Altered placental expression of neurotransmitter and stress-related molecules in first-episode psychosis during pregnancy: Implications for cytoarchitecture and function

First-episode psychosis during pregnancy (FEP-PW) is a rare but serious condition that intersects maternal mental health and placental-fetal biology. While psychosis is characterized by disruptions in perception and cognition, its impact on placental neuroendocrine signaling and fetal development remains poorly understood. The placenta, as a key mediator of intrauterine environment, expresses receptors involved in neurotransmission and stress response, potentially linking maternal psychopathology to fetal neurodevelopmental risk. This study investigates the expression of five critical neuroendocrine and stress-related molecules—dopamine receptor D2 (DRD2), serotonin receptor 1B (HTR1B), glucocorticoid receptor (NR3C1), 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2), and melatonin receptor 1B (MTNR1B)—in placental tissue from women with FEP-PW compared to healthy pregnant controls (HC-PW). Using a prospective case-control design, placental samples from 22 FEP-PW and 20 HC-PW women were analyzed. Gene expression was quantified by real-time quantitative polymerase chain reaction (RT-qPCR), and protein localization and abundance assessed via immunohistochemistry (IHC). Significant alterations in placental gene and protein expression were observed in FEP-PW placentas: DRD2, NR3C1, and HSD11B2 were markedly upregulated (all p < 0.001 at gene and protein levels), whereas HTR1B and MTNR1B were significantly downregulated compared to controls (p