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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- Detecting at-risk mental states for psychosis (ARMS) using machine learning ensembles and facial features(2023) LOCH, Alexandre Andrade; GONDIM, Joao Medrado; ARGOLO, Felipe Coelho; LOPES-ROCHA, Ana Caroline; ANDRADE, Julio Cesar; BILT, Martinus Theodorus van de; JESUS, Leonardo Peroni de; HADDAD, Natalia Mansur; CECCHI, Guillermo A.; MOTA, Natalia Bezerra; GATTAZ, Wagner Farid; CORCORAN, Cheryl Mary; ARA, AndersonAims: Our study aimed to develop a machine learning ensemble to distinguish ""at-risk mental states for psychosis"" (ARMS) subjects from control individuals from the general population based on facial data extracted from video-recordings.Methods: 58 non-help-seeking medication-naive ARMS and 70 healthy subjects were screened from a general population sample. At-risk status was assessed with the Structured Interview for Prodromal Syndromes (SIPS), and ""Subject's Overview"" section was filmed (5-10 min). Several features were extracted, e.g., eye and mouth aspect ratio, Euler angles, coordinates from 51 facial landmarks. This elicited 649 facial features, which were further selected using Gradient Boosting Machines (AdaBoost combined with Random Forests). Data was split in 70/30 for training, and Monte Carlo cross validation was used.Results: Final model reached 83 % of mean F1-score, and balanced accuracy of 85 %. Mean area under the curve for the receiver operator curve classifier was 93 %. Convergent validity testing showed that two features included in the model were significantly correlated with Avolition (SIPS N2 item) and expression of emotion (SIPS N3 item).Conclusion: Our model capitalized on short video-recordings from individuals recruited from the general population, effectively distinguishing between ARMS and controls. Results are encouraging for large-screening purposes in low-resource settings.
- 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.
- 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.
- Plasma levels of neurotrophin 4/5, NGF and pro-BDNF influence transition to mental disorders in a sample of individuals at ultra-high risk for psychosis(2023) LOCH, Alexandre Andrade; PINTO, Marcel Tavares Camilo; ANDRADE, Julio Cesar; JESUS, Leonardo Peroni de; MEDEIROS, Matheus Wanderley de; HADDAD, Natalia Mansur; BILT, Martinus Theodorus van de; TALIB, Leda Leme; GATTAZ, Wagner FaridBackground: Neurotrophins (NTs) and their precursors (pro-NTs) are polypeptides with important roles in neuronal development, differentiation, growth, survival and plasticity, as well as apoptosis and neuronal death. Imbalance in NT levels were observed in schizophrenia spectrum disorders, but evidence in ultra-high risk for psychosis (UHR) samples is scarce. Methods: A naturalistic sample of 87 non-help-seeking UHR subjects and 55 healthy controls was drawn from the general population. Blood samples were collected and NT-3, NT-4/5, BDNF, pro-BDNF, NGF, pro-NGF were analyzed through enzyme linked immunosorbent assay (ELISA). Information on cannabis and tobacco use was also collected. Logistic regression models and path analysis were used to control for confounders (tobacco, age, cannabis use). Results: NT-4/5 was significantly decreased, and pro-BDNF was significantly increased in UHR individuals compared to controls. Cannabis use and higher NGF levels were significantly related to transition to psychiatric disorders among UHR subjects. Increased pro-BDNF and decreased NT-4/5 influenced transition by the mediation of perceptual abnormalities. Conclusions: Our study shows for the first time that NTs are altered in UHR compared to healthy control individuals, and that they can be a predictor of transition to psychiatric illnesses in this population. Future studies should employ larger naturalistic samples to confirm the findings.
- 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.
- Inflammatory cytokines and white matter microstructure in the acute phase of first-episode psychosis: A longitudinal study(2023) SERPA, Mauricio; DOSHI, Jimit; JOAQUIM, Helena P. G.; VIEIRA, Erica L. M.; ERUS, Guray; CHAIM-AVANCINI, Tiffany M.; CAVALLET, Mikael; GUGLIELMI, Luiza Guilherme; SALLET, Paulo C.; TALIB, Leda; TEIXEIRA, Antonio L.; BILT, Martinus T. van de; MCGUIRE, Philip; GATTAZ, Wagner F.; DAVATZIKOS, Christos; BUSATTO, Geraldo F.; V, Marcus ZanettiObjectives: Schizophrenia-related psychosis is associated with abnormalities in white matter (WM) microstructure and structural brain dysconnectivity. However, the pathological process underlying such changes is unknown. We sought to investigate the potential association between peripheral cytokine levels and WM microstructure during the acute phase of first-episode psychosis (FEP) in a cohort of drug-naive patients.Methods: Twenty-five non-affective FEP patients and 69 healthy controls underwent MRI scanning and blood collection at study entry. After achieving clinical remission, 21 FEP were reassessed; 38 age and biological sex -matched controls also had a second assessment. We measured fractional anisotropy (FA) of selected WM regions -of-interest (ROIs) and plasma levels of four cytokines (IL-6, IL-10, IFN-& gamma;, and TNF-& alpha;).Results: At baseline (acute psychosis), the FEP group showed reduced FA relative to controls in half the examined ROIs. Within the FEP group, IL-6 levels were negatively correlated with FA values. Longitudinally, patients showed increments of FA in several ROIs affected at baseline, and such changes were associated with reductions in IL-6 levels.Conclusions: A state-dependent process involving an interplay between a pro-inflammatory cytokine and brain WM might be associated with the clinical manifestation of FEP. This association suggests a deleterious effect of IL-6 on WM tracts during the acute phase of psychosis.
- Cannabis use influences disorganized symptoms severity but not transition in a cohort of non-help-seeking individuals at-risk for psychosis from Sao Paulo, Brazil(2024) MEDEIROS, Matheus Wanderley de; ANDRADE, Julio Cesar; HADDAD, Natalia Mansur; MENDONCA, Melina; JESUS, Leonardo Peroni de; FEKIH-ROMDHANE, Feten; BILT, Martinus Theodorus van de; GATTAZ, Wagner Farid; LOCH, Alexandre AndradeBackground: Cannabis use is associated with an increased risk of developing a psychotic disorder. However, in individuals with at-risk mental states for psychosis (ARMS) this association is not clear, as well as the impact of cannabis use on symptom severity. The objective of this study was to evaluate the association of cannabis use patterns and ARMS risk status, transition to psychotic and psychiatric disorders, and psychopathology.Method: A sample of 109 ARMS and 197 control individuals was drawn from the general population. Lifetime, maximum and current amount of cannabis use were assessed with the South Westminster modified questionnaire. Participants were followed-up for a mean of 2.5 years and reassessed for transition to any psychiatric disorder. Results: There were no differences between ARMS and controls regarding lifetime use, current amount of use, or maximum amount of cannabis use. There were also no differences between those who transitioned to a psychiatric disorder and those who did not regarding cannabis use variables. In ARMS individuals, cannabis use was significantly related to disorganization symptoms.Conclusion: The results of this study suggest that cannabis plays a role in the psychopathology of ARMS individuals, leading to more severe symptomatology.