RODRIGO MACHADO VIEIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
34 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 34
- Increased Brain Lactate During Depressive Episodes and Reversal Effects by Lithium Monotherapy in Drug-Naive Bipolar Disorder A 3-T H-1-MRS Study(2017) MACHADO-VIEIRA, Rodrigo; ZANETTI, Marcus V.; OTADUY, Maria C.; SOUSA, Rafael T. De; SOEIRO-DE-SOUZA, Marcio G.; COSTA, Alana C.; CARVALHO, Andre F.; LEITE, Claudia C.; BUSATTO, Geraldo F.; ZARATE JR., Carlos A.; GATTAZ, Wagner F.Objective: Mitochondrial dysfunction and energy metabolism impairment are key components in the pathophysiology of bipolar disorder (BD) and may involve a shift from aerobic to anaerobic metabolism. Measurement of brain lactate in vivo using protonmagnetic resonance spectroscopy (H-1-MRS) represents an important tool to evaluate mitochondrial and metabolic dysfunction during mood episodes, as well as to monitor treatment response. To date, very few studies have quantified brain lactate in BD. In addition, no study has longitudinally evaluated lactate using H-1-MRS during depressive episodes or its association with mood stabilizer therapy. This study aimed to evaluate cingulate cortex (CC) lactate using 3-T H-1-MRS during acute depressive episodes in BD and the possible effects induced by lithium monotherapy. Methods: Twenty medication-free outpatients with short length of BD (80% drug-naive) in a current major depressive episode were matched with control subjects. Patients were treated for 6 weeks with lithium monotherapy at therapeutic doses in an open-label trial (blood level, 0.48 +/- 0.19 mmol/L). Cingulate cortex lactate was measured before (week 0) and after lithium therapy (week 6) using H-1-MRS. Antidepressant efficacy was assessed with the 21-item Hamilton Depression Rating Scale as the primary outcome. Results: Subjects with BD depression showed a significantly higher CC lactate in comparison to control subjects. Furthermore, a significant decrease in CC lactate was observed after 6 weeks of lithium treatment compared with baseline (P = 0.002). CC Lactate levels was associated with family history of mood disorders and plasma lithium levels. Conclusions: This is the first report of increased CC lactate in patients with bipolar depression and lower levels after lithium monotherapy for 6 weeks. These findings indicate a shift to anaerobic metabolism and a role for lactate as a state marker during mood episodes. Energy and redox dysfunction may represent key targets for lithium's therapeutic actions.
- Bcl-2 rs956572 Polymorphism is Associated with Increased Anterior Cingulate Cortical Glutamate in Euthymic Bipolar I Disorder(2013) SOEIRO-DE-SOUZA, Marcio Gerhardt; SALVADORE, Giacomo; MORENO, Ricardo Alberto; OTADUY, Maria Concepcion Garcia; CHAIM, Kalil T.; GATTAZ, Wagner F.; ZARATE JR., Carlos A.; MACHADO-VIEIRA, RodrigoB-cell lymphoma 2 (Bcl-2) is an important regulator of cellular plasticity and resilience. In bipolar disorder (BD), studies have shown a key role for a Bcl-2 gene single-nucleotide polymorphism (SNP) rs956572 in the regulation of intracellular calcium (Ca2+) dynamics, Bcl-2 expression/levels, and vulnerability to cellular apoptosis. At the same time, Bcl-2 decreases glutamate (Glu) toxicity in neural cells. Abnormalities in Glu function have been implicated in BD. In magnetic resonance spectroscopy (MRS) studies, anterior cingulated cortex (ACC) Glu levels have been reported to be increased in bipolar depression and mania, but no study specifically evaluated ACC Glu levels in BD-euthymia. Here, we compared ACC Glu levels in BD-euthymia compared with healthy subjects using H-1-MRS and also evaluated the selective role of the rs956572 Bcl-2 SNP in modulating ACC Glu and Glx (sum of Glu and glutamine) in euthymic-BD. Forty euthymic subjects with BD type 1 and forty healthy controls aged 18-40 were evaluated. All participants were genotyped for Bcl-2 rs956572 and underwent a 3-Tesla brain magnetic resonance imaging examination including the acquisition of an in vivo PRESS single voxel (2 cm(3)) H-1-MRS sequence to obtain metabolite levels from the ACC. Euthymic-BD subjects had higher Glu/Cre (creatine) and Glx/Cre compared with healthy controls. The Bcl-2 SNP AA genotype was associated with elevated ACC Glu/Cre and Glx/Cre ratio in the BD group but not in controls. The present study reports for the first time an increase in ACC Glu/Cre and Glx/Cre ratios in BD-euthymia. Also, Bcl-2 AA genotype, previously associated with lower Bcl-2 expression and increase intracellular Ca2+, showed to be associated with increased ACC Glu and Glx levels in euthymic-BD subjects. The present findings reinforce a key role for glutamatergic system dysfunction in the pathophysiology of BD, potentially involving modulatory effects by Bcl-2 in the ACC. Neuropsychopharmacology (2013) 38, 468-475; doi:10.1038/npp.2012.203; published online 17 October 2012
