Two Popular Antidepressants Found to Have Different Long-Term Effects on Mice Exposed to Them During Brain Development

Two Popular Antidepressants Found to Have Different Long-Term Effects on Mice Exposed to Them During Brain Development

Posted: January 29, 2015

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2010 NARSAD Independent Investigator grantee Anne M. Andrews, Ph.D., of the Semel Institute of the University of Southern California, located in Los Angeles, has been conducting research that asks the important question of whether the most popularly prescribed antidepressant medicines – drugs of the so-called SSRI class including Prozac (fluoxetine) and Lexapro (escitalopram) – have any measurable subsequent impact on the behavior of people who were exposed to them in the womb and during the first year of life.

An estimated 15 percent of pregnant women are diagnosed with depression and one-third of them are prescribed SSRI antidepressants. In the U.S., that amounts to about 200,000 women a year. It also means that about 200,000 infants born each year are exposed to these medications via the mother’s blood cells.

Dr. Andrews and a team of colleagues at UCLA, Penn State University and the University of Texas Health Science Center reported results of their research on the question of long-term SSRI effects in a paper published online December 19, 2014 in  Neuropsychopharmacology. The research does not study the impact of early-developmental SSRI exposure in people, but rather in mice, as it  is not possible to perform studies upon human fetuses and infants.

The study involved looking at behavioral phenomena in mice that bear relevance to human depression and anxiety in people. It entailed creating a line of mice whose brain development models that of the third trimester of human pregnancy. Various lines of mice were engineered so that their brain cells would express higher or lower amounts of the protein that is directly targeted by Prozac, Lexapro and other SSRI medicines. This protein is called the serotonin transporter, or SERT.

SSRI antidepressants reduce levels of the SERT protein. SERTs act to sweep up molecules of the neurotransmitter serotonin from the narrow gaps, or synapses, across which some brain cells communicate. Low SERT levels mean more serotonin remains in the gaps, a condition thought to enhance neural communication. One theory postulates that abnormally low levels of cell-to-cell communication contribute to depression.

One part of Dr. Andrews’ study had particularly interesting results. The mice exposed to Lexapro during the equivalent of the third human trimester had permanent changes in serotonin neurotransmission and as adults were less anxious than the mice exposed to Prozac. This was unexpected since the two medicines are assumed to have the same mechanism of action.

In mice engineered to completely lack the SERT protein, the team observed life-long increases in anxiety-related behavior and a condition called hyperserotonemia that is marked by a harmful excess of serotonin.

In sum, the study not only revealed dissimilarities in adult behavior but also in neurotransmission arising from developmental exposure to the two widely prescribed antidepressants; these effects were different from those generated when mice were genetically engineered to lack the SERT transporter protein. The study supports the view that serotonin helps modulate anxiety behavior. It also serves as a reminder that there is still much to be learned about the action and impacts of SSRI medicines, and the degree to which these are a consequence of their inhibition of SERT proteins in the brain.  

Read the paper abstract .