At least two considerations may account for this apparent paradox: 1) under some experimental conditions, proinflammatory cytokines have been associated with a neuroprotective role, [251; (for example, IFN-γ in low levels can induce neuroprotective microglia (Figure 2) [163,166,251]); and 2) whether these responses observed in the context of an acute stress paradigm in an animal model are applicable to endogenous MDD in humans remains unclear [251]. This evidence concerns the gene IFNG and major depressive disorder.