Maternal Prepartum Depression and Prenatal Exposure to SSRI Antidepressants Programs the Human Placental Metabolome

<title>Abstract</title> <p> <bold>Background</bold> One in ten pregnant women take selective serotonin reuptake inhibitors (SSRIs) to treat depression; however, the downstream effects of maternal depression and SSRIs on placental function and fetal development are incompletely understood. <bold>Methods</bold> This pilot study characterized the placental metabolome to explore the influence of both depression and SSRIs on the prenatal environment. Pregnant women were recruited and divided into three groups: 1) non-depressed, non-SSRI treated mothers (controls), 2) mothers with depression without SSRI treatment, and 3) mothers with depression and SSRI treatment. The presence and severity of depressive symptoms in pregnant mothers was assessed using the Hamilton Depression Rating Scale (HAM-D) and were categorized as control or depressed under different sets of increasingly discriminant values. Placenta samples were collected after parturition and analyzed for metabolite concentrations using proton nuclear magnetic resonance ( ¹ H NMR) spectroscopy. <bold>Results</bold> The analysis of 58 placenta samples revealed significant differences between depressed mothers with no SSRI treatment (HAM-D ≥ 10) versus controls (HAM-D &lt; 5). Significantly altered metabolites in depressed mothers with no treatment included glutamate, lysine, proline, and serine. Interestingly, placentas from depressed mothers treated with SSRIs show no separation when compared to controls, suggesting that the treatment may have minimized or altered depression-related placental programming. <bold>Conclusions</bold> SSRI treatment may counteract metabolomic disruptions associated with prenatal maternal depression. These findings suggest that the placenta may have a role as a biomarker for personalized risk assessment and replication of these placental programming effects is needed in a larger cohort. </p>