For example, in Juruena et al. (2013), it was investigated the combined GR/MR stimulation with just prednisolone, prednisolone and spironolactone, and spironolactone alone, and authors found a lack of MR response in treatment-resistant depression, suggesting that there is an MR malfunctioning, as a downregulation, or even a pharmacokinetics or pharmacodynamics effect. This evidence concerns the gene NR3C1 and depressive disorder.