MARCIO GERHARDT SOEIRO DE SOUZA
Projetos de Pesquisa
Unidades Organizacionais
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina
21 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 21
- 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- 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.
- Multiple levels of impaired neural plasticity and cellular resilience in bipolar disorder: Developing treatments using an integrated translational approach(2014) MACHADO-VIEIRA, Rodrigo; SOEIRO-DE-SOUZA, Marcio G.; RICHARDS, Erica M.; TEIXEIRA, Antonio L.; ZARATE JR., Carlos A.Objectives. This paper reviews the neurobiology of bipolar disorder (BD), particularly findings associated with impaired cellular resilience and plasticity. Methods. PubMed/Medline articles and book chapters published over the last 20 years were identified using the following keyword combinations: BD, calcium, cytokines, endoplasmic reticulum (ER), genetics, glucocorticoids, glutamate, imaging, ketamine, lithium, mania, mitochondria, neuroplasticity, neuroprotection, neurotrophic, oxidative stress, plasticity, resilience, and valproate. Results. BD is associated with impaired cellular resilience and synaptic dysfunction at multiple levels, associated with impaired cellular resilience and plasticity. These findings were partially prevented or even reversed with the use of mood stabilizers, but longitudinal studies associated with clinical outcome remain scarce. Conclusions. Evidence consistently suggests that BD involves impaired neural plasticity and cellular resilience at multiple levels. This includes the genetic and intra-and intercellular signalling levels, their impact on brain structure and function, as well as the final translation into behaviour/cognitive changes. Future studies are expected to adopt integrated translational approaches using a variety of methods (e.g., microarray approaches, neuroimaging, genetics, electrophysiology, and the new generation of -omics techniques). These studies will likely focus on more precise diagnoses and a personalized medicine paradigm in order to develop better treatments for those who need them most.
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, Ricardo- Early improvement of psychotic symptoms with lithium monotherapy as a predictor of later response in mania(2012) SOUSA, Rafael T. de; BUSNELLO, Joao V.; FORLENZA, Orestes V.; ZANETTI, Marcus V.; SOEIRO-DE-SOUZA, Marcio G.; BILT, Martinus T. van de; MORENO, Ricardo A.; ZARATE JR., Carlos A.; GATTAZ, Wagner F.; MACHADO-VIEIRA, RodrigoAlthough lithium has been the first line agent in the treatment of bipolar disorder (BD), few studies have evaluated lithium's efficacy in mania with psychosis and its association with later response. Furthermore, given the widespread concern about antipsychotic side effects, answering a question about whether lithium alone can manage to treat both psychotic and non-psychotic mania seems a very relevant one. The present study addresses the antipsychotic efficacy of lithium monotherapy in acute mania and early improvement of psychotic symptoms as a predictor of later response of manic symptoms. Forty-six patients presenting a manic episode (32 with psychotic features and 14 subjects without psychotic features) were treated for 4 weeks with lithium monotherapy and evaluated weekly using the Young Mania Rating Scale (YMRS). Subjects with rapid cycling, substance abuse/dependence, or mixed episodes were excluded. The overall antimanic efficacy of lithium in psychosis vs. non-psychosis groups was evaluated. In addition, early improvement of psychotic symptoms and its prediction of subsequent response (>50% decrease in total YMRS scores) or remission were evaluated. Lithium showed a similar efficacy in both psychosis and non-psychosis mania. Early improvement of psychotic symptoms was associated with clinical response and remission at endpoint.
- Major depressive disorder in breast cancer: A critical systematic review of pharmacological and psychotherapeutic clinical trials(2014) CARYALHO, Andre F.; HYPHANTIS, Thomas; SALES, Paulo Marcelo G.; SOEIRO-DE-SOUZA, Marcio G.; MACEDO, Danielle S.; CHA, Danielle S.; MCINTYRE, Roger S.; PAVLIDIS, NicholasBackground: While women with breast cancer often face varying levels of psychological distress, there is a subgroup whose symptomatology reaches a threshold for diagnosis of major depressive disorder (MDD). Major depressive disorder is known to influence patient outcomes, such as health-related quality of life and treatment adherence. There are no systematic reviews that evaluate pharmacological and psychotherapeutic treatment trials for MDD among individuals with breast cancer. Methods: Two authors independently searched MEDLINE, EMBASE, Cochrane and Clinical Trials.gov databases through February 20, 2013 without language restrictions. Core journals, reference lists and citation tracking were also searched. Articles on breast cancer patients were included if they (1) included participants with a diagnosis of MDD; (2) investigated pharmacological or psychotherapeutic treatments for MDD compared to placebo or usual care in a randomized controlled trial (RCT). Results: Two RCTs on antidepressant treatment met inclusion criteria. However, no RU's investigating the effects of psychological treatments for MDD in breast cancer were identified. Notwithstanding the paucity of data investigating the effects of psychological treatments for MDD in breast cancer, numerous psychotherapeutic strategies targeting depressive symptoms were identified. Mianserin had significant antidepressant effects when compared to placebo in a 6-week, parallel-group, RCT of Stage I-II breast cancer in women with MDD. Desipramine and paroxetine were reported to be no more efficacious than placebo in a 6-week, RU of Stage I-IV breast cancer in women with MDD. Conclusions: The evidence reviewed herein underscores the paucity of data available to guide clinicians in treatment decisions for MDD in individuals with breast cancer. Therefore, the treatment of MDD in breast cancer is primarily based on clinical experience. Some antidepressants (for example, paroxetine) should be avoided in women concurrently taking tamoxifen due to relevant interactions involving the cytochrome CYP2D6.
