PPM1D and depressive disorder: Secondly, we found that fluoxetine failed to rescue Wip1 KO-induced defects in depressive behaviors, hippocampal cellular senescence and γ-H2AX activity, whereas the application of fluoxetine effectively prevented these symptoms in CUMS-exposed C57BL/6 wildtype mice, indicating that the loss of Wip1 gene blocks the therapeutic effects of fluoxetine on depressive disorder.