During the past three decades, several groups reported compelling evidence showing that prolonged stress response (in particular sustained CRF and GCs release) may represent a biological mechanism triggering depression (Carroll, 1982; Holsboer, 2000; Pariante, 2003; Strohle and Holsboer, 2003) and obesity (Bjorntorp and Rosmond, 2000; Pasquali and Vicennati, 2000), even though psychosocial stress would exert only a modest effect on weight gain (Wardle et al., 2011). The gene discussed is CRH; the disease is obesity due to melanocortin 4 receptor deficiency.