ISG15 and depressive disorder: Interestingly, the aforementioned animal studies have shown a significant upregulation of STAT1, ISG15, and USP18 genes in the mouse brain, including the hippocampus (Wang and Campbell, 2005; Wang et al., 2008), a brain region involved in neurogenesis-dependent cognitive functions, such as memory and attention, often impaired in patients with depression (Moylan et al., 2013).