However, given that 7 of the CRHR1-risk variants are in 2 LD blocks linked to T2D and MDD (unpublished data) and the same PCOS-risk alleles of 4 variants are significantly linked and associated with T2D, we can not a priori exclude that the mental-metabolic contribution risk, at least for these variants, might underlie the PCOS-related maladaptive stress response [11] and the increased blood cortisol levels found in 50% PCOS patients [13, 32], which, as we previously hypothesized [33] and recently reported for CRHR2 [29], might per se contribute to T2D and MDD as well. This evidence concerns the gene CRHR2 and major depressive disorder.