MMP9 mRNA is a potential diagnostic and treatment monitoring marker for PTSD: Evidence from mice and humans

TY - JOUR

T1 - MMP9 mRNA is a potential diagnostic and treatment monitoring marker for PTSD: Evidence from mice and humans

AU - Chevalier, Céleste M

AU - Krampert, Luka

AU - Schreckenbach, Monika

AU - Schubert, Christine F

AU - Reich, Johanna

AU - Novak, Bozidar

AU - Schmidt, Mathias V

AU - Rutten, Bart P F

AU - Schmidt, Ulrike

N1 - Copyright © 2021 Elsevier B.V. and ECNP. All rights reserved.

PY - 2021/10

Y1 - 2021/10

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 PTSD-like 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.

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 PTSD-like 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.

U2 - 10.1016/j.euroneuro.2021.04.014

DO - 10.1016/j.euroneuro.2021.04.014

M3 - SCORING: Journal article

C2 - 34022747

VL - 51

SP - 20

EP - 32

JO - EUR NEUROPSYCHOPHARM

JF - EUR NEUROPSYCHOPHARM

SN - 0924-977X

ER -