Stanford Medicine Newsletter Updates For the Local Community


New insights into the environmental influences of autism

Joachim Hallmayer

Autism research has focused heavily on the possible genetic roots of the condition. But a new Stanford School of Medicine study of twins suggests that environmental factors play an unexpectedly large role in determining autism risk. The study—the largest ever of twins in which at least one twin in each pair had autism—represents a significant shift in scientists’ understanding of the potential cause of this common developmental disorder. Prior research attributed 90 percent of autism risk to genes; in contrast, the new study found that genes account for about 40 percent of autism risk, with environmental factors explaining the other 60 percent.

Research leader Joachim Hallmayer, MD, an associate professor of psychiatry and behavioral sciences, answers questions about the work with his co-author Linda Lotspeich, MD, a clinical professor of psychiatry and behavioral sciences. Lotspeich is also a child and adolescent psychiatrist who treats children at the Stanford Autism Center at Lucile Packard Children’s Hospital.

What is the impact of your new research?

Hallmayer: The role of environmental factors in determining autism risk has been underestimated. It took me a bit by surprise that the heritability of autism was so much lower than we previously thought. Prior research is much stronger in the other direction.

Linda Lotspeich

Lotspeich: This work will guide researchers in where to focus their efforts to understand the causes of autism. Based on these results, we need to look for environmental factors—but that doesn’t take away the fact that autism also has a genetic component and is still caused by unknown genes.

Why the big difference between your results and the earlier findings?

Hallmayer: We examined a much larger, more diverse population of twins with autism than many of the earlier studies. We linked two state-wide California databases—the database that tracks children’s use of state services for autism treatment and the state’s birth records. That allowed us to find all the twin pairs in California in which at least one twin has a diagnosis of autism and invite them to join the research. The result was that we had a much larger, better-categorized and more diverse sample of subjects than previous studies, which were conducted in the United Kingdom and Northern Europe.

Have previous studies led researchers in the wrong direction when looking for the causes of autism?

Hallmayer: No, I don’t think so. It is important to emphasize that, based on our study, genetic factors play a significant role. Genes depend on their environment. Understanding genetic factors will help to better understand the role of environmental factors. The reverse is also true. None of these factors can be studied in isolation. Research needs to take both sides into account. 

Lotspeich: Research on the underlying causes of autism now needs to focus on looking for the environmental factors that increase autism risk and understanding how they relate to genetic factors that cause autism. It’s essential that we look at genes and environment together.

What potential environmental causes of autism should scientists investigate now?

Hallmayer: That’s the multimillion dollar question. There is excellent evidence that children with autism differ from typically developing children starting quite early in life. Our study specifically points toward environmental factors that are shared between twin individuals. Scientists should look for something that happens early in life and affects both twin individuals—possibly events during pregnancy. For instance, a study by researchers at Kaiser Permanente found a modest increase in autism risk among children whose mothers took antidepressant drugs during pregnancy. That kind of risk factor needs to be investigated further.

What is the message in this research for parents of children with autism?

Lotspeich: Parents should take heart that we are moving closer to understanding the causes of autism, although our investigation is still at an early stage and doesn’t alter the current thinking on diagnosis or treatment. It’s worth noting that in 5 to 10 percent of children diagnosed with autism there will be a known genetic disorder such as Fragile X syndrome underlying the condition. Any child with autism spectrum disorder should have a genetic assessment. However, 90 to 95 percent of kids with autism don’t have an underlying known genetic disorder. These are the children that the new study examined, and they’re the ones for whom we now need to investigate the joint contributions of genes and environment to autism risk.

The study was published in the Archives of General Psychiatry in July.

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