Chronic social stress is associated with reduced cldn5 expression in the nucleus accumbens of stress-susceptible male mice and in the prefrontal cortex of stress-susceptible female mice, and this co-occurs with depression-like phenotypes and increased BBB permeability (Menard et al., 2017; Dion-Albert et al., 2022). This evidence concerns the gene CLDN5 and major depressive disorder.