Although the role of the NLRP3 complex in the response to psychological stressors and depression has not been directly examined, there is extensive evidence that the inflammatory cytokines controlled by this inflammasome are increased. There are a large number of studies reporting elevated levels of pro-inflammatory cytokines, including IL-1β, as well as IL-6 and TNFα, in depressed patients (Ader and Cohen, 1993; Dowlati et al., 2010; Hannestad et al., 2011; Howren et al., 2009). Meta-analysis reports the strongest and most consistent evidence for IL-6 and TNFα (Dowlati et al., 2010; Howren et al., 2009). There are several reports that IL-1β is increased in MDD (Leo et al., 2006; Levine et al., 1999; Owen et al., 2001; Thomas et al., 2005), but there has also been a negative meta-analysis (Dowlati et al., 2010). Another study found that antidepressant treatment reduces serum levels of IL-1β, but not TNFα, suggesting a role for IL-1β in treatment response (Hannestad et al., 2011) and as a possible biomarker of depression (Schmidt et al., 2011). Although the pathways and mechanisms underlying elevated IL-1β in depression have not been identified, it is interesting to consider the molecules known to activate the NLRP3 inflammasome (Table 2, Fig. 2).
