Annual Research Review: DNA methylation as a mediator in the association between risk exposure and child and adolescent psychopathology

Abstract

DNAm holds potential as a biomarker indexing both environmental risk exposure and vulnerability for child psychopathology. However, the extent to which it may represent a causal mediator is not clear. In future, collection of prospective risk exposure, DNAm and outcomes - as well as functional characterisation of epigenetic findings - will assist in determining the role of DNAm in the link between risk exposure and psychopathology.

Early environmental influences on the development of children's brain structure and function

“…67,68 Awareness about the mechanisms and potential factors that modify these associations opens a venue for the development of preventive and therapeutic measures. Epigenetic modifications seem to be an important mechanism that explains these associations; however, the cross-sectional nature of most epigenetic studies and the tissue specificity of the epigenetic changes are still challenges faced by the scientists devoted to investigating epigenetic markers as moderators of the effects of early life adversity on brain development and behavior.…”

Epigenetics, Early Adversity and Child and Adolescent Mental Health

“…The recent interest in epigenetics, from a developmental psychopathology perspective, stems from the potential of DNAm – whether as a causal mechanism or as a biomarker – to index both exposure to adversity and vulnerability for mental health problems [2]. Toward this end, there has been substantial activity on the “epigenetics” of adversity-related disorders, such as posttraumatic stress disorder [26] and borderline personality disorder [27].…”

“…Below, 3 key areas are discussed that can help clarify the role of DNAm in the link between adversity and mental health. We note that other areas not covered here are also important, such as genetic influence, cellular heterogeneity, temporal variability, replication and functional characterization of DNAm [2, 11]. …”

“…The ideas of “capturing” and “propagating” summarize a mediational hypothesis: that early adversity can have long-term mental health effects (at least partially) via changes in DNAm. However, at present, very few existing studies have adopted longitudinal designs capable of testing mediation (i.e., adversity → DNAm → mental health) – hence, published “mediational” studies are rare [2]. Moreover, as these studies have focussed on living children and adolescents, they have examined DNAm from peripheral tissues (e.g.…”

Commentary: Whither the epigenetics of child psychopathology? Some reflections provoked by Barker et al. (2018)

“… Barker et al.'s. () review addresses one of the most fundamental questions in the fields of child psychology and psychiatry – How can adverse experiences shape development to a sufficient degree and in profound and enduring ways to create long term risk for later mental disorder and disability? In particular they discuss the plausibility of differential methylation as an epigenetic mechanism by which such exposures can become neuro‐biologically embedded.…”