TNF and major depressive disorder: Additionally, a systematic review including 69 studies revealed that patients with MDD had higher levels of IL-6 and tumor necrosis factor-α (TNF-α) in cerebrospinal fluid and brain parenchyma compared with the control group [standardized mean difference (SMD) was 0.37, 95% CI: 0.17–0.57 and SMD 0.58, 95% CI 0.26–0.90, respectively] (61, 62).