INSR and major depressive disorder: Binding of the ligand to insulin receptors (IRs) generates intracellular signals via two main intracellular signaling pathways, the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K)-Serine/threonine kinase (Akt) pathway and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, which are known to be involved in depression pathophysiology [16,17].