CLAUDIA DA COSTA LEITE
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Radiologia, Faculdade de Medicina - Docente
LIM/44 - Laboratório de Ressonância Magnética em Neurorradiologia, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/44 - Laboratório de Ressonância Magnética em Neurorradiologia, Hospital das Clínicas, Faculdade de Medicina - Líder
17 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 17
- 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.
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.
- Lithium-associated anterior cingulate neurometabolic profile in euthymic Bipolar I disorder: A H-1-MRS study(2018) SOEIRO-DE-SOUZA, Marcio Gerhardt; OTADUY, Maria Concepcion Garcia; MACHADO-VIEIRA, Rodrigo; MORENO, Ricardo Alberto; NERY, Fabiano G.; LEITE, Claudia; LAFER, BenyObjective: In the treatment of Bipolar disorder (BD), achieving euthymia is highly complex and usually requires a combination of mood stabilizers. The mechanism of action in stabilizing mood has not been fully elucidated, but alterations in N-Acetylaspartate (NAA), Myo-Inositol (mI) and Choline (Cho) have been implicated. Proton magnetic resonance spectroscopy (H-1-MRS) is the gold standard technique for measuring brain NAA, Cho and mI in vivo. The objective of this study was to investigate the association of lithium use in BD type I and brain levels of NAA, mI and Cho in the (anterior cingulate cortex) ACC. Methods: 129 BD type I subjects and 79 healthy controls (HC) were submitted to a 3-Tesla brain magnetic resonance imaging scan (H-1-MRS) using a PRESS ACC single voxel (8cm(3)) sequence. Results: BD patients exhibited higher NAA and Cho levels compared to HC. Lithium prescription was associated with lower mI (combination + monotherapy) and higher NAA levels (monotherapy). Conclusion: The results observed add to the knowledge about the mechanisms of action of mood stabilizers on brain metabolites during euthymia. Additionally, the observed decrease in mI levels associated with lithium monotherapy is an in vivo finding that supports the inositol-depletion hypothesis of lithium pharmacodynamics.
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, Homero- 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.
- Anterior cingulate cortex neuro-metabolic changes underlying lithium-induced euthymia in bipolar depression: A longitudinal H-1-MRS study(2021) SOEIRO-DE-SOUZA, M. G.; SCOTTI-MUZZI, E.; FERNANDES, F.; SOUSA, R. T. De; LEITE, C. C.; OTADUY, M. C.; MACHADO-VIEIRA, R.The diagnosis and treatment of bipolar depression (BDep) poses complex clinical challenges for psychiatry. Proton magnetic resonance spectroscopy (H-1-MRS) is a useful imaging tool for investigating in vivo levels of brain neuro-metabolites, critical to understanding the process of mood dysregulation in Bipolar Disorder. Few studies have evaluated longitudinal clinical outcomes in BDep associated with H-1-MRS metabolic changes. This study aimed to longitudinally assess brain H-1-MRS metabolites in the anterior cingulate cortex (ACC) correlated with improvement in depression (from BDep to euthymia) after lithium treatment in BDep patients versus matched healthy controls (HC). Twenty-eight medication-free BDep patients and 28 HC, matched for age and gender, were included in this study. All subjects were submitted to a 3-Tesla brain H-1-MRS scan in the ACC using a single-voxel (8cm(3)) PRESS sequence at baseline. At follow-up (6 weeks), 14 BDep patients repeated the exam in euthymia. Patients with current BDep had higher baseline Myo-inositol/Cr (mI/Cr) and Choline/Cr (Cho/Cr) compared to HC. After six weeks, mI/Cr or Cho/Cr levels in subjects that achieved euthymia no longer differed to levels in HC, while high Cho/Cr levels persisted in non-responders . Elevated ACC mI/Cr and Cho/Cr in BDep might indicate increased abnormal membrane phospholipid metabolism and phosphatidylinositol (PI) cycle activity. Return of mI/Cr and Cho/Cr to normal levels after lithium-induced euthymia sug-gests a critical regulatory effect of lithium targeting the PI cycle involved in mood regulation.
- ACC Glu/GABA ratio is decreased in euthymic bipolar disorder I patients: possible in vivo neurometabolite explanation for mood stabilization(2021) SCOTTI-MUZZI, Estevao; CHILE, Thais; MORENO, Ricardo; PASTORELLO, Bruno Fraccini; LEITE, Claudia da Costa; HENNING, Anke; OTADUY, Maria Concepcion Garcia; VALLADA, Homero; SOEIRO-DE-SOUZA, Marcio GerhardtBipolar disorder (BD) is characterized by unstable mood states ranging from mania to depression. Although there is some evidence that mood instability may result from an imbalance between excitatory glutamatergic and inhibitory GABA-ergic neurotransmission, few proton magnetic resonance spectroscopy (H-1-MRS) studies have measured these two neurometabolites simultaneously in BD. The enzyme glutamic acid decarboxylase (GAD1) catalyzes the decarboxylation of glutamate (Glu) to GABA, and its single nucleotide polymorphisms (SNPs) might influence Glu/GABA ratio. Thus, we investigated Glu/GABA ratio in the dorsal anterior cingulate cortex (dACC) of euthymic BD type I patients and healthy controls (HC), and assessed the influence of both mood stabilizers and GAD1 SNPs on this ratio. Eighty-eight subjects (50 euthymic BD type I patients and 38 HC) underwent 3T H-1-MRS in the dACC (2 x 2 x 4.5 cm(3)) using a two-dimensional JPRESS sequence and all subjects were genotyped for 4 SNPs in the GAD1 gene. BD patients had lower dACC Glu/GABA ratio compared to HC, where this was influenced by anticonvulsant and antipsychotic medications, but not lithium. The presence of GAD1 rs1978340 allele A was associated with higher Glu/GABA ratio in BD, while patients without this allele taking mood stabilizers had a lower Glu/GABA ratio. The lowering of dACC Glu/GABA could be one explanation for the mood stabilizing action of anticonvulsants and antipsychotics in BD type I euthymia. Therefore, this putative role of Glu/GABA ratio and the influence of GAD1 genotype interacting with mood stabilization medication should be confirmed by further studies involving larger samples and other mood states. ClincalTrials.gov registration: NCT01237158.
- 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.
- Acc neuro-metabolic changes from bipolar depression to euthymia: repeated 1h-mrs measurement as a function of mood state and lithium efficacy(2020) SOEIRO-DE-SOUZA, M.; SCOTTI-MUZZI, E.; FERNANDES, F.; SOUZA, R. De; LEITE, C.; OTADUY, M.; MACHADO-VIEIRA, R.