EURIPEDES CONSTANTINO MIGUEL FILHO

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Departamento de Psiquiatria, Faculdade de Medicina - Docente
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina - Líder

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  • article 5 Citação(ões) na Scopus
    Maternal distress, DNA methylation, and fetal programing of stress physiology in Brazilian mother-infant pairs
    (2023) WILEY, Kyle S.; CAMILO, Caroline; GOUVEIA, Gisele; EUCLYDES, Veronica; PANTER-BRICK, Catherine; MATIJASEVICH, Alicia; FERRARO, Alexandre Archanjo; FRACOLLI, Lislaine Aparecida; CHIESA, Anna Maria; MIGUEL, Euripedes Constantino; POLANCZYK, Guilherme V.; BRENTANI, Helena
    Maternal prenatal psychosocial stress is associated with adverse hypothalamic-pituitary-adrenal axis (HPAA) function among infants. Although the biological mechanisms influencing this process remain unknown, altered DNA methylation is considered to be one potential mechanism. We investigated associations between maternal prenatal psychological distress, infant salivary DNA methylation, and stress physiology at 12 months. Mother's distress was measured via depression and anxiety in early and late pregnancy in a cohort of 80 pregnant adolescents. Maternal hair cortisol was collected during pregnancy. Saliva samples were collected from infants at 12 months to quantify DNA methylation of three stress-related genes (FKBP5, NR3C1, OXTR) (n = 62) and diurnal cortisol (n = 29). Multivariable linear regression was used to test for associations between prenatal psychological distress, and infant DNA methylation and cortisol. Hair cortisol concentrations in late pregnancy were negatively associated with two sites of FKBP5 (site 1: B = -22.33, p = .003; site 2: B = -15.60, p = .012). Infants of mothers with elevated anxiety symptoms in late pregnancy had lower levels of OXTR2 CpG2 methylation (B = -2.17, p = .03) and higher evening salivary cortisol (B = 0.41, p = .03). Furthermore, OXTR2 methylation was inversely associated with evening cortisol (B = -0.14, p-value <= .001). Our results are, to our knowledge, the first evidence that the methylation of the oxytocin receptor may contribute to the regulation of HPAA during infancy.
  • article 0 Citação(ões) na Scopus
    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 Ricardo
    Generative 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.
  • article 11 Citação(ões) na Scopus
    Alterations in microRNA of extracellular vesicles associated with major depression, attention-deficit/hyperactivity and anxiety disorders in adolescents
    (2023) HONORATO-MAUER, Jessica; XAVIER, Gabriela; OTA, Vanessa Kiyomi; CHEHIMI, Samar Nasser; MAFRA, Fernanda; CUOCO, Cassia; ITO, Lucas Toshio; ORMOND, Rafaella; ASPRINO, Paula Fontes; OLIVEIRA, Adrielle; BUGIGA, Amanda Victoria Gomes; TORRECILHAS, Ana Claudia; BRESSAN, Rodrigo; MANFRO, Gisele Gus; MIGUEL, Euripedes Constantino; ROHDE, Luis Augusto; PAN, Pedro Mario; SALUM, Giovanni Abrahao; PELLEGRINO, Renata; BELANGERO, Sintia; SANTORO, Marcos Leite
    Extracellular vesicles (EVs) are present in numerous peripheral bodily fluids and function in critical biological processes, including cell-to-cell communication. Most relevant to the present study, EVs contain microRNAs (miRNAs), and initial evidence from the field indicates that miRNAs detected in circulating EVs have been previously associated with mental health disorders. Here, we conducted an exploratory longitudinal and cross-sectional analysis of miRNA expression in serum EVs from adolescent participants. We analyzed data from a larger ongoing cohort study, evaluating 116 adolescent participants at two time points (wave 1 and wave 2) separated by three years. Two separate data analyses were employed: A cross-sectional analysis compared individuals diagnosed with Major Depressive Disorder (MDD), Anxiety disorders (ANX) and Attention deficit/Hyperactivity disorder (ADHD) with individuals without psychiatric diagnosis at each time point. A longitudinal analysis assessed changes in miRNA expression over time between four groups showing different diagnostic trajectories (persistent diagnosis, first incidence, remitted and typically developing/control). Total EVs were isolated, characterized by size distribution and membrane proteins, and miRNAs were isolated and sequenced. We then selected differentially expressed miRNAs for target prediction and pathway enrichment analysis. In the longitudinal analysis, we did not observe any statistically significant results. In the cross-sectional analysis: in the ADHD group, we observed an upregulation of miR-328-3p at wave 1 only; in the MDD group, we observed a downregulation of miR-4433b-5p, miR-584-5p, miR-625-3p, miR-432-5p and miR-409-3p at wave 2 only; and in the ANX group, we observed a downregulation of miR-432-5p, miR-151a-5p and miR-584-5p in ANX cases at wave 2 only. Our results identified previously observed and novel differentially expressed miRNAs and their relationship with three mental health disorders. These data are consistent with the notion that these miRNAs might regulate the expression of genes associated with these traits in genome-wide association studies. The findings support the promise of continued identification of miRNAs contained within peripheral EVs as biomarkers for mental health disorders.
