CCN2 and major depressive disorder: New findings from a large Mendelian Randomization study have suggested that plasma CCN2 is significantly causally-associated with neuroticism and possibly also with depression (p = 0.07), and that plasma CCN3 is significantly causally-associated with anxiety/panic attacks and agreeableness (43, 44); in bipolar disorder, neurotic and (negative) agreeableness traits are reliable predictors of depressive and manic symptoms, respectively (45).