Published online Jul 19, 2026. doi: 10.5498/wjp.117183
Revised: February 3, 2026
Accepted: March 13, 2026
Published online: July 19, 2026
Processing time: 163 Days and 9.6 Hours
Preeclampsia is associated with a markedly increased risk of perinatal mental health disorders; however, the biological mechanisms underlying this association remain poorly defined. Emerging evidence suggests that placental dysfunction and altered neuroendocrine stress responses contribute to increased psychological vulnerability in affected women.
To investigate associations between placental dysfunction biomarkers, neuroendocrine dysregulation, and the severity of perinatal anxiety and depressive symptoms in preeclampsia.
This prospective study (October 2022-October 2025) included 210 pregnant women: (1) 105 diagnosed with preeclampsia; and (2) 105 normotensive controls. Participants completed the Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety Disorder-7 (GAD-7), and State-Trait Anxiety Inventory at enrollment, during the third trimester, and at 6 weeks postpartum. Maternal serum soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), the sFlt-1/PlGF ratio, and salivary cortisol (hypothalamic-pituitary-adrenal axis activity) were measured, alongside clinical indicators, including blood pressure, proteinuria, and obstetric outcomes.
Compared with normotensive controls, women with preeclampsia exhibited significantly higher psychological distress, with elevated EPDS (12.8 ± 5.4 vs 6.2 ± 3.1, P < 0.001), GAD-7 (10.3 ± 4.2 vs 5.1 ± 2.8, P < 0.001), and State-Trait Anxiety Inventory-State scores (44.6 ± 9.8 vs 32.4 ± 7.2, P < 0.001). Clinically significant anxiety was more prevalent in the preeclampsia group (61.9% vs 18.1%, P < 0.001). The sFlt-1/PlGF ratios correlated positively with EPDS (r = 0.42) and GAD-7 (r = 0.38) scores (P < 0.001). Morning salivary cortisol was elevated in women with preeclampsia and depressive symptoms compared to those without depression (18.7 ± 4.3 nmol/L vs 14.2 ± 3.1 nmol/L, P = 0.002). Multivariable regression identified the sFlt-1/PlGF ratio (β = 0.28, P = 0.003), morning cortisol (β = 0.31, P = 0.001), and disease severity (β = 0.35, P < 0.001) as independent predictors of depressive symptom severity.
Preeclampsia is associated with increased perinatal anxiety and depressive symptoms, potentially mediated by placental dysfunction and hypothalamic-pituitary-adrenal axis activation, underscoring the need for integrated obstetric-psychiatric screening and early intervention.
Core Tip: This study highlights the strong association between preeclampsia and elevated perinatal anxiety and depressive symptoms, emphasizing the need for integrated obstetric-psychiatric care. By simultaneously assessing placental dysfunction biomarkers and neuroendocrine stress indicators, the study provides novel evidence for biological pathways linking preeclampsia with mental health vulnerability. Elevated soluble fms-like tyrosine kinase-1/placental growth factor ratios and increased morning cortisol were independently correlated with symptom severity, suggesting potential value in early risk stratification. These findings underscore the importance of routine psychological screening during pregnancy complicated by preeclampsia and support the development of targeted interventions to improve maternal mental health outcomes.