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Updated: Sep 26, 2025

Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants
Published on: June 13, 2021
Infection and higher cortisol during pregnancy and risk for depressive symptoms in adolescent offspring
Emily Lipner1, Shannon K Murphy1, Elizabeth C Breen2
1Department of Psychology and Neuroscience, Temple University, Weiss Hall, 1701 N. 13th Street, Philadelphia, PA 19122, USA.
Insights
Prenatal infection combined with elevated maternal stress hormones, like cortisol, during mid-pregnancy increases offspring depression risk. This highlights the combined impact of prenatal infection and stress on adolescent mental health.
Area of Science:
- Psychiatry
- Developmental Psychology
- Reproductive Health
Background:
- Prenatal infection is linked to offspring psychopathology, but its association with depression is inconsistent.
- Co-occurrence of prenatal infection and stress may predict depression in offspring.
- The role of prenatal stress biomarkers, such as cortisol, in conjunction with infection remains understudied.
Purpose of the Study:
- To investigate if maternal cortisol levels during pregnancy interact with infection to predict adolescent offspring depression.
- To examine the combined effects of prenatal infection and stress biomarkers on offspring mental health outcomes.
Main Methods:
- Utilized data from the Child Health and Development Studies (CHDS) prospective cohort.
- Included mother-offspring dyads (n=695) from the Adolescent Study subsample.
- Employed hierarchical multivariable regressions to analyze the interaction between maternal cortisol (first and second trimesters) and infection on offspring depression scores.
Main Results:
- A significant interaction was found between second-trimester maternal infection and higher maternal cortisol levels.
- This interaction predicted increased depression scores in adolescent offspring.
- Maternal education was controlled for in the analysis (p=0.04).
Conclusions:
- Elevated maternal cortisol may sensitize the mother-offspring dyad to the adverse effects of mid-pregnancy infection.
- This sensitization confers a greater risk for depressive symptomatology in adolescent offspring.
- The findings underscore the importance of considering combined prenatal adversities in understanding offspring mental health.
Abstract:
Prenatal infection, particularly at mid-gestation, has been associated with various psychopathological outcomes in offspring; however, findings linking prenatal infection to offspring depression outcomes have been mixed. Previous research indicates that it may be the co-occurrence of prenatal adversities (e.g., infection and stress) that are associated with depression outcomes in offspring. Nevertheless, no study to date has investigated whether higher levels of biomarkers linked to prenatal stress (e.g., cortisol) in the presence of infection may account for these outcomes. Participants were drawn from the Child Health and Development Studies (CHDS), a prospective, longitudinal study of pregnant women and their offspring. The present study included mother-offspring dyads from the Adolescent Study, a subsample of the CHDS cohort, whose offspring were assessed in adolescence and whose mothers also provided sera to be assayed for cortisol (n = 695). Hierarchical multivariable regressions were conducted to examine whether maternal cortisol during the first and second trimesters of pregnancy interacted with maternal infection to predict increased risk for symptoms of depression in adolescent offspring. There was a significant interaction of second trimester infection and higher cortisol on offspring depression scores during adolescence, controlling for maternal education (p = 0.04). Findings suggest that higher maternal cortisol may sensitize mothers and their offspring to the disruptive influences of infection during mid-pregnancy, conferring greater risk of depressive symptomatology in offspring.
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