  • conferenceObject
    Spatial Normalization Discrepancies Between Native and MNI152 Brain Template Scans in Gamma Ventral Capsulotomy Patients
    (2023) GIFF, Alexis; NOREN, Georg; MAGNOTTI, John; LOPES, Antonio Carlos; BATISTUZZO, Marcelo; HOEXTER, Marcelo; GREENBERG, Benjamin; MARSLAND, Richard; MIGUEL, Euripedes; RASMUSSEN, Steven; MCLAUGHLIN, Nicole
  • article 0 Citação(ões) na Scopus
    Longitudinal associations between positive attributes and psychopathology and their interactive effects on educational outcomes
    (2023) ROMANI-SPONCHIADO, Aline; VIDAL-RIBAS, Pablo; BRESSAN, Rodrigo Affonseca; MARI, Jair de Jesus; MIGUEL, Euripedes Constantino; GADELHA, Ary; ROHDE, Luis Augusto Paim; EVANS-LACKO, Sara; SALUM, Giovanni Abrahao; HOFFMANN, Mauricio Scopel
    Psychopathology is associated with impaired learning and early termination of schooling, whereas positive attributes are associated with better educational outcomes. However, it is important to understand if and how psychopathology and positive attributes longitudinally impact each other so we could shed light on where to intervene to promote educational outcomes through these constructs. A large prospective school-based community cohort of youths (5-15 years of age, 45% female) were assessed and followed up for 3 years (n = 2010; 80% retention). We assessed the longitudinal impact of positive attributes (Youth Strength Inventory) and psychopathology (bifactor model of Strengths and Difficulties Questionnaire) using a cross-lagged panel model. We also used generalized mixed effects models to investigate how these both constructs predict school dropout and literacy, adjusting for confounders and testing their interaction. Positive attributes negatively predicted, and were negatively predicted by, the general factor of psychopathology and conduct problems in the cross-lagged panel model. Positive attributes (OR = 0.57, 95% CI [0.44, 0.73], p < 0.001) and specific conduct symptoms (OR = 2.33, 95% CI [1.64, 3.33], p < 0.001) predicted school dropout, whereas the general factor of psychopathology predicted lower literacy ability (beta = - 0.08, 95% CI [- 0.11, - 0.05], p < 0.001). However, the protective association of positive attributes on school dropout decreases as the general factor of psychopathology increases. These findings provide new evidence that positive attributes and psychopathology mutually influence each other over development and have interactive effects on educational outcomes.
  • article 23 Citação(ões) na Scopus
    World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders - Version 3. Part I: Anxiety disorders
    (2023) BANDELOW, Borwin; ALLGULANDER, Christer; BALDWIN, David S.; COSTA, Daniel Lucas da Conceicao; DENYS, Damiaan; DILBAZ, Nesrin; DOMSCHKE, Katharina; ERIKSSON, Elias; FINEBERG, Naomi A.; HATTENSCHWILER, Josef; HOLLANDER, Eric; KAIYA, Hisanobu; KARAVAEVA, Tatiana; KASPER, Siegfried; KATZMAN, Martin; KIM, Yong-Ku; INOUE, Takeshi; LIM, Leslie; MASDRAKIS, Vasilios; MENCHON, Jose M.; MIGUEL, Euripedes C.; MOLLER, Hans-Jurgen; NARDI, Antonio E.; PALLANTI, Stefano; PERNA, Giampaolo; RUJESCU, Dan; STARCEVIC, Vladan; STEIN, Dan J.; TSAI, Shih-Jen; AMERINGEN, Michael Van; VASILEVA, Anna; WANG, Zhen; ZOHAR, Joseph
    Aim This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders (published in 2002, revised in 2008). Method A consensus panel of 33 international experts representing 22 countries developed recommendations based on efficacy and acceptability of available treatments. In total, 1007 RCTs for the treatment of these disorders in adults, adolescents, and children with medications, psychotherapy and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medications. Result This paper, Part I, contains recommendations for the treatment of panic disorder/agoraphobia (PDA), generalised anxiety disorder (GAD), social anxiety disorder (SAD), specific phobias, mixed anxiety disorders in children and adolescents, separation anxiety and selective mutism. Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are first-line medications. Cognitive behavioural therapy (CBT) is the first-line psychotherapy for anxiety disorders. The expert panel also made recommendations for patients not responding to standard treatments and recommendations against interventions with insufficient evidence. Conclusion It is the goal of this initiative to provide treatment guidance for these disorders that has validity throughout the world.
