MARIA CONCEPCION GARCIA OTADUY
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Radiologia, Hospital das Clínicas, Faculdade de Medicina
LIM/44 - Laboratório de Ressonância Magnética em Neurorradiologia, Hospital das Clínicas, Faculdade de Medicina
LIM/44 - Laboratório de Ressonância Magnética em Neurorradiologia, Hospital das Clínicas, Faculdade de Medicina
14 resultados
Resultados de Busca
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- 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.
- A Longitudinal MRI-study of the Effects of Lithium on Cortical Thickness and Brain Volume and its association with Clinical Response in Bipolar Disorder(2019) COSTA, Sabrina C. da; ZANETTI, Marcus V.; SUCHTING, Robert; SOUZA, Rafael T. de; OTADUY, Maria C.; LEITE, Claudia C.; BUSATTO, Geraldo F.; GATTAZ, Wagner F.; SOARES, Jair C.; MACHADO-VIEIRA, Rodrigo
- 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.
- Bimodal Effect of Lithium Plasma Levels on Hippocampal Glutamate Concentrations in Bipolar II Depression: A Pilot Study(2015) ZANETTI, Marcus V.; OTADUY, Maria C.; SOUSA, Rafael T. de; GATTAZ, Wagner F.; BUSATTO, Geraldo F.; LEITE, Claudia C.; MACHADO-VIEIRA, RodrigoBackground: The hippocampus has been highly implicated in the pathophysiology of bipolar disorder (BD). Nevertheless, no study has longitudinally evaluated hippocampal metabolite levels in bipolar depression under treatment with lithium. Methods: Nineteen medication-free BD patients (78.9% treatment-naive and 73.7% with BD type II) presenting an acute depressive episode and 17 healthy controls were studied. Patients were treated for 6 weeks with lithium in an open-label trial. N-acetyl aspartate (NAA), creatine, choline, myo-Inositol, and glutamate levels were assessed in the left hippocampus before (week 0) and after (week 6) lithium treatment using 3T proton magnetic resonance spectroscopy (1H-MRS). The metabolite concentrations were estimated using internal water as reference and voxel segmentation for partial volume correction. Results: At baseline, acutely depressed BD patients and healthy controls exhibited similar hippocampal metabolites concentrations, with no changes after 6 weeks of lithium monotherapy. A significant correlation between antidepressant efficacy and increases in NAA concentration over time was observed. Also, there was a significant positive correlation between the changes in glutamate concentrations over follow-up and plasma lithium levels at endpoint. Mixed effects model analysis revealed a bimodal effect of lithium plasma levels in hippocampal glutamate concentrations: levels of 0.2 to 0.49 mmol/L (n=9) were associated with a decrease in glutamate concentrations, whereas the subgroup of BD subjects with ""standard"" lithium levels (>= 0.50 mmol/L; n = 10) showed an overall increase in glutamate concentrations over time. Conclusions: These preliminary results suggest that lithium has a bimodal action in hippocampal glutamate concentration depending on the plasma levels.
