RODRIGO MACHADO VIEIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
16 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 16
conferenceObject Increased GDNF but not BDNF Plasma Levels in Type II Compared to Type I Bipolar Disorder(2013) ZANETTI, Marcus V.; TEIXEIRA, Antonio L.; CHAIM, Tiffany M.; SOUSA, Rafael T. de; TALIB, Leda L.; GATTAZ, Wagner F.; BUSATTO, Geraldo F.; MACHADO-VIEIRA, RodrigoBackground: The brain-derived neurotrophic factor (BDNF) is a neurotrophin important for synaptic plasticity and neurogenesis, whereas the glial cell-line derived neurotrophic factor (GDNF) modulates the activity of monoaminergic neurons and glial cells. Previous works have suggested that abnormal peripheral levels of these proteins might relate to different mood states in bipolar disorder (BD), but none study so far have evaluated it with regard to potential differences between the types I (BD-I) and II (BD-II) subtypes of the disorder. Methods: Eighteen BD-I and 19 BD-II patients presenting with an acute mood episode (depressive, manic or mixed), and 23 healthy controls were studied. Plasma levels of BDNF and GDNF were measured using enzyme-linked immunosorbent assay (ELISA). Results: BD-II individuals showed significantly increased levels of GDNF compared to both BD-I patients and controls (ANOVA, df=2, F= 5.74, p=0.005; Tukey for post hoc comparisons). When we focused our analysis on the treatment-naïve patients only (14 BD-I and 13 BD-II), this result became even more significant (ANOVA, df=2, F= 7.33, p=0.002). No significant between-groups differences were observed on BDNF levels. Also, no significant correlation was observed between BDNF or GDNF levels and depressive and manic symptoms. Conclusions: BD-II at an acute phase of the illness is associated with increased plasma levels of GDNF. Previous use of mood stabilizer and antipsychotic agents might produce a chronic effect on GDNF production.conferenceObject Increased Anterior Cingulate Glutamate Levels in Euthymic Bipolar I Disorder: A 1h MRS Study(2012) SOEIRO-DE-SOUZA, Marcio G.; OTADUY, Maria C. G.; LEITE, Claudia C.; MACHADO-VIEIRA, Rodrigo; MORENO, RicardoconferenceObject Lithium Monotherapy Increases Nitric Oxide Levels During Depressive Episodes in Bipolar Disorder(2013) SOUSA, Rafael T. de; ZANETTI, Marcus V.; MOURO, Margaret G.; HIGA, Elisa M. S.; GATTAZ, Wagner F.; MACHADO-VIEIRA, RodrigoBackground: Nitric Oxide (NO) is precursor of peroxynitrite, a molecule which causes oxidative stress. Several studies have associated bipolar disorder (BD) with altered NO and oxidative stress. Besides that, evidences suggest a dual role of NO in depression, since both increase or decrease in NO levels have been associated with antidepressant efficacy in preclinical models. The present study evaluates NO in subjects with bipolar depression before and after a 6-week lithium treatment. Also, NO in patients and controls was compared. Methods: Patients with BD in a depressive episode (n=22) were treated with lithium monotherapy for 6 weeks. Blood samples were collected at baseline and after 6-week lithium treatment, also compared to healthy controls (n=28). NO in patients at baseline and at endpoint and in healthy controls was measured with chemiluminescence method. Results: Patients in a depressive episode had an increase in NO levels from baseline to endpoint (Wilcoxon Signed Ranks Test, z=-2.11, p=0.035). NO levels showed no difference in patients compared to healthy controls. Conclusions: This is the first study evaluating lithium effects on NO levels. Increased NO after lithium treatment suggests a potential role of NO pathways in the therapeutics of mood disorders.conferenceObject The Burden of a Progressive Disease: Number of Manic Episodes and Lifetime History of Psychotic Symptoms Increases Dna Oxidation in Bipolar I Disorder(2012) SOEIRO-DE-SOUZA, Marcio G.; ANDREAZZA, Ana Cristina; MACHADO-VIEIRA, Rodrigo; YOUNG, Trevor; MORENO, RicardoconferenceObject Plasma Cortisol in First Episode Drug-Naive Mania: Differential Levels in Euphoric Versus Irritable Mood(2012) VALIENGO, Leandro L.; SOEIRO-DE-SOUZA, Marcui G.; MARQUES, Andrea H.; JURUENA, Mario F.; ANDREAZZA, Ana C.; GATTAZ, Wagner F.; MACHADO-VIERA, RodrigoBackground: Dysregulation of HPA axis have been widely described in subjects with bipolar disorder (BD), including changes in cortisol levels during mood episodes and euthymia. However, most of the studies were done with medicated BD patients with variable length of illness, which