[Stress, the immune system and depression]

Microglia, the macrophages of the brain, and T cells are essential for building up the structure and function of the corticolimbic system. The corticolimbic system regulates amongst others emotions. Patients with major depressive disorder (MDD) are characterized by premature senescent macrophages and T cells. Senescent immune cells easily adopt a pro-inflammatory state leading to low grade inflammation. Chronic stress is next to chronic viral infection a driver of immune cell senescence. In the EU-project MOODSTRATIFICATION we hypothesized that the dysfunctional senescent immune cells of MDD patients are responsible for such structural and functional corticolimbic abnormalities in MDD patients that they react to stress with dysregulated emotions and anxiety. This further increases stress, and makes a vicious circle possible. In MOODSTRATIFICATION we now have proof of principle that a correction of immune senescent macrophages and T cell system by anti-inflammatory agents and low dose IL-2 treatment has antidepressant effects.