CACNA1C and major depressive disorder: For instance, we can speculate that the down-regulation of Cacna1c expression contributed to increased anxiety-like behavior observed in females of all groups and in SI males, with MS females being most significantly affected because these animals also show dysregulated expression of Egr1 and Nr3c1. In addition, “normalized” Cacna1c expression is consistent with the lack of anxiety and depression-related phenotype in the double-stress male group.