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
231 resultados
Resultados de Busca
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- Polyenvironmental and polygenic risk scores and the emergence of psychotic experiences in adolescents(2021) V, Gabrielle de Oliveira S. Navarro; FONSECA, Lais; TALARICO, Fernanda; SPINDOLA, Leticia; SANTORO, Marcos L.; OTA, Vanessa K.; COGO-MOREIRA, Hugo; MARI, Jair; ROHDE, Luis A.; MIGUEL, Euripedes C.; BRESSAN, Rodrigo A.; PAN, Pedro M.; GADELHA, Ary; I, Sintia BelangeroPsychotic experiences (PE) are forms of hallucinations and delusions neither reaching the intensity and functional impairment required to be regarded as full psychotic symptoms nor a psychotic disorder. Here we investigated the ability to predict PE using multiple models (regressions, mediation and moderation) using polygenic risk score for psychotic experiences (PE-PRS), polygenic risk score for schizophrenia (SCZ-PRS), and polyenvironmental risk score (PERS) in youth from a Brazilian sample. The scores were not able to predict outcome, either when both scores were combined (PERS + PE-PRS and PERS + SCZ-PRS) or separately. Our results show that there is no association between PE and PRS or PERS among adolescents in our Brazilian sample. The lack of association may be a result of the absence of better representativeness regarding genetic and environmental factors of our population.
- Obsessive-compulsive symptoms are associated with psychiatric comorbidities, behavioral and clinical problems: a population-based study of Brazilian school children(2016) ALVARENGA, Pedro G.; ROSARIO, Maria C. do; CESAR, Raony C.; MANFRO, Gisele G.; MORIYAMA, Tais S.; BLOCH, Michael H.; SHAVITT, Roseli G.; HOEXTER, Marcelo Q.; COUGHLIN, Catherine G.; LECKMAN, James F.; MIGUEL, Euripedes C.Pediatric-onset obsessive-compulsive disorder (OCD) is underdiagnosed, and many affected children are untreated. The present study seeks to evaluate the presence and the clinical impact of OCD and obsessive-compulsive symptoms (OCS) in a large sample of school-age children. In Phase I, we performed an initial screening using the Family History Screen (FHS). In Phase II, we identified an ""at-risk"" sample, as well as a randomly selected group of children. A total of 2,512 children (6-12 years old) were assessed using the FHS, the Development and Well-Being Assessment (DAWBA), the Strengths and Difficulties Questionnaire (SDQ), and the Child Behavior Checklist (CBCL). Data analyses included descriptive and multivariate analytical techniques. 2,512 children (mean age: 8.86 +/- A 1.84 years; 55.0 % male) were categorized into one of the three diagnostic groups: OCD (n = 77), OCS (n = 488), and unaffected controls (n = 1,947). There were no significant socio-demographic differences (age, gender, socioeconomic status) across groups. The OCS group resembled the OCD on overall impairment, including school problems and delinquent behaviors. However, the OCD group did have significantly higher rates of several comorbid psychiatric disorders, including separation anxiety, generalized anxiety, and major depressive disorder, than OCS or unaffected controls. Moreover, the OCD group also scored higher than the SDQ, as well as on each of CBCL items rated by the parent. Our findings suggest that there is a psychopathological continuum between OCS and OCD in school-aged children. The presence of OCS is associated with functional impairment, which needs further investigation in longitudinal studies.
