MARTINUS THEODORUS VAN DE BILT
Índice h a partir de 2011
10
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
10 resultados
Resultados de Busca
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- Epistasis between COMT Val(158)Met and DRD3 Ser(9)Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission(2015) LOCH, Alexandre A.; BILT, Martinus T. van de; BIO, Danielle S.; PRADO, Carolina M. do; SOUSA, Rafael T. de; VALIENGO, Leandro L.; MORENO, Ricardo A.; ZANETTI, Marcus V.; GATTAZ, Wagner F.Objective: To assess the relationship between cognitive function, a proposed schizophrenia endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl transferase (COMT) Val(158)Met and dopamine receptor 3 (DRD3) Ser(9)Gly. Methods: Fifty-eight outpatients with schizophrenia/schizoaffective disorder and 88 healthy controls underwent neurocognitive testing and genotyping. Analyses of covariance (ANCOVAs) using age, sex, and years of education as covariates compared cognitive performance for the proposed genotypes in patients and controls. ANCOVAs also tested for the epistatic effect of COMT and DRD3 genotype combinations on cognitive performance. Results: For executive functioning, COMT Val/Val patients performed in a similar range as controls (30.70-33.26 vs. 35.53-35.67), but as COMT Met allele frequency increased, executive functioning worsened. COMT Met/Met patients carrying the DRD3 Ser/Ser genotype performed poorest (16.184 vs. 27.388-31.824). Scores of carriers of this COMT/DRD3 combination significantly differed from all DRD3 Gly/Gly combinations (p < 0.05), from COMT Val/Met DRD3 Ser/Gly (p = 0.02), and from COMT Val/Val DRD3 Ser/Ser (p = 0.01) in patients. It also differed significantly from all control scores (p < 0.001). Conclusion: Combined genetic polymorphisms related to dopamine neurotransmission might influence executive function in schizophrenia. Looking at the effects of multiple genes on a single disease trait (epistasis) provides a comprehensive and more reliable way to determine genetic effects on endophenotypes.
- Application of Lipidomics in Psychiatry: Plasma-Based Potential Biomarkers in Schizophrenia and Bipolar Disorder(2023) COSTA, Alana C.; RICA, Larissa B.; BILT, Martinus van de; ZANDONADI, Flavia S.; GATTAZ, Wagner F.; TALIB, Leda L.; SUSSULINI, AlessandraIn this study, we obtained a lipidomic profile of plasma samples from drug-naive patients with schizophrenia (SZ) and bipolar disorder (BD) in comparison to healthy controls. The sample cohort consisted of 30 BD and 30 SZ patients and 30 control individuals. An untargeted lipidomics strategy using liquid chromatography coupled with high-resolution mass spectrometry was employed to obtain the lipid profiles. Data were preprocessed, then univariate (t-test) and multivariate (principal component analysis and orthogonal partial least squares discriminant analysis) statistical tools were applied to select differential lipids, which were putatively identified. Afterward, multivariate receiver operating characteristic tests were performed, and metabolic pathway networks were constructed, considering the differential lipids. Our results demonstrate alterations in distinct lipid pathways, especially in glycerophospholipids, sphingolipids and glycerolipids, between SZ and BD patients. The results obtained in this study may serve as a basis for differential diagnosis, which is crucial for effective treatment and improving the quality of life of patients with psychotic disorders.
- A dopamine receptor D2 genetic polymorphism associated with transition to mental disorders in a cohort of individuals with at-risk mental state for psychosis(2023) MARQUES, Julia Hatagami; TALIB, Leda Leme; HORTENCIO, Lucas; ANDRADE, Julio Cesar; ALVES, Tania Maria; SERPA, Mauricio Henriques; YAMAMOTO, Guilherme Lopes; BILT, Martinus Theodorus van de; ROSSLER, Wulf; GATTAZ, Wagner Farid; LOCH, Alexandre AndradeObjectives: To test the association of 45 single nucleotide polymorphisms (SNPs) with transition to psychiatric disorders in a cohort of individuals at ultrahigh risk (UHR) mental state for psychosis.Methods: Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters, and non-converters were analyzed.Results: There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The dopamine receptor D2 gene (DRD2) SNP rs6277 was significantly more common among UHR who transitioned to psychosis (p o 0.001) and to UHR who transitioned to any psychiatric disorders (p = 0.001) when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR converters than UHR non-converters and control subjects (p = 0.003).Conclusion: Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at-risk mental states, warranting further investigation in larger samples.
- 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 .
