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

Mennesson, M.; Abdelkaoui, S.; Roullot-Lacarriere, V.; Tronel, S.; Cathala, A.; Lalanne, V.; Raux, P.-L.; Makrini, L.; Valjent, E.; Duffaud, A.; Claverie, D.; Vallee, M.; Desmedt, A.; Trousselard, M.; Revest, J.-M.

doi:10.1101/2025.07.02.661922

bioRxiv · 10.1101/2025.07.02.661922

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

Mennesson, M.·Abdelkaoui, S.·Roullot-Lacarriere, V.·Tronel, S.·Cathala, A.·Lalanne, V.·Raux, P.-L.·Makrini, L.·Valjent, E.·Duffaud, A.·Claverie, D.·Vallee, M.·Desmedt, A.·Trousselard, M.·Revest, J.-M.

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Abstract

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-1s potential as a blood biomarker and brain therapeutic target for PTSD.

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Mennesson, M., Abdelkaoui, S., Roullot-Lacarriere, V., Tronel, S., Cathala, A., Lalanne, V., Raux, P.-L., Makrini, L., Valjent, E., Duffaud, A., Claverie, D., Vallee, M., Desmedt, A., Trousselard, M., Revest, J.-M.. 2025-07-04. Stress-induced plasminogen activator inhibitor-1 (PAI-1) as a blood biomarker and brain risk factor for PTSD. https://doi.org/10.1101/2025.07.02.661922

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