Recurrent major depressive disorder: Imbalance of neurokinin (NK)-1 and NK-2 receptor expression in monocytes

Increasing evidence suggests that tachykinins are involved in the control of different pathological conditions, including psychiatric disorders. In this study we evaluated the expression of NK1 and NK2 receptors (NK-1R and NK-2R), as well as the effects of substance P (SP) and neurokinin A (NKA), in monocytes isolated from 15 healthy subjects and 15 patients with recurrent major depressive disorder (RMDD), under stable antidepressant therapy. NK-1R expression in monocytes from RMDD patients was significantly decreased as compared to healthy subjects, whereas NK-2R expression was markedly increased. Both NK-1R and NK-2R expression correlated with HAM-D, but not HAM-A, score. SP, NKA and selective NK-1R and NK-2R agonists stimulated TNF-α release in monocytes of both groups, with a significant higher effect observed in RMDD. Moreover they induced NF-κB activation, which was reversed by selective NK-1R and NK-2R antagonists, so demonstrating that it was receptor-mediated. The occurrence of a profound alteration in NK receptor expression in RMDD is a novel finding that suggests NK-1R and NK-2R pathways as possible relevant players in major depressive disorder, so improving our understanding of the complex pathogenesis of the disease.