MARCIO GERHARDT SOEIRO DE SOUZA
Projetos de Pesquisa
Unidades Organizacionais
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina
8 resultados
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- Anterior cingulate cortex neurometabolites in bipolar disorder are influenced by mood state and medication: A meta-analysis of H-1-MRS studies(2021) SCOTTI-MUZZI, Estevao; UMLA-RUNGE, Katja; SOEIRO-DE-SOUZA, Marcio GerhardtThe anterior cingulate cortex (ACC), a brain region that mediates affect and cognition by connecting the frontal cortex to limbic structures, has been consistently implicated in the neurobiology of Bipolar Disorder (BD). Proton magnetic resonance spectroscopy (H-1-MRS) studies have extensively compared in vivo neurometabolite levels of BD patients and healthy controls (HC) in the ACC. However, these studies have not been analyzed in a systematic review or meta-analysis and nor has the influence of mood state and medication on neurometabolites been examined in this cortical region. A systematic review and a meta-analysis of H-1-MRS studies comparing ACC neurometabolite profiles of adult BD patients and HC subjects was conducted, retrieving 27 articles published between 2000 and 2018. Overall increased ACC levels of Glx [glutamine (Gln) + glutamate)/Creatine], Gln, choline (Cho) and Cho/Creatine were found in BD compared to HC. Bipolar depression was associated with higher Cho levels, while euthymia correlated with higher glutamine (Gln) and Cho. Mood stabilizers appeared to affect ACC Glu and Gln metabolites. Increased ACC Cho observed in euthymia, depression and in medication-free groups could be considered a trait marker in BD and attributed to increased cell membrane phospholipid turnover. Overall increased ACC Glx was associated with elevated Gln levels, particularly influenced by euthymia, but no abnormality in Glu was detected. Further H-1-MRS studies, on other voxels, should assess more homogeneous (mood state-specific), larger BD samples and account for medication status using more sensitive H-1-MRS techniques.
- Altered brain creatine cycle metabolites in bipolar I disorder with childhood abuse: A H-1 magnetic resonance spectroscopy study(2021) BIO, Danielle Soares; MORENO, Ricardo Alberto; GARCIA-OTADUY, Maria Concepcion; NERY, Fabiano; LAFER, Beny; SOEIRO-DE-SOUZA, Marcio GerhardtBackground: Childhood abuse (CA) is a risk factor for a number of psychiatric disorders and has been associated with higher risk of developing bipolar disorders (BD). CA in BD has been associated with more severe clinical outcomes, but the neurobiological explanation for this is unknown. Few studies have explored in vivo measurement of brain metabolites using proton magnetic resonance spectroscopy (1H-MRS) in CA and no studies have investigated the association of CA severity with brain neurometabolites in BD. Objective: To investigate whether CA severity is associated with changes in anterior cingulate cortex (ACC) neurometabolite profile in BD and HC subjects. Methods: Fifty-nine BD I euthymic patients and fifty-nine HC subjects were assessed using the Childhood Trauma Questionnaire (CTQ) and underwent a 3-Tesla 1H-MRS scan. Severity of childhood abuse (physical, sexual and emotional) and its association with levels of brain metabolites was analyzed within each group. Results: BD patients had higher total scores on the CTQ and higher severity rates of sexual and physical abuse compared to HC subjects. Greater severity of physical and sexual abuse was associated with increased ACC PCr level and lower Cr/PCr ratio in the BD group only. Conclusion: Sexual and physical abuse in BD patients, but not in HC subjects, appeared to be associated with creatine metabolism in the ACC, which can influence neuronal mitochondrial energy production. Further studies should investigate whether this is the mechanism underlying the association between CA and worse clinical outcomes in BD.
- 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.
- Genetic polymorphism in the cacna1c is associated with glutamatergic neurometabolites in the anterior cingulate cortex in bipolar disorder(2021) SCOTTI-MUZZI, E.; CHILE, T.; VALLADA, H.; OTADUY, M. C.; SOEIRO-DE-SOUZA, M. G.
