Dysregulated Expression of Endoplasmic Reticulum Stress Gene Markers in Major Depressive Disorder and Post-Traumatic Stress Disorder

Abstract

The accumulation of unfolded/misfolded proteins in the endoplasmic reticulum is a condition known as endoplasmic reticulum stress (ER stress). This condition is combated by a series of signal transduction pathways collectively termed the unfolded protein response (UPR). Dysregulation of the ER stress response pathways is known to play a role in highly prevalent physical illnesses such as vascular disease, obesity, and type 2 diabetes. The association of ER stress and mental illnesses is less well understood. Here we show dysregulated expression of ER stress related response gene markers in individuals suffering from major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) among the Detroit Neighborhood Health Study (DNHS). Real-time quantitative PCR analysis shows dysregulation of E3 ubiquitin-protein ligase HRD1 (HRD1) expression in individuals with a history of PTSD, and dysregulation of activating transcription factor 4 (ATF4) expressions in individuals with a history of PTSD and in individuals with a history of MDD. These results suggest ER stress dysregulation among individuals experiencing PTSD and MDD in the Detroit community, and substantially contributes to the evidence of ER stress in mental illnesses.