Molecular and Cellular Effects of Traumatic Stress: Implications for PTSD

Abstract

Purpose of Review Posttraumatic stress disorder (PTSD) is characterized by hyperarousal and recurrent stressful memories after an emotionally traumatic event. Extensive research has been conducted to identify the neurobiological determinants that underlie the pathophysiology of PTSD. In this review, we examine evidence regarding the molecular and cellular pathophysiology of PTSD focusing on two primary brain regions: the vmPFC and the amygdala. Recent Findings This discussion includes a review of the molecular alterations related to PTSD, focusing mainly on changes to glucocorticoid receptor signaling. We also examine postmortem gene expression studies that have been conducted to date and the molecular changes that have been observed in peripheral blood studies of PTSD patients. Causal, mechanistic evidence is difficult to obtain in human studies, so we also review preclinical models of PTSD. Summary Integration of peripheral blood and postmortem studies with preclinical models of PTSD has begun to reveal the molecular changes occurring in patients with PTSD. These findings indicate that the pathophysiology of PTSD includes disruption of glucocorticoid signaling and inflammatory systems and occurs at the level of altered gene expression. We will assess the impact of these findings on the future of PTSD molecular research.

Investigating Individual Pre-trauma Susceptibility to a PTSD-Like Phenotype in Animals

“…In line with HPA dysfunction, glucocorticoid receptor polymorphisms have been thoroughly investigated (Yehuda, 2009). However, the overall prevalence of these polymorphs in people with PTSD has been found to be within normal range of the population (Girgenti et al, 2017), suggesting that it is a risk factor rather than a susceptibility/sequala factor: it is a measure that is not sensitive enough to separate those who will develop PTSD from those who won't. Another identified risk factor in humans is smaller hippocampal volume.…”

Trauma, PTSD, and the Developing Brain

“…A full review of such mechanisms is beyond the scope of this article; I refer readers elsewhere for further information on genetic mechanisms linking childhood adversity to mental and physical health [76,77], as well as the genetic and molecular mechanisms of PTSD reviewed in this special issue [78]. However, I highlight here some promising candidate pathways mediating the link between childhood trauma and psychopathology involving the glucocorticoid stress pathway.…”

Transcriptomic Organization of Human Posttraumatic Stress Disorder

“…Studies of the molecular underpinnings of PTSD have been limited largely to white blood cells , identifying altered expression levels of pro-inflammatory cytokines and genes related to glucocorticoid activity [31][32][33] . Here we report the first transcriptomewide analysis of gene expression changes in postmortem brain of a large cohort of PTSD subjects.…”