This study demonstrates for the first time both in vivo and in vitro that (1) repeated exposure to WIRS activates PDKI–SGK1–NDRG1–adhesion molecules (i.e., N-cadherin, α-catenin, and β-catenin) expression pathway via an increase in plasma corticosterone levels, (2) the activation of this signaling pathway causes excess arborization of oligodendrocyte processes, and (3) this abnormality in the oligodendrocytes is related to depression-like symptoms. Here, CDH2 is linked to major depressive disorder.