- 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.
bookPart Tratamento dos transtornos depressivos(2021) MORENO, Ricardo Alberto; MORENO, Doris Hupfeld; SOEIRO-DE-SOUZA, Márcio Gerhardt- Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group(2021) HAN, L. K. M.; DINGA, R.; HAHN, T.; CHING, C. R. K.; EYLER, L. T.; AFTANAS, L.; AGHAJANI, M.; ALEMAN, A.; BAUNE, B. T.; BERGER, K.; BRAK, I.; HENRY, C.; CASERAS, X.; CHAIM-AVANCINI, T. M.; ELVSåSHAGEN, T.; FAVRE, P.; FOLEY, S. F.; FULLERTON, J. M.; HOUENOU, J.; HOWELLS, F. M.; INGVAR, M.; COUVY-DUCHESNE, B.; KUPLICKI, R.; LAFER, B.; LANDéN, M.; FILHO, G. B.; MACHADO-VIEIRA, R.; MALT, U. F.; MCDONALD, C.; MITCHELL, P. B.; NABULSI, L.; OTADUY, M. C. G.; THOMPSON, P. M.; OVERS, B. J.; POLOSAN, M.; POMAROL-CLOTET, E.; RADUA, J.; CARBALLEDO, A.; RIVE, M. M.; ROBERTS, G.; RUHE, H. G.; SALVADOR, R.; Sarró S.; VELTMAN, D. J.; SATTERTHWAITE, T. D.; SAVITZ, J.; SCHENE, A. H.; SCHOFIELD, P. R.; SERPA, M. H.; CONNOLLY, C. G.; SIM, K.; SOEIRO-DE-SOUZA, M. G.; SUTHERLAND, A. N.; TEMMINGH, H. S.; PENNINX, B. W. J. H.; TIMMONS, G. M.; UHLMANN, A.; VIETA, E.; WOLF, D. H.; ZANETTI, M. V.; JAHANSHAD, N.; MARQUAND, A. F.; COLE, J. H.; SCHMAAL, L.; CULLEN, K. R.; DANNLOWSKI, U.; DAVEY, C. G.; OSIPOV, E.; DIMA, D.; DURAN, F. L. S.; ENNEKING, V.; FILIMONOVA, E.; FRENZEL, S.; FRODL, T.; FU, C. H. Y.; GODLEWSKA, B. R.; GOTLIB, I. H.; GRABE, H. J.; PORTELLA, M. J.; GROENEWOLD, N. A.; GROTEGERD, D.; GRUBER, O.; HALL, G. B.; HARRISON, B. J.; HATTON, S. N.; HERMESDORF, M.; HICKIE, I. B.; HO, T. C.; HOSTEN, N.; POZZI, E.; JANSEN, A.; KäHLER, C.; KIRCHER, T.; KLIMES-DOUGAN, B.; KRäMER, B.; KRUG, A.; LAGOPOULOS, J.; LEENINGS, R.; MACMASTER, F. P.; MACQUEEN, G.; RENEMAN, L.; MCINTOSH, A.; MCLELLAN, Q.; MCMAHON, K. L.; MEDLAND, S. E.; MUELLER, B. A.; MWANGI, B.; REPPLE, J.; ROSA, P. G. P.; SACCHET, M. D.; SäMANN, P. G.; SCHNELL, K.; SCHRANTEE, A.; GOIKOLEA, J. M.; SIMULIONYTE, E.; SOARES, J. C.; SOMMER, J.; STEIN, D. J.; STEINSTRäTER, O.; STRIKE, L. T.; THOMOPOULOS, S. I.; TOL, M.-J. van; VEER, I. M.; VERMEIREN, R. R. J. M.; HAARMAN, B. C. M.; WALTER, H.; WEE, N. J. A. van der; WERFF, S. J. A. van der; WHALLEY, H.; WINTER, N. R.; WITTFELD, K.; WRIGHT, M. J.; WU, M.-J.; VöLZKE, H.; YANG, T. T.; HAJEK, T.; ZANNIAS, V.; ZUBICARAY, G. I. de; ZUNTA-SOARES, G. B.; Abé C.; ALDA, M.; ANDREASSEN, O. A.; BøEN, E.; BONNIN, C. M.; CANALES-RODRIGUEZ, E. J.; CANNON, D.Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates. © 2020, The Author(s).
bookPart Transtorno depressivo e distimia(2021) MORENO, Doris Hupfeld; MORENO, Ricardo Alberto; SOEIRO-DE-SOUZA, Márcio Gerhardt