DANIELLE SOARES BIO
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
13 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.
- The ARIQUELI study: potentiation of quetiapine in bipolar I nonresponders with lithium versus aripiprazole(2013) MISSIO, Giovani; MORENO, Doris Hupfeld; FERNANDES, Fernando; BIO, Danielle Soares; SOEIRO-DE-SOUZA, Marcio Gehardt; SANTOS JR., Domingos Rodrigues dos; DAVID, Denise Petresco; COSTA, Luis Felipe; DEMETRIO, Frederico Navas; MORENO, Ricardo AlbertoBackground: The treatment of bipolar disorder (BD) remains a challenge due to the complexity of the disease. Current guidelines represent an effort to assist clinicians in routine practice but have several limitations, particularly concerning long-term treatment. The ARIQUELI (efficacy and tolerability of the combination of lithium or aripiprazole in young bipolar non or partial responders to quetiapine monotherapy) study aims to evaluate two different augmentation strategies for quetiapine nonresponders or partial responders in acute and maintenance phases of BD treatment. Methods/Design: The ARIQUELI study is a single-site, parallel-group, randomized, outcome assessor-blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic/hypomanic or mixed episode, aged 18 to 40 years, are eligible. After diagnostic assessments, patients initiated treatment in phase I with quetiapine. Nonresponders or partial responders after 8 weeks are allocated into one of two groups, potentiated with either lithium (0.5 to 0.8 mEq/l) or aripiprazole (10 or 15 mg). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blinded to the treatment. The primary outcome is the evaluation of changes in mean scores on the CGI-BP-M between baseline and the endpoint at the end of each study phase. Discussion: The ARIQUELI study is currently in progress, with patients undergoing acute treatment (phase I), potentiation (phase II) and maintenance (phase III). The study will be extended until January 2015. Trials comparing lithium and aripiprazole with potentiate treatment in young BD I nonresponders to quetiapine in monotherapy can provide relevant information on the safety of these drugs in clinical practice. Long-term treatment is an issue of great importance and should be evaluated further through more in-depth studies given that BD is a chronic disease.
- Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis(2013) BOURNE, C.; AYDEMIR, O.; BALANZA-MARTINEZ, V.; BORA, E.; BRISSOS, S.; CAVANAGH, J. T. O.; CLARK, L.; CUBUKCUOGLU, Z.; DIAS, V. V.; DITTMANN, S.; FERRIER, I. N.; FLECK, D. E.; FRANGOU, S.; GALLAGHER, P.; JONES, L.; KIESEPPA, T.; MARTINEZ-ARAN, A.; MELLE, I.; MOORE, P. B.; MUR, M.; PFENNIG, A.; RAUST, A.; SENTURK, V.; SIMONSEN, C.; SMITH, D. J.; BIO, D. S.; SOEIRO-DE-SOUZA, M. G.; STODDART, S. D. R.; SUNDET, K.; SZOKE, A.; THOMPSON, J. M.; TORRENT, C.; ZALLA, T.; CRADDOCK, N.; ANDREASSEN, O. A.; LEBOYER, M.; VIETA, E.; BAUER, M.; WORHUNSKY, P. D.; TZAGARAKIS, C.; ROGERS, R. D.; GEDDES, J. R.; GOODWIN, G. M.Objective: An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta-analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view. Method: Individual patient and control data were obtained from original authors for 11 measures from four common neuropsychological tests: California or Rey Verbal Learning Task (VLT), Trail Making Test (TMT), Digit Span and/or Wisconsin Card Sorting Task. Results: Impairments were found for all 11 test-measures in the bipolar group after controlling for age, IQ and gender (Ps <= 0.001, E.S. = 0.26-0.63). Residual mood symptoms confound this result but cannot account for the effect sizes found. Impairments also seem unrelated to drug treatment. Some test-measures were weakly correlated with illness severity measures suggesting that some impairments may track illness progression. Conclusion: This reanalysis supports VLT, Digit Span and TMT as robust measures of cognitive impairments in bipolar disorder patients. The heterogeneity of some test results explains previous differences in meta-analyses. Better controlling for confounds suggests deficits may be smaller than previously reported but should be tracked longitudinally across illness progression and treatment.
- Altered brain creatine cycle metabolites in bipolar I disorder with childhood abuse: A H-1 magnetic resonance spectroscopy study(2021) BIO, Danielle Soares; MORENO, Ricardo Alberto; GARCIA-OTADUY, Maria Concepcion; NERY, Fabiano; LAFER, Beny; SOEIRO-DE-SOUZA, Marcio GerhardtBackground: Childhood abuse (CA) is a risk factor for a number of psychiatric disorders and has been associated with higher risk of developing bipolar disorders (BD). CA in BD has been associated with more severe clinical outcomes, but the neurobiological explanation for this is unknown. Few studies have explored in vivo measurement of brain metabolites using proton magnetic resonance spectroscopy (1H-MRS) in CA and no studies have investigated the association of CA severity with brain neurometabolites in BD. Objective: To investigate whether CA severity is associated with changes in anterior cingulate cortex (ACC) neurometabolite profile in BD and HC subjects. Methods: Fifty-nine BD I euthymic patients and fifty-nine HC subjects were assessed using the Childhood Trauma Questionnaire (CTQ) and underwent a 3-Tesla 1H-MRS scan. Severity of childhood abuse (physical, sexual and emotional) and its association with levels of brain metabolites was analyzed within each group. Results: BD patients had higher total scores on the CTQ and higher severity rates of sexual and physical abuse compared to HC subjects. Greater severity of physical and sexual abuse was associated with increased ACC PCr level and lower Cr/PCr ratio in the BD group only. Conclusion: Sexual and physical abuse in BD patients, but not in HC subjects, appeared to be associated with creatine metabolism in the ACC, which can influence neuronal mitochondrial energy production. Further studies should investigate whether this is the mechanism underlying the association between CA and worse clinical outcomes in BD.
