Given the identification of Wfs1 as a genetic cause of MDD (Flint and Kendler, 2014) and previous studies demonstrating that behavioral resilience requires normal function of the mPFC (Russo et al., 2012), our data provide strong evidence that dysfunction in Wfs1-expressing pyramidal cells in the mPFC may contribute to MDD as a result of enhanced susceptibility to stress. The gene discussed is WFS1; the disease is major depressive disorder.