In the still ongoing debate on the bidirectional association between major depressive disorders and type 2 diabetes, as well as between depression and CVD risk [31], the present report on 389 obese individuals, mainly females, supports the following conclusions: (1) depressive symptoms, as assessed by BDI-II score, seem to raise PCSK9 levels, (2) depressive symptoms directly associate with HOMA-IR, a pre-diabetes related CV risk variable [32], and (3) 11% of such an effect operates via an indirect path, through PCSK9. Here, PCSK9 is linked to depressive disorder.