The primary aim of this study was to investigate whether a set of single nucleotide polymorphisms (SNPs) within two genes implicated in neuroplasticity and inflammatory processes (the mitogen activated protein kinase 1, MAPK1 (rs3810608, rs6928, rs13515 and rs8136867), and the cyclic AMP responsive element binding protein 1, CREB1 (rs889895, rs6740584, rs2551922 and rs2254137)) was associated with antidepressant treatment resistance (according to two different definitions), in 285 Major Depressive Disorder (MDD) patients.