Causal Relationship between Immune Cells and Postpartum Depression: A Bidirectional Two-Sample Mendelian Randomization Study
Abstract
Background: Postpartum depression (PPD) is influenced by immune factors, particularly immune cells. The causal relationship between these cells and PPD is unclear.
Methods: Bidirectional two-sample Mendelian randomization (TSMR) analysis was performed to determine the causal relationship between immune cell characteristics and PPD. The main analysis method used was the inverse variance weighted (IVW) method. To ensure the robustness, heterogeneity, and horizontal pleiotropy of the results, a comprehensive sensitivity analysis was conducted.
Results: Overall, 28 immune cell phenotypes were identified as causally related to the onset of PPD. Most of them were distributed in the B cell group and the Treg cell group. Further analysis revealed that 13 types of immune cells had a promoting effect on PPD, whereas 15 types of immune cells had a protective effect. In addition, the incidence of PPD was found to be causally related to CD62L on granulocyte [IVW: OR (95%): 1.183 (1.037 to 1.348), P = 0.012].
Conclusion: The study unveils the causal link between immune cells and susceptibility to postpartum depression from a genetic standpoint, providing new directions for drug development and precision medicine for PPD treatment.
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33. Zitti B, Hoffer E, Zheng W, et al (2023). Human skin-resident cd8(+) t cells require runx2 and runx3 for induction of cytotoxicity and expression of the integrin cd49a. Immunity, 56: 1285-1302 e7.
34. Momeni A, Eagler L, Lo CY, et al (2021). Neutrophils aid cellular therapeutics by enhancing glycoengineered stem cell recruitment and retention at sites of inflammation. Biomaterials, 276: 121048.
35. Kagamu H, Kitano S, Yamaguchi O, et al (2020). Cd4(+) t-cell immunity in the peripheral blood correlates with response to anti-pd-1 therapy. Cancer Immunol Res, 8: 334-344.
36. Pernaa N, Keskitalo S, Chowdhury I, et al (2022). Heterozygous premature termination in zinc-finger domain of kruppel-like factor 2 gene associates with dysregulated immunity. Front Immunol, 13: 819929.
37. Zhang J, Wei L, Tan H, et al (2024). Gut microbiota and postpartum depression: a Mendelian randomization study. Fron Psychiatry, 15: 1282742.
38. Sun Y, Fan C, Lei D (2024). Association between gut microbiota and postpartum depression: A bidirectional Mendelian randomization study. J Affect Disord, 362: 615–622.
39. Yu W, Su B, Wang C, et al (2024). Postpartum depression and autoimmune disease: a bidirectional Mendelian randomization study. Front Psychiatry, 15: 1425623.
40. Kang Z, Wu Q, Cao J, et al (2024). Causal relationship between Women's reproductive traits and postpartum depression: a multivariate mendelian randomization analysis. Front Genet, 15: 1434762.
2. Deligiannidis KM, Meltzer-Brody S, Maximos B, et al (2023). Zuranolone for the treatment of postpartum depression. Am J Psychiatry, 180: 668-675.
3. Steenland MW, Trivedi AN (2023). Association of medicaid expansion with postpartum depression treatment in arkansas. JAMA Health Forum, 4: e225603.
4. Ma JH, Wang SY, Yu HY, et al (2019). Prophylactic use of ketamine reduces postpartum depression in chinese women undergoing cesarean section. Psychiatry Res, 279: 252-258.
5. Osborne LM, Gilden J, Kamperman AM, et al (2020). T-cell defects and postpartum depression. Brain Behav Immun, 87: 397-403.
6. Rudzinskas SA, Goff AC, Mazzu MA, et al (2023). Intrinsically dysregulated cellular stress signaling genes and gene networks in postpartum depression. Mol Psychiatry, 28: 3023-3032.
7. Worthen RJ, Beurel E (2022). Inflammatory and neurodegenerative pathophysiology implicated in postpartum depression. Neurobiol Dis, 165: 105646.
8. Eid RS, Gobinath AR, Galea LAM (2019). Sex differences in depression: Insights from clinical and preclinical studies. Prog Neurobiol, 176: 86-102.
9. Sanderson E, Glymour MM, Holmes MV, et al (2022). Mendelian randomization. Nat Rev Methods Primers, 2:6.
10. Birney E (2022). Mendelian randomization. Cold Spring Harb Perspect Med, 12(4):a041302.
11. Jiang Y, Wei D, Xie Y (2023). Causal effects of opioids on postpartum depression: A bidirectional, two-sample mendelian randomization study. Front Psychiatry, 14: 1043854.
12. Li J, Li J, Shen L, et al (2023). Investigating the causal association of postpartum depression with cerebrovascular diseases and cognitive impairment: A mendelian randomization study. Front Psychiatry, 14: 1196055.
13. Ou Z, Gao Z, Wang Q (2023). Association between age at first birth and postpartum depression: A two-sample mendelian randomization analysis. Heliyon, 9: e20500.
14. Wisner KL, Sit DK, McShea MC, et al (2013). Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. JAMA Psychiatry, 70: 490-8.
15. Deng MG, Liu F, Liang Y, et al (2023). Association between frailty and depression: A bidirectional mendelian randomization study. Sci Adv, 9(38):eadi3902.
