NLRP3 and major depressive disorder: Barnes et al. provide substantial evidence through a systematic review that genetic variants including those in the IL-1β gene, contribute to the immune activation observed in individuals with depression, suggesting a genetic predisposition towards an inflammatory response [26].Multiple studies have demonstrated that rats subjected to chronic and unpredictable stressors show increased eATP levels in their hippocampal glial cells, indicating sustained activation of the P2X7R/NLRP3 axis.