TY - JOUR
T1 - MMP9 mRNA is a potential diagnostic and treatment monitoring marker for PTSD: Evidence from mice and humans
AU - Chevalier, C.M.
AU - Krampert, L.
AU - Schreckenbach, M.
AU - Schubert, C.F.
AU - Reich, J.
AU - Novak, B.
AU - Schmidt, M.V.
AU - Rutten, B.P.F.
AU - Schmidt, U.
N1 - Funding Information:
We thank the Private Horst Kübler Foundation, Munich, Germany, for generous funding of our studies. Moreover, we thank Prof. Dr. Matthias M. Weber and Dr. Wolfgang Burgmair for their tremendous support with logistics (TSST and DST experiments) as well as Cornel Babel for IT support.
Funding Information:
All experiments have been performed at the Max Planck institute of Psychiatry. Part of the consumables were funded by the Private Horst Kübler Foundation, München, Germany. The Horst Kübler Foundation had no role in study design, evaluation of results or decision to publish.
Publisher Copyright:
© 2021 Elsevier B.V. and ECNP
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Although matrix metalloproteinase 9 (MMP9) has been found associated with various psychiatric disorders and with threat memories in humans, its role in post-traumatic stress disorder (PTSD) and related animal models is understudied. Thus, we analyzed MMP9 mRNA expression kinetics during two different stress experiments, i.e., the Trier Social Stress Test and the dexamethasone suppression test (DST), in whole blood of two independent cohorts of PTSD patients vs. non-traumatized healthy controls (HC) and, moreover, in a mouse model of PTSD and in dexamethasone-treated mice. Besides MMP9, we quantified mRNA levels of four of its regulators, i.e., interleukin (IL)-1 receptor 1 and 2 (IL1R1, IL1R2), IL-6 receptor and tumor necrosis factor receptor 1 (TNFR1) in 10 patients exposed to the DST before vs. after successful PTSD psychotherapy vs. 13 HC and, except from Il6r, also in different brain regions of the PTSD mouse model. We are the first to show that blood MMP9 mRNA concentrations were elevated after acute dexamethasone in PTSD patients, improved upon partial remission of PTSD and were, furthermore, also elevated, together with its regulator Tnfr1, in the prefrontal cortex of PTSDlike mice. In contrast, blood TNFR1 and IL1R2 were markedly underexpressed in PTSD patients. In conclusion, we found translational evidence supporting that, I, TNFR1 and MMP9 mRNA expression might be involved in PTSD pathobiology, II, might constitute potential diagnostic blood biomarkers for PTSD and, importantly, III, post-dexamethasone blood MMP9 hyperexpression, which speculatively results from post-dexamethasone underexpression of IL1R2, might serve also as potential treatment monitoring biomarker for PTSD. (c) 2021 Elsevier B.V. and ECNP. All rights reserved.
AB - Although matrix metalloproteinase 9 (MMP9) has been found associated with various psychiatric disorders and with threat memories in humans, its role in post-traumatic stress disorder (PTSD) and related animal models is understudied. Thus, we analyzed MMP9 mRNA expression kinetics during two different stress experiments, i.e., the Trier Social Stress Test and the dexamethasone suppression test (DST), in whole blood of two independent cohorts of PTSD patients vs. non-traumatized healthy controls (HC) and, moreover, in a mouse model of PTSD and in dexamethasone-treated mice. Besides MMP9, we quantified mRNA levels of four of its regulators, i.e., interleukin (IL)-1 receptor 1 and 2 (IL1R1, IL1R2), IL-6 receptor and tumor necrosis factor receptor 1 (TNFR1) in 10 patients exposed to the DST before vs. after successful PTSD psychotherapy vs. 13 HC and, except from Il6r, also in different brain regions of the PTSD mouse model. We are the first to show that blood MMP9 mRNA concentrations were elevated after acute dexamethasone in PTSD patients, improved upon partial remission of PTSD and were, furthermore, also elevated, together with its regulator Tnfr1, in the prefrontal cortex of PTSDlike mice. In contrast, blood TNFR1 and IL1R2 were markedly underexpressed in PTSD patients. In conclusion, we found translational evidence supporting that, I, TNFR1 and MMP9 mRNA expression might be involved in PTSD pathobiology, II, might constitute potential diagnostic blood biomarkers for PTSD and, importantly, III, post-dexamethasone blood MMP9 hyperexpression, which speculatively results from post-dexamethasone underexpression of IL1R2, might serve also as potential treatment monitoring biomarker for PTSD. (c) 2021 Elsevier B.V. and ECNP. All rights reserved.
KW - Post-traumatic stress disorder
KW - Trier Social Stress Test (TSST)
KW - Dexamethasone suppression test
KW - Mouse model of PTSD
KW - PTSD biomarkers
KW - exposure therapy
KW - POSTTRAUMATIC-STRESS-DISORDER
KW - SERUM CONCENTRATIONS
KW - PERIPHERAL-BLOOD
KW - GENE-EXPRESSION
KW - TNF-ALPHA
KW - MATRIX-METALLOPROTEINASE-9
KW - MOUSE
KW - DEXAMETHASONE
KW - BIOMARKERS
KW - GLUCOCORTICOIDS
U2 - 10.1016/j.euroneuro.2021.04.014
DO - 10.1016/j.euroneuro.2021.04.014
M3 - Article
C2 - 34022747
SN - 0924-977X
VL - 51
SP - 20
EP - 32
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
ER -