- Inequality and barriers in psychosis prevention: A systematic review on clinical high-risk for psychosis studies from developing countries(2023) LOCH, Alexandre Andrade; LOPES-ROCHA, Ana Caroline; FEKIH-ROMDHANE, Feten; BILT, Martinus Theodorus van de; PABLO, Gonzalo Salazar de; FUSAR-POLI, PaoloBackground: The clinical high-risk for psychosis (CHR) paradigm is one of the best studied preventive paradigms in psychiatry. However, most studies have been conducted in high-income countries. It is unclear if knowledge from such countries applies to low and middle-income countries (LAMIC), and if there are specific limitations hindering CHR research there. Our aim is to systematically review studies on CHR from LAMIC. Methods: A multistep PRISMA-compliant literature search was performed in PubMed and Web of Science for articles published until 1/03/2022, conducted in LAMIC, addressing the concept and correlates of CHR. Study characteristics as well as limitations were reported. Corresponding authors of the included studies were invited to answer an online poll. Quality assessment was done with the MMAT. Results: A total of 109 studies were included in the review: none from low-income countries, 8 from lower middle-income countries, and 101 from upper middle-income countries. The most frequent limitations were small sample size (47.9%), cross-sectional design (27.1%), and follow-up issues (20.8%). Mean quality of included studies was of 4.4. Out of the 43 corresponding authors, 12 (27.9%) completed the online poll. They cited further limitations as few financial resources (66.7%), no involvement of population (58.2%) and cultural barriers (41.7%). Seventy five percent researchers reported that CHR research should be conducted differently in LAMIC compared to high-income countries, due to structural and cultural issues. Stigma was mentioned in three out of five sections of the poll. Discussion: Results show the discrepancy of available evidence on CHR in LAMIC, given the shortage of resources in such countries. Future directions should aim to increase the knowledge on individuals at CHR in such settings, and to address stigma and cultural factors that may play a role in the pathways toward care in psychosis.
- Addressing Mood Disorder Diagnosis' Stigma With an Honest, Open, Proud (HOP)-Based Intervention: A Randomized Controlled Trial(2021) MODELLI, Arlete; SETTI, Viviane P. Candal; BILT, Martinus Theodorus van de; GATTAZ, Wagner Farid; LOCH, Alexandre Andrade; ROSSLER, WulfIntroduction: The public stigma and self-stigma contribute to the dilemma of disclosing or not one's own mental illness diagnosis. Studies suggest that revealing it diminishes stress, besides helping with self-esteem. Honest, Open, Proud (HOP) is a group program that aids in the process of deciding on it, reducing its impact. Considering the relevance of this issue, the present study aimed to apply a HOP-based intervention in a group of patients diagnosed with mood disorders. Methods: A randomized controlled clinical trial was used, including 61 patients with mood disorders, of whom 31 were diagnosed with depression and 30 were diagnosed with bipolar disorder. They were randomly placed on the intervention (HOP) or the control group (unstructured psychoeducation). The evaluations occurred before (T0) and after (T1) the sessions. We administered eight scales, from which three presented relevant results: Coming Out with Mental Illness Scale (COMIS), Cognitive Appraisal of Stigma as a Stressor (CogApp), and Authenticity Scale. Results: The intervention groups (depression and bipolar) did not present a significant change regarding the decision to disclose their diagnostics. However, the depression group showed a decrease on the perception of stigma as a stressor (T0 = 0.50 vs. T1 = -1.45; p = 0.058). Improvements in post-intervention results were seen for both groups (depression and bipolar) on the Authenticity Scale-self-alienation subscale (T0 = 10.40 vs. T1 = 12.37, p = 0.058). Conclusion: Our HOP-based intervention appeared to be an important program to aid patients in facing stigma stress, showing positive effects, whether helping to diminish stress or to improve self-conscience, both of which have indirect effects on self-stigma. As it is a compact program, it can bring benefits when applying to public health institutions.
- Treatment of Patients with Recently Exacerbated Schizophrenia with Paliperidone Palmitate: A Pilot Study of Efficacy and Tolerability(2020) GATTAZ, Wagner F.; SARACCO-ALVAREZ, Ricardo; DALTIO, Claudiane Salles; BILT, Martinus T. Van de; ORTEGON, Jose Julian; VILLASENOR-BAYARDO, Sergio J.; LOUZA, Mario; ELKIS, Helio; SOARES, Bernardo; JARAMILLO, Patricia Cabrera; LAWSON, Fabio; DIAZ-GALVIS, LeonardoBackground: Paliperidone palmitate is a long-acting, second-generation antipsychotic (SGA) indicated for the treatment of acute exacerbations and maintenance treatment of adults with schizophrenia. This study addressed the response to paliperidone palmitate in Latin American patients with acute symptoms and recently diagnosed schizophrenia. Objective: Explore the efficacy and tolerability of paliperidone palmitate administered once a month for 4 months in patients with acute phase and recent diagnosis (within 1-6 years) of schizophrenia in 3 Latin American countries. Methods: This was a non-randomized, open-label, multicenter study with paliperidone palmitate injected intramuscularly in the deltoid muscle at an initial loading dose of 150 mg eq. (234 mg) on day 1 and 100 mg eq. (156 mg) on day 8 (+/- 4 days). The recommended maintenance dose was 75 mg eq. (117 mg) from day 36 to day 92. Efficacy was evaluated with PANSS and CGI-S. The last observation carried forward (LOCF) was used for efficacy analysis for imputation of missing data; no adjustments were made for multiplicity. Adverse events were evaluated during treatment. Results: The patient retention rate was 84.0% (144 patients received study drug; 121 finished the study). The percentage of patients with a reduction of at least 30% in PANSS total score compared to baseline gradually increased during the study, and at the end, 78.4% of patients showed response. The PANSS total score and CGI-S scores decreased significantly from baseline to LOCF endpoint (P <0.0001 for both); significant reduction in PANSS total score was observed at day 8 and persisted to the end of the study. Most common adverse events were muscle rigidity (11.8%), akathisia (11.1%), injection-site pain (7.6%), weight gain (7.6%), and insomnia (7.6%). Conclusion: Paliperidone palmitate was efficacious in Latin American patients studied with an acute exacerbation and recent diagnosis of schizophrenia, and no new safety signals were identified.
