twins in the study, 54 were identical and 138 were fraternal. At least one sibling in each pair was autistic, and every child was interviewed by researchers to confirm that diagnosis.

If autism was entirely a genetic disease, then scientists would expect that if one identical twin had the disorder, the other twin would too. And they’d expect that among fraternal twins, if one twin had the disorder, then the other would have a slightly higher risk of developing autism than the general population. Previous studies have indicated that if one non-twin sibling has autism, other siblings have about a 5 percent chance of developing the disorder.

But in the study, researchers found that only about 60 to 70 percent of the identical twins had dual autism diagnoses — lower than expected — and 20 to 30 percent of the fraternal twins had dual diagnoses — much higher than anticipated.

Those rates, along with the expected rates scientists would find if autism was entirely genetic or entirely environmentally caused, were plugged into a mathematical equation, and researchers determined that only about 38 percent of autism risk could be tied to genetics.

“The rates for the (fraternal) twin pairs were so high, I retyped all of the results because I thought we’d mixed them up,” said Dr. Joachim Hallmayer, an associate professor in psychiatry at Stanford and lead author of the study. “This draws attention to the environment, and to the possibility that shared environmental factors play a bigger role than we had previously assumed.”

Several scientists said they expect the new study to start shifting research toward early environmental factors, in particular prenatal conditions for developing fetuses.

Antidepressants’ role?

One study along those lines, also published in Monday’s Archives of General Psychiatry, looked at the possible role of maternal antidepressant use before and during pregnancy. The study of 298 autistic children in the Kaiser Permanente Northern California system found a two-fold increase in risk of the disorder when mothers took antidepressants at some point in the year before giving birth.

The study doesn’t prove that the antidepressants actually caused autism, and researchers stressed that women taking such drugs should not stop if they are pregnant or about to become pregnant. But they added that studies like theirs are increasingly important, especially given the new information about environmental effects on autism.

“We’re just beginning to scratch the surface,” said Lisa Croen, director of the Autism Research Program at the Kaiser Division of Research in Oakland, and lead author of the antidepressant study. “We have to continue to look at genetic factors, but it’s really important to look at non-genetic factors too — and (what’s) critical will be looking at them together.”

— Reach Erin Allday at eallday@sfchronicle.com

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