DANIELLE SOARES BIO
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
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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 Met (158) modulates facial emotion recognition in bipolar I disorder mood episodes(2012) SOEIRO-DE-SOUZA, Marcio Gerhardt; BIO, Danielle Soares; DAVID, Denise Petresco; SANTOS JR., Domingos Rodrigues dos; KERR, Daniel Shikanai; GATTAZ, Wagner Farid; MACHADO-VIEIRA, Rodrigo; MORENO, Ricardo AlbetoBackground: One of the many cognitive deficits reported in bipolar disorder (BD) patients is facial emotion recognition (FER), which has recently been associated with dopaminergic catabolism. Catechol-O-methyltransferase (COMT) is one of the main enzymes involved in the metabolic degradation of dopamine (DA) in the prefrontal cortex (PFC). The COMT gene polymorphism rs4680 (Val(158)Met) Met allele is associated with decreased activity of this enzyme in healthy controls. The objective of this study was to evaluate the influence of Val(158)Met on FER during manic and depressive episodes in BD patients and in healthy controls. Materials and methods: 64 BD type I patients (39 in manic and 25 in depressive episodes) and 75 healthy controls were genotyped for COMT rs4680 and assessed for FER using the Ekman 60 Faces (EK60) and Emotion Hexagon (Hx) tests. Results: Bipolar manic patients carrying the Met allele recognized fewer surprised faces, while depressed patients with the Met allele recognized fewer ""angry"" and ""happy"" faces. Healthy homozygous subjects with the Met allele had higher FER scores on the Hx total score, as well as on ""disgust"" and ""angry"" faces than other genotypes. Conclusion: This is the first study suggesting that COMT rs4680 modulates FER differently during BD episodes and in healthy controls. This provides evidence that PFC DA is part of the neurobiological mechanisms of social cognition. Further studies on other COMT polymorphisms that include euthymic BD patients are warranted. ClinicalTrials.gov Identifier: NCT00969.
conferenceObject COMT allele (Met(158)) modulates facial emotion recognition in bipolar disorder I mood episodes and in healthy controls(2012) BIO, D. S.; SOEIRO-DE-SOUZA, M. G.; MORENO, D. H.; MORENO, R. A.Background: One of the many cognitive deficits reported in Bipolar Disorder (BD) patients is facial emotion recognition (FER), which has recently been associated with dopaminergic catabolism. Catechol-O-methyltransferase (COMT) is one of the main enzymes involved in the metabolic degradation of dopamine (DA) in the prefrontal cortex (PFC). The COMT gene polymorphism rs4680 (Val 158 Met) Met allele is associated with decreased activity of this enzyme in healthy controls. The objective of this study was to evaluate the influence of Val158 Met on FER during manic and depressive episodes in BDI patients and in healthy controls. Materials & Methods: 64 BD type I patients (39 in manic and 25 in depressive episodes) and 75 healthy controls were genotyped for COMT rs4680 and assessed for FER using the Ekman 60 Faces (EK60) and Emotion Hexagon (Hx) tests. Results: Bipolar manic patients carrying the Met allele recognized fewer surprised faces, while depressed patients with the Met allele recognized fewer angry and happy faces. Healthy homozygous subjects with the COMT Met allele had higher FER scores on the Hx total score, as well as on disgust and angry faces than other genotypes. Conclusion: This is the first study suggesting that COMT rs4680 modulates FER differently during BD episodes and in healthy controls. This provides evidence that PFC DA is part of the neurobiological mechanisms of social cognition. DA receptor stimulation alterations during BD mood episodes might explain the contrasting results found in BD compared to controls. Further studies on other COMT polymorphisms that include euthymic BD patients are warranted.- The impact of the CACNA1C risk allele on limbic structures and facial emotions recognition in bipolar disorder subjects and healthy controls(2012) SOEIRO-DE-SOUZA, Marcio Gerhardt; OTADUY, Maria Concepcion Garcia; DIAS, Carolina Zadres; BIO, Danielle S.; MACHADO-VIEIRA, Rodrigo; MORENO, Ricardo AlbertoIntroduction: Impairments in facial emotion recognition (PER) have been reported in bipolar disorder (BD) during all mood states. FER has been the focus of functional magnetic resonance imaging studies evaluating differential activation of limbic regions. Recently, the alpha 1-C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene has been described as a risk gene for BD and its Met allele found to increase CACNA1C mRNA expression. In healthy controls, the CACNA1C risk (Met) allele has been reported to increase limbic system activation during emotional stimuli and also to impact on cognitive function. The aim of this study was to investigate the impact of CACNA1C genotype on FER scores and limbic system morphology in subjects with BD and healthy controls. Material and methods: Thirty-nine euthymic BD I subjects and 40 healthy controls were submitted to a PER recognition test battery and genotyped for CACNA1C. Subjects were also examined with a 3D 3-Tesla structural imaging protocol. Results: The CACNA1C risk allele for BD was associated to FER impairment in BD, while in controls nothing was observed. The CACNA1C genotype did not impact on amygdala or hippocampus volume neither in BD nor controls. Limitations: Sample size. Conclusion: The present findings suggest that a polymorphism in calcium channels interferes FER phenotype exclusively in BD and doesn't interfere on limbic structures morphology.
- 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.- Burden of maternal bipolar disorder on at-risk offspring: A controlled study on family planning and maternal care(2012) MORENO, Doris Hupfeld; BIO, Danielle Soares; PETRESCO, Sandra; PETRESCO, Denise; GUTT, Elisa Kijner; SOEIRO-DE-SOUZA, Marcio Gerhardt; MORENO, Ricardo AlbertoIntroduction: Bipolar disorder (BD) is a highly incapacitating disease typically associated with high rates of familial dysfunction. Despite recent literature suggesting that maternal care is an important environmental factor in the development of behavioral disorders, it is unclear how much maternal care is dysfunctional in BD subjects. Objective: The objective of this study was to characterize maternal care in DSM-IV/SCID diagnosed BD type I subjects compared to healthy controls with (PD) and without (NPD) other psychiatric diagnoses. Materials and methods: Thirty-four BD mothers and 106 controls underwent an interview about family planning and maternal care, obstetrical complications, and mother-child interactions. K-SADS-PL questions about violence exposure were used to ascertain domestic violence and physical/sexual abuse. Results: BD mothers were less likely to have stable unions (45.5%; p < 0.01) or to live with the biological father of their children (33.3%; p < 0.01), but had higher educational level and higher rates of social security use/retirement. They also had fewer children and used less contraceptive methods than controls. Children of BD women had higher rates of neonatal anoxia, and reported more physical abuse (16.1%; p = 0.02) than offspring of NPD mothers. Due to BD mothers' symptoms, 33.3% of offspring suffered physical and/or psychological abuse. Limitations: Post hoc analysis, and the use of questions as a surrogate of symptoms as opposed to validated instruments. Conclusion: This is one of few reports confirming that maternal care given by BD women is dysfunctional. BD psychopathology can lead to poor maternal care and both should be considered important environmental risk factors in BD, suggesting that BD psychoeducation should include maternal care orientation.