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New Research Ties Antidepressant Use in Pregnancy to Brain Malformation

Researchers at the University of North Carolina (UNC) at Chapel Hill have found that women treated with SSRI antidepressants are significantly more likely to have children born with an abnormal brain structure known as a Chiari I malformation, or CIM.Researchers at the University of North Carolina (UNC) at Chapel Hill have found that women treated with SSRI antidepressants are significantly more likely to have children born with an abnormal brain structure known as a Chiari I malformation, or CIM. CIM is not present at birth and symptoms may not manifest until adolescence or adulthood. A paper cited by the UNC scientists reported that 23% of CIM cases had a condition known as spinal cord syrinx (also called syringomyelia), a disorder that damages the spinal cord and leads to weakness in the arms and legs, headaches, severe pain, and loss of bladder control. 35% of CIM cases required surgical treatment.

The association between maternal SSRI use and Chiari I malformation found in this study was particularly strong. The researchers compared children whose mothers received a diagnosis of depression and took SSRIs during pregnancy with children whose mothers had no history of depression and no SSRI exposure. The results were remarkable. Eighteen percent of the children exposed to SSRIs had Chiari I malformations, versus 2% of unexposed children. Statistically, this meant that children whose mothers took SSRIs during pregnancy were ten times more likely to develop CIM than children not exposed. 

It is necessary when studying SSRIs to rule out, if possible, the impact of depression itself, since the children exposed to SSRIs were also the children of mothers diagnosed with depression. To assess the impact of depression itself without any SSRI exposure, the scientists compared the children of mothers who had been diagnosed with depression but did not take antidepressants during pregnancy with a group of children who had no history of maternal depression and no SSRI exposure. In the absence of any SSRI exposure, the children of depressed mothers had no significantly increased risk of CIM compared to the children of mothers with no diagnosis of depression. This suggests that depression itself played little role in the study findings.

The researchers also found that the duration of exposure also increased the likelihood of a child having CIM. "Children exposed to SSRIs in all 3 trimesters were significantly more likely to meet criteria for CIM than matched comparison children [those who were exposed for less than 3 trimesters]." The timing of the exposure to SSRIs also made a difference. Children exposed at conception were more likely to meet criteria for CIM than those not exposed at conception. The authors write, "Exposure at conception is a proxy for exposure during organogenesis," and note that most theories trace the origins of CIM to "early fetal development." These findings regarding duration and timing of exposure also point to antidepressants, not depression itself, as the cause of the increased risk of CIM.

This study adds yet one more defect to a growing list of birth defects, including autism, that, like CIM, appear to have their origins in early fetal development, a stage at which serotonin, the brain chemical most affected by SSRI antidepressants, plays a critical role. As the authors themselves stated, "Serotonin plays an important role in craniofacial development. Therefore we predicted that CIM would be elevated in exposed children."

Summary Information

Rate of Chiari I Malformation in Children of Mothers with Depression
with and without Prenatal SSRI Exposure

Rebecca C. Knickmeyer, Ph.D.1; Samantha Meltzer-Brody, M.D.1; Sandra Woolson, M.Ph.1; Robert M. Hamer, Ph.D.1,2; J. Keith Smith, M.D., Ph.D.3; Kenneth Lury, M.D.3; John H. Gilmore, M.D.1

  1. Department of Psychiatry, University of North Carolina at Chapel Hill
  2. Department of Biostatistics, University of North Carolina at Chapel Hill
  3. Department of Radiology, University of North Carolina at Chapel Hill

Neuropsychopharmacology, published online, May 19, 2014, in advance of print publication

This work was supported by the National Institutes of Health (MH064065, MH070890, and HD053000 to Dr. Gilmore, MH083045 to Dr. Knickmeyer) and the Foundation of Hope for the Research and Treatment of Mental Illness.

Additional Studies Linking Antidepressants to Autism


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