Studies of postmortem brain tissue from patients with depression has found reduced expression of claudin-5, particularly in the nucleus accumbens and hippocampus, along with increased expression of FoxO1 and of histone deactylase 1 (HDAC1), both of which repress the CLDN5 gene (Menard et al., 2017; Dudek et al., 2020; Greene et al., 2020). Here, CLDN5 is linked to major depressive disorder.