The P2X7 receptor in mood disorders: Emerging target in immunopsychiatry, from bench to bedside

Psychiatric disorders are among the most burdensome disorders worldwide. Though therapies have evolved over the last decades, treatment resistance still affects many patients. Recently, neuroimmune systems have been identified as important factors of mood disorder biology. The underlying dysregulation in neuroimmune cross-talk is driven by genetic risk factors and accumulating adverse environmental influences like chronic psychosocial stress. These result in a cluster of proinflammatory cytokines and quantitative and functional changes of immune cell populations (e.g., microglia, monocytes, T cells), varying by disease entity and state. Among the emerging immune targets, purinergic signalling revolving around the membranous and ATP specific P2X7 receptor (P2X7R) has gained wider attention and clinical studies making use of antagonistic drugs are on-going. Still, no clinically meaningful applications have been identified so far. A major problem is the often overly simplified approach taken to translate findings from bench to bedside. Therefore, the present review focuses on purinergic signalling via P2X7R in the context of recent advances in immunopsychiatric mood disorder research. Our aim is to provide an overview of the current P2X7R-related findings, from bench to bedside. First, we summarize the characteristics of purinergic signalling and P2X7R, followed by a depiction of genetic and clinical data connecting P2X7R to mood disorders. We close with our perspective on current developments and discuss changes necessary to translate the evident potential of P2X7R signalling modulation into meaningful clinical application.