MARCIO GERHARDT SOEIRO DE SOUZA
Projetos de Pesquisa
Unidades Organizacionais
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina
24 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 24
- 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 The association between family functioning and childhood trauma and cognition in patients with bipolar disorder type I(2013) BIO, D. S.; MONTEIRO, R. O.; SOEIRO-DE-SOUZA, M.; MORENO, D.; MORENO, R. A.Objective: Bipolar disorder (BD) is characterized by high levels of childhood trauma as well as of cognitive dysfunction. Our aim is to investigate the association between these two factors in bipolar patients and in healthy controls. Methods: A total of 35 patients with BD in euthymia, aged between 18 and 40 years old, were recruited at Hospital das Clinicas in São Paulo, Brazil. Ninety four healthy volunteers (HC) (predominantly medical students) aged between 18 and 40 years old, with no current or past history of psychiatric disorder, were recruited from the University of São Paulo. Information about early life stress was obtained using the Childhood Trauma Questionnaire (CTQ). Cognitive function was assessed through a comprehensive and standardized neuropsychological test battery, including social cognition – Facial Emotional Recognized (FER). Results: In the BD group we observed: that physical abuse was significantly associated with reduced scores on verbal recall (p = 0.04) and with fewer recognized of “fear” faces (p = 0.02); sexual abuse and physical neglect were significantly associated with reduced scores on executive function scales (p = 0.02 to p = 0.04); emotional neglect was significantly associated only with reduced scores on recognized of “anger” faces; emotional abuse was significantly associated with reduced scores on attentional process (p = 0.02), verbal task from the Wechsler Abbreviated Scale of Intelligence (WASI) (p = 0.01), and recognized “anger” faces; pshysical neglect was yet significantly associated with reduced scores on verbal and performance tasks and IQ from the WASI (p = 0.02 to p < 0.001), and FER scores on the Emotion Hexagon (Hx) tests and e Ekman 60 Faces (EK60) total scores. In the control HC, Emotional Neglect and Physical Neglect was significantly associated with reduced scores on verbal and performance tasks and IQ from the WASI (p = 0.02 to p < 0.001), working memory (p = 0.01) and executive function (p = 0.01to p = 0.007); Emotional Neglect and Sexual Abuse was significantly associated with reduced scores on verbal fluency; and significantly reduced scores on FER was observed in emotional abuse (p = 0.03), Physical Neglect (p = 0.04 to p = 0.008) and Sexual Abuse (p = 0.04). Discussion: Our results indicate that childhood trauma is associated with a reduction in cognitive function across cognitive domains in patients with BD and HC, in particular social cognition, working memory and executive function as well as general cognition.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 efficacy in bipolar depression with flexible dosing: A six-week, open-label, proof-of-concept study(2014) MACHADO-VIEIRA, Rodrigo; ZANETTI, Marcus V.; SOUSA, Rafael T. De; SOEIRO-DE-SOUZA, Marcio G.; MORENO, Ricardo A.; BUSATTO, Geraldo F.; GATTAZ, Wagner F.Lithium has a narrow therapeutic index with a subtle balance between effectiveness and adverse effects. Current guidelines recommend the use of lithium as a treatment for acute bipolar depression; however, the therapeutic range for the treatment has not been fully defined. Recently, the adjunctive lower lithium dose in bipolar depression has revealed potential efficacy; however, no study has investigated it predominantly in monotherapy. In this open-label, proof-of-concept study, 31 individuals with bipolar disorder during a depressive episode were randomized and 29 were followed up for six weeks with flexible lithium dosing. All subjects had a 21-item Hamilton Rating Scale for Depression (HAM-D) score of >= 18 at baseline. Subjects were divided into two groups, with higher (Li >= 0.5 mEq/l) or lower (Li <0.5 mEq/l) blood lithium levels. Response and remission rates were evaluated using the HAM-D scores. Following 6 weeks of lithium treatment, the remission rate for all patients was 62.0%. The plasma lithium levels did not impact the clinical response. However, subjects with higher blood lithium levels had an increased prevalence of nausea, restlessness, headaches and cognitive complaints. The results indicate that the lithium dose for the treatment of bipolar depression in an individual should be based on the clinical efficacy and side-effects. In the context of personalized psychiatric treatments, it is necessary to evaluate the therapeutic action of lithium with individual regimens in order to develop more tolerable and effective treatment approaches.
