Antidepressant use during pregnancy:Exploring novel (neuro)biological effects in rat mothers and offspring

During pregnancy, 5-15% of women experience a major depressive disorder, and 2.5-5.5% of women are prescribed selective serotonin reuptake inhibitor (SSRI) antidepressants. Rodent experiments help us better understand the effects of maternal depressive-like symptoms and SSRI use on child (neuro)development.The aim of this PhD thesis was to examine potential mechanisms linking perinatal SSRI antidepressant exposure to long-term health outcomes, using a rat model of maternal depressive-like symptoms.To start, we collected and analyzed all published rodent studies on behavioral outcomes after perinatal exposure to SSRIs. We found reduced activity and exploration behavior, a more passive stress-coping style, and less efficient sensory processing. We then studied the gut microbiome, the placenta, and the brain in order to better understand how these behavioral effects arise. First, we monitored the bacteria and their associated metabolites in the pregnant female’s gut. Important features of the transition from pregnancy to lactation were altered in females that received SSRI treatment, especially in “depressive-like” females. Second, we examined gene expression in the placenta, but found no major differences. Third, we found that perinatal SSRI exposure was associated with increased myelin-related gene expression in one area of the brain, but decreased myelin-related gene expression in another, potentially reflecting an altered pattern of brain maturation. This effect was stronger in males than females, similar to behavioral findings.We hope that this research, by shaping future animal and human studies, will help mitigate the potential adverse effects of SSRI treatment (or lack thereof) on both mothers and children