New Warnings about Perinatal Antidepressant Exposure

Studies have shown that it is important for both the mother’s and the fetus’ well-being to treat maternal depression. As such, the use of antidepressants during pregnancy has increased. However, new research now shows that treatment with certain antidepressants just before and just after delivery may actually have a negative impact on the baby’s brain circuitry. The research was published in a recent issue of the Proceedings of the National Academy of Sciences.

Dr. Kimberly L Simpson, associate professor in the department of neurobiology and anatomical sciences at the University of Mississippi Medical Center, and colleagues studied rats to see the effects of pre- and postnatal exposure to the selective serotonin reuptake inhibitor (SSRI) citalopram on the cortical wiring organization. First, since previous research has pointed to a possible link between disrupted serotonin system and developmental disorders such as autistic spectrum disorder, the researchers examined rats that were perinatally exposed to citalopram to determine if they exhibited similar behaviors associated with autism spectrum disorder. Simpson et al. found that pups who were exposed to 10 mg/kg twice daily as neonates displayed an exaggerated freezing response to a novel tone, the reduction of exploration of a novel object, and increased disinterest in play as compared to the pups that had been exposed solely to an saline solution. These behaviors extended through adulthood. Interestingly, these phenomena seemed to affect only the male pups.

The researchers also looked at the serotonergic raphe system of male rats after perinatal treatment with the SSRI. Simpson et al. found reductions in SERT-ir cortical density in limbic areas, such as the hippocampus and medial prefrontal cortex, as well as in sensory territories of cortex. In addition, they found that SERT-ir axons had a morphology that contrasted with the typical arrangement of sequentially connected boutons in these fine-caliber fibers.

Since autistic spectrum disorder has been associated with changes in the corpus callosum and disconnection among long corticocortical pathways, Simpson et al. also examined how citalopram affected the integrity of the corpus callosum. The researchers found that perinatal exposure affected myelination of callosal axons, induced a two- to sixfold increase in aberrant axon morphology, and lead to a reduction in callosal connectivity.

Ultimately, the authors noted that this study stresses the importance of balanced serotonin levels. They commented, “These findings indicate that 5-HT homeostasis is required for proper brain maturation and that fetal/infant exposure to SSRIs should be examined in humans, particularly those with developmental dysfunction, such as autism.”

In a statement to the press, Dr Thomas R Insel, director of the National Institute of Mental Health, discussed the importance of the study. “While one must always be cautious extrapolating from medication effects in rats to medication effects in people, these new results suggest an opportunity to study the mechanisms by which antidepressants influence brain and behavioral development,” he explained. “These studies will help to balance the mental health needs of pregnant mothers with possible increased risk to their offspring.”

References:

Simpson KL, Weaver KJ, de Villers-Sidani E, et al. Perinatal antidepressant exposure alters cortical network function in rodents. Proc Natl Acad Sci U S A. 2011;108(45):18465-70.
NIMH. Perinatal antidepressant stunts brain development in rats. Press release. Oct. 24, 2011.