conferenceObject Influence of childhood trauma on personality development in bipolar patients and healthy controls(2013) MONTEIRO, R.; BIO, D. Soares; SOEIRO-DE-SOUZA, M.; MISSIO, G.; MORENO, D.; MORENO, R. A.Objective: Bipolar disorder (BD) is characterized by high levels of childhood trauma and they can be detrimental in relation to the formation of personality. The aim of this study is to investigate the association between childhood trauma and BD personality compared to healthy controls (HC). Methods: A total of 27 euthimic BD patients, aged between 18 and 40 years old, were recruited at Hospital das Clinicas in São Paulo, Brazil. Twenty HC (predominantly medical students) aged between 18 and 35 years old, with no current or past history of psychiatric disorder, were recruited from the University of São Paulo. Information about early life stress was obtained using the Childhood Trauma Questionnaire (CTQ). Personality Formation was assessed through NEO-PI-R personality test – based on the Big Five personality traits: Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness to Experience. Results: In the BD group the main significant associations were: physical abuse with concientiousness (p = 0.03); emotional neglect with agreeableness (p =0.03) and emotional abuse with conscientiousness (p = 0.04). There were no significant differences in HC group. Comparing BD and HC physical abuse was associated with concientiousness (p = 0.03) and emotion Neglecent was associated with agreeableness (p = 0.03). Discussion: Our results indicate that childhood trauma can be associated with personality traits in BD patients but not in HC, mainly regarding concientiousness and emotional neglect.- Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis(2013) BOURNE, C.; AYDEMIR, O.; BALANZA-MARTINEZ, V.; BORA, E.; BRISSOS, S.; CAVANAGH, J. T. O.; CLARK, L.; CUBUKCUOGLU, Z.; DIAS, V. V.; DITTMANN, S.; FERRIER, I. N.; FLECK, D. E.; FRANGOU, S.; GALLAGHER, P.; JONES, L.; KIESEPPA, T.; MARTINEZ-ARAN, A.; MELLE, I.; MOORE, P. B.; MUR, M.; PFENNIG, A.; RAUST, A.; SENTURK, V.; SIMONSEN, C.; SMITH, D. J.; BIO, D. S.; SOEIRO-DE-SOUZA, M. G.; STODDART, S. D. R.; SUNDET, K.; SZOKE, A.; THOMPSON, J. M.; TORRENT, C.; ZALLA, T.; CRADDOCK, N.; ANDREASSEN, O. A.; LEBOYER, M.; VIETA, E.; BAUER, M.; WORHUNSKY, P. D.; TZAGARAKIS, C.; ROGERS, R. D.; GEDDES, J. R.; GOODWIN, G. M.Objective: An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta-analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view. Method: Individual patient and control data were obtained from original authors for 11 measures from four common neuropsychological tests: California or Rey Verbal Learning Task (VLT), Trail Making Test (TMT), Digit Span and/or Wisconsin Card Sorting Task. Results: Impairments were found for all 11 test-measures in the bipolar group after controlling for age, IQ and gender (Ps <= 0.001, E.S. = 0.26-0.63). Residual mood symptoms confound this result but cannot account for the effect sizes found. Impairments also seem unrelated to drug treatment. Some test-measures were weakly correlated with illness severity measures suggesting that some impairments may track illness progression. Conclusion: This reanalysis supports VLT, Digit Span and TMT as robust measures of cognitive impairments in bipolar disorder patients. The heterogeneity of some test results explains previous differences in meta-analyses. Better controlling for confounds suggests deficits may be smaller than previously reported but should be tracked longitudinally across illness progression and treatment.
conferenceObject The Burden of a Progressive Disease: Number of Manic Episodes and Lifetime History of Psychotic Symptoms Increases Dna Oxidation in Bipolar I Disorder(2012) SOEIRO-DE-SOUZA, Marcio G.; ANDREAZZA, Ana Cristina; MACHADO-VIEIRA, Rodrigo; YOUNG, Trevor; MORENO, RicardoconferenceObject Plasma Cortisol in First Episode Drug-Naive Mania: Differential Levels in Euphoric Versus Irritable Mood(2012) VALIENGO, Leandro L.; SOEIRO-DE-SOUZA, Marcui G.; MARQUES, Andrea H.; JURUENA, Mario F.; ANDREAZZA, Ana C.; GATTAZ, Wagner F.; MACHADO-VIERA, RodrigoBackground: Dysregulation of HPA axis have been widely described in subjects with bipolar disorder (BD), including changes in cortisol levels during mood episodes and euthymia. However, most of the studies were done with medicated BD patients with variable length of illness, which was shown to interfere on peripheral cortisol levels. Therefore, the present study aims to evaluate plasma cortisol levels in drug-naïve BD subjects during the first manic episode, as well as investigate the relationship between plasma cortisol levels and manic symptomatology. Methods: Twenty-six drug-naïve patients were enrolled meeting criteria for a first manic episode in bipolar I disorder. Severity of mania was assessed using the Young Mania Rating Scale (YMRS). The control group included 27 healthy subjects matched by age and gender. Cortisol was quantified using a direct radioimmunoassay. Results: Plasma cortisol levels were decreased during first manic episode compared to healthy controls. Higher cortisol levels were positively associated with the presence of irritability (dysphoria), while elated mania showed lower cortisol levels compared to controls. Conclusions: Higher cortisol in dysphoric mania compared to predominantly elated/euphoric mania may indicate a clinical and neurobiological polymorphic phenomenon, potentially involving a higher biological sensitivity to stress in the presence of irritable mood. The present findings highlight the importance to dd a dimensional approach to the traditional categorical diagnosis for future neurobiological studies in BD.
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