HELIO ELKIS
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Psiquiatria, Faculdade de Medicina - Docente
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
18 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 18
- Cognitive outcomes after tDCS in schizophrenia patients with prominent negative symptoms: Results from the placebo-controlled STARTS trial(2021) BULUBAS, Lucia; GOERIGK, Stephan; GOMES, July S.; BREM, Anna-Katharine; CARVALHO, Juliana B.; PINTO, Bianca S.; ELKIS, Helio; GATTAZ, Wagner F.; PADBERG, Frank; BRUNONI, Andre R.; VALIENGO, LeandroCognitive deficits and negative symptoms in schizophrenia are associated with poor functional outcomes and limited in terms of treatment. The Schizophrenia Treatment With Electric Transcranial Stimulation (STARTS) trial has shown efficacy of transcranial direct current stimulation (tDCS) for improving negative symptoms. In this secondary analysis, we investigate its effects on cognitive performance. In STARTS, a double-blinded, sham controlled, randomized clinical trial, patients were treated with twice-daily, 20-min, 2-mA fronto-temporal tDCS over 5 days or sham-tDCS. In 90 patients, we evaluated the cognitive performance up to 12 weeks post-treatment. We found that active-tDCS showed no beneficial effects over sham-tDCS in any of the tests. Based on a 5-factor cognitive model, improvements of executive functions and delayed memory were observed in favor of shamtDCS. Overall, the applied active-tDCS protocol, primarily designed to improve negative symptoms, did not promote cognitive improvement. We discuss possible protocol modification potentially required to increase tDCS effects on cognition. ClinicalTrials.gov identifier: NCT02535676
- Treatment of Negative Symptoms of Schizophrenia With tDCS (Transcranial Direct Current Stimulation): A Randomized, Sham-Controlled, Double-Blinded Clinical Trial(2018) VALIENGO, Leandro; BILT, Martinus Theodorus van de; SERPA, Mauricio; GORDON, Pedro; HELKIS, Helio; GATTAZ, Wagner Farid; LACERDA, Acioly; BRUNONI, Andre
- Which are the best evidence-based therapeutic options for clozapine and ECT resistant schizophrenia? A case-report(2021) DAMIANO, Rodolfo Furlan; AVRICHIR, Belquiz S.; MELZER-RIBEIRO, Debora L.; SALLET, Paulo Clemente; ELKIS, HelioThis is a case description of a patient with clozapine and ECT resistance schizophrenia with several suicide attempts. We discussed evidence-based clinical decisions to deal with such conditions.
- Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness(2016) TORRES, Ulysses S.; DURAN, Fabio L. S.; SCHAUFELBERGER, Maristela S.; CRIPPA, Jose A. S.; LOUZA, Mario R.; SALLET, Paulo C.; KANEGUSUKU, Caroline Y. O.; ELKIS, Helio; GATTAZ, Wagner F.; BASSITT, Debora P.; ZUARDI, AntonioW.; HALLAK, Jaime Eduardo C.; LEITE, Claudia C.; CASTRO, Claudio C.; SANTOS, Antonio Carlos; MURRAY, Robin M.; BUSATTO, Geraldo F.Background: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinalMRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, information from cross-sectional neuroimaging studies directly comparing first-episode and chronic schizophrenia patients to healthy controls may also be useful to further clarify this issue. With the recent interest in multisite mega-analyses combining structural MRI data from multiple centers aiming at increased statistical power, the present multisite voxel-basedmorphometry (VBM) studywas carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertainwhich (if any) of such structural abnormalities would be specifically correlated to potential clinical moderators, including cumulative exposure to antipsychotics, age of onset, illness duration and overall illness severity. Methods: Wegathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) fromfour previousmorphometricMRI studies (1.5 T) carried out in the same geographical region of Brazil. Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8) software with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) algorithm. Group effects on regional gray matter (GM) volumes were investigated through whole-brain voxel-wise comparisons using General LinearModel Analysis of Co-variance (ANCOVA), always including total GMvolume, scan protocol, age and gender as nuisance variables. Finally, correlation analyseswere performed between the aforementioned clinical moderators and regional and global brain volumes. Results: First-episode schizophrenia subjects displayed subtle volumetric deficits relative to controls in a circumscribed brain regional network identified only in small volume-corrected (SVC) analyses (p < 0.05, FWE-corrected), including the insula, temporolimbic structures and striatum. Chronic schizophrenia patients, on the other hand, demonstrated an extensive pattern of regional GM volume decreases relative to controls, involving bilateral superior, inferior and orbital frontal cortices, right middle frontal cortex, bilateral anterior cingulate cortices, bilateral insulae and right superior and middle temporal cortices (p < 0.05, FWE-corrected over the whole brain). GM volumes in several of those brain regionswere directly correlated with age of disease onset on