CAROLINA MARTINS DO PRADO
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
6 resultados
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Agora exibindo 1 - 6 de 6
- Does BDNF genotype influence creative output in bipolar I manic patients?(2012) SOEIRO-DE-SOUZA, Marcio Gerhardt; POST, Robert M.; SOUSA, Mario Lucio de; MISSIO, Giovani; PRADO, Carolina Martins do; GATTAZ, Wagner F.; MORENO, Ricardo A.; MACHADO-VIEIRA, RodrigoIntroduction: Creativity is a complex human ability influenced by affective and cognitive components but little is known about its underlying neurobiology. Bipolar Disorder (BD) is highly prevalent among creative individuals. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophic factor, and has been implicated in the pathophysiology of BD. In contrast to the better functioning of the BDNF polymorphism (Val(66)Met) Val allele, the Met allele decreases BDNF transport and has been associated with worsened performance on several cognitive domains in euthymic BD subjects and controls. We hypothesized that the Val allele is associated with increased creativity in bipolar disorder. Materials and methods: Sixty-six subjects with BD (41 in manic and 25 in depressive episodes) and 78 healthy volunteers were genotyped for BDNF Val(66)Met and tested for creativity using the Barrow Welsh Art Scale (BWAS) and neuropsychological tests. Results: Manic patients with the Val allele (Met-) had higher BWAS scores than Met+ carriers. This relationship was not observed among patients in depressive episodes or among control subjects. BDNF Met allele status showed no association with cognitive function in any of the groups. Conclusion: As postulated, these findings suggest that the better functioning allele of BDNF may selectively facilitate creative thinking in subjects with manic episodes, but not in controls or depressives. Further studies exploring the role of BDNF in the neurobiology of creativity in BD and in euthymic phases are warranted.
conferenceObject Clinical Use of Genetic Polymorphisms as Markers of Refractoriness in Schizophrenia(2012) BILL, Martinus T. van de; PRADO, Carolina M.; OJOPI, Elida P. B.; LOCH, Alexandre A.; ZANETTI, Marcus V.; SOUSA, Rafael A. T.; MACHADO-VIEIRA, Rodrigo; GATTAZ, Wagner F.Background: Pharmacogenetics studies have demonstrated the importance of various neurotransmitter systems in mediating drug effectiveness. Due to the importance of the dopaminergic system in the activity of antipsychotics, proteins that regulate the availability of dopamine may influence the response to drug treatment, as the enzyme catechol-O-methyl-transferase (COMT), which catalyzes the breakdown of dopamine. Some associations have already been described between Val108/158Met polymorphism and response, with individuals carrying the Met allele presenting the best answer. However, most of the findings reported have not been universally replicated. Methods: The study enrolled 89 schizophrenia patients divided in two groups: 59 refractory patients according to IPAP algorithm (International Psychopharmacology Algorithm Project) and 30 non-refractory patients. Polymorphisms in COMT (rs4680), HTR2A (T102C, rs6314, rs1928042), HTR2C (rs6318, rs3813929), CHRNA7(rs7164043), BDNF (rs6265), DRD3 (rs6280) and GRM8 (rs7778604) genes were evaluated by allelic discrimination using the TaqMan® system. Results: regarding the polymorphism rs4680 (Val158Met) of the COMT gene, among the non-refractory patients we found 7% AA, 50% AG and 43% GG genotypes. Among refractory patients we found 20% AA, 59% AG and 21% GG. After the X2 test, we found a difference in the genotype distribution between the two groups (p=0.043). For the other polymorphisms in genes HTR2A, HTR2C, CHRNA7, BDNF, DRD3, and GRM8, no significant difference was found. Conclusions: Our findings do not confirm previous data. In our study there is a higher prevalence of individuals homozygous for Met in the refractory group and a higher prevalence of individuals homozygous for Val the non-refractory (p=0.043).- COMT polymorphisms as predictors of cognitive dysfunction during manic and mixed episodes in bipolar I disorder(2012) SOEIRO-DE-SOUZA, Marcio Gerhardt; MACHADO-VIEIRA, Rodrigo; BIO, Danielle Soares; PRADO, Carolina Martins Do; MORENO, Ricardo AlbertoObjective: The dopaminergic system plays an important role in the prefrontal cortex (PFC) and is believed to mediate cognitive dysfunction (CD) in bipolar disorder (BD). The enzyme catechol-O-methyltransferase (COMT) is involved in the catabolism of dopamine in the PFC, and an association between COMT single nucleotide polymorphisms (SNPs) and BD has been reported. COMT SNPs have also been associated with executive and working memory performance in healthy subjects, patients with schizophrenia, and euthymic BD patients. The objective of this study was to investigate the association between COMT SNPs and acute CD during BD mood episodes. Methods: Seventy-two symptomatic, medication-free subjects with bipolar I disorder (BD-I) and 76 healthy controls were evaluated using neuropsychological tests, and genotyped for COMT SNPs rs4680 and rs165599. Results: Patients undergoing mania and mixed episodes carrying the COMT allele G had better performance on executive function, memory, verbal fluency, and intelligence tests. Moreover, an interaction was detected between the COMT allele G and the Young Mania Rating Scale in BD CD. Conclusions: Allele G from COMT SNPs rs4680 and rs165599 may represent reliable state-dependent predictors of global CD during manic and mixed episodes in BD. Further studies in larger samples are necessary to confirm these findings.