- Obsessive-compulsive symptom dimensions in a population-based, cross-sectional sample of school-aged children(2015) ALVARENGA, Pedro G.; CESAR, Raony C.; LECKMAN, James F.; MORIYAMA, Tais S.; TORRES, Albina R.; BLOCH, Michael H.; COUGHLIN, Catherine G.; HOEXTER, Marcelo Q.; MANFRO, Gisele G.; POLANCZYK, Guilherme V.; MIGUEL, Euripedes C.; ROSARIO, Maria C. doBackground: Obsessive-compulsive disorder can be expressed as four potentially overlapping obsessive-compulsive symptom (OCS) dimensions (OCSD) (""symmetry/ordering"", ""contamination/cleaning"", ""aggressive/sexual/religious"" and ""collecting/hoarding""). In clinical samples, some dimensions are more familial and associated with increased psychiatric comorbidity and malfunctioning. However, data concerning OCS and OCSD are scarce in non-clinical samples, particularly among children. The present study aims to estimate: (1) the prevalence and sex/age distribution of OCS/OCSD in a community-based sample of schoolchildren; (2) the association between OCS and additional clinical factors; and (3) the degree of familial aggregation of OCS/OCSD. Methods: OCS and OCSD were evaluated in 9937 Brazilian school-children (6-12 years-old) and their biological relatives using the Family History Screen. Data analyses included gradient estimated equations and post-hoc tests. Results: We included data on 9937 index-children, 3305 siblings (13-18 years-old), and 16,218 parents. Biological mothers were the informants in 87.6% of the interviews. OCS were present in 14.7% of the index-children; 15.6% of their siblings; 34.6% of their mothers and 12.1% of their fathers. The prevalence of OCS and each of the OCSD gradually increased from ages 6 to 12 years. Overall, OCS in children were associated with the presence of other psychiatric symptoms, as well as behavioral/school impairment. OCS and each of the four OCSD aggregated significantly within families. Conclusions: OCS are prevalent and associated with psychiatric symptoms and clinical impairment among school-aged children. OCSD aggregate within families in a dimension-specific fashion. These findings suggest a natural continuum between OCS and OCD with regard to their dimensional character.
- Using supervised machine learning on neuropsychological data to distinguish OCD patients with and without sensory phenomena from healthy controls(2021) STAMATIS, Caitlin A.; BATISTUZZO, Marcelo C.; TANAMATIS, Tais; MIGUEL, Euripedes C.; HOEXTER, Marcelo Q.; TIMPANO, Kiara R.Objectives While theoretical models link obsessive-compulsive disorder (OCD) with executive function deficits, empirical findings from the neuropsychological literature remain mixed. These inconsistencies are likely exacerbated by the challenge of high-dimensional data (i.e., many variables per subject), which is common across neuropsychological paradigms and necessitates analytical advances. More unique to OCD is the heterogeneity of symptom presentations, each of which may relate to distinct neuropsychological features. While researchers have traditionally attempted to account for this heterogeneity using a symptom-based approach, an alternative involves focusing on underlying symptom motivations. Although the most studied symptom motivation involves fear of harmful events, 60-70% of patients also experience sensory phenomena, consisting of uncomfortable sensations or perceptions that drive compulsions. Sensory phenomena have received limited attention in the neuropsychological literature, despite evidence that symptoms motivated by these experiences may relate to distinct cognitive processes. Methods Here, we used a supervised machine learning approach to characterize neuropsychological processes in OCD, accounting for sensory phenomena. Results Compared to logistic regression and other algorithms, random forest best differentiated healthy controls (n = 59; balanced accuracy = .70), patients with sensory phenomena (n = 29; balanced accuracy = .59), and patients without sensory phenomena (n = 46; balanced accuracy = .62). Decision-making best distinguished between groups based on sensory phenomena, and among the patient subsample, those without sensory phenomena uniquely displayed greater risk sensitivity compared to healthy controls (d = .07, p = .008). Conclusions Results suggest that different cognitive profiles may characterize patients motivated by distinct drives. The superior performance and generalizability of the newer algorithms highlights the utility of considering multiple analytic approaches when faced with complex data. Practitioner points Practitioners should be aware that sensory phenomena are common experiences among patients with OCD. OCD patients with sensory phenomena may be distinguished from those without based on neuropsychological processes.
- Defining clinical severity in adults with obsessive-compulsive disorder(2015) STORCH, Eric A.; NADAI, Alessandro S. De; ROSARIO, Maria Conceicao do; SHAVITT, Roseli G.; TORRES, Albina R.; FERRAO, Ygor A.; MIGUEL, Euripedes C.; LEWIN, Adam B.; FONTENELLE, Leonardo F.Objective: The Yale Brown Obsessive Compulsive Scale (Y-BOCS) is the most commonly used instrument to assess the clinical severity of obsessive compulsive symptoms. Treatment determinations are often based on Y-BOCS score thresholds. However, these benchmarks are not empirically based, which may result in non-evidence based treatment decisions. Accordingly, the present study sought to derive empirically-based benchmarks for defining obsessive compulsive symptom severity. Method: Nine hundred fifty-four adult patients with obsessive compulsive disorder (OCD), recruited through the Brazilian Research Consortium on Obsessive Compulsive Spectrum Disorders, were evaluated by experienced clinicians using a structured clinical interview, the Y-BOCS, and the Clinical Global Impressions Severity scale (CGI-Severity). Results: Similar to results in treatment-seeking children with OCD, our findings demonstrated convergence between the Y-BOCS and global OCD severity assessed by the CGI-Severity (Nagelkerke R-2 = .48). Y-BOCS scores of 0-13 corresponded with 'mild symptoms' (CGI-Severity = 0-2), 14-25 with 'moderate symptoms' (CGI-Severity = 3), 26-34 with 'moderate-severe symptoms' (CGI-Severity = 4) and 35-40 with 'severe symptoms' (CGI-Severity = 5-6). Neither age nor ethnicity was associated with Y-BOCS scores, but females demonstrated more severe obsessive compulsive symptoms than males (d = .34). Time spent on obsessions/compulsions, interference, distress, resistance, and control were significantly related to global OCD severity although the symptom resistance item pairing demonstrated a less robust relationship relative to other components of the Y-BOCS. Conclusions: These data provide empirically-based benchmarks on the Y-BOCS for defining the clinical severity of treatment seeking adults with OCD, which can be used for normative comparisons in the clinic and for future research.
