Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma

Abstract

Adverse childhood experiences (ACEs) may be referred to by other terms (e.g., early life adversity or stress and childhood trauma) and have a lifelong impact on mental and physical health. For example, childhood trauma has been associated with posttraumatic stress disorder (PTSD), anxiety, depression, bipolar disorder, diabetes, and cardiovascular disease. The heritability of ACE-related phenotypes such as PTSD, depression, and resilience is low to moderate, and, moreover, is very variable for a given phenotype, which implies that gene by environment interactions (such as through epigenetic modifications) may be involved in the onset of these phenotypes. Currently, there is increasing interest in the investigation of epigenetic contributions to ACE-induced differential health outcomes. Although there are a number of studies in this field, there are still research gaps. In this review, the basic concepts of epigenetic modifications (such as methylation) and the function of the hypothalamic-pituitary-adrenal (HPA) axis in the stress response are outlined. Examples of specific genes undergoing methylation in association with ACE-induced differential health outcomes are provided. Limitations in this field, e.g., uncertain clinical diagnosis, conceptual inconsistencies, and technical drawbacks, are reviewed, with suggestions for advances using new technologies and novel research directions. We thereby provide a platform on which the field of ACE-induced phenotypes in mental health may build.

When mummy and daddy get under your skin: A new look at how parenting affects children's DNA methylation, stress reactivity, and disruptive behavior

“…Preliminary findings now suggest similar mechanisms may operate in humans. Several studies have found an association between methylation levels at a number of genes and exposure to early life adversity, such as maltreatment and parental separation (Jiang, Postovit, Cattaneo, Binder, & Aitchison, 2019; Vinkers et al., 2015). In particular, hypermethylation at the glucocorticoid receptor (GR) gene, a key regulator of the HPA axis, has been repeatedly found in individuals who have experienced early life adversity (for a review see Palma‐Gudiel, Córdova‐Palomera, Leza, & Fañanás, 2015).…”

AVPR1A main effect and OXTR-by-environment interplay in individual differences in depression level

“…However, other researchers failed to detect such effects ( Culverhouse et al., 2018 ; Van der Auwera et al., 2017 ). Between study heterogeneity may be attributed to inherited epigenetic patterns ( Jiang et al., 2019 ) and environmental factors other than childhood trauma, which cause induced differential health outcomes via epigenetic reprogramming ( Jiang et al., 2019 ). Therefore, some scientists have focused on other psychosocial factors including peculiarities of child-parent relations, familial support, parenting behavior ( Cao et al., 2018 ; Van Assche et al., 2016 ), and peer relationships with respect to depressive symptomatology; however, such attempts are scarce.…”

Intermittent Hypoxia Promotes Functional Neuroprotection from Retinal Ischemia in Untreated First-Generation Offspring: Proteomic Mechanistic Insights

“…As examples, early life stress can impact a variety of neuropsychiatric conditions later in life. 2 , 3 Similarly, cardiovascular disease, cancer, and even aging itself are influenced by a myriad of adverse stress stimuli experienced during childhood. 4 , 5 In fact, epigenetic modifications secondary to stress and environmental change not only can affect phenotypes across the lifespan but can also affect phenotypes in progeny.…”