Of the 9 ion channel receptors that we examined, P2RX7, TRPV1, and P2RY1 were upregulated in female patients during a depressive episode, and P2RY1 expression was positively related to depression severity along with 2 other ion channel receptors, TRPV4 and P2RX1. Here, TRPV4 is linked to major depressive disorder.