Compared with Vrk2<sup>+/+</sup> mice, the density of mushroom and thin spines in the ventral hippocampus was significantly altered in Vrk2<sup>-/-</sup> mice, which is in line with the phosphoproteomic analyses showing dysregulated synapse-associated proteins and pathways in Vrk2<sup>-/-</sup> mice.<h4>Conclusions</h4>Vrk2 deficiency mice showed behavioral abnormalities that mimic human depressive phenotypes, which may serve as a useful murine model for studying the pathophysiology of depression. This evidence concerns the gene VRK2 and depressive symptom measurement.