A Systematic Review of DNA Methylation and Gene Expression Studies in Posttraumatic Stress Disorder, Posttraumatic Growth, and Resilience

Abstract

Most people will experience a traumatic event within their lifetime. One commonly recognized response to trauma exposure is posttraumatic stress disorder (PTSD). The biological underpinnings of PTSD, including epigenetic mechanisms of DNA methylation and gene expression, have been studied intensively. However, psychological posttrauma responses vary widely and can include positive outcomes, such as posttraumatic growth (PTG) and, more commonly, resilience. The aim of this systematic review was to summarize the current DNA methylation and gene expression data with respect to three potential posttrauma responses: PTSD, PTG, and resilience. A literature search identified 486 studies, 51 of which were deemed eligible for inclusion (total N = 10,633). All included studies examined PTSD and consistently implicated DNA methylation and gene expression changes in hypothalamic-pituitary-adrenal axis and inflammatory genes. Ten studies acknowledged resilience as a posttrauma response, but only two studies examined epigenetics and gene expression using a scale to measure resilience. Low resilience was associated with gene expression patterns in immune and dopamine genes, and high resilience was associated with a blunted inflammatory response. No studies examined epigenetic or gene expression changes associated with PTG. These findings highlight a focus on pathogenic research, which has failed to adequately acknowledge and measure positive posttrauma outcomes of PTG and resilience. Future research should examine DNA methylation and gene expression changes associated with PTG and resilience in addition to PTSD in order to gain a more comprehensive picture of an individual's well-being following exposure to trauma.

The Interplay between Child Maltreatment and Stressful Life Events during Adulthood and Cardiovascular Problems—A Representative Study

“…Genetic factors, such as FK506 binding protein 5 (FKBP5) and G-protein coupled type-I CRH receptor (CRHR1), strongly influence individual stress reactivity [77]. The relevance of epigenetic modifications onto stress response and the development of health problems after stressful events has become more evident in studies during the last decade, particularly in stress-axis-, immune-and transmitter-related genes [78,79]. Further determinants encompass cognitive appraisal [80] and psychological coping resources [26].…”

Resilience: Safety in the Aftermath of Traumatic Stressor Experiences

“…Also entering the mix are multiple neurobiological elements, including numerous genetic factors that code for specific processes (e.g., neuropeptide Y or particular neurotrophins) and particular epigenetic changes may similarly imbue individuals with greater resilience (e.g., La Greca et al, 2013;Schmeltzer et al, 2016). These epigenetic changes could result in enhanced immune or endocrine functioning that are essential for adaptation (Mehta et al, 2020). Similarly, while some inflammatory processes have been associated with varied illnesses, epigenetic changes can act against cytokine-mediated inflammation and might thereby protect against stressorrelated psychological and physical disturbances (e.g., Wang et al, 2018).…”

“…Numerous experiential and individual difference factors (e.g., gender, ethnoracial status, age, earlier stressor encounters) that could exacerbate or diminish the actions of stressors have been established (Anisman et al, 2018). Likewise, genetic and epigenetic factors that code for particular biological features (e.g., processes related to glucocorticoid or neurotrophin functioning) are tied to the occurrence of behavioral and physical disturbances (Suri et al, 2013;Szyf et al, 2016;Mehta et al, 2020), and glucocorticoids influence epigenetic responses to stress (Reul et al, 2014).…”

Epigenome‐Wide Study of Posttraumatic Stress Disorder Symptom Severity in a Treatment‐Seeking Adolescent Sample

“…Epigenome‐wide methylation studies (EWAS), like GWAS, offer an agnostic approach to examining epigenetic associations and are a valuable tool to aid in the identification of biological pathways involved in PTSD. To date, several EWAS have been conducted in relation to PTSD and have provided support for genes involved in the stress response system, such as hypothalamic–pituitary–adrenal (i.e., HPA) axis genes and inflammatory genes (see recent review by Mehta et al., 2020). Although this promising literature has been growing, it is important to note that to our knowledge, all DNAm studies of PTSD to date have been conducted in adult samples.…”