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- Title
Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms.
- Authors
Lipner, Emily; Mac Giollabhui, Naoise; Breen, Elizabeth C.; Cohn, Barbara A.; Krigbaum, Nickilou Y.; Cirillo, Piera M.; Olino, Thomas M.; Alloy, Lauren B.; Ellman, Lauren M.
- Abstract
Key Points: Question: What is the association between prenatal maternal inflammation and symptoms of depression in their adolescent-aged offspring? Findings: In this cohort study including 674 mother-offspring dyads, higher second trimester levels of interleukin 6 were associated with greater depressive symptoms in adolescent offspring. Moreover, childhood internalizing and externalizing symptoms mediated sex-differentiated pathways from maternal inflammation to offspring symptoms in adolescence. Meaning: The findings suggest that there may be specific pathways to adolescent depression that begin in utero and are differentiated by fetal sex and timing of exposure to prenatal inflammation. This cohort study evaluates associations between maternal inflammatory biomarkers in pregnancy and depressive symptoms in their offspring. Importance: Prenatal maternal inflammation has been associated with major depressive disorder in offspring in adulthood as well as with internalizing and externalizing symptoms in childhood; however, the association between prenatal inflammation and offspring depression in adolescence has yet to be examined. Objective: To determine whether maternal levels of inflammatory biomarkers during pregnancy are associated with depressive symptomatology in adolescent-aged offspring and to examine how gestational timing, offspring sex, and childhood psychiatric symptoms impact these associations. Design, Setting, and Participants: This was an observational study of a population-based birth cohort from the Child Health and Development Studies (CHDS), which recruited almost all mothers receiving obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, California, between June 1959 and September 1966. Pregnancy data and blood sera were collected from mothers, and offspring psychiatric symptom data were collected in childhood (ages 9-11 years) and adolescence (ages 15-17 years). Mother-offspring dyads with available maternal prenatal inflammatory biomarkers during first and/or second trimesters and offspring depressive symptom data at adolescent follow-up were included. Data analyses took place between March 2020 and June 2023. Exposures: Levels of inflammatory biomarkers (interleukin 6 [IL-6], IL-8, IL-1 receptor antagonist [IL-1RA], and soluble tumor necrosis factor receptor-II) assayed from maternal sera in the first and second trimesters of pregnancy. Main Outcomes and Measures: Self-reported depressive symptoms at adolescent follow-up. Results: A total of 674 mothers (mean [SD] age, 28.1 [5.9] years) and their offspring (350 male and 325 female) were included in this study. Higher second trimester IL-6 was significantly associated with greater depressive symptoms in offspring during adolescence (b, 0.57; SE, 0.26); P =.03). Moderated mediation analyses showed that childhood externalizing symptoms significantly mediated the association between first trimester IL-6 and adolescent depressive symptoms in male offspring (b, 0.18; 95% CI, 0.02-0.47), while childhood internalizing symptoms mediated the association between second trimester IL-1RA and adolescent depressive symptoms in female offspring (b, 0.80; 95% CI, 0.19-1.75). Conclusions and Relevance: In this study, prenatal maternal inflammation was associated with depressive symptoms in adolescent-aged offspring. The findings of the study suggest that pathways to adolescent depressive symptomatology from prenatal risk factors may differ based on both the timing of exposure to prenatal inflammation and offspring sex.
- Subjects
CALIFORNIA; PRENATAL depression; MENTAL depression; DEPRESSION in women; DEPRESSION in adolescence; DEPRESSION in men; INTERNALIZING behavior
- Publication
JAMA Psychiatry, 2024, Vol 81, Issue 5, p498
- ISSN
2168-622X
- Publication type
Article
- DOI
10.1001/jamapsychiatry.2023.5458