DANIELLE SOARES BIO
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
4 resultados
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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.
conferenceObject Genetic Polymorphisms Related to Dopamine, Serotonine and BDNF Might be Specific to Particular Symptom Dimensions in Schizophrenia(2012) LOCH, Alexandre A.; BIO, Danielle S.; BILT, Martinus T. van de; PRADO, Carolina M.; ZANETTI, Marcus V.; GATTAZ, Wagner F.Background: Schizophrenia is held to be result of multiple small-effect genes and their interplay with environment. Several of these genes have been discovered, but their exact role in the disease is unclear. The objective of this study is to assess relationship between genetic polymorphisms and specific symptom dimensions in schizophrenia. Methods: Fifty-three outpatients with schizophrenia from the Institute of Psychiatry, Sao Paulo,Brazil, were selected. Psychopathology was evaluated through SCID-I, PANSS and neuropsychological assessment. Genotyping was performed by real-time PCR allelic discrimination. Polymorphisms HTR2A-T102C,-rs6314 and -rs1928042, HTR2C-rs6318 and -rs3813929, DRD3-rs6280, BDNF-rs6265 and COMT-rs4680 were analyzed. Associations between genetic polymorphisms and psychopathology were measured. Factor analysis was performed between psychopathological measures yielding symptom dimensions. Generalized linear models were conducted between these dimensions and positively related genetic polymorphisms; models were repeated including cofactor “refractoriness”. Results: HTR2C(rs6318) genotype CC(ser/ser) and DRD3 genotype CC(gly/gly) were related to worst cognition(p=0.01-0.03). DRD3 genotype TT(ser/ser) was associated with negative symptoms(p=0.04-0.05). BDNF genotype GA(val/met) and COMT genotype GG(val/val) were associated with positive symptoms(p=0.00-0.04). Factor analysis yielded 7 symptom dimensions: cognition was related to DRD3 and HTR2C-rs6318 (B=1.01,p=0.00;B=-0.92,p=0.04,respectively). Disorganization-catatonia was related to BDNF and HTR2C-rs6318 (B=-0.62,p=0.05;B=1.01,p=0.03,respectively). Paranoid-influence delusions were related to DRD3, HTR2C-rs6318 and HTR2A-rs1928042 (B=-1.03,p=0.00;B=-1.31,p=0.00;B=-1.04,p=0.04,respectively). Other delusions/hallucinations were related to DRD3, HTR2C-rs3813929 and BDNF (B=-1.1,p=0.01;B=-1.00,p=0.03;B=0.80,p=0.01,respectively). Negative symptoms were related to refractoriness (B=1.10,p=0.00). Dimensions hallucinations/bizarre delusion and tactile hallucinations did not correlate with any predictor. Conclusions: Our study proposes that genetic polymorphisms might be specific in determining certain symptom dimensions in schizophrenia, suggesting differential underlying physiopathological mechanisms for them.- 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.
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.