TNF and depressive disorder: As noted, depression is strongly connected to chronic inflammation, and NSAIDs, by inhibiting cyclooxygenase (COX) activity and reducing prostaglandin (PG) synthesis, indirectly regulate the NF-κB signaling pathway, thus decreasing the release of pro-inflammatory cytokines like interleukins and TNF-α, which may mitigate the inflammatory responses involved in depression (140).