A reduction of the central NPY level and/or function was observed in experimental and clinical depression (Caberlotto et al. 1999; Caberlotto and Hurd 1999), whereas central administration of NPY or Y1R agonist [Leu31,Pro34]-PYY produced antidepressant-like effects in rats and mice (Stogner and Holmes 2000; Redrobe et al. 2002; Ishida et al. 2007; Morales-Medina et al. 2012a; Desai et al. 2014); moreover, these effects were blocked by Y1R antagonists (Redrobe et al. 2002; Ishida et al. 2007; Desai et al. 2014). The gene discussed is NPY; the disease is major depressive disorder.