SVC analyses for conjoined (first-episode and chronic) schizophrenia groups. There were also widespread foci of significant negative correlation between duration of illness and relative GM volumes, but such findings remained significant only for the right dorsolateral prefrontal cortex after accounting for the influence of age of disease onset. Finally, significant negative correlations were detected between life-time cumulative exposure to antipsychotics and total GM and white matter volumes in schizophrenia patients, but no significant relationship was found between indices of antipsychotic usage and relative GM volume in any specific brain region. Conclusion: The above data indicate that brain changes associated with the diagnosis of schizophrenia are more widespread in chronic schizophrenia compared to first-episode patients. Our findings also suggest that relative GM volume deficits may be greater in (presumably more severe) cases with earlier age of onset, as well as varying as a function of illness duration in specific frontal brain regions. Finally, our results highlight the potentially complex effects of the continued use of antipsychotic drugs on structural brain abnormalities in schizophrenia, as we found that cumulative doses of antipsychotics affected brain volumes globally rather than selectively on frontal-temporal regions. (C) 2016 The Authors.
- Efficacy of electroconvulsive therapy augmentation for partial response to clozapine: a pilot randomized ECT - sham controlled trial(2017) MELZER-RIBEIRO, Debora Luciana; RIGONATTI, Sergio Paulo; KAYO, Monica; AVRICHIR, Belquiz S.; RIBEIRO, Rafael Bernardon; SANTOS, Bernardo dos; FORTES, Marisa; ELKIS, HelioBackground: Thirty percent of schizophrenia patients are treatment-resistant. Objective: This is a single-blinded sham-controlled trial to assess the efficacy of electroconvulsive therapy (ECT) as augmentation strategy in patients with clozapine-resistant schizophrenia. Methods: Twenty three subjects were randomly assigned to 12 sessions of ECT (N = 13) or placebo (Sham ECT) (N = 10). The primary outcome was improvement on psychotic symptoms as measured by the mean reduction of the PANSS positive subscale. The assessments were performed by blind raters. Results: At baseline both groups were similar, except for negative and total symptoms of the PANSS, which were higher in the Sham group. At the endpoint both groups had a significant decrease from basal score. In the ECT group the PANSS total score decreased 8.78%, from 81.23 to 74.75 (p - 0.042), while the positive subscale had a mean reduction of 19% (19.31 to 16.17, p = 0.006). In the Sham group, the mean reduction of PANSS total score was 15.27% (96.80 to 87.43; p = 0.036), and the PANSS positive subscale decreased 27.81% (22.90 to 19.14, p = 0.008). The CGI score in ECT group decreased 23.0% (5.23 to 4.17; p = 0.001) and decreased 24.31% in the Sham ECT group (5.80 to 4.86; p = 0.004). Discussion: In this pilot study, we found no difference between the groups.
- Understanding the impact of persistent symptoms in schizophrenia: Cross-sectional findings from the Pattern study(2015) HARO, Josep Maria; ALTAMURA, Carlo; CORRAL, Ricardo; ELKIS, Helio; EVANS, Jonathan; MALLA, Ashok; KREBS, Marie-Odile; ZINK, Mathias; BERNASCONI, Corrado; LALONDE, Justine; NORDSTROEM, Anna-LenaBackground: The high societal burden of schizophrenia is largely caused by the persistence of symptoms and accompanying functional impairment. To date, no studies have specifically assessed the course of persistent symptoms or the individual contributions of positive and negative symptoms to patient functioning. The cross-sectional analysis of the Pattern study provides an international perspective of the burden of schizophrenia. Methods: Clinically stable outpatients from 140 study centers across eight countries (Argentina, Brazil, Canada, France, Germany, Italy, Spain and the United Kingdom) were assessed using clinical rating scales: Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia (CGI-SCH) Scale and the Personal and Social Performance (PSP) Scale. Additional measures included patient-reported outcomes, patient sociodemographic variables, living situation, employment and resource use. Results: Overall, 1379 patients were assessed and analyzed and had similar sociodemographic characteristics across countries, with 61.6% having persistent positive and/or negative symptoms. Positive and negative symptoms had been persistent for a mean of 9.6 and 8.9 years (SD: 8.8 and 9.6), respectively. Approximately 86% of patients had a functional disability classified as greater than mild. Patients with a higher PANSS Negative Symptom Factor Score were more likely to have a poorer level of functioning. Conclusions: This analysis examines individual contributions of persistent positive and negative symptoms on patient functioning in different countries. A high prevalence of patients with persistent symptoms and functional impairment was a consistent finding across countries. Longitudinal observations are necessary to assess how to improve persistent symptoms of schizophrenia and overall patient functioning.
