CACNA1C and major depressive disorder: In this respect, DNA sequence variation of CACNA1C has been widely recognized as a susceptibility factor for depressive psychopathology,45 and methylation changes of CACNA1C have likewise been associated with early-life stress,51, 52 a risk factor for depressive disorders.53 Similarly, depressive behavior is likely modulated by IGF2. 54, 55 Also, MAPK11 is one of the four p38 mitogen-activated protein kinases, the activity of which has been linked to depression and related phenotypes.56, 57