TNF and major depressive disorder: Direct evidence of inflammation in depression comes from meta-analyses of cross-sectional studies of inflammatory markers in depression, which have shown increased concentrations of circulating C-reactive protein (CRP), interleukin 6 (IL-6), interleukin-12 (IL-12), tumor necrosis factor-α (TNFα), and reductions in interleukin-4 (IL-4) in acute depression (Howren et al., 2009, Dowlati et al., 2010, Haapakoski et al., 2015, Goldsmith et al., 2016, Köhler et al., 2017).