TNF and major depressive disorder: In addition, mechanistic studies have suggested depression itself may impair cognitive function via several pathophysiological paths, including an elevation of glucocorticoids through hypothalamic–pituitary–adrenal axis dysfunction, an increase in pro-inflammatory cytokines (e.g., tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6), and deficits in nerve growth factors (e.g., brain-derived neurotrophic factor).