A significant virus effect was observed for most behavioural tests with no difference between unstressed vs stressed AAV-shRNA-Cldn5-injected animals, indicating that artificial opening of the BBB in the PFC is sufficient to induce anxiety- and depression-like behaviours in female mice without prior acute stress exposure (Fig. 3h, p = 0.0129 for elevated plus maze open arms, p = 0.0084 for splash test, p < 0.0001 for sucrose preference, p = 0.0453 for forced swim test). The gene discussed is CLDN5; the disease is major depressive disorder.