RAFAEL AUGUSTO TEIXEIRA DE SOUSA
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
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- Epistasis between COMT Val(158)Met and DRD3 Ser(9)Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission(2015) LOCH, Alexandre A.; BILT, Martinus T. van de; BIO, Danielle S.; PRADO, Carolina M. do; SOUSA, Rafael T. de; VALIENGO, Leandro L.; MORENO, Ricardo A.; ZANETTI, Marcus V.; GATTAZ, Wagner F.Objective: To assess the relationship between cognitive function, a proposed schizophrenia endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl transferase (COMT) Val(158)Met and dopamine receptor 3 (DRD3) Ser(9)Gly. Methods: Fifty-eight outpatients with schizophrenia/schizoaffective disorder and 88 healthy controls underwent neurocognitive testing and genotyping. Analyses of covariance (ANCOVAs) using age, sex, and years of education as covariates compared cognitive performance for the proposed genotypes in patients and controls. ANCOVAs also tested for the epistatic effect of COMT and DRD3 genotype combinations on cognitive performance. Results: For executive functioning, COMT Val/Val patients performed in a similar range as controls (30.70-33.26 vs. 35.53-35.67), but as COMT Met allele frequency increased, executive functioning worsened. COMT Met/Met patients carrying the DRD3 Ser/Ser genotype performed poorest (16.184 vs. 27.388-31.824). Scores of carriers of this COMT/DRD3 combination significantly differed from all DRD3 Gly/Gly combinations (p < 0.05), from COMT Val/Met DRD3 Ser/Gly (p = 0.02), and from COMT Val/Val DRD3 Ser/Ser (p = 0.01) in patients. It also differed significantly from all control scores (p < 0.001). Conclusion: Combined genetic polymorphisms related to dopamine neurotransmission might influence executive function in schizophrenia. Looking at the effects of multiple genes on a single disease trait (epistasis) provides a comprehensive and more reliable way to determine genetic effects on endophenotypes.
- Formal Thought Disorder and language impairment in schizophrenia(2013) RADANOVIC, Marcia; SOUSA, Rafael T. de; VALIENGO, Leandro L.; GATTAZ, Wagner Farid; FORLENZA, Orestes VicenteSchizophrenia is a psychiatric illness in which disorders of thought content are a prominent feature. The disruption of normal flow of thought, or ""Formal Thought Disorder"" (FTD), has been traditionally assessed through the content and form of patients' speech, and speech abnormalities in schizophrenia were considered as a by-product of the disruption in conceptual structures and associative processes related to psychosis. This view has been changed due to increasing evidence that language per se is impaired in schizophrenia, especially its semantic, discursive, and pragmatic aspects. Schizophrenia is currently considered by some authors as a ""language related human specific disease"" or ""logopathy"", and the neuroanatomical and genetic correlates of the language impairment in these patients are under investigation. Such efforts may lead to a better understanding about the pathophysiology of this devastating mental disease. We present some current concepts related to FTD as opposed to primary neurolinguistic abnormalities in schizophrenia.
- Antidepressant Efficacy of Adjunctive Aerobic Activity and Associated Biomarkers in Major Depression: A 4-Week, Randomized, Single-Blind, Controlled Clinical Trial(2016) SIQUEIRA, Cristiana Carvalho; VALIENGO, Leandro L.; CARVALHO, Andre F.; SANTOS-SILVA, Paulo Roberto; MISSIO, Giovani; SOUSA, Rafael T. de; NATALE, Georgia Di; GATTAZ, Wagner F.; MORENO, Ricardo Alberto; MACHADO-VIEIRA, RodrigoBackground Major depressive disorder (MDD) is a highly prevalent, heterogeneous and systemic medical condition. Treatment options are limited, and recent studies have suggested that physical exercise can play an important role in the therapeutics of MDD. The aim of this study was to evaluate the antidepressant efficacy of adjunctive aerobic activity in association with pharmacotherapy (selective serotonin reuptake inhibitor) in symptomatic MDD as well as its association with physiological biomarkers. Methods In this randomized, single-blind, add-on, controlled clinical trial, 57 patients (18-55 years of age) were followed-up for 28 days. All patients were drug-free, had been diagnosed with symptomatic MDD and received flexible dose of sertraline during the trial. Patients were randomized to either a 4-week program (4x/week) of add-on aerobic exercise (exercise group, N = 29) or no activity (control group, N = 28). Depression severity was assessed using the Hamilton Rating Scale for Depression (HAM-D) as the primary outcome. At baseline and endpoint, all patients underwent a comprehensive metabolic/cardiopulmonary exercise testing-including determination of maximal oxygen uptake (VO(2)max), VO2 at the second ventilatory threshold (VO2-VT2), and oxygen pulse (O-2 pulse). Results Depression scores significantly decreased in both groups after intervention. Importantly, patients in the aerobic exercise group required lower sertraline dose compared to the control group (sertraline monotherapy). The VO(2)max and O-2 pulse parameters increased over time only in the exercise group and remained unchanged in the control group. Conclusions The present findings suggest that a 4-week training of aerobic exercise significantly improves functional capacity in patients with MDD and may be associated with antidepressant efficacy. This approach may also decrease the need for higher doses of antidepressants to achieve response. Further studies in unmedicated and treatment-resistant MDD patients are needed in order to confirm the utility of short-term aerobic exercise as an alternative therapeutic approach in MDD.