- Decreased AKT1/mTOR pathway mRNA expression in short-term bipolar disorder(2015) MACHADO-VIEIRA, Rodrigo; ZANETTI, Marcus V.; TEIXEIRA, Antonio L.; UNO, Miyuki; VALIENGO, Leandro L.; SOEIRO-DE-SOUZA, Marcio G.; OBA-SHINJO, Sueli M.; SOUSA, Rafael T. de; ZARATE JR., Carlos. A.; GATTAZ, Wagner F.; MARIE, Suety K. N.Strong evidence implicates intracellular signaling cascades dysfunction in the pathophysiology of Bipolar Disorder (BD). Regulation of AKT/mTOR pathway is a critical signaling pathway in synaptic neurotransmission and plasticity, also modulating cell proliferation and migration. Gene expression of the AKT/mTOR pathway was assessed in 25 BD (DSM-IV-TR criteria) unmedicated depressed individuals at baseline and after 6 weeks of lithium therapy and 31 matched healthy controls. Decreases in blood AKT/ and mTOR mRNA expression, as well as in BAD/BCL-2 expression ratio were observed in short-term BD patients during depressive episodes in comparison to healthy controls. There was no significant change in the expression of AKT1, mTOR, BCL-2, BAD and NDUFA6 after lithium therapy in the total group of BD subjects. However, the changes in AKT1 expression after lithium treatment were positively correlated with depression improvement. An integrated activity within this pathway was observed at both baseline and post-treatment. The present results support an integrated AKT/mTOR signaling pathway activity in a similar fashion to the described in previous human postmortem and rodents brain studies. Overall, the results reinforce a role for AKT1 and mTOR in the pathophysiology of BD and support the relevance of blood mRNA expression as a valid surrogate biological source to study brain intracellular signaling cascades changes and convergent molecular pathways in psychiatric disorders.
- Plasma cortisol in first episode drug-naive mania: Differential levels in euphoric versus irritable mood(2012) VALIENGO, Leandro L.; SOEIRO-DE-SOUZA, Marcio G.; MARQUES, Andrea H.; MORENO, Doris H.; JURUENA, Mario F.; ANDREAZZA, Ana Cristina; GATTAZ, Wagner F.; MACHADO-VIEIRA, RodrigoBackground: Dysregulation of HPA axis has 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-naive BD subjects during the first manic episode, as well as investigate the relationship between plasma cortisol levels and manic symptomatology. Methods: Twenty-six drug-naive 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. Limitation: Data including larger samples are lacking. Conclusion: 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 add a dimensional approach to the traditional categorical diagnosis for future neurobiological studies in BD.
- Role of quetiapine beyond its clinical efficacy in bipolar disorder: From neuroprotection to the treatment of psychiatric disorders (Review)(2015) SOEIRO-DE-SOUZA, Marcio G.; DIAS, Vasco Videira; MISSIO, Giovanni; BALANZA-MARTINEZ, Vicent; VALIENGO, Leandro; CARVALHO, Andre F.; MORENO, Ricardo AlbertoThe aim of the present review was to discuss the following aspects of treatment with quetiapine in psychiatric disorders: i) Neurocognition and functional recovery in bipolar disorder (BD); ii) neuroprotective profile in different models; and iii) potential off-label indications. A PubMed search was conducted of articles published in English between 2000 and 2012 on quetiapine, cross-referenced with the terms 'anxiety', 'attention deficit disorder', 'borderline personality disorder', 'dementia', 'insomnia', 'major depressive disorder' (MDD), 'obsessive-compulsive disorder', 'post-traumatic stress disorder', 'remission', 'cognition', 'neurobiology', 'neuroprotection', 'efficacy' and 'effectiveness'. Articles were selected from meta-analyses, randomized clinical trials and open trials, and the results were summarized. Quetiapine, when studied in off-label conditions, has shown efficacy as a monotherapy in MDD and general anxiety disorder. Quetiapine also appears to exhibit a small beneficial effect in dementia. The review of other conditions was affected by methodological limitations that precluded any definitive conclusions on the efficacy or safety of quetiapine. Overall, the present review shows evidence supporting a potential role for quetiapine in improving cognition, functional recovery and negative symptoms in a cost-effective manner in BD. These benefits of quetiapine are potentially associated with its well-described neuroprotective effects; however, further studies are clearly warranted.
- «
- 1 (current)
- 2
- 3
- »