  • article 20 Citação(ões) na Scopus
    World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders - Version 3. Part II: OCD and PTSD
    (2023) BANDELOW, Borwin; ALLGULANDER, Christer; BALDWIN, David S.; COSTA, Daniel Lucas da Conceicao; DENYS, Damiaan; DILBAZ, Nesrin; DOMSCHKE, Katharina; HOLLANDER, Eric; KASPER, Siegfried; MOELLER, Hans-Juergen; ERIKSSON, Elias; FINEBERG, Naomi A.; HAETTENSCHWILER, Josef; KAIYA, Hisanobu; KARAVAEVA, Tatiana; KATZMAN, Martin A.; KIM, Yong-Ku; INOUE, Takeshi; LIM, Leslie; MASDRAKIS, Vasilios; MENCHON, Jose M.; MIGUEL, Euripedes C.; NARDI, Antonio E.; PALLANTI, Stefano; PERNA, Giampaolo; RUJESCU, Dan; STARCEVIC, Vladan; STEIN, Dan J.; TSAI, Shih-Jen; AMERINGEN, Michael Van; VASILEVA, Anna; WANG, Zhen; ZOHAR, Joseph
    Aim: This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders which was published in 2002 and revised in 2008. Method: A consensus panel of 34 international experts representing 22 countries developed recommendations based on efficacy and acceptability of the treatments. In this version, not only medications but also psychotherapies and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medication treatments. Result: The present paper (Part II) contains recommendations based on published randomised controlled trials (RCTs) for the treatment of OCD (n = 291) and PTSD (n = 234) in children, adolescents, and adults. The accompanying paper (Part I) contains the recommendations for the treatment of anxiety disorders. For OCD, first-line treatments are selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT). Internet-CBT was also superior to active controls. Several second-line medications are available, including clomipramine. For treatment-resistant cases, several options are available, including augmentation of SSRI treatment with antipsychotics and other drugs. Other non-pharmacological treatments, including repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS) and others were also evaluated. For PTSD, SSRIs and the SNRI venlafaxine are first-line treatments. CBT is the psychotherapy modality with the best body of evidence. For treatment-unresponsive patients, augmentation of SSRI treatment with antipsychotics may be an option. Conclusion: OCD and PTSD can be effectively treated with CBT and medications.
  • article 13 Citação(ões) na Scopus
    Association between chemosensory impairment with neuropsychiatric morbidity in post-acute COVID-19 syndrome: results from a multidisciplinary cohort study
    (2023) DAMIANO, Rodolfo Furlan; NETO, Deusdedit Brandao; OLIVEIRA, Joao Vitor Ribeiro; SANTOS, Jonatas Magalhaes; ALVES, Julia Vallin Rodrigues; GUEDES, Bruno F.; NITRINI, Ricardo; ARAUJO, Adriana Ladeira de; OLIVEIRA, Melaine; BRUNONI, Andre R.; VOEGELS, Richard Louis; BENTO, Ricardo Ferreira; BUSATTO, Geraldo; MIGUEL, Euripedes Constantino; FORLENZA, Orestes V.; PINNA, Fabio de Rezende
    Preliminary methodologically limited studies suggested that taste and smell known as chemosensory impairments and neuropsychiatric symptoms are associated in post-COVID-19. The objective of this study is to evaluate whether chemosensory dysfunction and neuropsychiatric impairments in a well-characterized post-COVID-19 sample. This is a cohort study assessing adult patients hospitalized due to moderate or severe forms of COVID-19 between March and August 2020. Baseline information includes several clinical and hospitalization data. Further evaluations were made using several different reliable instruments designed to assess taste and smell functions, parosmia, and neuropsychiatric disorders (using standardized psychiatric and cognitive measures). Out of 1800 eligible individuals, 701 volunteers were assessed on this study. After multivariate analysis, patients reporting parosmia had a worse perception of memory performance (p < 0.001). Moderate/severe hypogeusia was significantly associated with a worse performance on the word list memory task (p = 0.012); Concomitant moderate/severe olfactory and gustatory loss during the acute phase of COVID-19 was also significantly associated with episodic memory impairment (p = 0.006). We found a positive association between reported chemosensory (taste and olfaction) abnormalities and cognition dysfunction in post-COVID-19 patients. These findings may help us identify potential mechanisms linking these two neurobiological functions, and also support the speculation on a possible route through which SARS-CoV-2 may reach the central nervous system.
