ITPR1 (alias, IP3R) genetic variation was recently associated with reduced hippocampal volume in two independent MDD cohorts, which lead the authors to speculate that mood disorders, and specifically cognitive changes, may involve mechanisms related to ITPR, endoplasmic reticulum (ER) stress, the unfolded protein response (UPR) system and GSK3β signalling56. This evidence concerns the gene GSK3B and major depressive disorder.