Our results indicate that levels of the key tight junction protein claudin-5 are decreased in the hippocampus of human brain from individuals diagnosed with depression and schizophrenia, while mRNA and protein levels of claudin-5, claudin-12 and ZO-1 are associated with the age of onset and duration of schizophrenia, bipolar disorder and depression. This evidence concerns the gene CLDN5 and major depressive disorder.