In accordance with previous findings that link low plasma tPA levels to depression, it was equally demonstrated that plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of tPA, is upregulated in both the hippocampus and prefrontal cortexes in animal models of depression as well as in the serum of human patients with symptoms of depression [65,66]. Here, SERPINE1 is linked to depressive disorder.