Similarly, IGF1/IGF1R signaling declined during pregnancy, which is notable given that IGF1 deficiency in the hippocampus is linked to depression (Torres Aleman, 2005; Mitschelen et al., 2011) Wnt5a signaling in endothelial cells also declined during pregnancy compared with virgin (Fig. 5b). This evidence concerns the gene IGF1R and major depressive disorder.