Stress increases the risk for major depressive disorder (MDD), overeating, and alcohol dependence (AD). The neuropeptide Y system is one of the best-known modulators of the stress response, and some of its effects are mediated through the neuropeptide Y receptor Y2 (NPY2R). The functional NPY2R variant rs6857715 (C-599T) has been implicated in both obesity and AD, but with opposing alleles. The present study explored whether rs6857715 is also associated with MDD. Analysis of the overall sample

more »

... 595 MDD cases; 1295 controls) showed an association with the AD risk allele C [P = 0.020, odds ratio (OR) (C-allele) = 1.18]. The association remained significant after excluding MDD patients with AD/alcohol abuse [P = 0.038, OR (C-allele) = 1.18]; increased weight/appetite [P = 0.006, OR (C-allele) = 1.23]; or both [P = 0.008, OR (Callele) = 1.25]. The present findings suggest that the NPY2R rs6857715 C-allele makes a genuine contribution toward MDD.