We searched within PubMed using the keywords “type 2 diabetes, T2D, major depressive disorder, MDD, depression, stress, hypothalamic-pituitary-adrenal axis, HPA, CRH, CRHR, norepinephrine” and included articles reporting valuable concepts on the association of chronic stress, the CRH system, norepinephrine (NE), depression, and T2D, including the genes CRHR1 and CRHR2. The gene discussed is CRH; the disease is major depressive disorder.