Abstract
Depressive symptoms during pregnancy are common and may have impact on the developing child. Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed antidepressant treatment, but unfortunately, these treatments can also negatively affect the behavioral development and health of a child during pregnancy. In addition, serotonin (5-HT) exerts neurotrophic actions with thus far not fully known effects in the offspring. The neurotrophic growth factor (NGF) is involved in neuronal cell survival and differentiation, and altered placenta levels have been found to increase the risk for pregnancy complications, similar to those found in women treated with SSRIs. We therefore investigated whether the NGF signaling pathway was altered in the placenta from women treated with SSRIs (n = 12) and compared them with placenta from depressed (n = 12) and healthy mothers (n = 12). Results from immunohistochemical stainings revealed that placental NGF protein levels of SSRI-treated women were increased in both trophoblasts and endothelial cells compared with depressed and control women. In addition, downstream of the NGF receptor TrkA, increased levels of the signaling proteins ROCK2 and phosphorylated Raf-1 were found in stromal cells and a tendency towards increased levels of ROCK2 in trophoblasts and endothelial cells in SSRI-treated women when compared to healthy controls. SSRI-treated women also displayed increased levels of phosphorylated ROCK2 in all placental cell types studied in comparison with depressed and control women. Interestingly, in placental endothelial cells from depressed women, NGF levels were significantly lower compared to control women, but ROCK2 levels were increased compared with control and SSRI-treated women. Taken together, these results show that the NGF signaling and downstream pathways in the placenta are affected by SSRI treatment and/or antenatal depression. This might lead to an altered placental function, although the clinical relevance of our findings still needs to be investigated.
Highlights
Almost 20% of women suffer from depressive symptoms during pregnancy and 4–7% are diagnosed with major depressive disorders [1,2,3,4]
It has been shown that selective serotonin reuptake inhibitors (SSRIs) treatment as well as antenatal depression can cause behavioral disorders, why it remains unclear which effects are caused by the antenatal depression per se and what is caused by the pharmacological treatment of the depression
In this study we have shown that the neurotrophic growth factor (NGF) signaling pathway is altered in the placenta of SSRItreated women in comparison with depressed women and healthy controls
Summary
Almost 20% of women suffer from depressive symptoms during pregnancy and 4–7% are diagnosed with major depressive disorders [1,2,3,4]. When antidepressant treatment is needed during pregnancy, selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed as they are considered to be efficient, safe and have relatively few side-effects [5,6,7]. SSRI treatment during pregnancy has been associated with an increased risk of poor pregnancy outcomes including premature birth, impaired fetal placental function and decreased fetal body and head growth, but these outcomes are found in offspring of mothers with antenatal depression (reviewed by [14,15,16,17]). It has been shown that SSRI treatment as well as antenatal depression can cause behavioral disorders (reviewed in [14,15,16,17]), why it remains unclear which effects are caused by the antenatal depression per se and what is caused by the pharmacological treatment of the depression
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