TY - JOUR
T1 - Elevated systemic expression of ER stress related genes is associated with stress-related mental disorders in the Detroit Neighborhood Health Study
AU - Nevell, Lisa
AU - Zhang, Kezhong
AU - Aiello, Allison E.
AU - Koenen, Karestan
AU - Galea, Sandro
AU - Soliven, Richelo
AU - Zhang, Chao
AU - Wildman, Derek E.
AU - Uddin, Monica
N1 - For work unrelated to this project, Sandro Galea is funded in part by a grant from Merck Pharmaceuticals; Derek Wildman is funded in part from Lung , LLC, receives Honoraria from Elsevier, INC; and Allison Aiello consults for SCA Tork. Lisa Nevell, Kezhong Zhang, Karestan Koenen, Richelo Soliven, Chao Zhang, and Monica Uddin declare no conflict of interest.
This study was supported by the National Institutes of Health (A.E.A., grant numbers DA022720 , DA022720-S1 , and RC1MH088283 ); the Wayne State University School of Medicine Post-Doctoral Research Fellowship (L.N.); the American Association of Anatomists Post-doctoral Fellowship (L.N.); and the National Science Foundation (D.W., grant number BCS 0827546 ).
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
KW - Cardiovascular diseases
KW - Case-control studies
KW - Endoplasmic reticulum stress
KW - Epidemiology
KW - Gene expression pattern analysis
KW - Matched-pair analysis
KW - Metabolic diseases
KW - Unfolded protein response
UR - https://www.scopus.com/pages/publications/84897462186
UR - https://www.scopus.com/pages/publications/84897462186#tab=citedBy
U2 - 10.1016/j.psyneuen.2014.01.013
DO - 10.1016/j.psyneuen.2014.01.013
M3 - Article
C2 - 24703171
AN - SCOPUS:84897462186
SN - 0306-4530
VL - 43
SP - 62
EP - 70
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
ER -