Use of Prozac in Young Mice May Lead to Abnormal Adult Behavior, Study Says

Mice exposed to a common antidepressant, fluoxetine (Prozac), in early postnatal development exhibited symptoms of depression and anxiety-related emotional disorders in adulthood, according to a new study, presented 26 October at the Society for Neuroscience's Annual Meeting in San Diego. The study has potential implications for the prescription of fluoxetine to pregnant women and young children, the researchers said.

The research by Mark Ansorge, Mingming Zhou, Alena Lira, Rene Hen, and Jay Gingrich at Columbia University will be published in the 26 October issue of the journal Science.

Serotonin Reuptake Inhibitors (SSRIs) such as Prozac are increasingly being used to treat psychiatric conditions in children and pregnant women, yet little is known about their effects on the developing nervous system. Serotonin is most commonly known for its influence on mood, anxiety, aggression, sleep, appetite, and cognition. During early life, serotonin also aids in brain development.

"This is an area that has received some attention, but perhaps not enough," said Gingrich. "One of the main implications of our research is that their may be a developmental explanation for depression through events occurring early in life."

In the study, the investigators deployed a strategy using drug treatment in normal and genetically engineered mice to investigate whether early postnatal inhibition of serotonin transporter (5-HTT) function alters emotional behavior later in life. Mice with full, intermediate and abolished 5-HTT gene expression were treated with either saline (control) or fluoxetine from postnatal day 4 to postnatal day 21.

They then tested the mice as adults several weeks after fluoxetine exposure was stopped. At this point, the adult mice were exposed to three novel environments to test their reactions.

A normal reaction to a stressful situation is to try to escape as quickly as possible. But in the mice that had been treated with fluoxetine, their normal adaptive behavior had changed, and instead of trying to escape, they remained in one place, as if trying to "stand there and take it." In other environments, the same mice showed a significantly decreased interest in their new environments and markedly less exploratory activity.

At the conclusion of Gingrich's presentation in San Diego, he stressed the need for caution in interpreting these findings, saying that more research and clinical trials will be required to determine the effects of antidepressants on the early development of children. The new findings should not cause doctors to rule out using anti-depressants in emotionally unwell mothers, he advised, as failure to do so could also have traumatic consequences for her and the child.

"People deserve to have their symptoms alleviated," Gingrich said. "Depression is a disease which can be debilitating, and untreated psychiatric disorders are also harmful to the fetus. As a practicing psychiatrist, my recommendations to patients would be the same before this research as after it."

— Jessica Lawrence-Hurt

28 October 2004