INDUCTION OF DEPRESSION BY EXPOSURE TO DAMP ...

with depression decrease with treatment (Tuglu et al., 2003; Narita et al., 2006).
However, correlations between inflammatory markers and depression may be the result
of improper study design (Haack et al., 1999). Thus, it is not fully understood if the
inflammatory markers are a causative factor or just associated with depression. It is also
possible that inflammation is the causative factor in some, but not all cases of depression.
Adding to the evidence supporting associations (causative or otherwise) between
inflammatory markers and depression, multiple studies comparing genetic mutations
indicated several polymorphisms in the TNF-α and IFN-α genes. The mutations result in
higher productions of those cytokines and conveyed a higher risk for depression or
dysthmia (Jun et al., 2003; Fertuzinhos et al., 2004). However, the dysthmia markers
may not reliably decrease with treatment (Anisman et al., 1999).
In vivo and in vitro studies for several antidepressants have shown either direct or
indirect anti-inflammatory properties (Castanon et al., 2004; Yirmiya et al., 2001; Kenis
& Maes, 2002; Castanon et al., 2002). In vitro studies with TCAs, monoamine oxidase
inhibitors (MOAIs), and SSRIs have shown direct anti-inflammatory effects on immune
cells stimulated with LPS (Xia et al., 1996). One study suggests that TCAs may raise
TNF-α levels (Hinze-Selch et al., 2000). The anti-inflammatory effect may be the result
of an increase in the production of anti-inflammatory cytokines, as demonstrated by
several in vivo studies (Narita et al., 2006; Tuglu et al., 2003; Castanon et al., 2004).
Besides direct anti-inflammatory effects, other studies have shown that
antidepressants have indirect anti-inflammatory properties. A study by O’Sullivan et. al.
(O'Sullivan et al., 2008) showed that the anti-inflammatory effects of noradrenaline
reuptake inhibitors (NRIs) are likely due to the anti-inflammatory affects of the excess
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