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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- 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.
- 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.
conferenceObject GAD1 POLYMORPHISMS ARE ASSOCIATED WITH GLUTAMATERGIC ACTIVITY IN THE ANTERIOR CINGULATE IN BIPOLAR I DISORDER(2017) SOEIRO-DE-SOUZA, Marcio; MACHADO-VIEIRA, Rodrigo; MORENO, Ricardo; CHILE, Thais; GOUVEIA, Gisele; PASTORELLO, Bruno; LEITE, Claudia; HENNING, Anke; OTADUY, Maria Concepcion; VALLADA, HomeroconferenceObject 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- The CACNA1C risk allele rs1006737 is associated with age-related prefrontal cortical thinning in bipolar I disorder(2017) SOEIRO-DE-SOUZA, M. G.; LAFER, B.; MORENO, R. A.; NERY, F. G.; CHILE, T.; CHAIM, K.; LEITE, C. da Costa; MACHADO-VIEIRA, R.; OTADUY, M. C. G.; VALLADA, H.Calcium channels control the inflow of calcium ions into cells and are involved in diverse cellular functions. The CACNA1C gene polymorphism rs1006737 A allele has been strongly associated with increased risk for bipolar disorder (BD) and with modulation of brain morphology. The medial prefrontal cortex (mPFC) has been widely associated with mood regulation in BD, but the role of this CACNA1C polymorphism in mPFC morphology and brain aging has yet to be elucidated. One hundred seventeen euthymic BD type I subjects were genotyped for CACNA1C rs1006737 and underwent 3 T three-dimensional structural magnetic resonance imaging scans to determine cortical thickness of mPFC components (superior frontal cortex (sFC), medial orbitofrontal cortex (mOFC), caudal anterior cingulate cortex (cACC) and rostral anterior cingulate cortex (rACC)). Carriers of the CACNA1C allele A exhibited greater left mOFC thickness compared to non-carriers. Moreover, CACNA1C A carriers showed age-related cortical thinning of the left cACC, whereas among A non-carriers there was not an effect of age on left cACC cortical thinning. In the sFC, mOFC and rACC (left or right), a negative correlation was observed between age and cortical thickness, regardless of CACNA1C rs1006737 A status. Further studies investigating the direct link between cortical thickness, calcium channel function, apoptosis mechanism and their underlying relationship with aging-associated cognitive decline in BD are warranted.
- Proton spectroscopy of the thalamus in a homogeneous sample of patients with easy-to-control juvenile myoclonic epilepsy(2017) LEITE, Claudia da Costa; VALENTE, Kette Dualibi Ramos; FIORE, Lia Arno; OTADUY, Maria Concepción GarcíaAbstract Objective: Juvenile myoclonic epilepsy (JME) is a subtype of genetically determined generalized epilepsy that does not present abnormalities on conventional magnetic resonance imaging. The aim of this study was to identify metabolic alterations in the thalamus in a clinically homogeneous sample of patients with easy-to-control JME, using short-echo time proton magnetic resonance spectroscopy (MRS). Materials and Methods: We performed single-voxel (2 cm × 2 cm × 2 cm), short-echo time (TE = 35 ms) proton MRS of the thalamus in 21 patients with JME and in 14 healthy age-matched controls. We quantified N-acetylaspartate (NAA), total NAA, creatine (Cr), choline, and myo-inositol (MI), as well as the sum of glutamate and glutamine signals, all scaled to internal water content, and we calculated metabolite ratios using Cr as a reference. Values of p < 0.05 were considered significant. Results: The MI level and the MI/Cr ratio were significantly lower in the thalami of patients diagnosed with JME than in those of the controls. Other metabolites and their ratios did not differ significantly between the two groups. Conclusion: In our sample of 21 JME patients, we identified lower levels of MI in the thalamus. No significant abnormalities were observed in the concentrations or ratios of other metabolites.
- Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study(2017) MEREGE-FILHO, Carlos Alberto Abujabra; OTADUY, Maria Concepcion Garcia; SA-PINTO, Ana Lucia de; OLIVEIRA, Maira Okada de; GONCALVES, Livia de Souza; HAYASHI, Ana Paula Tanaka; ROSCHEL, Hamilton; PEREIRA, Rosa Maria Rodrigues; SILVA, Clovis Artur; BRUCKI, Sonia Maria Dozzi; LEITE, Claudia da Costa; GUALANO, BrunoIt has been hypothesized that dietary creatine could influence cognitive performance by increasing brain creatine in developing individuals. This double-blind, randomized, placebo-controlled, proof-of-principle study aimed to investigate the effects of creatine supplementation on cognitive function and brain creatine content in healthy youth. The sample comprised 67 healthy participants aged 10 to 12 years. The participants were given creatine or placebo supplementation for 7 days. At baseline and after the intervention, participants undertook a battery of cognitive tests. In a random subsample of participants, brain creatine content was also assessed in the regions of left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe by proton magnetic resonance spectroscopy (1H-MRS) technique. The scores obtained from verbal learning and executive functions tests did not significantly differ between groups at baseline or after the intervention (all p > 0.05). Creatine content was not significantly different between groups in left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe (all p > 0.05). In conclusion, a 7-day creatine supplementation protocol did not elicit improvements in brain creatine content or cognitive performance in healthy youth, suggesting that this population mainly relies on brain creatine synthesis rather than exogenous creatine intake to maintain brain creatine homeostasis.
