Background: The role of endoplasmic reticulum (ER) stress response in mental illness is not well understood. Human studies and animal models of depression show elevated brain ER stress response. In addition, some ER stress associated disorders (e.g. cardiovascular disease) show higher rates of depression compared to the general population, raising the possibility that ER stress response contributes to depression risk. It remains unknown, however, if ER stress response is present among individuals suffering from other stress-related mental illness, and whether such a response would be evident in a non-clinical sample. This study tests for systemic changes in ER stress response associated with Major Depressive Disorder (MDD) or post-traumatic stress disorder (PTSD) among community-dwelling individuals. Methods: We analyzed expression of BiP, EDEM1, CHOP, and XBP1, the major indicators of ER stress response, with real-time PCR in leukocyte-derived RNA samples from 86 participants of the Detroit Neighborhood Health Study. Participants were selected based on the presence of either past year MDD or past year PTSD; controls were age and sex matched.