title: Recurrent major depressive disorder: Imbalance of neurokinin (NK)-1 and NK-2 receptor expression in monocytes.
abstract: 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 NK(1) and NK(2) 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.
authors.affiliation: Department of Health Sciences, School of Medicine, University "A. Avogadro", Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bardelli
authors.forename: Angela
authors.initials: A
authors.lastname: Amoruso
authors.forename: Elena
authors.initials: E
authors.lastname: Manzetti
authors.forename: Luigia Grazia
authors.initials: LG
authors.lastname: Fresu
authors.forename: Roberta
authors.initials: R
authors.lastname: Valsesia
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zeppegno
authors.forename: Sandra
authors.initials: S
authors.lastname: Brunelleschi
mesh_terms: D003865:Major Depressive Disorder / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015288:Neurokinin A / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D018377:Neurotransmitter Agents; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D015288:Neurokinin A