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, Ricardo- Lithium efficacy in bipolar depression with flexible dosing: A six-week, open-label, proof-of-concept study(2014) MACHADO-VIEIRA, Rodrigo; ZANETTI, Marcus V.; SOUSA, Rafael T. De; SOEIRO-DE-SOUZA, Marcio G.; MORENO, Ricardo A.; BUSATTO, Geraldo F.; GATTAZ, Wagner F.Lithium has a narrow therapeutic index with a subtle balance between effectiveness and adverse effects. Current guidelines recommend the use of lithium as a treatment for acute bipolar depression; however, the therapeutic range for the treatment has not been fully defined. Recently, the adjunctive lower lithium dose in bipolar depression has revealed potential efficacy; however, no study has investigated it predominantly in monotherapy. In this open-label, proof-of-concept study, 31 individuals with bipolar disorder during a depressive episode were randomized and 29 were followed up for six weeks with flexible lithium dosing. All subjects had a 21-item Hamilton Rating Scale for Depression (HAM-D) score of >= 18 at baseline. Subjects were divided into two groups, with higher (Li >= 0.5 mEq/l) or lower (Li <0.5 mEq/l) blood lithium levels. Response and remission rates were evaluated using the HAM-D scores. Following 6 weeks of lithium treatment, the remission rate for all patients was 62.0%. The plasma lithium levels did not impact the clinical response. However, subjects with higher blood lithium levels had an increased prevalence of nausea, restlessness, headaches and cognitive complaints. The results indicate that the lithium dose for the treatment of bipolar depression in an individual should be based on the clinical efficacy and side-effects. In the context of personalized psychiatric treatments, it is necessary to evaluate the therapeutic action of lithium with individual regimens in order to develop more tolerable and effective treatment approaches.
- Multiple levels of impaired neural plasticity and cellular resilience in bipolar disorder: Developing treatments using an integrated translational approach(2014) MACHADO-VIEIRA, Rodrigo; SOEIRO-DE-SOUZA, Marcio G.; RICHARDS, Erica M.; TEIXEIRA, Antonio L.; ZARATE JR., Carlos A.Objectives. This paper reviews the neurobiology of bipolar disorder (BD), particularly findings associated with impaired cellular resilience and plasticity. Methods. PubMed/Medline articles and book chapters published over the last 20 years were identified using the following keyword combinations: BD, calcium, cytokines, endoplasmic reticulum (ER), genetics, glucocorticoids, glutamate, imaging, ketamine, lithium, mania, mitochondria, neuroplasticity, neuroprotection, neurotrophic, oxidative stress, plasticity, resilience, and valproate. Results. BD is associated with impaired cellular resilience and synaptic dysfunction at multiple levels, associated with impaired cellular resilience and plasticity. These findings were partially prevented or even reversed with the use of mood stabilizers, but longitudinal studies associated with clinical outcome remain scarce. Conclusions. Evidence consistently suggests that BD involves impaired neural plasticity and cellular resilience at multiple levels. This includes the genetic and intra-and intercellular signalling levels, their impact on brain structure and function, as well as the final translation into behaviour/cognitive changes. Future studies are expected to adopt integrated translational approaches using a variety of methods (e.g., microarray approaches, neuroimaging, genetics, electrophysiology, and the new generation of -omics techniques). These studies will likely focus on more precise diagnoses and a personalized medicine paradigm in order to develop better treatments for those who need them most.
