A significant body of evidence supports the hypothesis that innate immune gene induction in brain causes negative affect and depression-like behavior (Raison et al. 2009). Patients with major depression have increased blood proinflammatory markers and antidepressant therapy is associated with decreases in markers. In addition to increased innate immune gene expression, human depression involves structural changes in hippocampus with multiple studies finding hippocampal volume is decreased in patients with depression (Videbech and Ravnkilde 2004). Other studies have associated loss of hippocampal neurogenesis, the formation of new neurons, with depression and hippocampal shrinkage. Interestingly, antidepressants increase hippocampal neurogenesis in models of depression and increase humans hippocampal volume during reversal of depression (Dranovsky and Hen 2006). Stress, multiple addictive drugs, innate immune genes and other factors that precipitate depression, reduce hippocampal neurogenesis (Tanapat et al. 2001; Malberg and Duman 2003; Gregus et al. 2005). Factors that reduce neurogenesis increase depression-like behavior (Johnson et al. 2006). Activation of NF-κB is necessary for stress induced inhibition of neurogenesis and induction of depression-like behavior (Koo and Duman 2008) as well as social defeat models of
