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
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- Creatine Supplementation in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Trial(2013) ALVES, Christiano R. R.; SANTIAGO, Bianca M.; LIMA, Fernanda R.; OTADUY, Maria C. G.; CALICH, Ana Luisa; TRITTO, Aline C. C.; PINTO, Ana Lucia de Sa; ROSCHEL, Hamilton; LEITE, Claudia C.; BENATTI, Fabiana B.; BONFA, Eloisa; GUALANO, BrunoObjective. To investigate the efficacy and safety of creatine supplementation in fibromyalgia patients. Methods. A 16-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted. Fibromyalgia patients were randomly assigned to receive either creatine monohydrate or placebo in a double-blind manner. The patients were evaluated at baseline and after 16 weeks. Muscle function, aerobic conditioning, cognitive function, quality of sleep, quality of life, kidney function, and adverse events were assessed. Muscle phosphorylcreatine content was measured through P-31 magnetic resonance spectroscopy. Results. After the intervention, the creatine group presented higher muscle phosphorylcreatine content when compared with the placebo group (+80.3% versus -2.7%; P = 0.04). Furthermore, the creatine group presented greater muscle strength than the placebo group in the leg press and chest press exercises (+9.8% and +1.2% for creatine versus -0.5% and -7.2% for placebo, respectively; P = 0.02 and P = 0.002, respectively). Isometric strength was greater in the creatine group than in the placebo group (+6.4% versus -3.2%; P = 0.007). However, no general changes were observed in aerobic conditioning, pain, cognitive function, quality of sleep, and quality of life. Food intake remained unaltered and no side effects were reported. Conclusion. Creatine supplementation increased intramuscular phosphorylcreatine content and improved lower- and upper-body muscle function, with minor changes in other fibromyalgia features. These findings introduce creatine supplementation as a useful dietary intervention to improve muscle function in fibromyalgia patients.
conferenceObject Associations Between Medial Prefrontal Cerebral Metabolic Features and Clinical Characteristics in Obsessive-compulsive Disorder(2016) BATISTUZZO, Marcelo C.; HOEXTER, Marcelo; COSTA, Fabiana; SHAVITT, Roseli; LOPES, Antonio C.; CAPPI, Carolina; VATTIMO, Edoardo; MATHIS, Alice de; DINIZ, Juliana B.; HENNING, Anke; PASTORELLO, Bruno; MIGUEL, Euripedes C.; OTADUY, Maria C.conferenceObject Dorsal anterior cingulate lactate and glutathione levels in euthymic bipolar I disorder: 1H-MRS study(2016) SOEIRO-DE-SOUZA, M.; MORENO, R.; MORENO, D.; PASTORELLO, B.; HENNING, A.; OTADUY, M. C.- 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- Dorsal Anterior Cingulate Lactate and Glutathione Levels in Euthymic Bipolar I Disorder: H-1-MRS Study(2016) SOEIRO-DE-SOUZA, Marcio Gerhardt; PASTORELLO, Bruno F.; LEITE, Claudia da Costa; HENNING, Anke; MORENO, Ricardo A.; OTADUY, Maria Concepcion GarciaOxidative stress and mitochondrial dysfunction are 2 closely integrated processes implicated in the physiopathology of bipolar disorder. Advanced proton magnetic resonance spectroscopy techniques enable the measurement of levels of lactate, the main marker of mitochondrial dysfunction, and glutathione, the predominant brain antioxidant. The objective of this study was to measure brain lactate and glutathione levels in bipolar disorder and healthy controls. Eighty-eight individuals (50 bipolar disorder and 38 healthy controls) underwent 3T proton magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (2x2x4.5cm(3)) using a 2-D JPRESS sequence. Lactate and glutathione were quantified using the ProFit software program. Bipolar disorder patients had higher dorsal anterior cingulate cortex lactate levels compared with controls. Glutathione levels did not differ between euthymic bipolar disorder and controls. There was a positive correlation between lactate and glutathione levels specific to bipolar disorder. No influence of medications on metabolites was observed. This is the most extensive magnetic resonance spectroscopy study of lactate and glutathione in bipolar disorder to date, and results indicated that euthymic bipolar disorder patients had higher levels of lactate, which might be an indication of altered mitochondrial function. Moreover, lactate levels correlated with glutathione levels, indicating a compensatory mechanism regardless of bipolar disorder diagnosis.
