MARCIO GERHARDT SOEIRO DE SOUZA
Projetos de Pesquisa
Unidades Organizacionais
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina
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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.- 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.
- The ARIQUELI study: potentiation of quetiapine in bipolar I nonresponders with lithium versus aripiprazole(2013) MISSIO, Giovani; MORENO, Doris Hupfeld; FERNANDES, Fernando; BIO, Danielle Soares; SOEIRO-DE-SOUZA, Marcio Gehardt; SANTOS JR., Domingos Rodrigues dos; DAVID, Denise Petresco; COSTA, Luis Felipe; DEMETRIO, Frederico Navas; MORENO, Ricardo AlbertoBackground: The treatment of bipolar disorder (BD) remains a challenge due to the complexity of the disease. Current guidelines represent an effort to assist clinicians in routine practice but have several limitations, particularly concerning long-term treatment. The ARIQUELI (efficacy and tolerability of the combination of lithium or aripiprazole in young bipolar non or partial responders to quetiapine monotherapy) study aims to evaluate two different augmentation strategies for quetiapine nonresponders or partial responders in acute and maintenance phases of BD treatment. Methods/Design: The ARIQUELI study is a single-site, parallel-group, randomized, outcome assessor-blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic/hypomanic or mixed episode, aged 18 to 40 years, are eligible. After diagnostic assessments, patients initiated treatment in phase I with quetiapine. Nonresponders or partial responders after 8 weeks are allocated into one of two groups, potentiated with either lithium (0.5 to 0.8 mEq/l) or aripiprazole (10 or 15 mg). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blinded to the treatment. The primary outcome is the evaluation of changes in mean scores on the CGI-BP-M between baseline and the endpoint at the end of each study phase. Discussion: The ARIQUELI study is currently in progress, with patients undergoing acute treatment (phase I), potentiation (phase II) and maintenance (phase III). The study will be extended until January 2015. Trials comparing lithium and aripiprazole with potentiate treatment in young BD I nonresponders to quetiapine in monotherapy can provide relevant information on the safety of these drugs in clinical practice. Long-term treatment is an issue of great importance and should be evaluated further through more in-depth studies given that BD is a chronic disease.
- 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, HomeroconferenceObject 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.