ANA SOLEDADE GRAEFF MARTINS

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LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina

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Autor e Coautores FMUSP-HC Normalizados: LUIS AUGUSTO PAIM ROHDE ×

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Agora exibindo 1 - 7 de 7
  • article 16 Citação(ões) na Scopus
    An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder
    (2016) LIMA, Leandro de Araujo; FEIO-DOS-SANTOS, Ana Cecilia; BELANGERO, Sintia Iole; GADELHA, Ary; BRESSAN, Rodrigo Affonseca; SALUM, Giovanni Abrahao; PAN, Pedro Mario; MORIYAMA, Tais Silveira; GRAEFF-MARTINS, Ana Soledade; TAMANAHA, Ana Carina; ALVARENGA, Pedro; KRIEGER, Fernanda Valle; FLEITLICH-BILYK, Bacy; JACKOWSKI, Andrea Parolin; BRIETZKE, Elisa; SATO, Joao Ricardo; POLANCZYK, Guilherme Vanoni; MARI, Jair de Jesus; MANFRO, Gisele Gus; ROSARIO, Maria Conceicao do; MIGUEL, Euripedes Constantino; PUGA, Renato David; TAHIRA, Ana Carolina; SOUZA, Viviane Neri; CHILE, Thais; GOUVEIA, Gisele Rodrigues; SIMOES, Sergio Nery; CHANG, Xiao; PELLEGRINO, Renata; TIAN, Lifeng; GLESSNER, Joseph T.; HASHIMOTO, Ronaldo Fumio; ROHDE, Luis Augusto; SLEIMAN, Patrick M. A.; HAKONARSON, Hakon; BRENTANI, Helena
    Many studies have attempted to investigate the genetic susceptibility of Attention-Deficit/Hyperactivity Disorder (ADHD), but without much success. The present study aimed to analyze both single-nucleotide and copy-number variants contributing to the genetic architecture of ADHD. We generated exome data from 30 Brazilian trios with sporadic ADHD. We also analyzed a Brazilian sample of 503 children/adolescent controls from a High Risk Cohort Study for the Development of Childhood Psychiatric Disorders, and also previously published results of five CNV studies and one GWAS meta-analysis of ADHD involving children/adolescents. The results from the Brazilian trios showed that cases with de novo SNVs tend not to have de novo CNVs and vice-versa. Although the sample size is small, we could also see that various comorbidities are more frequent in cases with only inherited variants. Moreover, using only genes expressed in brain, we constructed two ""in silico"" protein-protein interaction networks, one with genes from any analysis, and other with genes with hits in two analyses. Topological and functional analyses of genes in this network uncovered genes related to synapse, cell adhesion, glutamatergic and serotoninergic pathways, both confirming findings of previous studies and capturing new genes and genetic variants in these pathways.
  • article 51 Citação(ões) na Scopus
    Mechanisms underpinning inattention and hyperactivity: neurocognitive support for ADHD dimensionality
    (2014) SALUM, G. A.; SONUGA-BARKE, E.; SERGEANT, J.; VANDEKERCKHOVE, J.; GADELHA, A.; MORIYAMA, T. S.; GRAEFF-MARTINS, A. S.; MANFRO, G. G.; POLANCZYK, G.; ROHDE, L. A. P.