16. Bowden J, Davey Smith G, and Burgess S (2015). Mendelian randomization with invalid instruments: Effect estimation and bias detection through egger regression. Int J Epidemiol, 44: 512-25.
17. Orru V, Steri M, Sidore C, et al (2020). Complex genetic signatures in immune cells underlie autoimmunity and inform therapy. Nat Genet, 52: 1036-1045.
18. Burgess S, Butterworth A, Thompson SG (2013). Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol, 37: 658-65.
19. Sang N, Gao RC, Zhang MY, et al (2022). Causal relationship between sleep traits and risk of systemic lupus erythematosus: A two-sample mendelian randomization study. Front Immunol, 13: 918749.
20. Bae SC, Lee YH (2018). Vitamin d level and risk of systemic lupus erythematosus and rheumatoid arthritis: A mendelian randomization. Clin Rheumatol, 37: 2415-2421.
21. Huang S, Tian F, Yang X, et al (2022). Physical activity and systemic lupus erythematosus among european populations: A two-sample mendelian randomization study. Front Genet, 12: 784922.
22. Sidore C, Busonero F, Maschio A, et al (2015). Genome sequencing elucidates sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers. Nat Genet, 47: 1272-1281.
23. Bowden J, Davey Smith G, Haycock PC, et al (2016). Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol, 40: 304-14.
24. Burgess S, Thompson SG (2017). Interpreting findings from mendelian randomization using the mr-egger method. Eur J Epidemiol, 32: 377-389.
25. Xiang K, Wang P, Xu Z, et al (2021). Causal effects of gut microbiome on systemic lupus erythematosus: A two-sample mendelian randomization study. Front Immunol, 12: 667097.
26. Sun W, Zhang L, Liu W, et al (2021). Stroke and myocardial infarction: A bidirectional mendelian randomization study. Int J Gen Med, 14: 9537-9545.
27. Hemani G, Zheng J, Elsworth B, et al (2018). The mr-base platform supports systematic causal inference across the human phenome. Elife, 7:e34408.
28. Oyetunji A, Chandra P (2020). Postpartum stress and infant outcome: A review of current literature. Psychiatry Res, 284: 112769.
29. Lewkowitz AK, Whelan AR, Ayala NK, et al (2024). The effect of digital health interventions on postpartum depression or anxiety: A systematic review and meta-analysis of randomized controlled trials. Am J Obstet Gynecol, 230: 12-43.
30. Bassler K, Schulte-Schrepping J, Warnat-Herresthal S, et al (2019). The myeloid cell compartment-cell by cell. Annu Rev Immunol, 37: 269-293.
31. Ng LG, Liu Z, Kwok I, et al (2023). Origin and heterogeneity of tissue myeloid cells: A focus on gmp-derived monocytes and neutrophils. Annu Rev Immunol, 41: 375-404.
32. Guintivano J, Aberg KA, Clark SL, et al (2022). Transcriptome-wide association study for postpartum depression implicates altered b-cell activation and insulin resistance. Mol Psychiatry, 27: 2858-2867.
33. Zitti B, Hoffer E, Zheng W, et al (2023). Human skin-resident cd8(+) t cells require runx2 and runx3 for induction of cytotoxicity and expression of the integrin cd49a. Immunity, 56: 1285-1302 e7.
34. Momeni A, Eagler L, Lo CY, et al (2021). Neutrophils aid cellular therapeutics by enhancing glycoengineered stem cell recruitment and retention at sites of inflammation. Biomaterials, 276: 121048.
35. Kagamu H, Kitano S, Yamaguchi O, et al (2020). Cd4(+) t-cell immunity in the peripheral blood correlates with response to anti-pd-1 therapy. Cancer Immunol Res, 8: 334-344.
36. Pernaa N, Keskitalo S, Chowdhury I, et al (2022). Heterozygous premature termination in zinc-finger domain of kruppel-like factor 2 gene associates with dysregulated immunity. Front Immunol, 13: 819929.
37. Zhang J, Wei L, Tan H, et al (2024). Gut microbiota and postpartum depression: a Mendelian randomization study. Fron Psychiatry, 15: 1282742.
38. Sun Y, Fan C, Lei D (2024). Association between gut microbiota and postpartum depression: A bidirectional Mendelian randomization study. J Affect Disord, 362: 615–622.
39. Yu W, Su B, Wang C, et al (2024). Postpartum depression and autoimmune disease: a bidirectional Mendelian randomization study. Front Psychiatry, 15: 1425623.
40. Kang Z, Wu Q, Cao J, et al (2024). Causal relationship between Women's reproductive traits and postpartum depression: a multivariate mendelian randomization analysis. Front Genet, 15: 1434762.
| Files | ||
| Issue | Vol 54 No 10 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v54i10.20139 | |
| Keywords | ||
| Postpartum depression Immune cells Causal inference Genetic variation Mendelian randomization | ||
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How to Cite
1.
Zhu Y, Cheng F, Wang W, Yang X, He M, Zhang Z, Zhu L. Causal Relationship between Immune Cells and Postpartum Depression: A Bidirectional Two-Sample Mendelian Randomization Study. Iran J Public Health. 2025;54(10):2212-2222.
