EURIPEDES CONSTANTINO MIGUEL FILHO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Psiquiatria, Faculdade de Medicina - Docente
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina - Líder
58 resultados
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- Population neuroscience: challenges and opportunities for psychiatric research in low- and middle-income countries(2020) CIRILLO, Alessandra; DINIZ, Elton; GADELHA, Ary; ASEVEDO, Elson; AXELRUD, Luiza K.; MIGUEL, Euripedes C.; ROHDE, Luis Augusto; BRESSAN, Rodrigo A.; PAN, Pedro; MARI, Jair de J.Objective: Population neuroscience is an emerging field that combines epidemiology and neuroscience to study how genes and the environment shape typical and atypical brain functioning. The objective of this study was to review key studies on population neuroscience from low- and middle-income countries (LMICs) and to identify potential gaps vis-a-vis studies conducted in high-income countries. Methods: We conducted a systematic review to search for longitudinal cohort studies investigating the development of psychiatric disorders in children and adolescents in LMICs. We performed an electronic search in the EMBASE and MEDLINE databases from inception to July 5th, 2019. Results: We found six cohorts from four countries that met our search criteria: three cohorts from Brazil, one from China, one from South Africa, and one from Mauritius. Relevant examples of findings from these studies are reported. Conclusion: Our results demonstrate the impact of the valuable science output these cohort designs promote, allowing LMICs to have a share in frontline global psychiatry research. National and international funding agencies should invest in LMIC population neuroscience in order to promote replication and generalization of research from high-income countries.
- Gene expression changes associated with trajectories of psychopathology in a longitudinal cohort of children and adolescents(2020) OTA, Vanessa Kiyomi; SANTORO, Marcos Leite; SPINDOLA, Leticia Maria; PAN, Pedro Mario; SIMABUCURO, Andressa; XAVIER, Gabriela; VIEIRA-FONSECA, Tamiris; ZANARDO, Evelin Aline; SANTOS, Felipe Rodolfo Camargo dos; SCHAFER, Julia Luiza; KULIKOWSKI, Leslie Domenici; GALANTE, Pedro A. F.; ASPRINO, Paula Fontes; BRIETZKE, Elisa; GRASSI-OLIVEIRA, Rodrigo; ROHDE, Luis Augusto; MIGUEL, Euripedes Constantino; GADELHA, Ary; MARI, Jair Jesus; BRESSAN, Rodrigo Affonseca; SALUM, Giovanni Abrahao; BELANGERO, Sintia IoleWe aimed to identify blood gene expression patterns associated to psychopathological trajectories retrieved from a large community, focusing on the emergence and remission of general psychiatric symptoms. Hundred and three individuals from the Brazilian High-Risk Cohort Study (BHRCS) for mental disorders were classified in four groups according to Child Behavior Checklist (CBCL) total score at the baseline (w0) and after 3 years (w1): low-high (L-H) (N = 27), high-low (H-L) (N = 12), high-high (H-H) (N = 34) and low-low (L-L) groups (N = 30). Blood gene expression profile was measured using Illumina HT-12 Beadchips, and paired analyses comparing w0 and w1 were performed for each group. Results: 98 transcripts were differentially expressed comparing w0 and w1 in the L-H, 33 in the H-L, 177 in the H-H and 273 in the L-L. Of these, 66 transcripts were differentially expressed exclusively in the L-H; and 6 only in the H-L. Cross-Lagged Panel Models analyses revealed that RPRD2 gene expression at w1 might be influenced by the CBCL score at w0. Moreover, COX5B, SEC62, and NDUFA2 were validated with another technique and were also differentially regulated in postmortem brain of subjects with mental disorders, indicating that they might be important not only to specific disorders, but also to general psychopathology and symptoms trajectories. Whereas genes related to metabolic pathways seem to be associated with the emergence of psychiatric symptoms, mitochondrial inner membrane genes might be important over the course of normal development. These results suggest that changes in gene expression can be detected in blood in different psychopathological trajectories.
- 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, HelenaMany 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.