was shown to interfere on peripheral cortisol levels. Therefore, the present study aims to evaluate plasma cortisol levels in drug-naïve BD subjects during the first manic episode, as well as investigate the relationship between plasma cortisol levels and manic symptomatology. Methods: Twenty-six drug-naïve patients were enrolled meeting criteria for a first manic episode in bipolar I disorder. Severity of mania was assessed using the Young Mania Rating Scale (YMRS). The control group included 27 healthy subjects matched by age and gender. Cortisol was quantified using a direct radioimmunoassay. Results: Plasma cortisol levels were decreased during first manic episode compared to healthy controls. Higher cortisol levels were positively associated with the presence of irritability (dysphoria), while elated mania showed lower cortisol levels compared to controls. Conclusions: Higher cortisol in dysphoric mania compared to predominantly elated/euphoric mania may indicate a clinical and neurobiological polymorphic phenomenon, potentially involving a higher biological sensitivity to stress in the presence of irritable mood. The present findings highlight the importance to dd a dimensional approach to the traditional categorical diagnosis for future neurobiological studies in BD.conferenceObject Clinical Use of Genetic Polymorphisms as Markers of Refractoriness in Schizophrenia(2012) BILL, Martinus T. van de; PRADO, Carolina M.; OJOPI, Elida P. B.; LOCH, Alexandre A.; ZANETTI, Marcus V.; SOUSA, Rafael A. T.; MACHADO-VIEIRA, Rodrigo; GATTAZ, Wagner F.Background: Pharmacogenetics studies have demonstrated the importance of various neurotransmitter systems in mediating drug effectiveness. Due to the importance of the dopaminergic system in the activity of antipsychotics, proteins that regulate the availability of dopamine may influence the response to drug treatment, as the enzyme catechol-O-methyl-transferase (COMT), which catalyzes the breakdown of dopamine. Some associations have already been described between Val108/158Met polymorphism and response, with individuals carrying the Met allele presenting the best answer. However, most of the findings reported have not been universally replicated. Methods: The study enrolled 89 schizophrenia patients divided in two groups: 59 refractory patients according to IPAP algorithm (International Psychopharmacology Algorithm Project) and 30 non-refractory patients. Polymorphisms in COMT (rs4680), HTR2A (T102C, rs6314, rs1928042), HTR2C (rs6318, rs3813929), CHRNA7(rs7164043), BDNF (rs6265), DRD3 (rs6280) and GRM8 (rs7778604) genes were evaluated by allelic discrimination using the TaqMan® system. Results: regarding the polymorphism rs4680 (Val158Met) of the COMT gene, among the non-refractory patients we found 7% AA, 50% AG and 43% GG genotypes. Among refractory patients we found 20% AA, 59% AG and 21% GG. After the X2 test, we found a difference in the genotype distribution between the two groups (p=0.043). For the other polymorphisms in genes HTR2A, HTR2C, CHRNA7, BDNF, DRD3, and GRM8, no significant difference was found. Conclusions: Our findings do not confirm previous data. In our study there is a higher prevalence of individuals homozygous for Met in the refractory group and a higher prevalence of individuals homozygous for Val the non-refractory (p=0.043).conferenceObject Early Improvement with Lithium in Classic Mania Predicts Later Response(2012) MACHADO-VIEIRA, Rodrigo; LUCKENBAUGH, David A.; SOEIRO-DE-SOUZA, Marcia G.; BUSNELLO, Joao V.; GATTAZ, Wagner F.; ZARATE JR., Carlos A.Background: Lithium is a first line approach for acute episodes and maintenance treatment of bipolar disorder (BD). Despite lithium ́s clinical efficacy in treating BD mania, studies evaluating early improvement and subsequent treatment response are sparse. This study investigated whether early improvement (within one week of treatment) to lithium monotherapy predicted later response and remission in individuals with BD mania. Methods: BD-I patients (n=46) experiencing a manic episode received lithium monotherapy for four weeks (initial dose: 600mg/day, adjusted to therapeutic levels); individuals experiencing a mixed episode, rapid cyclers, previous non-responders to lithium, and those with current drug abuse/dependence were excluded. Symptoms were rated using the Young Mania Rating Scale (YMRS) weekly. Results: Thirty-three percent of the total sample responded to lithium within the first week of treatment, as assessed by a ≥50% decrease from baseline YMRS scores; 63% responded by study endpoint. In addition, 39% of the total sample (18/46) showed early improvement, defined as an at least 20% decrease in YMRS scores after one week of treatment. In this group, 79% responded to lithium by study endpoint. Meanwhile, among those showing less than 20% improvement at Week 1, only 23% responded to lithium by study endpoint. Conclusions: Early improvement in response to lithium monotherapy in subjects with BD during a manic episode predicted later response and remission. The findings provide a valuable clinical tool for early identification of those patients most likely to benefit from lithium in clinical practice.conferenceObject A Longitudinal Study on the Neurobiological Basis of Antidepressant Efficacy in Bipolar II Disorder(2012) MACHADO-VIEIRA, Rodrigo; ZANETTI, Marcus V.; OTADUY, Maria C.; SOUSA, Rafael T. De; LEITE, Claudia C.; BUSATTO, Geraldo F.; GATTAZ, Wagner F.Background: Bipolar II disorder is a chronic and disabling psychiatric disorder, with subjects spending up to half of their time depressed. Current guidelines recommend the proof of concept agent lithium as a valuable treatment for acute bipolar II depression. However, little is known about the neurobiological basis of the antidepressant efficacy in bipolar II disorder. Methods: Fourteen drug-free individuals with a DSM-IV diagnosis of bipolar II disorder (BD-II) during a depressive episode (HAM-D≥18) were followed-up in a 6-week open-label trial with lithium monotherapy. All subjects had less than three lifetime mood episodes. 1H-MRS was performed at baseline and after 6 weeks (with additional 7Li-MRS at endpoint) Results: Lithium monotherapy showed a significant antidepressant efficacy in bipolar II depression. Post-treatment with lithium induced a significant increase in glutamate levels in the anterior cingulate cortex (ACC) compared to baseline levels, which was associated with brain lithium levels and clinical improvement of depressive symptoms. Conclusions: Our findings support a key role for ACC glutamate levels in the pathophysiology and therapeutics of Bipolar II disorder. These findings have important clinical and theoretical implications, also suggesting a potential role for glutamate as a valuable therapeutic target in Bipolar II depression. Keyword(s): bipolar disorder, depression, lithium, imaging, biomarkerconferenceObject Increased Lactate Levels During Depressive Episodes and Reversal Effects by Lithium Monotherapy in Subjects with Bipolar Disorder(2013) MACHADO-VIEIRA, Rodrigo; ZANETTI, Marcus V.; OTADUY, Maria C. G.; SOUSA, Rafael T. de; COSTA, Alana C.; CHAIM, Tiffany M.; LEITE, Claudia C.; BUSATTO, Geraldo F.; GATTAZ, Wagner F.Background: Altered energy metabolism has been widely described in Bipolar Disorder (BD). However, brain lactate levels have been only evaluated in few studies with heterogeneous samples using magnetic resonance spectroscopy (MRS). These findings support the presence of dysfunctional brain energy production as a central component in the pathophysiology of BD. However, no study to date has evaluated brain lactate levels specifically in bipolar depression or even the effects of lithium treatment in brain lactate levels in subjects with BD. Methods: Twenty-four BD individuals (up to 5 years of illness duration) presenting with an acute depressive episode underwent MRS at baseline and after 6 weeks of lithium therapy at therapeutic doses. Lactate levels were measures in the cingulated cortex (CC). Clinical assessment was performed weekly using the 21-item Hamilton Depression Rating Scale (HDRS) and the Young Mania Rating Scale (YMRS). A group of age and gender-matched healthy controls (n=18) was also studied. Results: BD patients exhibited increased brain lactate in the CC relative to healthy controls at baseline. A significant decrease in brain lactate levels was observed after 6 weeks of lithium treatment, and correlated with clinical response (reduction ≥ 50% in HDRS scores). Conclusions: Lithium treatment produces a significant decrease in brain lactate levels of acutely depressed BD patients. This suggests that the clinical efficacy of lithium is also associated with reduction in the shift from aerobic to anaerobic metabolism observed in BD.- Soluble Tumor Necrosis Factor Receptor 1 and 2 in Bipolar Depression and the Association with Lithium Treatment(2014) SOUSA, Rafael T. de; ZANETTI, Marcus V.; GATTAZ, Wagner F.; MACHADO-VIEIRA, Rodrigo; TEIXEIRA, Antonio L.