ABSTRACT
BACKGROUND: Neurokinin 1 receptors (NK-1R) have been involved in several psychiatric disorders including major depression, but less is known for bipolar disorder (BD). METHOD: We compared NK-1R expression and Substance P (SP) ability to induce NF-κB activation in monocytes from BD patients and healthy donors (HD), also looking for the effects of tobacco smoke. After informed written consent, 20 euthymic BD patients, either bipolar type 1 (BDI) or type 2 (BDII), and 14 age-matched healthy donors (HD) were enrolled. NK-1R expression in monocytes was evaluated by Western blot and expressed as the ratio between NK-1R and Na(+)/K(+)-ATPase protein expressions. NF-κB activation was assessed by measuring the nuclear content of the p50 subunit (ELISA kit). RESULTS: NK-1R expression was significantly reduced (P<0.001) in monocytes from BD patients as compared to HD, with no major differences between BDI and BDII patients. Tobacco smoke enhanced NK-1R expression in HD, but not in BD patients. Un-stimulated monocytes from BD patients presented a constitutively higher (P<0.05) content of nuclear p50 subunit as compared to HD. SP and an NK-1R agonist induced NF-κB activation, with a higher effect in HD: this effect was receptor-mediated as it was abrogated by an NK-1R antagonist. LIMITATIONS: As a pilot study enrolling 20 BD patients, an obvious limitation is the sample size. CONCLUSIONS: Our results show the existence of a relevant alteration in NK-1R expression in BD patients and further suggest SP involvement in BD, so improving our understanding of the underlying mechanisms of this disease.
Subject(s)
Bipolar Disorder/metabolism , Monocytes/metabolism , NF-kappa B/metabolism , Receptors, Neurokinin-1/metabolism , Substance P/metabolism , Adult , Blotting, Western , Female , Gene Expression Regulation , Humans , Male , Middle Aged , Pilot Projects , Signal Transduction , Sodium-Potassium-Exchanging ATPase/metabolismABSTRACT
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.
Subject(s)
Depressive Disorder, Major/metabolism , Receptors, Neurokinin-1/metabolism , Receptors, Neurokinin-2/metabolism , Female , Humans , Male , Middle Aged , Monocytes/metabolism , NF-kappa B/metabolism , Neurokinin A/pharmacology , Neurotransmitter Agents/pharmacology , Receptors, Neurokinin-1/agonists , Receptors, Neurokinin-2/agonists , Substance P/pharmacology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
OBJECTIVE: The aim of the present study is to provide an epidemiological study about suicide in Verbano-Cusio-Ossola province, between January 1990 and December 2000. DESIGN: The present study is based on the acquisition of data through the examination of model 45, that registers all the cases of violent death and suicide, filed in Verbania Republic Procuration. SETTING: The Verbano-Cusio-Ossola province extends 2,255 Km 2 and counts 161,248 inhabitants. The Procuration in Verbania has territorial jurisdiction on the whole province of our study. MAIN OUTCOME MEASURES: The data obtained were presented in terms of descriptive analysis, evaluation of standardised rates of the province of Verbano-Cusio-Ossola. In order to appreciate the differences in comparison with the mean rates of northern Italy. Standardised Mortality Rates (SMRs) with the confidential intervals (IC 95%) have been used. RESULTS: In the eleven years period considered, 297 cases of suicide were notified at the Court with a rate of 16.74 per 100,000 inhabitants. The trend of suicide in the period examined is heterogeneous with significant differences between males and females. The analysis of SMRs points out that the incidence of suicide is higher in the province of VCO than in Italy in the same decade and that this difference is mostly due to an higher rate of suicide among women. The analysis of social-demographic parameters of the examined population confirms the data from international literature: suicide is more present in elderly, in widowers and in the retired. CONCLUSIONS: The present study means to provide a description of the suicide phenomenon, in a specific geographical and cultural context, in order to point out the problematic sides in a diagnostic-clinical point of view that may be an incentive to a larger preventive care.