conferenceObject Semantic fluency impairment in unilateral mesial temporal sclerosis related epilepsy is associated with extensive white matter involvement: a diffusion tensor imaging study(2017) PERES, Matheus; CASTRO, Bettina; MESSAS, Cristiane; MARTUCCI, Caio; CHAIM, Khalil; PASTORELLO, Bruno; VALERIO, Rosa; JORGE, Carmen; LYRA, Katarina; OTADUY, Maria; LEITE, Claudia; CASTRO, Luiz- Substantia nigra fractional anisotropy is not a diagnostic biomarker of Parkinson's disease: A diagnostic performance study and meta-analysis(2017) HIRATA, Fabiana C. C.; SATO, Joao R.; VIEIRA, Gilson; LUCATO, Leandro T.; LEITE, Claudia C.; BOR-SENG-SHU, Edson; PASTORELLO, Bruno F.; OTADUY, Maria C. G.; CHAIM, Khallil T.; CAMPANHOLO, Kenia R.; NOVAES, Natalia P.; MELO, Luciano Magalhaes; GONCALVES, Marcia R.; NASCIMENTO, Felipe Barjud Pereira do; TEIXEIRA, Manoel Jacobsen; BARBOSA, Egberto Reis; AMARO JR., Edson; CARDOSO, Ellison FernandoObjectives Our goal was to estimate the diagnostic accuracy of substantia nigra fractional anisotropy (SN-FA) for Parkinson's disease (PD) diagnosis in a sample similar to the clinical setting, including patients with essential tremor (ET) and healthy controls (HC). We also performed a systematic review and meta-analysis to estimate mean change in SN-FA induced by PD and its diagnostic accuracy. Methods Our sample consisted of 135 subjects: 72 PD, 21 ET and 42 HC. To address inter-scanner variability, two 3.0-T MRI scans were performed. MRI results of this sample were pooled into a meta-analysis that included 1,432 subjects (806 PD and 626 HC). A bivariate model was used to evaluate diagnostic accuracy measures. Results In our sample, we did not observe a significant effect of disease on SN-FA and it was uninformative for diagnosis. The results of the meta-analysis estimated a 0.03 decrease in mean SN-FA in PD relative to HC (CI: 0.01-0.05). However, the discriminatory capability of SN-FA to diagnose PD was low: pooled sensitivity and specificity were 72 % (CI: 68-75) and 63 % (CI: 58-70), respectively. There was high heterogeneity between studies (I-2 = 91.9%). Conclusions SN-FAcannot be used as an isolatedmeasure to diagnose PD.
- Corpus callosum diffusion abnormalities in refractory epilepsy associated with hippocampal sclerosis(2017) LYRA, Katarina P.; CHAIM, Khallil T.; LEITE, Claudia C.; PARK, Eun J.; ANDRADE, Celi S.; PASSARELLI, Valmir; VALERIO, Rosa M. F.; JORGE, Carmen L.; CASTRO, Luiz H. M.; OTADUY, Maria C. G.Objectives: To detect by diffusion tensor imaging (DTI) the extent of microstructural integrity changes of the corpus callosum (CC) in patients with hippocampal sclerosis (HS) and to evaluate possible association with clinical characteristics. Methods: Fourty-two patients with temporal lobe epilepsy (TLE) and HS and 30 control subjects were studied with DTI. We grouped patients according to lesion side (left or right) HS. Mean diffusivity (MD), fractional anisotropy (FA), radial (RD) and axial diffusivity (AD) were extracted from five segments in CC midsagittal section obtained by automatic segmentation. CC DTI findings were compared between groups. We also evaluated association of DTI changes and clinical characteristics. Results: HS patients displayed decreased FA and increased MD and RD in the anterior, mid-posterior and posterior CC segments, compared to controls. No differences were observed in AD. Patients reporting febrile seizure as the initial precipitating event presented more intense diffusion changes. No differences were seen comparing left and right HS. Age at epilepsy onset, disease duration and seizure frequency were not associated with DTI findings. Conclusions: This is one of the largest series of TLE-HS patients evaluating CC white matter fiber integrity by DTI, which allowed us to study how some clinical characteristics, such as seizure frequency, disease duration and lesion side, are related to CC integrity. Occurrence of febrile seizure was the only factor that had significant impact on tract integrity. Diffusion changes were not restricted to the posterior part of the CC; we observed the same changes for the anterior part of the CC. Diffusion changes were characterized by an increase in RD, while the AD remained intact for all regions of the CC.