Stress-induced plasminogen activator inhibitor-1 (PAI-1) as a blood biomarker and brain risk factor for PTSD

Mennesson M(1), Abdelkaoui S(2), Roullot-Lacarrière V(2), Tronel S(2), Cathala
A(2), Lalanne V(2), Raux PL(2), Makrini L(3), Valjent E(4), Duffaud AM(5)(6),
Claverie D(5)(6), Vallée M(2), Desmedt A(2), Trousselard M(5)(6)(7)(8), Revest
JM(9)(10).

Author information:
(1)Univ. Bordeaux, Inserm, Neurocentre Magendie, U1215, F-33000, Bordeaux,
France. .
(2)Univ. Bordeaux, Inserm, Neurocentre Magendie, U1215, F-33000, Bordeaux,
France.
(3)Institut de Génomique Fonctionnelle (IGF), Univ. Montpellier CNRS, Inserm,
34094, Montpellier, France.
(4)Institut for Neurosciences of Montpellier (INM), Univ. Montpellier, CNRS,
Inserm, 34000, Montpellier, France.
(5)Unité de Neurophysiologie du Stress, Département Neurosciences & Contraintes
Opérationnelles, Institut de Recherche Biomédicale des Armées (IRBA), 91223,
Brétigny-sur-Orge, France.
(6)French Society for Traumatic Stress Studies (FSTSS), 44600, Saint-Nazaire,
France.
(7)École de Psychologues Praticiens (EPP), 23 rue du Montparnasse, 75006, Paris,
France.
(8)Univ. Lorraine, Inserm, INSPIIRE, UMR 1319, F-54000, Nancy, France.
(9)Univ. Bordeaux, Inserm, Neurocentre Magendie, U1215, F-33000, Bordeaux,
France. .
(10)French Society for Traumatic Stress Studies (FSTSS), 44600, Saint-Nazaire,
France. .

Post-traumatic stress disorder (PTSD) is a severe stress-related psychiatric
condition triggered by traumatic life-threatening events, characterized notably
by an altered memory profile. Although clinically well-documented, no specific
biomarker exists. This translational study identifies plasminogen activator
inhibitor-1 (PAI-1) as a brain risk factor for PTSD, thereby supporting its
potential as a blood-derived biomarker. Mice with genetically ablated PAI-1 were
protected from developing a PTSD-like memory profile. Conversely, mice
exhibiting PTSD-like cognitive impairment showed increased blood PAI-1 levels,
correlating with their profile severity. In the brain, PAI-1 levels were
specifically increased in the dorsal hippocampus, a key region for cognitive
functions and in the etiology of PTSD. Finally, a longitudinal study of soldiers
revealed that those developing PTSD symptoms exhibit rising blood PAI-1 levels
over a 12-month period. Its significant association with various indicators of
PTSD-related psychological distress attests to PAI-1’s potential as a blood
biomarker and brain therapeutic target for PTSD.

© 2026. The Author(s).

DOI: 10.1038/s41380-026-03564-w
PMID: 41912791

Conflict of interest statement: Competing interests: The author declares no
competing interests.

Auteurs Bordeaux Neurocampus