Identification of DNA Methylation Changes That Predict Onset of Post-traumatic Stress Disorder and Depression Following Physical Trauma.

Carina A Martin,Chen Lai,Martin Schrieber,Hyung-Suk Kim,Sijung Yun,Rany Vorn,Jessica Gill

doi:10.3389/fnins.2021.738347

Abstract

Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly experienced after exposure to highly stressful events, including physical trauma, yet, biological predictors remain elusive. Methylation of DNA may provide key insights, as it likely is reflective of factors that may increase the risk in trauma patients, as DNA methylation is altered by previous stressors. Here, we compared DNA methylation patterns using bisulfite sequencing in patients with a physical trauma that required more than a 24-h hospitalization (n = 33). We then compared DNA methylation in patients who developed and compared the following groups (1) PTSD and MDD; n = 12), (2) MDD (patients with MDD only; n = 12), and (3) control (patients who did not have PTSD or MDD; n = 9), determined by the PTSD Checklist (PCL-5) and Quick Inventory of Depressive Symptomatology (QIDS) at 6-months follow-up. We identified 17 genes with hypermethylated cytosine sites and 2 genes with hypomethylated sites in comparison between PTSD and control group. In comparison between MDD and control group, we identified 12 genes with hypermethylated cytosine sites and 6 genes with hypomethylated sites. Demethylation of these genes altered the CREB signaling pathway in neurons and may represent a promising therapeutic development target for PTSD and MDD. Our findings suggest that epigenetic changes in these gene regions potentially relate to the onset and symptomology of PTSD and MDD and could be used as potential biomarkers in predicting the onset of PTSD or MDD following traumatic events.

Highlights

Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are common psychiatric disorders that can develop in individuals who have experienced exposure to extreme stress or a traumatic event (Klengel et al, 2014; Ryan et al, 2016)
We previously reported the upregulation of inflammatory cytokines genes and plasma proteins levels in military personnel with PTSD and MDD (Gill et al, 2014; Guardado et al, 2016)
Major Depressive Disorder vs. Control In comparison between MDD and control group, we identified 12 genes with hypermethylated cytosine sites and 6 genes with hypomethylated sites common in Day1 and Day2 batches (Table 3)

Summary

Introduction

Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are common psychiatric disorders that can develop in individuals who have experienced exposure to extreme stress or a traumatic event (Klengel et al, 2014; Ryan et al, 2016). It is not clear how the onset of PTSD occurs, making it very difficult to predict and develop methods for prevention (Qi et al, 2016) This is a critical issue, as PTSD and MDD have been linked to flashbacks, nightmares, avoidance behaviors, negative mood/thoughts, and/or alterations in arousal, which include exaggerated startle, and sleep disturbance (Klengel et al, 2014; Blacker et al, 2019). Both conditions cause major impacts on quality of life, and often, inhibit a person’s ability to participate in activities they enjoy. PTSD and depression have been associated with lower quality of life in military personnel (Gill et al, 2014) and suicidal behavior (Sareen et al, 2007)

Methods

Results

Conclusion