We hypothesized that: (a) MDD with high CRP inflammation (MDD-High) would exhibit higher serum leptin and insulin and lower adiponectin concentrations than healthy controls (HC) and MDD patients with normative CRP inflammation (MDD-Low); (b) within MDD-High subjects, higher serum insulin/leptin and lower adiponectin concentrations would be correlated with lower blood oxygen level-dependent (BOLD) signal change within the striatum, insula, and thalamus during anticipation of rewards. This evidence concerns the gene LEP and major depressive disorder.