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Studies Examine Autism's Link to Antidepressants, Other Factors

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A preliminary but provocative new study finds women who take antidepressants during pregnancy have a moderately higher risk of having a child with autism, according to a paper published in the Archives of General Psychiatry.

Another study, published in the same issue of the journal and examining autism in pairs of identical and fraternal twins, finds that environmental factors play a greater role than previously believed in the development of autism, underscoring the need to understand nongenetic causes of autism.

The research on antidepressants and autism is thought to be the first to look for and identify such a link. Results indicated a doubling in risk of autism if the mother filled a prescription for antidepressants at any point in the year before delivery. The risk tripled if she filled the prescription during the first trimester of pregnancy.

The findings don't speak to whether antidepressants cause autism, and the work needs to be replicated, the authors cautioned. The data, though, do indicate that the drugs have "possible adverse outcomes in children" and deserve further study, said Lisa Croen, first author on the study and an epidemiologist in the research division of Kaiser Permanente Northern California, the big managed-health plan.

"A lot of people might get a little worried about these findings and change something they're doing—which they shouldn't. It indicates to us that there's more to look at," said Dr. Croen, who also is an author on the twins study.

The researchers, sifting through medical records, identified 298 children diagnosed with autism or a similar disorder and looked back in time to the characteristics of the mothers. These children and mothers were compared with 1,507 children without autism and their mothers.

The relationship between autism in the child and the mother's use of antidepressants—predominantly the category known as selective serotonin reuptake inhibitors, or SSRIs—remained even after researchers statistically accounted for the effects of other factors that might be related to either condition, such as maternal age, ethnicity and education, as well as baby birth weight and where the baby was born. In the twins study, a team including researchers from the University of California San Francisco Institute for Human Genetics, Kaiser Permanente and the California Department of Public Health identified sets of twins born in California between 1987 and 2004 in which at least one twin was diagnosed with autism or a related disorder. They conducted genetic testing on 192 twin pairs to determine whether they were identical or fraternal and recorded whether each individual qualified for an autism diagnosis.

Then they compared autism rates in fraternal twins versus identical twins, when one twin had it and also when both twins had it. If autism were a completely genetic disorder, both twins in each identical-twin pair would have it, the researchers figured. And if it were caused completely by environmental factors, the autism rates in fraternal twin pairs and identical twin pairs would be the same.

The results indicate that roughly half the risk of autism was accounted for by environmental factors—far more than detected in previous studies, according to Joachim Hallmayer, psychiatry professor at Stanford University School of Medicine and first author on the study. It "shows clearly that we have to take both environment and genes seriously, and we have to study much more the interactions between genes and environment," Dr. Hallmayer said. Environmental factors shared by twins, particularly during the prenatal period and right after birth, may contribute to autism, he said.

In the antidepressant study, researchers tried teasing apart whether the mother's mental state or the antidepressants were linked with autism. The results indicated an association with the treatment, not with the mother's mental state.

If the pattern can be replicated in a broader population of children, the findings "will add to the growing list of cautions about exposing children and adolescents to medications without a very clear demonstrated need," said John March, director of neurosciences medicine at the Duke Clinical Research Institute, who wasn't involved in the study. Because of limited information in the medical records, researchers weren't able to look at other important factors that might also affect fetal development such as ultrasounds and pain medicines, he added.

Previous research has shown that people with autism have female relatives with a greater likelihood of depression or anxiety. So what looks like a link between antidepressants and autism could actually be a genetic predisposition to this cluster of conditions, said Fred Volkmar, director of Yale University's Child Study Center, who wasn't involved in the current study.

Doctors and patients must weigh the risk of taking antidepressants in pregnancy against risks to the unborn child of untreated depression in the mother. A woman who is depressed may not eat regularly or keep prenatal checkups—possibly putting her baby at more risk than if she took antidepressants, said Mason Turner, Kaiser Permanente San Francisco's chief of psychiatry.