  • article 1 Citação(ões) na Scopus
    Deviations from a typical development of the cerebellum in youth are associated with psychopathology, executive functions and educational outcomes
    (2023) BORGES, Marina S.; HOFFMANN, Mauricio S.; SIMIONI, Andre; AXELRUD, Luiza K.; TEIXEIRA, Danielle S.; ZUGMAN, Andre; JACKOWSKI, Andrea; PAN, Pedro M.; BRESSAN, Rodrigo A.; PARKER, Nadine; GERMANN, Jurgen; BADO, Patricia P.; SATTERTHWAITE, Theodore D.; MILHAM, Michael P.; CHAKRAVARTY, M. Mallar; ROHDE, Luis Augusto Paim; MIGUEL, Euripedes Constantino; PAUS, Tomas; SALUM, Giovanni A.
    Background Understanding deviations from typical brain development is a promising approach to comprehend pathophysiology in childhood and adolescence. We investigated if cerebellar volumes different than expected for age and sex could predict psychopathology, executive functions and academic achievement. Methods Children and adolescents aged 6-17 years from the Brazilian High-Risk Cohort Study for Mental Conditions had their cerebellar volume estimated using Multiple Automatically Generated Templates from T1-weighted images at baseline (n = 677) and at 3-year follow-up (n = 447). Outcomes were assessed using the Child Behavior Checklist and standardized measures of executive functions and school achievement. Models of typically developing cerebellum were based on a subsample not exposed to risk factors and without mental-health conditions (n = 216). Deviations from this model were constructed for the remaining individuals (n = 461) and standardized variation from age and sex trajectory model was used to predict outcomes in cross-sectional, longitudinal and mediation analyses. Results Cerebellar volumes higher than expected for age and sex were associated with lower externalizing specific factor and higher executive functions. In a longitudinal analysis, deviations from typical development at baseline predicted inhibitory control at follow-up, and cerebellar deviation changes from baseline to follow-up predicted changes in reading and writing abilities. The association between deviations in cerebellar volume and academic achievement was mediated by inhibitory control. Conclusions Deviations in the cerebellar typical development are associated with outcomes in youth that have long-lasting consequences. This study highlights both the potential of typical developing models and the important role of the cerebellum in mental health, cognition and education.
  • article 0 Citação(ões) na Scopus
    Brain activation during fear extinction recall in unmedicated patients with obsessive-compulsive disorder
    (2023) DINIZ, Juliana Belo; BAZAN, Paulo Rodrigo; PEREIRA, Carlos Alberto de Braganca; SARAIVA, Erlandson Ferreira; RAMOS, Paula Roberta Camargo; OLIVEIRA, Amanda Ribeiro de; REIMER, Adriano Edgar; HOEXTER, Marcelo Queiroz; MIGUEL, Euripedes Constantino; SHAVITT, Roseli Gedanke; BATISTUZZO, Marcelo Camargo
    Specific brain activation patterns during fear conditioning and the recall of previously extinguished fear responses have been associated with obsessive-compulsive disorder (OCD). However, further replication studies are necessary. We measured skin-conductance response and blood oxygenation level-dependent responses in unmedicated adult patients with OCD (n = 27) and healthy participants (n = 22) submitted to a two-day fear conditioning experiment comprising fear conditioning, extinction (day 1) and extinction recall (day 2). During conditioning, groups differed regarding the skin conductance reactivity to the aversive stimulus (shock) and regarding the activation of the right opercular cortex, insular cortex, putamen, and lingual gyrus in response to conditioned stimuli. During extinction recall, patients with OCD had higher responses to stimuli and smaller differences between responses to conditioned and neutral stimuli. For the entire sample, the higher the response delta between conditioned and neutral stimuli, the greater the dACC activation for the same contrast during early extinction recall. While activation of the dACC predicted the average difference between responses to stimuli for the entire sample, groups did not differ regarding the activation of the dACC during extinction recall. Larger unmedicated samples might be necessary to replicate the previous findings reported in patients with OCD.