TNF and major depressive disorder: Previous studies have demonstrated that distinct cytokines, including interleukin-1beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α), known to be upregulated both in the periphery and in the brain of patients with major depressive disorder (MDD), are able to increase blood brain barrier (BBB) permeability (Deli et al., 1995, Didier et al., 2003, Schwaninger et al., 1999) and ultimately to cause changes in discrete brain regions, including the hippocampus (Wang et al., 2008).