conferenceObject Brain aging in bipolar disorder: An analysis of data from the ENIGMA Bipolar Disorder Working Group(2019) EYLER, L. T.; ABE, C.; BAUNE, B.; BOEN, B.; BONIN, M.; BUSATTO, G.; CHAIM-AVANCINI, T.; DANNLOWSKI, U.; ELVSASHAGEN, T.; FULLERTON, J.; OTADUY, M. Garcia; GOIKOLEA, J.; GROTEGERD, D.; HAHN, T.; HENRY, C.; HOUENOU, J.; HOWELLS, F.; JIMENEZ, E.; LAFER, B.; LANDEN, M.; MACHADO-VIEIRA, R.; MALT, U.; MITCHELL, P.; OVERS, B.; POMAROL-CLOTET, E.; ROBERTS, G.; ROSA, P.; SATTERTHWAITE, T.; SOEIRO-DE-SOUZA, M.; STEIN, D.; TEMMINGH, H.; THOMOPOULOS, S.; UHLMANN, A.; VIETA, E.; WOLF, D.; ZANETTI, M.; HAN, L.; SCHMAAL, L.; THOMPSON, P.; CHING, C.; ANDREASSEN, O.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.conferenceObject A Longitudinal MRI-Study of the Effects of Lithium on Cortical Thickness and Brain Volume and its Association With Clinical Response in Bipolar Disorder(2017) COSTA, Sabrina Correa da; ZANETTI, Marcus V.; SOUZA, Rafael T.; OTADUY, Maria C.; LEITE, Claudia C.; BUSATTO, Geraldo F.; QUEVEDO, Joao L.; GATTAZ, Wagner F.; SOARES, Jair C.; MACHADO-VIEIRA, Rodrigo- A Selective Association between Central and Peripheral Lithium Levels in Remitters in Bipolar Depression: A 3T-Li-7 Magnetic Resonance Spectroscopy Study(2016) MACHADO-VIEIRA, R.; OTADUY, M. C.; ZANETTI, M. V.; SOUSA, R. T. De; DIAS, V. V.; LEITE, C. C.; FORLENZA, O. V.; BUSATTO, G. F.; SOARES, J. C.; GATTAZ, W. F.ObjectiveThe objective of this study was to evaluate brain lithium levels using Li-7 magnetic resonance spectroscopy after 6 weeks of lithium therapy in bipolar depression to test the hypothesis that brain and plasma lithium are correlated. It was also tested whether responders and remitters have different pharmacokinetics, blood and brain lithium levels (ratio) compared with those presenting suboptimal antidepressant improvement. MethodTwenty-three patients with bipolar disorder (I and II) during depressive episodes were included and followed up for 6 weeks at the University of Sao Paulo using flexible dose of lithium (450-900 mg/day). Sixteen patients were drug-naive. At endpoint, patients underwent a Li-7-MRS scan and brain lithium concentrations were calculated. ResultsA significant association between central and peripheral lithium levels was found only in remitters (r = 0.7, P = 0.004) but not in non-remitters (r = -0.12, P = 0.76). Also, brain lithium (but not plasma) was inversely correlated with age (r = -0.46, P = 0.025). Plasma lithium did not correlate with any clinical outcome, lithium dosage or adverse effects. ConclusionThese findings suggest that non-remitters may not transport lithium properly to the brain, which may underlie treatment resistance to lithium in BD. Future studies with Li-7-MRS integrated with the evaluation of blood-brain barrier transport mechanisms and longitudinal clinical outcomes in BD and aging are warranted.
- A Longitudinal (6-week) 3T H-1-MRS Study on the Effects of Lithium Treatment on Anterior Cingulate Cortex Metabolites in Bipolar Depression(2015) MACHADO-VIEIRA, Rodrigo; GATTAZ, Wagner F.; ZANETTI, Marcus V.; SOUSA, Rafael T. De; CARVALHO, Andre F.; SOEIRO-DE-SOUZA, Marcio G.; LEITE, Claudia C.; OTADUY, Maria C.The anterior cingulate cortex (ACC) is a key area in mood regulation. To date, no Longitudinal study has specifically evaluated lithium's effects on ACC metabolites using H-1-MRS, as well as its association with clinical improvement in bipolar depression. This H-1-MRS (TE=35 ms) study evaluated 24 drug-free BD patients during depressive episodes and after lithium treatment at therapeutic levels. Brain metabolite levels (N-acetyl aspartate (NM), creatine (tCr), choline, myo-inositol, and glutamate levels) were measured in the ACC at baseline (week 0) and after lithium monotherapy (week 6). The present investigation showed that ACC glutamate (Glu/tCr) and glutamate +glutamine (Glx/tCr) significantly increased after six weeks of lithium therapy. Regarding the association with clinical improvement, remitters showed an increase in myoinositol levels (ml/tCr) after lithium treatment compared to non-remitters. The present findings reinforce a role for ACC glutamate-glutamine cycling and myoinositol pathway as key targets for lithium's therapeutic effects in BD.