Peripheral Immune Regulation of Depression: Within Sight but Beyond Reach?

Increasing attention is being paid to the role of immune responses in depression research. However, clinical studies designed from the perspective of peripheral immune regulation have not shown very effective results. Is there a translational potential for immune regulation in depression? This review provides new insights for future research on peripheral immune regulation in depression. First, the peripheral-central interaction of immune inflammation represented an important mechanism in stress susceptibility. Second, the changes in peripheral immune and related factors in patients with depression were depicted to provide a foundation for the development of diagnostic and prognostic evaluation kits for depression. Finally, clinical trial results indicated that immunomodulation is an effective adjunctive therapy for depression. In conclusion, this review proposes an integrative "peripheral-central immune interactome" framework that positions immune dysregulation as a potential contributory factor-rather than a sole driver or mere correlate-of stress susceptibility and treatment-resistant depression.