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, Ricardo- Does BDNF genotype influence creative output in bipolar I manic patients?(2012) SOEIRO-DE-SOUZA, Marcio Gerhardt; POST, Robert M.; SOUSA, Mario Lucio de; MISSIO, Giovani; PRADO, Carolina Martins do; GATTAZ, Wagner F.; MORENO, Ricardo A.; MACHADO-VIEIRA, RodrigoIntroduction: Creativity is a complex human ability influenced by affective and cognitive components but little is known about its underlying neurobiology. Bipolar Disorder (BD) is highly prevalent among creative individuals. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophic factor, and has been implicated in the pathophysiology of BD. In contrast to the better functioning of the BDNF polymorphism (Val(66)Met) Val allele, the Met allele decreases BDNF transport and has been associated with worsened performance on several cognitive domains in euthymic BD subjects and controls. We hypothesized that the Val allele is associated with increased creativity in bipolar disorder. Materials and methods: Sixty-six subjects with BD (41 in manic and 25 in depressive episodes) and 78 healthy volunteers were genotyped for BDNF Val(66)Met and tested for creativity using the Barrow Welsh Art Scale (BWAS) and neuropsychological tests. Results: Manic patients with the Val allele (Met-) had higher BWAS scores than Met+ carriers. This relationship was not observed among patients in depressive episodes or among control subjects. BDNF Met allele status showed no association with cognitive function in any of the groups. Conclusion: As postulated, these findings suggest that the better functioning allele of BDNF may selectively facilitate creative thinking in subjects with manic episodes, but not in controls or depressives. Further studies exploring the role of BDNF in the neurobiology of creativity in BD and in euthymic phases are warranted.
- MRI investigation of a 6-week trial of lithium in medication-free patients with bipolar depression(2014) ZANETTI, M. V.; OTADUY, M. C. G.; SOUSA, R. T. de; SOEIRO-DE-SOUZA, M. G.; CHAIM, K. T.; GATTAZ, W. F.; BUSATTO, G. F.; LEITE, C. C.; MACHADO-VIEIRA, R.
conferenceObject 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.- Early improvement of psychotic symptoms with lithium monotherapy as a predictor of later response in mania(2012) SOUSA, Rafael T. de; BUSNELLO, Joao V.; FORLENZA, Orestes V.; ZANETTI, Marcus V.; SOEIRO-DE-SOUZA, Marcio G.; BILT, Martinus T. van de; MORENO, Ricardo A.; ZARATE JR., Carlos A.; GATTAZ, Wagner F.; MACHADO-VIEIRA, RodrigoAlthough lithium has been the first line agent in the treatment of bipolar disorder (BD), few studies have evaluated lithium's efficacy in mania with psychosis and its association with later response. Furthermore, given the widespread concern about antipsychotic side effects, answering a question about whether lithium alone can manage to treat both psychotic and non-psychotic mania seems a very relevant one. The present study addresses the antipsychotic efficacy of lithium monotherapy in acute mania and early improvement of psychotic symptoms as a predictor of later response of manic symptoms. Forty-six patients presenting a manic episode (32 with psychotic features and 14 subjects without psychotic features) were treated for 4 weeks with lithium monotherapy and evaluated weekly using the Young Mania Rating Scale (YMRS). Subjects with rapid cycling, substance abuse/dependence, or mixed episodes were excluded. The overall antimanic efficacy of lithium in psychosis vs. non-psychosis groups was evaluated. In addition, early improvement of psychotic symptoms and its prediction of subsequent response (>50% decrease in total YMRS scores) or remission were evaluated. Lithium showed a similar efficacy in both psychosis and non-psychosis mania. Early improvement of psychotic symptoms was associated with clinical response and remission at endpoint.