Epigenetics, Early Adversity and Child and Adolescent Mental Health

Abstract

Epigenetic modification, such as DNA methylation (DNAm), is a mechanism that can help explain how early adversities can engender long-term vulnerability for mental health problems. At present, there is preliminary evidence to support the possibility of epigenetic mediation: environmental factors are reported to influence offspring DNAm, which in turn associate with child and adolescent psychopathology. However, all analyses have been correlational in nature and, as these studies have focussed on children and adolescents, DNAm has been based on peripheral tissue (cord blood, whole blood, buccal cells). Therefore, the extent to which DNAm could represent a causal mechanism (e.g., a surrogate of central nervous system function) or a biomarker (i.e., an indicator of the pathological process leading to disease) is unclear. This short report has 2 main components. First, 2 studies are summarized, one a candidate gene study and the other an epigenome-wide association study in which DNAm was reported to (partially) mediate the link between adversity and child development. Second, there is a discussion of (1) the “tissue issue,” (2) maximizing the interpretability of candidate gene and epigenome-wide approaches, and (3) the need for examining DNAm as a potential biomarker for mental health. It is argued that advances within these 3 areas will make clearer the role of DNAm in the link between adversity and child and adolescent mental health.

Using the life course health development model to address pediatric mental health disparities

“…This transmission suggests that behavior is not only learned through one's personal experiences but also through the experiences of ancestors. Epigenetic modification, including DNA methylation is a mechanism that can help explain how early adversities increase risk for mental health problems (Barker, 2018).…”

“…There is also evidence supporting epigenetic changes as a mechanism for altering gene expression that occurs with ACEs (Lang et al, 2020). Despite promising evidence, however, generalizations cannot be made about epigenetic changes because many studies have low sample size and rely on self-report of ACEs, among other methodological issues (Barker, 2018). Consequently, understanding of DNA methylation as a causal mechanism between adversity and mental health disorders is unclear (Barker, 2018).…”

“…Environmental influences occurring early in development may have effects that persist into adulthood due to interactions between gene functions and the environment (Brockie et al, 2013). For example, discoveries about epigenetic and telomere changes related to ACEs reveal these interactions (Barker, 2018; Lang et al, 2020). In a systematic review, Lang et al found evidence that telomere length may be altered by exposure to ACEs, especially with recent exposure to adverse experiences (Lang et al, 2020).…”

Measures of Early-life Behavior and Later Psychopathology in the LifeCycle Project - EU Child Cohort Network: A Cohort Description

“…Epigeneticallymodified loci have been linked to a wide range of mental disorders such as schizophrenia, 40 as well as childhood onset disorders such as ADHD, 41 and ASD, 42 but conflicting and non-replicated associations mean that the causal relationships remain poorly understood. 43 LifeCycle mental health studies can currently analyse DNA methylation data on 14,368 offspring cohort participants (Figure 5), measured at birth (cord or placenta blood; N=7,783), childhood (0-12 years; N=3,055), adolescence (…”

Long-term effects of early adversity on the mental health of college students: The mitigating effect of physical exercise

“…Life course theory proposes that early adversity has long-term effects on individuals’ physical and mental health, resulting in the individual’s physical and mental health disadvantages throughout life ( Matthias and Klaus, 2016 ; Bellis et al, 2019 ; Sieber et al, 2020 ). Some studies demonstrated that adolescents who experience early adversity tend to show more behavioral problems ( Barker, 2018 ; Wenming et al, 2020 ), and early adversity is significantly associated with depression and anxiety in middle school students ( Junmei et al, 2020 ). Compared to university students who grew up living with their parents, those who had been left behind in childhood were reported to have higher levels of mental disorders, including suicidal ideation ( Liu et al, 2021 ).…”