- Association of the COMT Met(158) allele with trait impulsivity in healthy young adults(2013) SOEIRO-DE-SOUZA, Marcio Gerhardt; STANFORD, Matthew S.; BIO, Danielle Soares; MACHADO-VIEIRA, Rodrigo; MORENO, Ricardo AlbertoDopamine (DA) is considered to be an important neurotransmitter in the control of impulsive behavior, however, its underlying mechanisms have not been fully elucidated. Catechol-O-methyltransferase (COMT) is a key enzyme in the catabolism of DA within the prefrontal cortex (PFC) and has been suggested to play a role in the mediation of impulsive behavior. The COMT single nucleotide polymorphism (SNP) rs4680 (Val(158)Met) Met allele has been shown to decrease COMT enzyme activity and is associated with improved PFC cognitive function (intelligence and executive functions). Studies have associated the rs4680 genotype with impulsivity as a symptom in attention deficit hyperactivity disorder and substance abuse. However, only a few studies have assessed the effects of rs4680 on impulsiveness in healthy subjects, the results of which remain controversial. The Barratt Impulsiveness Scale (BIS-11) was applied to 82 healthy volunteers (including 42 females) who were genotyped for COMT rs4680. Subjects carrying the Met/Met genotype scored higher for the BIS-11 second-order factor Non-planning than carriers of the Val/Val genotype. No interaction between gender*genotype was detected. Age, gender and education had no effect on the results. The COMT rs4680 Met/Met genotype was associated with higher impulsivity on the BIS-11 second-order factor Non-planning. These results suggest that COMT enzyme activity may be important in the regulation of impulsiveness among young adults. Further studies involving larger samples should be conducted to confirm the results of the present study.
- 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.
- The impact of limbic system morphology on facial emotion recognition in bipolar I disorder and healthy controls(2013) BIO, Danielle Soares; SOEIRO-DE-SOUZA, Marcio Gerhardt; OTADUY, Maria Concepcion Garcia; MACHADO-VIEIRA, Rodrigo; MORENO, Ricardo AlbertoIntroduction: Impairments in facial emotion recognition (FER) have been reported in bipolar disorder (BD) subjects during all mood states. This study aims to investigate the impact of limbic system morphology on FER scores in BD subjects and healthy controls. Material and methods: Thirty-nine euthymic BD I (type I) subjects and 40 healthy controls were subjected to a battery of FER tests and examined with 3D structural imaging of the amygdala and hippocampus. Results: The volume of these structures demonstrated a differential pattern of influence on FER scores in BD subjects and controls. In our control sample, larger left and right amygdala demonstrated to be associated to less recognition of sadness faces. In BD group, there was no impact of amygdala volume on FER but we observed a negative impact of the left hippocampus volume in the recognition of happiness while the right hippocampus volume positively impacted on the scores of happiness. Conclusion: Our results indicate that amygdala and hippocampus volumes have distinct effects on FER in BD subjects compared to controls. Knowledge of the neurobiological basis of the illness may help to provide further insights on the role of treatments and psychosocial interventions for BD. Further studies should explore how these effects of amygdala and hippocampus volumes on FER are associated with social networks and social network functioning.
- 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.
- Gender effects of the COMT Val(158)Met genotype on verbal fluency in healthy adults(2013) SOEIRO-DE-SOUZA, Marcio Gerhardt; BIO, Danielle Soares; DAVID, Denise Petresco; MISSIO, Giovani; LIMA, Bruno; FERNANDES, Fernando; MACHADO-VIEIRA, Rodrigo; MORENO, Ricardo AlbertoCognitive performance in healthy individuals is associated with gender differences in specific tests; a female advantage has been demonstrated in language tests, whereas a male advantage has been demonstrated in spatial relation examinations. The prefrontal cortex (PFC) mediates important cognitive domains and is influenced by dopamine (DA) activity. The single nucleotide polymorphism (SNP) rs4680 in the catechol-O-methyltransferase (COMT) gene results in an amino acid substitution from valine (Val) to methionine (Met). The Met allele has been demonstrated to decrease COMT enzyme activity and improve PFC cognitive function. COMT regulates DA activity in the PFC and exhibits gender effects. The aim of the present study was to investigate the gender-specific effects of the COMT genotype on cognition in healthy young adults. Seventy-six healthy subjects were genotyped for COMT rs4680 and submitted to an extensive range of neuropsychological tests assessing aspects of PFC function. The COMT Met allele influenced the performance of executive function. The results revealed gender effects of the COMT rs4680 Met allele on verbal fluency, with positive effects in males and negative effects in females. This suggested that DA activity affects cognitive function in different ways, according to gender.