Bilirubin and postpartum depression: an observational and Mendelian randomization study

Yi Liu; Zhihao Wang; Duo Li; Bin Lv

doi:10.3389/fpsyt.2024.1277415

Bilirubin and postpartum depression: an observational and Mendelian randomization study

Front Psychiatry. 2024 Mar 8:15:1277415. doi: 10.3389/fpsyt.2024.1277415. eCollection 2024.

Authors

Yi Liu^#^{1

2}, Zhihao Wang^#³, Duo Li^#⁴, Bin Lv¹

Affiliations

¹ Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.
² Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China.
³ Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.
⁴ Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

^# Contributed equally.

Abstract

Background: Postpartum depression (PPD) is one of the most common complications of delivery and is usually disregarded. Several risk factors of PPD have been identified, but its pathogenesis has not been completely understood. Serum bilirubin has been found to be a predictor of depression, whose relationship with PPD has not been investigated.

Methods: Observational research was performed followed by a two-sample Mendelian randomization (MR) analysis. From 2017 to 2020, the clinical data of pregnant women were retrospectively extracted. Logistic regression and random forest algorithm were employed to assess the risk factors of PPD, including the serum levels of total bilirubin and direct bilirubin. To further explore their potential causality, univariable and multivariable Mendelian randomization (MVMR) were conducted. Sensitivity analyses for MR were performed to test the robustness of causal inference.

Results: A total of 1,810 patients were included in the PPD cohort, of which 631 (34.87%) were diagnosed with PPD. Compared with the control group, PPD patients had a significantly lower level of total bilirubin (9.2 μmol/L, IQR 7.7, 11.0 in PPD; 9.7 μmol/L, IQR 8.0, 12.0 in control, P < 0.001) and direct bilirubin (2.0 μmol/L, IQR 1.6, 2.6 in PPD; 2.2 μmol/L, IQR 1.7, 2.9 in control, P < 0.003). The prediction model identified eight independent predictive factors of PPD, in which elevated total bilirubin served as a protective factor (OR = 0.94, 95% CI 0.90-0.99, P = 0.024). In the MR analyses, genetically predicted total bilirubin was associated with decreased risk of PPD (IVW: OR = 0.86, 95% CI 0.76-0.97, P = 0.006), which remained consistent after adjusting educational attainment, income, and gestational diabetes mellitus. Conversely, there is a lack of solid evidence to support the causal relationship between PPD and bilirubin.

Conclusion: Our results suggested that decreased total bilirubin was associated with the incidence of PPD. Future studies are warranted to investigate its potential mechanisms and illuminate the pathogenesis of PPD.

Keywords: Mendelian randomization; oxidative stress; postpartum depression; risk factors; serum bilirubin.

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.