- DNA METHYLATION ASSOCIATED TO PSYCHOPATHOLOGY IN CHILDREN AND ADOLESCENTS: DETECTING DIFFERENTIALLY METHYLATED REGIONS(2019) SPINDOLA, Leticia; SANTORO, Marcos; PAN, Pedro; TALARICO, Fernanda; CARVALHO, Carolina Muniz; SALUM JUNIOR, Giovanni; ROHDE, Luis Augusto; MIGUEL, Euripedes Constantino; MARCH, Michael; SLEIMAN, Patrick; PELLEGRINO, Renata; BRESSAN, Rodrigo; OTA, Vanessa; HAKONARSON, Hakon; BELANGERO, Sintia
- Positive Attributes Buffer the Negative Associations Between Low Intelligence and High Psychopathology With Educational Outcomes(2016) HOFFMANN, Mauricio Scope; LEIBENLUFT, Ellen; STRINGARIS, Argyris; LAPORTE, Paola Paganella; PAN, Pedro Mario; GADELHA, Ary; MANFRO, Gisele Gus; MIGUEL, Euripedes Constantino; ROHDE, Luis Augusto; SALUM, Giovanni AbrahaoObjective: This study examines the extent to which children's positive attributes are distinct from psychopathology. We also investigate whether positive attributes change or ""buffer"" the impact of low intelligence and high psychopathology on negative educational outcomes. Method: In a community sample of 2,240 children (6-14 years of age), we investigated associations among positive attributes, psychopathology, intelligence, and negative educational outcomes. Negative educational outcomes were operationalized as learning problems and poor academic performance. We tested the discriminant validity of psychopathology versus positive attributes using confirmatory factor analysis (CFA) and propensity score matching analysis (PSM), and used generalized estimating equations (GEE) models to test main effects and interactions among predictors of educational outcomes. Results: According to both CFA and PSM, positive attributes and psychiatric symptoms were distinct constructs. Positive attributes were associated with lower levels of negative educational outcomes, independent of intelligence and psychopathology. Positive attributes buffer the negative effects of lower intelligence on learning problems, and higher psychopathology on poor academic performance. Conclusion: Children's positive attributes are associated with lower levels of negative school outcomes. Positive attributes act both independently and by modifying the negative effects of low intelligence and high psychiatric symptoms on educational outcomes. Subsequent research should test interventions designed to foster the development of positive attributes in children at high risk for educational problems.
- Long-term stability of the cortical volumetric profile and the functional human connectome throughout childhood and adolescence(2021) SATO, Joao Ricardo; BIAZOLI, Claudinei Eduardo; ZUGMAN, Andre; PAN, Pedro Mario; BUENO, Ana Paula Arantes; MOURA, Luciana Monteiro; GADELHA, Ary; PICON, Felipe Almeida; JR, Edson Amaro; SALUM, Giovanni Abrahao; MIGUEL, Euripedes Constantino; ROHDE, Luis Augusto; BRESSAN, Rodrigo Affonseca; JACKOWSKI, Andrea ParolinThere is compelling evidence showing that between-subject variability in several functional and structural brain features is sufficient for unique identification in adults. However, individuation of brain functional connectomes depends on the stabilization of neurodevelopmental processes during childhood and adolescence. Here, we aimed to (1) evaluate the intra-subject functional connectome stability over time for the whole brain and for large scale functional networks and (2) determine the long-term identification accuracy or 'fingerprinting' for the cortical volumetric profile and the functional connectome. For these purposes, we analysed a longitudinal cohort of 239 children and adolescents scanned in two sessions with an interval of approximately 3 years (age range 6-15 years at baseline and 9-18 years at follow-up). Corroborating previous results using short between-scan intervals in children and adolescents, we observed a moderate identification accuracy (38%) for the whole functional profile. In contrast, identification accuracy using cortical volumetric profile was 95%. Among the large-scale networks, the default-mode (26.8%), the frontoparietal (23.4%) and the dorsal-attention (27.6%) networks were the most discriminative. Our results provide further evidence for a protracted development of specific individual structural and functional connectivity profiles.
