The monocyte-T-lymphocyte theory of depression, devised by Smith and Maes (Smith, 1991; Maes et al., 1995b) in the early 1990s, proposes that increased proinflammatory cytokine secretion in the form of IL-1β, TNF-α, and IFN-γ is responsible for the initiation and maintenance of a depressive episode. The gene discussed is IL1B; the disease is major depressive disorder.