Upregulation of PDE4 induced by CACS may inhibit CREB-BDNF-mediated neurogenesis in the hippocampus, which is associated with the pathogenesis of depression and anxiety (O'Donnell and Zhang, 2004; Xu et al., 2011; Wang et al., 2014; Zhang et al., 2017). The gene discussed is CREB1; the disease is major depressive disorder.