Anales RANF

S14-04 VALIDATING P2X7R AS RISK FACTOR FOR MOOD DISORDERS Jan M. Deussing Max Planck Institute of Psychiatry, Molecular Neurogenetics, Kraepelinstr. 2-10, 80804 Munich, Germany. Mood disorders are prime contributors to global disease burden. The persistent lack of progress with regards to pharmacotherapy stands in stark contrast to the pandemic magnitude of the disease. For example, major depression is currently affecting 300 million people world wide. Alterations of inflammatory pathways in depressed patients including altered concentration of circulating pro-inflammatory cytokine levels have been put forward as a potential pathophysiological mechanism. The purinergic P2X7 receptor (P2X7R) has attracted considerable interest as a potential target for various central nervous system pathologies including affective and neurodegenerative disorders. The P2X7R plays an important role regulating the release of interleukin- 1β and other cytokines. Comprehensive investigation of the P2X7R Gln460Arg missense mutation (rs2230912), which has been associated with major depression and bipolar disorder, has substantially contributed to validate P2X7R as a potential genetic risk factor. Using genetic mouse models by introducing human P2X7R variants into the mouse as mammalian model organism we could demonstrate that the mood disorder associated variant P2X7R-Gln460Arg represents a genetic risk factor, which in conjunction with stress is able to convey susceptibility to mood disorders. Here, we will present latest results from cell type-specific inactivation of P2X7R in the central nervous system as well novel insights from different P2X7R reporter mouse lines.