The Effect of Antenatal Depression and Selective Serotonin Reuptake Inhibitor Treatment on Nerve Growth Factor Signaling in Human Placenta

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.