Date of Award

January 2025

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Kieran O'Donnell

Abstract

The developmental origins of health and disease posits that in utero exposures and early life experiences increases susceptibility to a host of pathologies. Maternal psychopathology, specifically maternal prenatal anxiety, has been studied as an in utero stressor that can affect childhood development and epigenetic aging. In the current study, we analyzed the longitudinal effects of maternal prenatal anxiety on epigenetic aging, assessed sex-specific effects, and tested the contribution of cellular heterogeneity to these findings. Using the longitudinal Basal Influences on Baby Development (BIBO) cohort, we performed a mixed model for repeated measures to determine how prenatal and postnatal anxiety (State-Trait Anxiety Inventory) affect epigenetic aging according to the Pediatric-Buccal-Epigenetic (PedBE) clock at 6-, 10-, and 14-years across 146 individuals and 392 methylomes. For secondary analyses we assessed Tanner stages of puberty at the 10-year timepoint and performed cell-type deconvolution analysis to examine the contribution of puberty and biosample cell heterogeneity, respectively, to our primary findings. Despite no differences in chronological age, females had higher PedBE age compared to males at all three timepoints. In males, but not females, increasing prenatal STAI scores was associated with increased PedBE age. However, no significant association emerged between postnatal anxiety and PedBE aging in either males or females. We found no differences in proportion of epithelial cells across males and females at any timepoint. While males at the 10-year timepoint had higher Tanner scores than females, there were no associations between pubertal development and PedBE-derived epigenetic aging. These findings highlight the importance of the prenatal environment on developmental processes, including epigenetic aging. Future work should probe the biological and social processes that explain why maternal prenatal anxiety affects epigenetic aging in a sex-specific manner. Our results underscore the need for improved behavioral health interventions to pregnant individuals, which has implications for both their health and their developing child.

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This is an Open Access Thesis.

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