Are Antidepressants Linked to Autism?

July 4, 2011— -- Women with depression who are pregnant or hoping to get pregnant may be alarmed at new research that points to a link between the use of selective serotonin reuptake inhibitors (SSRIs), a type of antidepressant, and the occurrence of autism in unborn kids.

More research may be needed to establish a solid link, however -- and doctors said pregnant women with depression still need treatment.

In the study, published in the journal Archives of General Psychiatry, researchers led by Lisa Croen of Kaiser Permanente Northern California reviewed the medical records of more than 1,600 children, 298 of whom had autism spectrum disorders (ASDs). They found that the risk of having a child with autism spectrum disorder was about twice as high among women who took SSRIs in the year before delivery. That risk was even four times higher in women who took SSRIs during their first trimester. SSRIs include such well-known brands as Prozac, Zoloft, Paxil and Celexa.

But though these numbers may seem alarming, the authors warn that they shouldn't be over-interpreted.

In the general population, they wrote, "the fraction of cases of ASD that may be attributed to use of antidepressants by the mother during pregnancy is less than 3 percent...and it is reasonable to conclude that prenatal SSRI exposure is very unlikely to be a major risk factor for ASD."

These results could also be due to chance, the authors say, since there were only 20 women in the study who took SSRIs and had a child with ASD.

There are also a number of other plausible explanations for the study findings, including an association between the depression itself and ASD as well as the possibility of exposure to SSRIs through breast milk.

While they urged caution in interpreting the results, they said they believe the results do suggest a modest link between SSRIs and autism.

"Further studies are needed to replicate and extend these findings," they wrote.

The researchers and other autism experts also stress the importance of balancing the needs of a depressed mother against the harm that could be done to the fetus by SSRIs. Depression, they say, should not be ignored -- and pregnant women would be making a mistake if, because of this study, they stop taking antidepressants they need. The researchers urged that they first talk with their doctors.

"As a general practice, I believe most [primary care physicians] discourage women considering pregnancy to avoid using medications that are not necessary, but the benefits of SSRIs in treating depression and as alternatives to other measures have to be weighed on an individual basis," said Catherine Lord, director of the University of Michigan Autism and Communication Disorders Center in Ann Arbor.

"Major depression is a serious disease that needs treatment and the associations [in this study], while statistically significant, are not sufficient to change that," said Dr. Shlomo Shinnar, professor of neurology, pediatrics and epidemiology and population health at Montefiore Medical Center in New York.

"Health care providers could consider a trial of therapy or counseling prior to instituting SSRI use in women of childbearing years," said Dr. Susan L. Hyman, associate professor of pediatrics at Golisano Children's Hospital at the University of Rochester Medical Center in Rochester, N.Y.

Environment Plays a Bigger Role than Genetics

Another study, also released Monday, found that among twins, the environment plays a bigger role in the development of autism than genetics, a surprising finding in light of previous research.

Three past studies on twins have estimated about 90 percent of the risk of autism is attributable to genes. But researchers led by Dr. Joachim Hallmayer, an associate professor at the Stanford School of Medicine in Palo Alto, Calif., compared 192 sets of twins -- cases in which one had an autism spectrum disorder and the other did not. They looked at both identical and fraternal twins.

"The results suggest that environmental factors common to twins explain about 58 percent of the liability to autism," the authors wrote. "Although genetic factors also play an important role, they are of substantially lower magnitude than estimates from prior twin studies of autism."

But exactly what those environmental factors are, Hallmayer said, is "the multimillion dollar question."

Experts who were not involved with this study say that this research adds to the growing body of literature that suggests non-genetic factors strongly influence the development of autism.

"This seems particularly important as the reports of an increasing incidence of autism would be more difficult to reconcile with an almost purely genetic cause," said Dr. David Beversdorf, an associate professor at the University of Missouri in Columbia. Over the past 30 years, the number of children with autism has increased from about 4 in 10,000 to about 40 in 10,000.

These environmental stressors seem to have the greatest impact while in utero.

"[They] are having an impact during the time that the brain is undergoing its greatest and fastest growth spurt and evolution and has cells at different levels of maturity and immaturity and, therefore, is potentially more sensitive to certain stressors," said Dr. Max Wiznitzer, associate professor of pediatric neurology at Case Western Reserve University School of Medicine in Cleveland. "That is why, in my opinion, the 'environment' is the womb."

While more and more research is contributing to the understanding of where autism fits in the "nature vs. nurture" debate, there is still a lot left to learn about precisely what genetic and environmental factors are and whether or not they interact.

"This is an important area for future research, but our knowledge today does not yet permit assertions as to environmental causes and ways to lessen risk," said Beversdorf.