    Background. Taxometric and behavioral genetic studies suggest that attention deficit hyperactivity disorder (ADHD) is best modeled as a dimension rather than a category. We extended these analyses by testing for the existence of putative ADHD-related deficits in basic information processing (BIP) and inhibitory-based executive function (IB-EF) in individuals in the subclinical and full clinical ranges. Consistent with the dimensional model, we predicted that ADHD-related deficits would be expressed across the full spectrum, with the degree of deficit linearly related to the severity of the clinical presentation. Method. A total of 1547 children (aged 6-12 years) participated in the study. The Development and Well-Being Assessment (DAWBA) was used to classify children into groups according to levels of inattention and hyperactivity independently: (1) asymptomatic, (2) subthreshold minimal, (3) subthreshold moderate and (4) clinical ADHD. Neurocognitive performance was evaluated using a two-choice reaction time task (2C-RT) and a conflict control task (CCT). BIP and IB-EF measures were derived using a diffusion model (DM) for decomposition of reaction time (RT) and error data. Results. Deficient BIP was found in subjects with minimal, moderate and full ADHD defined in terms of inattention (in both tasks) and hyperactivity/impulsivity dimensions (in the 2C-RT). The size of the deficit increased in a linear manner across increasingly severe presentations of ADHD. IB-EF was unrelated to ADHD. Conclusions. Deficits in BIP operate at subclinical and clinical levels of ADHD. The linear nature of this relationship provides support for a dimensional model of ADHD in which diagnostic thresholds are defined in terms of clinical and societal burden rather than representing discrete pathophysiological states.
  • article 138 Citação(ões) na Scopus
    High risk cohort study for psychiatric disorders in childhood: rationale, design, methods and preliminary results
    (2015) SALUM, Giovanni Abrahao; GADELHA, Ary; PAN, Pedro Mario; MORIYAMA, Tais Silveira; GRAEFF-MARTINS, Ana Soledade; TAMANAHA, Ana Carina; ALVARENGA, Pedro; KRIEGER, Fernanda Valle; FLEITLICH-BILYK, Bacy; JACKOWSKI, Andrea; SATO, Joao Ricardo; BRIETZKE, Elisa; POLANCZYK, Guilherme Vanoni; BRENTANI, Helena; MARI, Jair de Jesus; ROSARIO, Maria Conceicao Do; MANFRO, Gisele Gus; BRESSAN, Rodrigo Affonseca; MERCADANTE, Marcos Tomanik; MIGUEL, Euripedes Constantino; ROHDE, Luis Augusto
    The objective of this study is to present the rationale, methods, design and preliminary results from the High Risk Cohort Study for the Development of Childhood Psychiatric Disorders. We describe the sample selection and the components of each phases of the study, its instruments, tasks and procedures. Preliminary results are limited to the baseline phase and encompass: (i) the efficacy of the oversampling procedure used to increase the frequency of both child and family psychopathology; (ii) interrater reliability and (iii) the role of differential participation rate. A total of 9937 children from 57 schools participated in the screening procedures. From those 2512 (random =958; high risk =1554) were further evaluated with diagnostic instruments. The prevalence of any child mental disorder in the random strata and high-risk strata was 19.9% and 29.7%. The oversampling procedure was successful in selecting a sample with higher family rates of any mental disorders according to diagnostic instruments. Interrater reliability (kappa) for the main diagnostic instrument range from 0.72 (hyperkinetic disorders) to 0.84 (emotional disorders). The screening instrument was successful in selecting a sub-sample with high risk for developing mental disorders. This study may help advance the field of child psychiatry and ultimately provide useful clinical information.
  • conferenceObject
    Dimensional approach to bipolar symptoms in childhood and early adolescence
    (2012) PAN, Pedro Mario; GADELHA, Ary; MORIYAMA, Tais; COGO-MOREIRA, Hugo; SALUM, Giovanni Abrahao; GRAEFF-MARTINS, Ana Soledade; ALVARENGA, Pedro; BRIETZKE, Elisa; BERNARDES, Thomas; ROHDE, Luis Augusto; MIGUEL, Euripedes Constantino; BRESSAN, Rodrigo A.