- Analysis of fractional anisotropy and mean diffusivity in refractory and non-refractory idiopathic generalized epilepsies(2018) LOBATO, Mauricio; GARCIA, Lucas; AMARO JR., Edson; OTADUY, Maria; JORGE, Carmen; CASTRO, Luiz H.Purpose: To compare white matter bundles and fiber tract changes in seizure-free and non-seizure-free idiopathic generalized epilepsy (IGE) patients. Method: Forty adult patients with IGE underwent a 3 T brain MRI with DTI sequences. According to seizure control status, eighteen patients were classified as refractory (R) if they had presented at least one incapacitating seizure in the previous six months, while on appropriate antiepileptic drug treatment. Twenty two seizure-free patients with adequate seizure control were considered non-refractory (NR). We compared fractional anisotropy (FA) and mean diffusivity (MD) values in sixteen white matter tracts in the R and NR groups, and in twenty healthy subjects. Results: R and NR groups did not differ in gender, age and education. We found decreased FA in two tracts in the R group (forceps major and right uncinate fasciculus) and approaching statistical significance in two tracts in the NR group (right cingulate gyrus and right uncinate fasciculus) group, as well as increased MD in six tracts in the R group (forceps minor, left thalamic anterior radiation, right inferior longitudinal fasciculus, right longitudinal superior parietal and temporal fasciculi, and right cingulate gyrus) and in five tracts in the NR group (forceps minor, left thalamic anterior radiation, right inferior longitudinal fasciculus, right longitudinal superior parietal and temporal fasciculi), compared to controls. No differences were noted comparing FA and MD values between R and NR groups. Conclusions: In our patient population, refractory IGE patients on adequate antiepileptic drug treatment did not present more severe white matter tract involvement compared to non-refractory patients.
- Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative(2020) SIMPSON, Helen Blair; HEUVEL, Odile A. van den; MIGUEL, Euripedes C.; REDDY, Y. C. Janardhan; STEIN, Dan J.; LEWIS-FERNANDEZ, Roberto; SHAVITT, Roseli Gedanke; LOCHNER, Christine; POUWELS, Petra J. W.; NARAYANAWAMY, Janardhanan C.; VENKATASUBRAMANIAN, Ganesan; HEZEL, Dianne M.; VRIEND, Chris; BATISTUZZO, Marcelo C.; HOEXTER, Marcelo Q.; JOODE, Niels T. de; COSTA, Daniel Lucas; MATHIS, Maria Alice de; SHESHACHALA, Karthik; NARAYAN, Madhuri; BALKOM, Anton J. L. M. van; BATELAAN, Neeltje M.; VENKATARAM, Shivakumar; CHERIAN, Anish; MARINCOWITZ, Clara; PANNEKOEK, Nienke; STOVEZKY, Yael R.; MARE, Karen; LIU, Feng; OTADUY, Maria Concepcion Garcia; PASTORELLO, Bruno; RAO, Rashmi; KATECHIS, Martha; METER, Page Van; WALL, MelanieBackground Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2-3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. Methods We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. Discussion Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it.
- Effect of age, diet, and tissue type on PCr response to creatine supplementation(2017) SOLIS, Marina Yazigi; ARTIOLI, Guilherme Giannini; OTADUY, Maria Concepcion Garcia; LEITE, Claudia da Costa; ARRUDA, Walquiria; VEIGA, Raquel Ramos; GUALANO, BrunoCreatine/phosphorylcreatine (PCr) responses to creatine supplementation may be modulated by age, diet, and tissue, but studies assessing this possibility are lacking. Therefore we aimed to determine whether PCr responses vary as a function of age, diet, and tissue. Fifteen children, 17 omnivorous and 14 vegetarian adults, and 18 elderly individuals (""elderly"") participated in this study. Participants were given placebo and subsequently creatine (0.3 g center dot kg(-1) center dot day(-1)) for 7 days in a singleblind fashion. PCr was measured through phosphorus magnetic resonance spectroscopy (P-31-MRS) in muscle and brain. Creatine supplementation increased muscle PCr in children (P < 0.0003) and elderly (P < 0.001), whereas the increase in omnivores did not reach statistically significant difference (P < 0.3348). Elderly had greater PCr increases than children and omnivores (P < 0.0001 for both), whereas children experienced greater PCr increases than omnivores (P < 0.0022). In relation to diet, vegetarians (P < 0.0001), but not omnivores, had significant increases in muscle PCr content. Brain PCr content was not affected by creatine supplementation in any group, and delta changes in brain PCr (-0.7 to +3.9%) were inferior to those in muscle PCr content (+10.3 to +27.6%; P < 0.0001 for all comparisons). PCr responses to a standardized creatine protocol (0.3 g center dot kg(-1) center dot day(-1) for 7 days) may be affected by age, diet, and tissue. Whereas creatine supplementation was able to increase muscle PCr in all groups, although to different extents, brain PCr was shown to be unresponsive overall. These findings demonstrate the need to tailor creatine protocols to optimize creatine/PCr accumulation both in muscle and in brain, enabling a better appreciation of the pleiotropic properties of creatine. NEW & NOTEWORTHY A standardized creatine supplementation protocol (0.3 g center dot kg(-1) center dot day(-1) for 7 days) effectively increased muscle, but not brain, phosphorylcreatine. Older participants responded better than younger participants whereas vegetarians responded better than omnivores. Responses to supplementation are thus dependent on age, tissue, and diet. This suggests that a single ""universal"" protocol, originally designed for increasing muscle creatine in young individuals, may lead to heterogeneous muscle responses in different populations or even no responses in tissues other than skeletal muscle.