- Relationships between childhood maltreatment, impairment in executive functions and disruptive behavior disorders in a community sample of children(2020) BERNARDES, Elisa Teixeira; MANITTO, Alicia Matijasevich; MIGUEL, Euripedes Constantino; PAN, Pedro Mario; BATISTUZZO, Marcelo Camargo; ROHDE, Luis Augusto; POLANCZYK, Guilherme V.Evidence points to an independent relationship among childhood maltreatment, impairments in executive functions (EF) and disruptive behavior disorders (DBD). However, it is still not fully understood how these three factors are interrelated. This study evaluated the association between childhood maltreatment and DBD testing the role of EF performance as a mediator or moderator. We studied a probabilistic school-based sample of 2016 children from 6 to 12 years. Mental disorders were assessed using the Development and Well-Being Assessment with parents and children. Children answered questions about exposure to child maltreatment and were evaluated with a set of cognitive tasks addressing inhibitory control, working memory, cognitive flexibility and planning. Childhood maltreatment was strongly associated with DBD (OR = 7.7, CI 95% 4.5-12.9). No association was found between childhood maltreatment and EF performance. Children with DBD showed worse performance in cognitive flexibility, which was not identified as a mediator or moderator of the association between childhood maltreatment and DBD. Results indicate that the association between maltreatment and disruptive behavior occurs regardless of performance in executive function in a community sample. Future studies are essential to confirm these findings and elucidate the cognitive mechanisms involved in this association.
- Assessing atypical brain functional connectivity development: An approach based on generative adversarial networks(2023) SANTOS, Pedro Machado Nery Dos; MENDES, Sergio Leonardo; BIAZOLI, Claudinei; GADELHA, Ary; SALUM, Giovanni Abrahao; MIGUEL, Euripedes Constantino; ROHDE, Luis Augusto; SATO, Joao RicardoGenerative Adversarial Networks (GANs) are promising analytical tools in machine learning applications. Characterizing atypical neurodevelopmental processes might be useful in establishing diagnostic and prognostic biomarkers of psychiatric disorders. In this article, we investigate the potential of GANs models combined with functional connectivity (FC) measures to build a predictive neurotypicality score 3-years after scanning. We used a ROI-to-ROI analysis of resting-state functional magnetic resonance imaging (fMRI) data from a community-based cohort of children and adolescents (377 neurotypical and 126 atypical participants). Models were trained on data from neurotypical participants, capturing their sample variability of FC. The discriminator subnetwork of each GAN model discriminated between the learned neurotypical functional connectivity pattern and atypical or unrelated patterns. Discriminator models were combined in ensembles, improving discrimination performance. Explanations for the model's predictions are provided using the LIME (Local Interpretable Model-Agnostic) algorithm and local hubs are identified in light of these explanations. Our findings suggest this approach is a promising strategy to build potential biomarkers based on functional connectivity.
- Cross-Sectional and Longitudinal Associations of Temperament and Mental Disorders in Youth(2019) HOFFMANN, Mauricio Scopel; PAN, Pedro Mario; MANFRO, Gisele Gus; MARI, Jair de Jesus; MIGUEL, Euripedes Constantino; BRESSAN, Rodrigo Affonseca; ROHDE, Luis Augusto; SALUM, Giovanni AbrahaoHere we evaluate the cross-sectional and longitudinal associations between temperament and mental disorders in adolescents. Temperament was assessed in a cohort of 1540 youths by the revised self-report Early Adolescence Temperament Questionnaire (EATQ-R) at baseline and confirmatory factor analyses were used to test the best empirical model. Mental disorders were assessed by parental interview using the Development and Well-Being Behavior Assessment at baseline and at 3-year follow-up. Participants were grouped into Typically Developing Comparisons, Phobias, Distress, Attention-Deficit/Hyperactivity Disorder (ADHD) and Disruptive Behavior Disorders (DBD). Logistic regression models tested the effects of temperament on incidence and remission of mental disorders. The bifactor model of EATQ-R presented the best fit. Distress, ADHD and DBD have lower levels of effortful control in baseline. Adjusted longitudinal analysis showed that effortful control predicted lower incidence of Phobias (OR 0.74; p=0.018), distress (OR 0.74; p=0.014) and DBD (OR 0.68; p=0.037). Temperament factors did not predicted remission rates.
- Socioeconomic status in children is associated with spontaneous activity in right superior temporal gyrus (Mar, 10.1007/s11682-019-00073-z, 2019)(2020) BIAZOLI JR., Claudinei Eduardo; SALUM, Giovanni Abrahao; GADELHA, Ary; REBELLO, Keila; MOURA, Luciana Monteiro; PAN, Pedro Mario; BRIETZKE, Elisa; MIGUEL, Euripedes Constantino; ROHDE, Luis Augusto; BRESSAN, Rodrigo Affonseca; JACKOWSKI, Andrea Parolin; SATO, Joao RicardoThe original version of this article contained mistakes. The surname of Elisa Brietzke was misspelled as ""Brietske"".