In the present study, in order to assess whether cerebrovascular pathology mediates the inter-relationships of Hp genotype, depressive symptoms, and frontal lobe volume, we further adjusted the analysis of interaction of Hp genotype with number of depression symptoms on total frontal lobe and superior frontal gyrus volumes for white matter hyperintensities volume, but the results were only mildly attenuated. This evidence concerns the gene HP and major depressive disorder.