RESUMO
Although depression is known to be an independent risk factor for cardiovascular disorders, the mechanisms behind this connection are not well understood. However, the reduction in the number of endothelial progenitor cells (EPCs) in patients with cardiovascular risk factors has led us to hypothesize that depression influences the number of EPCs. EPCs labeled with CD34, CD133 and vascular endothelial growth factor receptor-2 (VEGFR2) antibodies were counted by flow cytometry in the peripheral blood (PB) of 33 patients with a current episode of major depression and of 16 control subjects. Mature (CD34+/VEGFR2+) and immature (CD133+/VEGFR2+) EPC counts were decreased in patients (vs controls; P<0.01 for both comparisons), and there was a significant inverse relationship between EPC levels and the severity of depressive symptoms (P<0.01 for both EPC phenotypes). Additionally, we assayed the plasma levels of VEGF, C-reactive protein (CRP) and tumor necrosis factor (TNF)-alpha and observed significantly elevated TNF-alpha concentrations in patients (vs controls; P<0.05) and, moreover, a significant inverse correlation between TNF-alpha and EPC levels (P<0.05). Moreover, by means of a quantitative RT-PCR approach, we measured CD34, CD133 and VEGFR2 mRNA levels of PB samples and found a net trend toward a decrease in all the investigated EPC-specific mRNA levels in patients as compared with controls. However, statistical significance was reached only for VEGFR2 and CD133 levels (P<0.01 for both markers). This is the first paper that demonstrates evidence of decreased numbers of circulating EPCs in patients with a current episode of major depression.
Assuntos
Transtorno Depressivo Maior/sangue , Células Endoteliais/patologia , Células-Tronco/patologia , Antígeno AC133 , Adulto , Análise de Variância , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos CD34/genética , Antígenos CD34/metabolismo , Proteína C-Reativa/metabolismo , Células Endoteliais/metabolismo , Feminino , Citometria de Fluxo/métodos , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/genética , Peptídeos/metabolismo , RNA Mensageiro/metabolismo , Índice de Gravidade de Doença , Estatística como Assunto , Células-Tronco/metabolismo , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Data from the United States and from several European countries show that patients with major mood disorders, schizophrenia and social phobia smoke at significantly higher rates than the general population. However, there are no published results on this field from Central Europe, including Hungary. In the present study, the rate of current and lifetime smoking of the consecutively screened outpatients with DSM-IV unipolar major depression (n=92), bipolar disorder (n=60), schizophrenia (n=80), schizoaffective disorder (n=42) and panic disorder without major depression (n=60) were assessed and the data were compared to the controls (n=5503), representative for the general population of Hungary. The results showed that, compared to controls, the rates of current and lifetime smoking were significantly higher among patients with unipolar major depression, bipolar disorder, schizophrenia and schizoaffective disorder, but not among patients with panic disorder without major depression. The findings support previous findings from other countries on the strong relationship between cigarette smoking and major mood and schizophrenic spectrum disorders.
RESUMO
In glial cell cultures, iodothyronine 5'-deiodinase type II is stimulated by dibutyryl cAMP. Serum-free medium increases enzyme activity and prolongs the half-life of the enzyme. T4 and rT3 specifically inhibit this activity. We tested whether enzyme inactivation by T4 was mediated by changes in cytosolic free calcium concentration and/or phospholipid turnover. Intracellular calcium concentration was decreased either by chelation of extracellular calcium or by chelation of extracellular and intracellular calcium. Neither basal hypothyroid 5'-deiodinase activity nor its inactivation by T4 were modified in such experimental conditions, compared with control cells incubated in normal calcium-containing medium. T4 by itself had no effect on the cytosolic free calcium concentration for up to 20 min. Studies on phospholipid turnover included norepinephrine in parallel to T4 as positive stimulation control. While norepinephrine clearly accelerated phosphoinositide turnover, there was no effect of T4 on any phospholipid turnover. These results suggest that neither cytosolic free calcium nor phospholipid turnover is involved in T4-dependent modulation of 5'-deiodinase type II activity in astrocytes in culture.