- Plasma Metabolite Profiles in First Episode Psychosis: Exploring Symptoms Heterogeneity/Severity in Schizophrenia and Bipolar Disorder Cohorts(2020) JOAQUIM, Helena P. G.; COSTA, Alana C.; TALIB, Leda L.; DETHLOFF, Frederik; SERPA, Mauricio H.; ZANETTI, Marcus V.; BILT, Martinus van de; TURCK, Christoph W.Introduction The first symptoms of psychosis are frequently shared amongst several neuropsychiatry disorders, which makes the differentiation by clinical diagnosis challenging. Early recognition of symptoms is important in the management of psychosis. Therefore, the implementation of molecular biomarkers will be crucial for transforming the currently used diagnostic and therapeutic approach, improving insights into the underlying biological processes and clinical management. Objectives To define a set of metabolites that supports diagnosis or prognosis of schizophrenia (SCZ) and bipolar disorder (BD) at first onset psychosis. Methods Plasma samples from 55 drug-naive patients, 28 SCZ and 27 BD, and 42 healthy controls (HC). All participants underwent a seminaturalistic treatment regimen, clinically evaluated on a weekly basis until achieving clinical remission. All clinical or sociodemographic aspects considered for this study were equivalent between the groups at first-onset psychosis time point. The plasma samples were analyzed by untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) using reversed-phase and hydrophilic interaction chromatography. The acquired molecular features were analyzed with MetaboAnalyst. Results We identified two patient groups with different metabolite profiles. Both groups are composed of SCZ and BD patients. We found differences between these two groups regarding general symptoms of PANSS score after remission (p = 0.008), and the improvement of general symptoms (delta of the score at remission minus the baseline) (-0.50 vs. -0.33, p = 0.019). Conclusion Our results suggest that plasma metabolite profiles cluster clinical remission phenotypes based on PANSS general psychopathology scores.
- A randomized clinical trial of home-based telepsychiatric outpatient care via videoconferencing: design, methodology, and implementation(2015) HUNGERBUEHLER, Ines; LEITE, Rodrigo Fonseca Martins; BILT, Martinus Theodorus van de; GATTAZ, Wagner FaridBackground: Healthcare providers are continuously challenged to find innovative, cost-effective alternatives and to scale up existent services to meet the growing demand upon mental health care delivery. Due to continuous advances in technologies, telepsychiatry has become an effective tool for psychiatric care. In 2012, the Institute of Psychiatry of the University of Sao Paulo Medical School started a randomized clinical trial of home-based telepsychiatric outpatient care via videoconferencing. Objective: The objective of this article is to describe the design, methodology and implementation of a pilot project, which aimed to verify the applicability and efficiency of psychiatric attendance via Internet-based videoconferencing in a resource-constrained environment. Methods: The project consisted of a 12 months follow-up study with a randomized clinical trial, which compared various quality indicators between home-based telepsychiatric aftercare via videoconferencing and face-to-face aftercare. Results: The final sample comprised 107 outpatients (53 in the telepsychiatry group and 54 in the control group). Among 1,227 realized consultations, 489 were held by videoconferencing. Satisfaction with the aftercare by videoconferencing and the medication delivery was high among patients. Attending psychiatrists were satisfied with the assistance by videoconferencing. Discussion: The experiences during this pilot project have overall been very positive and psychiatric outpatient care by videoconferencing seems viable to treat patients even in a resource-constrained environment.
- Translation and validation of the Structured Interview for Prodromal Syndromes (SIPS) to Portuguese(2021) DINIZ, Gabriel N.; SANTOS, Pedro A. M. F.; ANDRADE, Julio C.; ALVES, Tania M.; HORTENCIO, Lucas; BILT, Martinus T. van de; ROESSLER, Wulf; GATTAZ, Wagner F.; LOCH, Alexandre A.