Epigenetic age has become a tool for estimating accelerated or decelerated biological age across the lifespan. Several epigenetic clocks have been developed to produce accurate age estimates from DNA methylation (DNAm) intensities at specific sets of cytosine-guanine dinucleotide (CpG) sites. [1] Deviations of chronological age from epigenetic age estimates may represent accelerated or decelerated biological aging, as determined at the time of measurement. These aging characteristics may serve as early markers of both exposure to healthy and unhealthy environments and related risks of disrupted development, disease, and premature death. [1], [2], [3]

Maternal depression is a mental health condition that is particularly prevalent among those living in poverty, in which 25-40% of mothers experience elevated depression, including those who are enrolled in voluntary parenting support programs. [4], [5] Elevated maternal depressive symptoms can undermine the secure parent-child attachment needed for healthy infant social-emotional development. [6], [7] During pregnancy, maternal depression may elicit epigenetic and other psychobiological responses that influence offspring development. [8] At sub-clinical levels, maternal depressive symptoms can still be disruptive to mother-child interactions and infant development. [9], [10], [11] Although depression has been associated with age acceleration in the mother [12], little is known about whether prenatal maternal depression is related to offspring epigenetic age. Further, to our knowledge, no studies have incorporated subclinical depressive symptoms during pregnancy in analyses of offspring epigenetic age.

A small number of studies have reported a relationship between maternal prenatal depression and offspring epigenetic age deceleration. [13], [14], [15] In particular, this cluster of findings suggests that physiological (e.g., glucocorticoid levels) and behavioral responses to maternal depression, when exposed in utero, may influence offspring developmental processes. [14] However, these findings must be replicated in diverse populations. [14], [15] Specifically, research is needed to examine whether maternal depression is related to offspring epigenetic age, including deceleration or acceleration, within populations that also experience high adversity, including poverty and discrimination. These psychosocial adversities may interact with maternal mental health and result in unique infant biological aging profiles [14] and, relatedly, higher risks for negative infant developmental outcomes. [6], [16], [17]

There are a multitude of epigenetic clocks available to estimate epigenetic age. These clocks are stronger predictors of many age-related health outcomes than other measures, including chronological age, and are believed to represent molecular processes that underly biological aging. [1], [18] Certain sites in the epigenome, likely those that are most dynamic, reflect the “ticks” of the clock, which may change in response to psychosocial experiences. The rate of epigenetic change is greater during childhood, warranting models trained specifically in pediatric populations. [19] The pediatric-specific, buccal epithelial (PedBE) clock was recently developed specifically for buccal epithelial cell types in pediatric populations. [20] Previous analyses suggest that the PedBE clock may perform better than other clocks in predicting chronological age in young populations. [20] Evidence generated using the PedBE clock points to a fetal origin of pediatric biological aging that is related to maternal mental health. [21] The development of the PedBE clock has provided a novel method to examine with greater accuracy the relationships between maternal psychosocial exposures and infant epigenetic age acceleration or deceleration. Epigenetic age as an early biological marker may help elucidate the mechanisms of developmental health and inform the timing of intervention strategies.

The objective of this study was to characterize the relationship between a range of prenatal maternal depressive symptoms and the level of epigenetic age acceleration or deceleration in offspring, as estimated using the PedBE clock. We hypothesized a significant association between maternal prenatal depressive symptoms and offspring epigenetic age residuals (estimates of biological age deceleration/acceleration) at 3-5 weeks of age.