Latent profiles analysis of maternal perinatal stress and their association with NR3C1 expression in the perinatal period

Abstract

Maternal psychosocial stress during the perinatal period is highly prevalent and a major risk factor for maternal and child health. However, the operationalization of perinatal stress remains fragmented, and its biological embedding is poorly understood. This study aimed to (1) identify latent profiles of maternal perinatal stress and (2) examine their association with maternal NR3C1 expression, a molecular marker of hypothalamic?pituitary?adrenal (HPA) axis regulation reflecting glucocorticoid receptor availability and feedback sensitivity. A total of 241 mothers were recruited during pregnancy and followed up at three months postpartum. Validated measures of state anxiety, depressive symptoms, perceived stress, and pregnancy-related distress were collected in the second and third trimesters and postpartum. Saliva samples were obtained for RNA extraction, and NR3C1 gene expression was quantified using qPCR. Latent profile analysis (LPA) was conducted to classify participants according to psychosocial stress indicators. Results supported a three-profile solution: high (21.2%), moderate (34.4%), and low stress (44.3%). Women in the high-stress profile reported elevated levels across all indicators, while those in the low-stress profile showed consistently lower scores. A one-way ANOVA revealed significant differences in NR3C1 expression across profiles, with the high-stress group displaying the lowest levels and the low-stress group the highest. Given that higher NR3C1 expression is generally interpreted as indicating more efficient HPA axis negative feedback regulation, these findings suggest that cumulative psychosocial stress is associated with reduced glucocorticoid receptor expression and potentially diminished stress-regulatory capacity. This integrative approach advances understanding of biological embedding of perinatal stress and highlights need for targeted support.