As in SUDs, proinflammatory cytokines are implicated in the pathophysiology of depression. Like bacterial lipopolysaccharide, exogenous TNF-α and IL-1 administration to rodents (both centrally and peripherally) produce“sickness behaviour“, a con stellation of physical and neuropsychiatric symptoms resembling depression (Dantzer 2001a; 2001b). In non-human primates, a ligand that recognizes activated microglia found lipopolysaccharide-induced microglial activation within hours, an effect most likely mediated through cytokine secretion (Hannestad et al. 2012). Likewise, proinflammatory cytokine levels are elevated in isolated and co-occurring depressive disorders (Penninx et al. 2003; Kahl et al. 2006; O’Brien et al. 2007) and abate with antidepressant therapy (Lanquillon et al. 2000; Narita et al. 2006a; O’Brien et al. 2007).
