Moreover, when CRP concentrations were used as a covariate, the significant negative correlation between leptin and gain versus non-gain BOLD signal change within the left insula (r =  − 0.30, p = 0.005) and the left dorsolateral putamen (r =  − 0.24, p = 0.025) remained the same within the MDD group, the positive relationship between leptin and gain versus non-gain BOLD signal change within the left insula (r = 0.38, p = 0.013) and the left dorsolateral putamen (r = 0.38, p = 0.011) in the HC group remained similar as well. The gene discussed is LEP; the disease is major depressive disorder.