Impact of Early Environment on Children's Mental Health: Lessons From DNA Methylation Studies With Monozygotic Twins

Abstract

Over the past decade, epigenetic analyses have made important contributions to our understanding of healthy development and a wide variety of adverse conditions such as cancer and psychopathology. There is increasing evidence that DNA methylation is a mechanism by which environmental factors influence gene transcription and, ultimately, phenotype. However, differentiating the effects of the environment from those of genetics on DNA methylation profiles remains a significant challenge. Monozygotic (MZ) twin study designs are unique in their ability to control for genetic differences because each pair of MZ twins shares essentially the same genetic sequence with the exception of a small number of de novo mutations and copy number variations. Thus, differences within twin pairs in gene expression and phenotype, including behavior, can be attributed in the majority of cases to environmental effects rather than genetic influence. In this article, we review the literature showing how MZ twin designs can be used to study basic epigenetic principles, contributing to understanding the role of early in utero and postnatal environmental factors on the development of psychopathology. We also highlight the importance of initiating longitudinal and experimental studies with MZ twins during pregnancy. This approach is especially important to identify: (1) critical time periods during which the early environment can impact brain and mental health development, and (2) the specific mechanisms through which early environmental effects may be mediated. These studies may inform the optimum timing and design for early preventive interventions aimed at reducing risk for psychopathology.

Does MAOA increase susceptibility to prenatal stress in young children?

“…There is increasing support for the role of early life adversity, in particular, prenatal adversity, in shaping disruptive behavior pathways (Aizer et al , 2015, Chiarella et al , 2015, Clark et al , 2015, Hanson et al , 2015, Ronald et al , 2010). How (and whether) these pathways are modulated by child MAOA genotype is just beginning to be examined (Hill et al , 2013, Hohmann et al , 2016, Wakschlag et al , 2010a).…”

“…Moreover, as frequency, patterns, and topography of cigarette smoking are known to fluctuate significantly across gestation, prospective measurement of PTE that includes biomarker confirmation of reports is needed to most accurately capture this environmental exposure (Dukic et al , 2007, Estabrook et al , 2015, Pickett et al , 2005). Yet, even with ideal measurement of PTE, disentangling this particular exposure from the concomitant exposures is critical (Chiarella et al , 2015). As rates of cigarette smoking in the general population decline, PTE is increasingly intertwined with psychosocial stress during pregnancy (Flemming et al , 2015) but studies of PTE, including our previous study on MAOA x PTE (Wakschlag et al , 2010a), lack adequate control of PSE.…”

The Value of Twins for Health and Medical Research: A Third of a Century of Progress

“…Well-studied examples of epigenetic processes include the covalent addition of a methyl group (CH 3 ) to the cytosine nucleotide of a cytosine-guanine sequence (CpG site) and the covalent addition of an acetyl group (C 2 H 3 O) to DNA-packaging histone proteins. Epigenetic changes are intrinsic to mammalian development and are often susceptible to influence by environmental conditions that can be internal (e.g., fetal nutrient availability) or external (e.g., socioeconomic status; Chiarella et al, 2015). Studies involving genome-wide analysis of DNA methylation have begun to identify causal mechanisms and diagnostic biomarkers for complex human diseases (Mikeska & Craig, 2014).…”

Epigenetic Mechanisms in the Neurodevelopmental Theory of Depression

“…Furthermore, he hypothesised that this is a repeating process, which leads to the formation of a new organism [1]. However, studies reporting on the importance of epigenetics in the aetiology of mental disorders have appeared only recently [2][3][4].…”