  • article 0 Citação(ões) na Scopus
    An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder (vol 6, 22851, 2016)
    (2016) LIMA, Leandro de Araujo; FEIO-DOS-SANTOS, Ana Cecilia; BELANGERO, Sintia Iole; GADELHA, Ary; BRESSAN, Rodrigo Affonseca; SALUM, Giovanni Abrahao; PAN, Pedro Mario; MORIYAMA, Tais Silveira; GRAEFF-MARTINS, Ana Soledade; TAMANAHA, Ana Carina; ALVARENGA, Pedro; KRIEGER, Fernanda Valle; FLEITLICH-BILYK, Bacy; JACKOWSKI, Andrea Parolin; BRIETZKE, Elisa; SATO, Joao Ricardo; POLANCZYK, Guilherme Vanoni; MARI, Jair de Jesus; MANFRO, Gisele Gus; ROSARIO, Maria Conceiao do; MIGUEL, Euripedes Constantino; PUGA, Renato David; TAHIRA, Ana Carolina; SOUZA, Viviane Neri; CHILE, Thais; GOUVEIA, Gisele Rodrigues; SIMOES, Sergio Nery; CHANG, Xiao; PELLEGRINO, Renata; TIAN, Lifeng; GLESSNER, Joseph T.; HASHIMOTO, Ronaldo Fumio; ROHDE, Luis Augusto; SLEIMAN, Patrick M. A.; HAKONARSON, Hakon; BRENTANI, Helena
  • article 32 Citação(ões) na Scopus
    Developments and challenges in the diagnosis and treatment of ADHD
    (2013) DIAS, Taciana G. Costa; KIELING, Christian; GRAEFF-MARTINS, Ana Soledade; MORIYAMA, Tais S.; ROHDE, Luis A.; POLANCZYK, Guilherme V.
    Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, often associated with other psychiatric comorbidities, functional impairments, and poor long-term outcomes. The objective of this selected review is to describe current advances and challenges in the diagnosis and treatment of ADHD. The disorder is associated with neurobiological underpinnings and is highly heterogeneous in various aspects, such as symptom profiles, cognitive impairments, and neurobiological and genetic features. The efficacy and safety of short-term pharmacological treatments across the life cycle is well studied, but further research investigating long-term treatment, impact of treatment in preschoolers, and non-pharmacological interventions is needed. Future research is also needed to better characterize the neurodevelopmental pathways of the disorder, linking clinical and neurobiological information, less investigated populations, and new interventions.
  • article 52 Citação(ões) na Scopus
    Specificity of basic information processing and inhibitory control in attention deficit hyperactivity disorder
    (2014) SALUM, G. A.; SERGEANT, J.; SONUGA-BARKE, E.J.S.; VANDEKERCKHOVE, J.; GADELHA, A.; PAN, P. M.; MORIYAMA, T. S.; GRAEFF-MARTINS, A. S.; ALVARENGA, P. Gomes de; ROSARIO, M. C. do; MANFRO, G. G.; POLANCZYK, G.; ROHDE, L. A. P.
    Background Both inhibitory-based executive functioning (IB-EF) and basic information processing (BIP) deficits are found in clinic-referred attention deficit hyperactivity disorder (ADHD) samples. However, it remains to be determined whether: (1) such deficits occur in non-referred samples of ADHD; (2) they are specific to ADHD; (3) the co-morbidity between ADHD and oppositional defiant disorder/conduct disorder (ODD/CD) has additive or interactive effects; and (4) IB-EF deficits are primary in ADHD or are due to BIP deficits. Method We assessed 704 subjects (age 6-12 years) from a non-referred sample using the Development and Well-Being Assessment (DAWBA) and classified them into five groups: typical developing controls (TDC; n=378), Fear disorders (n=90), Distress disorders (n=57), ADHD (n=100), ODD/CD (n=40) and ADHD+ODD/CD (n=39). We evaluated neurocognitive performance with a Two-Choice Reaction Time Task (2C-RT), a Conflict Control Task (CCT) and a Go/No-Go (GNG) task. We used a diffusion model (DM) to decompose BIP into processing efficiency, speed-accuracy trade-off and encoding/motor function along with variability parameters. Results Poorer processing efficiency was found to be specific to ADHD. Faster encoding/motor function differentiated ADHD from TDC and from fear/distress whereas a more cautious (not impulsive) response style differentiated ADHD from both TDC and ODD/CD. The co-morbidity between ADHD and ODD/CD reflected only additive effects. All ADHD-related IB-EF classical effects were fully moderated by deficits in BIP. Conclusions Our findings challenge the IB-EF hypothesis for ADHD and underscore the importance of processing efficiency as the key specific mechanism for ADHD pathophysiology.