- Cortical surface abnormalities are different depending on the stage of schizophrenia: A cross-sectional vertexwise mega-analysis of thickness, area and gyrification(2021) ROSA, Pedro Gomes Penteado; ZUGMAN, Andre; CERQUEIRA, Carlos Toledo; SERPA, Mauricio Henriques; DURAN, Fabio Luis de Souza; ZANETTI, Marcus Vinicius; BASSITT, Debora Pastore; ELKIS, Helio; CRIPPA, Jose Alexandre S.; SALLET, Paulo Clemente; GATTAZ, Wagner Farid; HALLAK, Jaime Eduardo Cecilio; LOUZA, Mario Rodrigues; GADELHA, Ary; JACKOWSKI, Andrea Parolin; BRESSAN, Rodrigo Affonseca; BUSATTO FILHO, GeraldoBackground: Brain magnetic resonance imaging studies have not investigated the cortical surface comprehensively in schizophrenia subjects by assessing thickness, surface area and gyrification separately during the first episode of psychosis (FEP) or chronic schizophrenia (ChSch). Methods: We investigated cortical surface abnormalities in 137 FEP patients and 240 ChSch subjects compared to 297 Healthy Controls (HC) contributed by five cohorts. Maps showing results of vertexwise between-group comparisons of cortical thickness, area, and gyrification were produced using T1-weighted datasets processed using FreeSurfer 5.3, followed by validated quality control protocols. Results: FEP subjects showed large clusters of increased area and gyrification relative to HC in prefrontal and insuli cortices (Cohen's d: 0.049 to 0.28). These between-group differences occurred partially beyond the effect of sample. ChSch subjects displayed reduced cortical thickness relative to HC in smaller fronto-temporal foci (d:-0.73 to-0.35), but not beyond the effect of sample. Differences between FEP and HC subjects were associated with male gender, younger age, and earlier illness onset, while differences between ChSch and HC were associated with treatment-resistance and first-generation antipsychotic (FGA) intake independently of sample effect. Conclusions: Separate assessments of FEP and ChSch revealed abnormalities that differed in regional distribution, phenotypes affected and effect size. In FEP, associations of greater cortical area and gyrification abnormalities with earlier age of onset suggest an origin on anomalous neurodevelopment, while thickness reductions in ChSch are at least partially explained by treatment-resistance and FGA intake. Associations of between-group differences with clinical variables retained statistical significance beyond the effect of sample.
- Identifying strategies to improve PANSS based dimensional models in schizophrenia: Accounting for multilevel structure, Bayesian model and clinical staging(2022) HIGUCHI, Cinthia H.; COGO-MOREIRA, Hugo; FONSECA, Lais; ORTIZ, Bruno B.; CORRELL, Christoph U.; NOTO, Cristiano; CORDEIRO, Quirino; FREITAS, Rosana de; ELKIS, Helio; I, Sintia Belangero; BRESSAN, Rodrigo A.; GADELHA, AryBackground: Dimensional approaches can decompose a construct in a set of continuous variables, improving the characterization of complex phenotypes, such as schizophrenia. However, the five-factor model of the Positive and Negative Syndrome Scale (PANSS), the most used instrument in schizophrenia research, yielded poor fits in most confirmatory factor analysis (CFA) studies, raising concerns about its applications. Thus, we aimed to identify dimensional PANSS CFA models with good psychometric properties by comparing the traditional CFA with three methodological approaches: Bayesian CFA, multilevel modeling, and Multiple Indicators Multiple Causes (MIMIC) modeling.Methods: Clinical data of 700 schizophrenia patients from four centers were analyzed. We first performed a traditional CFA. Next, we tested the three techniques: 1) a Bayesian CFA; 2) a multilevel analysis using the centers as level; and 3) a MIMIC modeling to evaluate the impact of clinical staging on PANSS factors and items. Results: CFA and Bayesian CFA produced poor fit models. However, when adding a multilevel structure to the CFA model, a good fit model emerged. MIMIC modeling yielded significant differences in the factor structure between the clinical stages of schizophrenia. Sex, age, age of onset, and duration of illness did not significantly affect the model fit.Conclusion: Our comparison of different CFA methods highlights the need for multilevel structure to achieve a good fit model and the potential utility of staging models (rather than the duration of illness) to deal with clinical heterogeneity in schizophrenia. Large prospective samples with biological data should help to understand the interplay between psychometrics concerns and neurobiology research.
