Work

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

Year: 2026

Type: article

Abstract: 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<0.05, p < 0.01 respectively at gene level and p < 0.01, p < 0.001 at protein level). These findings indicate dysregulated dopaminergic, serotonergic, glucocorticoid, and melatonin signaling pathways in the placenta associated with maternal psychosis. Our results provide novel evidence of distinct placental molecular adaptations in FEP-PW, reflecting heightened maternal stress and disrupted neurohormonal environments. These alterations may contribute to adverse placental function and influence fetal neurodevelopmental trajectories, underscoring the placenta’s role as a critical mediator in the maternal-placental-fetal axis in psychiatric disorders. Further research is needed to clarify the functional consequences and explore these molecules as potential biomarkers or therapeutic targets in perinatal psychiatry. • First-episode psychosis during pregnancy (FEP-PW) is a rare but serious condition that intersects maternal mental health and placental-fetal biology. • Significant alterations in placental gene and protein expression were observed in FEP-PW placentas (DRD2, NR3C1, and HSD11B2 were markedly upregulated, whereas HTR1B and MTNR1B were significantly downregulated. • Our results provide novel evidence of distinct placental molecular adaptations in FEP-PW, reflecting heightened maternal stress and disrupted neurohormonal environments.

Source: Psychoneuroendocrinology

DOI: 10.1016/j.psyneuen.2026.107751