B3870 - Childhood adversity DNA methylation and risk for depression A longitudinal study of promoting factors and sensitive periods i - 27/09/2021
Exposure to childhood adversity is one of the strongest risk factors for depression across the life course, increasing risk for both child- and adult-onsets of the disorder by at least twofold and possibly explaining one-third of all mental disorders. Accumulating research suggests epigenetic processes may be a key biological pathway through which adversity creates this long-term mental health vulnerability. Dozens of human and animal studies have shown that adversity can program the epigenome through DNA methylation (DNAm) marks, which do not alter the sequence of the genome, but can influence how genes are expressed. Our interdisciplinary team has been studying the relationship between adversity, DNAm, and depression risk in the ALSPAC. Our work to date has revealed three main novel findings. First, not only does adversity shape these DNAm marks in both childhood (at age 7) and adolescence (at age 15), but there is a replicated sensitive period between 3-5 years when children’s epigenomes are especially vulnerable to the effects of adversity. Second, these adversity-induced DNAm differences are temporally dynamic, having discernable patterns of stability and change across childhood and adolescence that reflect latent, and transitory effects of adversity on the epigenome. Third, these DNAm marks are not only a molecular record of adversity exposure, but also appear to mediate, meaning explain in part, how adversity influences both risk for – and protection against – subsequent depressive symptoms.
We seek to build from these insights to conduct secondary analyses of newly-released ALSPAC data to identify epigenetically-linked sensitive periods shaping risk and resilience to depression. We and others have shown there is substantial variation in how people respond to adversity; not all children who experience early-life adversity go on to have mental health problems. Yet, little is currently understood about the modifiable protective factors and mechanisms that drive resilient processes. Here we propose to test our central hypothesis that both liability and protection from depression across the lifecourse begins some time during the first five years of life and arises, in part, via the effects of experience-dependent plasticity shifts in DNAm that occur during an early postnatal sensitive period.