TNF and major depressive disorder: Mechanistic studies demonstrating how improving insomnia alters pain processing and depression pathophysiology are ongoing, but 1 common pathway may be the insomnia and sleep disruption links with heightened inflammation.65,89–91 Irwin et al92 recently performed a meta-analysis of 72 studies that evaluated the relationship between CRP, IL-6, and/or TNF-α and sleep disturbances.