Currently, three PDE4-selective inhibitors, roflumilast, apremilast and crisaborole, have been developed for clinical use, in respiratory and inflammatory disorders [14–16], and additional PDE4 inhibitors have been developed and tested for a variety of indications, including depression, schizophrenia, and disorders of learning and memory [17, 18]. This evidence concerns the gene PDE4A and depressive disorder.