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Related Experiment Video

Updated: Jan 17, 2026

Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants
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Mendelian randomization study on the causal link between reproductive behavior and postpartum depression.

Jinghui Zou1, Cheng Li2, Hong Ma3

  • 1Department of Obstetrics, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China.

Medicine
|September 17, 2025
PubMed
Summary

This study used Mendelian randomization to find that earlier age at first sexual intercourse (AFS) and age at first birth (AFB) reduce postpartum depression (PPD) risk, while a higher lifetime number of sexual partners (LNSP) increases it.

Keywords:
Mendelian randomizationagefirst birthfirst intercoursepostpartum depressionsexual partners

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Area of Science:

  • Reproductive health
  • Psychiatric genetics
  • Epidemiology

Background:

  • Postpartum depression (PPD) is a significant public health concern affecting maternal well-being.
  • The etiological factors contributing to PPD risk, particularly those with a potential genetic basis, require further investigation.
  • Understanding the causal pathways linking reproductive behaviors to PPD is crucial for targeted interventions.

Purpose of the Study:

  • To investigate the potential causal relationships between key reproductive milestones and the risk of developing postpartum depression (PPD).
  • Specifically, to examine the independent effects of age at first sexual intercourse (AFS), lifetime number of sexual partners (LNSP), and age at first birth (AFB) on PPD risk.
  • To employ robust genetic epidemiological methods to establish causality and differentiate from mere correlation.

Main Methods:

  • Utilized Mendelian randomization (MR), a genetic instrumental variable approach, to infer causal effects.
  • Employed aggregated genome-wide association study (GWAS) data for AFS, LNSP, and AFB as exposures, and PPD as the outcome.
  • Applied multiple MR methods (IVW, MR Egger, weighted median, etc.) and performed sensitivity analyses (Cochran's Q, MR-Egger intercept, leave-one-out) to assess robustness and rule out pleiotropy.

Main Results:

  • A significant inverse causal relationship was observed between age at first sexual intercourse (AFS) and PPD risk (OR=0.417).
  • A significant inverse causal relationship was also found between age at first birth (AFB) and PPD risk (OR=0.842).
  • Conversely, a significant positive causal relationship was identified between a higher lifetime number of sexual partners (LNSP) and increased PPD risk (OR=1.965).
  • Sensitivity analyses confirmed the robustness of these causal associations and indicated no significant horizontal pleiotropy.

Conclusions:

  • Age at first sexual intercourse (AFS), lifetime number of sexual partners (LNSP), and age at first birth (AFB) are causally associated with the risk of postpartum depression (PPD).
  • Earlier AFS and AFB are associated with a reduced risk of PPD, suggesting protective effects.
  • Increased LNSP is identified as a significant risk factor for developing PPD, highlighting a potential vulnerability.