A new study, conducted by a team of biologists led by Dr. Marilyn Vera-Chang and Dr. Vance Trudeau at the University of Ottawa, found that exposure to antidepressant drugs led to stress hormone suppression, or cortisol deficiency, in zebrafish. This adverse effect was passed on to offspring and was long-lasting, spanning over three consecutive generations.
These findings are significant because they suggest that humans, particularly pregnant mothers who are given fluoxetine (Prozac) as a first-line treatment for “postpartum depression” and anxiety, may experience similar effects that extend to their children. Vera-Chang and Trudeau explain:
“This may be a cause for concern given the high prescription rates of [fluoxetine] FLX to pregnant women and the potential long-term negative impacts on humans exposed to these therapeutic drugs.”
In a recent interview with medical express, the researchers added, “What most people don’t realize is that the mechanisms in fish and humans are actually quite similar, if not identical. This means that there are potentially serious implications for humans.”
Fluoxetine is the active ingredient in commonly-prescribed antidepressant drugs, such as Prozac. Prescribing these drugs is the first line of treatment for expecting mothers who are exhibiting depressive symptoms. Previous research has demonstrated that fluoxetine readily crosses the placental barrier and therefore, the fetus is susceptible to disruptive effects during a very crucial developmental period. The focus of this research, however, was on examining any potential long-term consequences related to fluoxetine exposure and prenatal development.
“Even though evidence exists for SSRI-induced disruption of the HPA axis following prenatal exposure, critically missing is any knowledge about the long-term consequences manifested in adulthood and in future generations,” Vera-Chang and Trudeau write.
In this study, a team of researchers examined the impact of 6-day fluoxetine exposure in zebrafish. Their results found that exposure to fluoxetine suppressed the stress hormone, cortisol.
Cortisol plays a critical role in organisms’ adaptability and survival. Having enough cortisol enables one to respond behaviorally to stressors. The dampening of this response in humans is associated with experiences such as “burnout, chronic fatigue, fibromyalgia, immune disorders, and post-traumatic stress disorder [PTSD], among others,” the authors note.
Further, they found that the effect of fluoxetine exposure lasted three generations and was more severe for male zebrafish. This disruption persisted across generations without any signs of diminishment.
Male zebrafish, especially, were seen to demonstrate reduced locomotor and exploratory behaviors. In other words, they moved less. Such impaired behavioral responses were linked to blunted cortisol levels. Disruption of cortisol levels appeared to change an organism’s ability to respond to its environment in behavioral and psychological ways through the alteration of neural, endocrine, and molecular responses.
The authors end their paper with the following remark:
“In conclusion, a 6-d FLX [fluoxetine] exposure during ZF [zebrafish] brain development to a concentration within the lower range of that detected in the cord blood of FLX-treated pregnant women (HFL) leads to a male-specific impairment of cortisol synthesis for at least three consecutive generations.”
As Vera-Chang and Trudeau remarked in their medical express interview:
“This is an important demonstration that, in an animal model, even a brief ancestral exposure to a common antidepressant modifies the stress response and critical coping behaviors for several generations.”
And, that clinical interventions may have a significant bearing on people’s wellbeing in the future.
“The future discussion should take into account that such medication have longer-term effects than we ever imagined, as our work clearly shows that what we do today can influence future generations.”
Vera-Chang, M. N., St-Jacques, A. D., Gagné, R., Martyniuk, C. J., Yauk, C. L., Moon, T. W., & Trudeau, V. L. (2018). Transgenerational hypocortisolism and behavioral disruption are induced by the antidepressant fluoxetine in male zebrafish Danio rerio. Proceedings of the National Academy of Sciences, 115(52), E12435-E12442. doi: 10.1073/pnas.1811695115