- 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.
- Sensory phenomena associated with repetitive behaviors in obsessive-compulsive disorder: An exploratory study of 1001 patients(2012) FERRAO, Ygor Arzeno; SHAVITT, Roseli Gedanke; PRADO, Helena; FONTENELLE, Leonardo F.; MALAVAZZI, Dante Marino; MATHIS, Maria Alice de; HOUNIE, Ana Gabriela; MIGUEL, Euripedes Constantino; ROSARIO, Maria Conceicao doA substantial number of patients with obsessive-compulsive disorder (OCD) report compulsions that are preceded not by obsessions but by subjective experiences known as sensory phenomena. This study aimed to investigate the frequency, severity, and age at onset of sensory phenomena in OCD, as well as to compare OCD patients with and without sensory phenomena in terms of clinical characteristics. We assessed 1,001 consecutive OCD patients, using instruments designed to evaluate the frequency/severity of OC symptoms, tics, anxiety, depression, level of insight and presence/severity of sensory phenomena. All together, 651 (65.0%) subjects reported at least one type of sensory phenomena preceding the repetitive behaviors. Considering the sensory phenomena subtypes, 371 (57.0%) patients had musculoskeletal sensations, 519 (79.7%) had externally triggered ""just-right"" perceptions, 176 (27.0%) presented internally triggered ""just right,"" 144 (22.1%) had an ""energy release,"" and 240 (36.9%) patients had an ""urge only"" phenomenon. Sensory phenomena were described as being as more severe than were obsessions by 102(15.7%) patients. Logistic regression analysis showed that the following characteristics were associated with the presence of sensory phenomena: higher frequency and greater severity of the symmetry/ordering/arranging and contamination/washing symptom dimensions; comorbid Tourette syndrome, and a family history of tic disorders. These data suggest that sensory phenomena constitute a poorly understood psychopathological aspect of OCD that merits further investigation.
- Can early improvement be an indicator of treatment response in obsessive-compulsive disorder? Implications for early-treatment decision-making(2013) COSTA, Daniel Lucas da Conceicao; SHAVITT, Roseli Gedanke; CESAR, Raony Cassab Castro; JOAQUIM, Marines Alves; BORCATO, Sonia; VALERIO, Carolina; MIGUEL, Euripedes Constantino; DINIZ, Juliana BeloIn major depression, early response to treatment has been strongly associated with final outcome. We aimed to investigate the ability of early improvement (4 weeks) to predict treatment response at 12 weeks in DSM-IV-defined obsessive-compulsive disorder (OCD) patients treated with serotonin reuptake inhibitors (SRI). We conducted an SRI practical trial with 128 subjects. Inclusion criteria: age range 18-65 years-old, baseline Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score > 16, and absence of previous adequate pharmacological treatment. Systematic assessments were performed at baseline, 4 and 12 weeks of treatment. Treatment response at 12 weeks was defined as a 35% or greater reduction in baseline Y-BOCS score. Stepwise logistic regression was used to test the relationship between early improvement and treatment response at 12 weeks, taking into account additional potential predictive factors. Different thresholds of early improvement were tested and their predictive power was calculated. Early improvement, defined as a 20% or greater reduction from baseline Y-BOCS score at 4 weeks, predicted response at 12 weeks with 75.6% sensitivity and 61.9% specificity. According to a logistic regression including demographic and clinical features as explaining variables, early improvement was the best predictor of treatment response (OR = 1.05, p < 0.0001). Only 19.8% of patients who did not improve at 4 weeks were responders after 12 weeks. In contrast, 55.3% of the individuals who showed early improvement were responders at 12 weeks (Pearson Chi-Square = 17.06, p < 0.001). Early improvement predicted OCD treatment response with relatively good sensitivity and specificity, such that its role in early decision-making warrants further investigation in wider samples. Trial registration: clinicaltrials.gov Identifier NCT00680602.