- Schizophrenia TreAtment with electRic Transcranial Stimulation (STARTS): design, rationale and objectives of a randomized, double-blinded, sham-controlled trial(2019) VALIENGO, Leandro; GORDON, Pedro Caldana; DE CARVALHO, Juliana Barbosa; RIOS, Rosa Maria; KOEBE, Stephanie; SERPA, Mauricio Henrique; VAN DE BILT, Martinus; LACERDA, Acioly; ELKIS, Helio; GATTAZ, Wagner Farid; BRUNONI, André RussowskyAbstract Introduction Schizophrenia is a severe mental disorder. While some antipsychotic medications have demonstrated efficacy in treating positive symptoms, there is no widely recognized treatment for negative symptoms, which can cause significant distress and impairment for patients with schizophrenia. Here we describe the rationale and design of the STARTS study (Schizophrenia TreAtment with electRic Transcranial Stimulation), a clinical trial aimed to test the efficacy of a non-pharmacological treatment known as transcranial direct current stimulation (tDCS) for treating the negative symptoms of schizophrenia Methods The STARTS study is designed as a randomized, sham-controlled, double-blinded trial evaluating tDCS for the treatment of the negative symptoms of schizophrenia. One-hundred patients will be enrolled and submitted to 10 tDCS sessions over the left dorsolateral prefrontal cortex (anodal stimulation) and left temporoparietal junction (cathodal stimulation) over 5 consecutive days. Participants will be assessed using clinical and neuropsychological tests before and after the intervention. The primary outcome is change in the Positive and Negative Syndrome Scale (PANSS) negative subscale score over time and across groups. Biological markers, including blood neurotrophins and interleukins, genetic polymorphisms, and motor cortical excitability, will also be assessed. Results The clinical results will provide insights about tDCS as a treatment for the negative symptoms of schizophrenia, and the biomarker investigation will contribute towards an improved understanding of the tDCS mechanisms of action. Conclusion Our results could introduce a novel therapeutic technique for the negative symptoms of schizophrenia. Clinical trial registration: ClinicalTrials.gov, NCT02535676 .
- Patterns of clozapine and other antipsychotics prescriptions in patients with treatment-resistant schizophrenia in community mental health centers in Sao Paulo, Brazil(2015) SILVEIRA, Ana Stella de Azevedo; ROCHA, Deyvis Macarof Loureiro Vasconcelos; ATTUX, Cecilia Ribeiro de Faissol; DALTIO, Claudiane Sales; SILVA, Leticia Aparecida da; ELKIS, Helio; KANE, John Michael; BRESSAN, Rodrigo AffonsecaBackground: Despite of its global underuse, clozapine is still the golden standard antipsychotic for patients with treatment-resistant schizophrenia (TRS). Objective: To evaluate the patterns of clozapine and other antipsychotic drugs prescription in TRS in community mental health centers in Sao Paulo, Brazil. Methods: A multiple-choice questionnaire was applied to fifteen psychiatrists at five centers inquiring about patients' clinical condition, adherence to oral treatment and current antipsychotic treatment. History of previous and current antipsychotic treatment was collected through medical chart review. Results: Out of 442 schizophrenia patients, 103 (23.3%) fulfilled the criteria for TRS. Fifty-eight patients (56.3%) were receiving polypharmacy; 30 (29.1%) were on atypical antipsychotic monotherapy, 14 (13.6%) were on typical antipsychotic monotherapy, 25 (24.3%) were taking depot antipsychotic medication and only 22 (21.4%) were receiving clozapine. Discussion: As well as in other parts of the world, many TRS patients (78.6%) receive other drugs instead of clozapine in Sao Paulo, the best evidence-based medication for patients with TRS. The government should make every effort to provide medical training and the equipment and logistic support to adequately serve those who could benefit from clozapine treatment at the community health centers.