Cortisol trajectories measured prospectively across thirty years of female development following exposure to childhood sexual abuse: Moderation by epigenetic age acceleration at midlife.

Lasting changes in the hypothalamic-pituitary-adrenal (HPA) axis are a potential indication of the biological embedding of early life adversity, yet, prospective and repeatedly collected data are needed to confirm this relation. Likewise, integrating information from multiple biological systems, such as the HPA axis and the epigenome, has the potential to identify individuals with enhanced embedding of early life adversity. The current study reports results from the Female Growth and Development Study, a 30-year prospective cohort study of childhood sexual abuse (CSA). Females exposed to substantiated CSA and a demographically-similar comparison condition were enrolled and resting state cortisol concentrations were sampled on seven subsequent occasions across childhood, adolescence, and adulthood. Differences in participants' cortisol trajectories were examined in relation to prior CSA exposure and DNA methylation-derived epigenetic age acceleration at midlife. Bilinear spline growth models revealed a trajectory where cortisol secretion increased until approximately age twenty and then declined into mid-life, consistent with normative trends. However, cortisol concentrations peaked at a lower level and transitioned to the decline phase at an earlier age for females in the CSA condition with increased epigenetic age acceleration. Robustness tests across three independent measures of epigenetic age acceleration demonstrated similar results for lower peak cortisol levels and earlier ages at transition. Results suggest that CSA is associated with significant changes in HPA-axis activity over extended periods of time with these changes most pronounced in females with accelerated epigenetic aging in mid-life. Implications for biological embedding models of early life adversity and adulthood health are discussed.