- Association study between functional polymorphisms in the TNF-alpha gene and obsessive-compulsive disorder(2012) CAPPI, Carolina; MUNIZ, Renan Kawano; SAMPAIO, Aline Santos; CORDEIRO, Quirino; BRENTANI, Helena; PALACIOS, Selma A.; MARQUES, Andrea H.; VALLADA, Homero; MIGUEL, Euripedes Constantino; GUILHERME, Luiza; HOUNIE, Ana GabrielaObsessive-compulsive disorder (OCD) is a prevalent psychiatric disorder of unknown etiology. However, there is some evidence that the immune system may play an important role in its pathogenesis. In the present study, two polymorphisms (rs1800795 and rs361525) in the promoter region of the cytokine tumor necrosis factor-alpha (TNFA) gene were genotyped in 183 OCD patients and in 249 healthy controls. The statistical tests were performed using the PLINK (R) software. We found that the A allele of the TNFA rs361525 polymorphism was significantly associated with OCD subjects, according to the allelic x association test (p=0.007). The presence of genetic markers, such as inflammatory cytokines genes linked to OCD, may represent additional evidence supporting the rote of the immune system in its pathogenesis.
- Comorbidity, age of onset and suicidality in obsessive-Compulsive disorder (OCD): An international collaboration(2017) BRAKOULIAS, V.; STARCEVIC, V.; BELLOCH, A.; BROWN, C.; FERRAO, Y. A.; FONTENELLE, L. F.; LOCHNER, C.; MARAZZITI, D.; MATSUNAGA, H.; MIGUEL, E. C.; REDDY, Y. C. J.; ROSARIO, M. C. do; SHAVITT, R. G.; SUNDAR, A. Shyam; STEIN, D. J.; TORRES, A. R.; VISWASAM, K.Objectives: To collate data from multiple obsessive-compulsive disorder (OCD) treatment centers across seven countries and five continents, and to report findings in relation to OCD comorbidity, age of onset of OCD and comorbid disorders, and suicidality, in a large clinical and ethnically diverse sample, with the aim of investigating cultural variation and the utility of the psychiatric diagnostic classification of obsessive-compulsive and related disorders. Methods: Researchers in the field of OCD were invited to contribute summary statistics on current and lifetime psychiatric comorbidity, age of onset of OCD and comorbid disorders and suicidality in their patients with OCD. Results: Data from 3711 adult patients with primary OCD came from Brazil (n = 955), India (n = 802), Italy (n = 750), South Africa (n = 565), Japan (n = 322), Australia (n = 219), and Spain (n = 98). The most common current comorbid disorders were major depressive disorder (28.4%; n = 1055), obsessive-compulsive personality disorder (24.5%, n = 478), generalized anxiety disorder (19.3%, n = 716), specific phobia (19.2%, n = 714) and social phobia (18.5%, n = 686). Major depression was also the most commonly co-occurring lifetime diagnosis, with a rate of 50.5% (n = 1874). OCD generally had an age of onset in late adolescence (mean = 17.9 years, SD = 1.9). Social phobia, specific phobia and body dysmorphic disorder also had an early age of onset. Co-occurring major depressive disorder, generalized anxiety disorder and psychotic disorders tended to have a later age of onset than OCD. Suicidal ideation within the last month was reported by 6.4% (n = 200) of patients with OCD and 9.0% (n = 314) reported a lifetime history of suicide attempt. Conclusions: In this large cross-continental study, comorbidity in OCD was common. The high rates of comorbid major depression and anxiety disorders emphasize the need for clinicians to assess and monitor for these disorders. Earlier ages of onset of OCD, specific phobia and social phobia may indicate some relatedness between these disorders, but this requires further study. Although there do not appear to be significant cultural variations in rates or patterns of comorbidity and suicidality, further research using similar recruitment strategies and controlling for demographic and clinical variables may help to determine whether any sociocultural factors protect against suicidal ideation or psychiatric comorbidity in patients with OCD.