Elevated systemic expression of ER stress related genes is associated with stress-related mental disorders in the Detroit Neighborhood Health Study

Lisa Nevell, Kezhong Zhang, Allison E. Aiello, Karestan Koenen, Sandro Galea, Richelo Soliven, Chao Zhang, Derek E. Wildman, Monica Uddin

Research output: Contribution to journalArticlepeer-review


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. Results: Relative to controls, MDD is associated with a 1.34-fold increase in BiP (P= 0.004), 1.35-fold increase in EDEM1 (P= 0.001), 1.68-fold increase in CHOP (P= 0.002), and 1.60-fold increase in XBP1 (P= 0.004). These results remained significant after correction for multiple testing. In contrast, PTSD is associated with a 1.27-fold increase in EDEM1 expression only (P= 0.027), a result that is attenuated to non-significance following adjustment for multiple testing; however, a subsample of participants with past month PTSD showed elevated expression of BiP and EDEM1 (uncorrected P value 0.049 and 0.017, respectively). Conclusions: These data indicate systemic and persistent activation of the ER stress response pathway in MDD among community-dwelling individuals. Systemic activation of the ER stress response may also occur in PTSD among persons with more recent symptoms.

Original languageEnglish (US)
Pages (from-to)62-70
Number of pages9
StatePublished - May 2014
Externally publishedYes


  • Cardiovascular diseases
  • Case-control studies
  • Endoplasmic reticulum stress
  • Epidemiology
  • Gene expression pattern analysis
  • Matched-pair analysis
  • Metabolic diseases
  • Unfolded protein response

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry


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