In this naturalistic longitudinal study, linear mixed models were used to analyze the relation between BDNF, IL-6, TNF-α, and depression severity (determined by the Montgomery-Åsberg Depression Rating Scale; MADRS) in 99 patients with severe LLD before ECT (T0), three weeks after the first ECT (T1), and one week after the last ECT (T2). This evidence concerns the gene BDNF and major depressive disorder.