- Association study between COMT (158)Met and creativity scores in bipolar disorder and healthy controls(2014) SOEIRO-DE-SOUZA, Marcio Gerhardt; POST, Robert; MACHADO-VIEIRA, Rodrigo; PRADO, Carolina Martins do; MORENO, Ricardo Alberto; AKISKAL, Hagop; AKISKAL, Kareen K.Background: Bipolar disorder (BD) patients have been reported to be associated higher creativity abilities, and recent data tend to support the hypothesis that dopaminergic system that could be associated with creativity. Catechol-O-methyltransferase (COMT) is one of the major enzymes involved in the metabolic degradation of dopamine. The COMT gene polymorphism (rs4680 or Val(158)Met) Met allele is reported to cause decreased activity of this enzyme in prefrontal cortex and improve performance in several cognitive domains. Objective: The objective of this study was to evaluate the influence of Val(158)Met on creativity in BD type I and healthy controls. Methods: Ninety-seven healthy volunteers and 120 BD type I were genotyped for COMT rs4680 and tested for creativity (Barrow Welsh Art Scale - BWAS) and intelligence Wechsler Abbreviated Scale of Intelligence (WASI). Results: COMT Met allele positively influenced creativity scores in healthy controls but not in BD subjects during mood episodes and euthymia. The presence of allele Met did not influence IQ scores. No influence of IQ total score on creativity was observed. Limitations: control group presented higher IQ scores and euthymic group was under medication use. Discussion: Our research suggests positive effect of COMT rs4680 (allele Met) on creativity scores in healthy controls. One possible interpretation is that creativity is more likely to be associated with lesser degrees of bipolarity. The fact that the same results were not observed in BD may be associated to dysfunctions in the dopaminergic system that characterizes this disorder. Further studies with larger samples and other types of BD should explore the role of the dopaminergic system in creativity.
conferenceObject COMT polymorphisms as predictors of cognitive dysfunction during manic and mixed episodes in bipolar I disorder(2012) SOEIRO-DE-SOUZA, M. G.; MACHADO-VIEIRA, R.; BIO, D. S.; PRADO, C. M. Do; MORENO, R. A.Introduction: The dopaminergic system plays an important role in prefrontal cortex (PFC) and is believed to mediate cognitive dysfunction (CD) in Bipolar Disorder (BD). The enzyme catechol- O-methyltransferase (COMT) is involved in the catabolism of dopamine in the PFC, and an association between COMT single nucleotide polymorphisms (snp) and BD has been reported. Also, COMT snp have been associated with executive and working memory performance in healthy subjects, schizophrenics and euthymic BD patients. Materials & Methods: Sixty-two symptomatic, medication-free Bipolar I Disorder patients and 72 healthy controls were evaluated using neuropsychological tests, and genotyped for COMT snp rs4680 and 165599. Results: Patients undergoing mania and mixed episodes carrying allele G of rs4680 or rs165599 had better performance on executive function, memory and intelligence tests. Conclusion: This is the first study that reports a genetic explanation to why cognitive dysfunction varies in BD episodes. Allele G from COMT snp rs4680 and rs165599 may represent reliable state- dependent predictors of global cognitive dysfunction during manic and mixed episodes in Bipolar I Disorder. Further studies in larger samples are necessary to confirm these findings.conferenceObject Refractoriness in Schizophrenia is not Associated with Cyp2d6 and Cyp2c19 Genotypes(2012) BILT, Martinus T. van de; PRADO, Carolina M.; OJOPI, Elida P. B.; ZANETTI, Marcus V.; LOCH, Alexandre A.; SOUSA, Rafael A. T.; MACHADO-VIEIRA, Rodrigo; GATTAZ, Wagner F.Background: All genes that encode the CYP450 enzymes are highly polymorphic, leading to different metabolic profiles. While for antidepressants it’s possible to make dose adjustments based on the CYP2D6 and CYP2C19 genotypes, there are currently no evidences validating genotype based adjustments for antipsychotics. Therefore, we aimed to investigate the hypothesis that the prevalence of ultra-rapid metabolizers of neuroleptics would be increased among refractory schizophrenia patients. Methods: 89 schizophrenia patients were enrolled and divided in two groups: 59 refractory patients according to IPAP algorithm (International Psychopharmacology Algorithm Project) and 30 non-refractory patients. Polymorphisms in CYP2D6 and CYP2C19 genes were evaluated by allelic discrimination using the TaqMan® system. The following alleles were investigated: CYP2D6*1, *2, *3, *4, *5, *6, *9, *10, *15, *17, *29, *35, *39, *40, *41 beyond copy number variations and alleles CYP2C19*1, *2, *3 and *17. The phenotypes were classified in extensive metabolizers (EMs), poor metabolizers (PMs), intermediary metabolizers (IMs) and ultra-rapid metabolizers (UMs). Results: The distribution of the CYP2D6 and CYP2C19 phenotypes were as follows: CYP2D6: - Non-refractory: 13.3%PM + IM, 86.6%EM and 0.0% UM - Refractory: 13.5%PM + IM, 86.4%EM and 0.0%UM CYP2C19: - Non-refractory: 16.6%PM + IM, 53.3%EM and 30.0% UM - Refractory: 27.1%PM + IM, 40.6%EM and 32.2%UM Statistical analysis showed no significant difference between the distribution of the CYP2D6 phenotypes (p=0.244) and CYP2C19 predicted phenotypes (p = 0.755) among the two groups. Conclusions: Our findings do not reinforce the inclusion of genotyping of these genes as a tool in the clinical decision making in refractory schizophrenia.