LEDA LEME TALIB
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
9 resultados
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- BDNF blood levels after electroconvulsive therapy in patients with mood disorders: An updated systematic review and meta-analysis(2023) PELOSOF, Rebeca; SANTOS, Leonardo A. dos; FARHAT, Luis C.; GATTAZ, Wagner F.; TALIB, Leda; BRUNONI, Andre R.Objectives Studies have suggested Brain-Derived Neurotrophic Factors (BDNF) increase after electroconvulsive therapy (ECT) although they were methodologically limited and enrolled small sample sizes. We aimed at updating a systematic review and meta-analysis to explore BDNF changes after ECT for the treatment of depression. Methods PubMed, PsycInfo, Embase and Global health were searched (March, 2021). Clinical trials that measured BDNF in the blood before and after ECT in adults (>= 18 years old) with depression (major depressive disorder or bipolar disorder) were eligible. Data were pooled through random-effects meta-analyses. Results Twenty-eight studies involving 778 participants were included. Meta-analysis showed a significant increase in BDNF levels after ECT (Hedges' g = 0.28; 95% CI: 0.10, 0.46) while there was evidence of significant heterogeneity (I-2 = 67.64%) but not publication bias/small-study effect. Subgroup analyses and meta-regressions were underpowered to detect significant differences. Meta-analysis of depression severity scores demonstrated a considerable larger treatment effect in reducing depressive symptoms after ECT (Hedge's g = -3.72 95% CI: -4.23, -3.21). Conclusion This updated review showed that BDNF blood levels increased after ECT treatment. However, there was still evidence of substantial heterogeneity and there were limited sample sizes to investigate factors driving the variability of effects across studies. Importantly, the increase in BDNF levels was substantially smaller than the observed in depressive symptomatology, which could be indicative that the former was independent than the latter. Additional studies with larger sample sizes are currently required.
- 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.
- Whole-brain DTI parameters associated with tau protein and hippocampal volume in Alzheimer's disease(2023) MAGALHAES, Thamires Naela Cardoso; CASSEB, Raphael Fernandes; GERBELLI, Christian Luiz Baptista; PIMENTEL-SIVA, Luciana Ramalho; NOGUEIRA, Mateus Henrique; TEIXEIRA, Camila Vieira Ligo; CARLETTI, Ana Flavia Mac Knight; REZENDE, Thiago Junqueira Ribeiro de; JOAQUIM, Helena Passarelli Giroud; TALIB, Leda Leme; FORLENZA, Orestes Vicente; CENDES, Fernando; BALTHAZAR, Marcio Luiz FigueredoThe causes of the neurodegenerative processes in Alzheimer's disease (AD) are not completely known. Recent studies have shown that white matter (WM) damage could be more severe and widespread than whole-brain cortical atrophy and that such damage may appear even before the damage to the gray matter (GM). In AD, Amyloid-beta (A beta(42)) and tau proteins could directly affect WM, spreading across brain networks. Since hippocampal atrophy is common in the early phase of disease, it is reasonable to expect that hippocampal volume (HV) might be also related to WM integrity. Our study aimed to evaluate the integrity of the whole-brain WM, through diffusion tensor imaging (DTI) parameters, in mild AD and amnestic mild cognitive impairment (aMCI) due to AD (with A beta(42) alteration in cerebrospinal fluid [CSF]) in relation to controls; and possible correlations between those measures and the CSF levels of A beta(42), phosphorylated tau protein (p-Tau) and total tau (t-Tau). We found a widespread WM alteration in the groups, and we also observed correlations between p-Tau and t-Tau with tracts directly linked to mesial temporal lobe (MTL) structures (fornix and hippocampal cingulum). However, linear regressions showed that the HV better explained the variation found in the DTI measures (with weak to moderate effect sizes, explaining from 9% to 31%) than did CSF proteins. In conclusion, we found widespread alterations in WM integrity, particularly in regions commonly affected by the disease in our group of early-stage disease and patients with Alzheimer's disease. Nonetheless, in the statistical models, the HV better predicted the integrity of the MTL tracts than the biomarkers in CSF.
- Cholinesterase Inhibitors Response Might Be Related to Right Hippocampal Functional Connectivity in Mild Alzheimer's Disease(2023) RIZZI, Liara; MAGALHAES, Thamires Naela Cardoso; LECCE, Natalie; MORAES, Adriel dos Santos; CASSEB, Raphael Fernandes; TEIXEIRA, Camila Vieira Ligo; CAMPOS, Brunno Machado de; REZENDE, Thiago Junqueira Ribeiro de; TALIB, Leda Leme; FORLENZA, Orestes Vicente; CENDES, Fernando; BALTHAZAR, Marcio Luiz FigueredoBackground: The response to cholinesterase inhibitors (ChEIs) treatment is variable in patients with Alzheimer's disease (AD). Patients and physicians would benefit if these drugs could be targeted at those most likely to respond in a clinical setting. Therefore, this study aimed to evaluate the ability of cerebrospinal fluid (CSF) AD biomarkers, hippocampal volumes, and Default Mode Network functional connectivity to predict clinical response to ChEIs treatment in mild AD.Methods: We followed up on 39 mild AD patients using ChEIs at therapeutic doses. All subjects underwent clinical evaluation, neuropsychological assessment, magnetic resonance imaging examination, and CSF biomarkers quantification at the first assessment. The Mini-Mental Status Examination (MMSE) was used to measure the global cognitive status before and after the follow-up. ""Responders"" were considered as those who have remained stable or improved the MMSE score between evaluations and ""Nonresponders"" as those who have worsened the MMSE score. We performed univariate and multivariate logistic regressions to predict the clinical response from each biomarker.Results: About 35.89% of patients were classified as ""Responders"" to ChEIs treatment after the follow-up. The multivariate model with measures of Right Hippocampus (RHIPPO), adjusted for gender and interval between assessments, was significant (odds ratio: 1.09 [95% confidence interval, 1.00-1.19], p = 0.0392). This model achieved an accuracy of 77.60%.Conclusion: Our findings suggest that the functional connectivity of RHIPPO might be an early imaging biomarker to predict clinical response to ChEIs drugs in mild AD. Impact statementThe functional connectivity of the right hippocampus showed a direct relationship with the clinical response to cholinesterase inhibitors (ChEIs) treatment in patients with mild Alzheimer's disease. Transposing our findings to clinical settings could allow physicians to prescribe ChEIs for patients for whom treatment would be most beneficial.
- 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.
- 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.
- Revisiting global cognitive and functional state 13 years after a clinical trial of lithium for mild cognitive impairment(2023) DAMIANO, Rodolfo Furlan; LOUREIRO, Julia Cunha; PAIS, Marcos Vasconcelos; PEREIRA, Rodrigo Furtado; CORRADI, Marina de Menezes; SANTI, Talita Di; BEZERRA, Gustavo Antonio Marcolongo; RADANOVIC, Marcia; TALIB, Leda Leme; FORLENZA, Orestes VicenteObjectives: To re-evaluate a sample of older adults enrolled in a randomized controlled trial of lithium for amnestic mild cognitive impairment (MCI) after 11 to 15 years, re-assessing their current (or last available) global cognitive and functional state.Methods: We recalled all former participants of the Lithium-MCI trial conducted by our group between 2009 and 2012 to perform a single-blinded, cross-sectional evaluation of their global clinical state to compare the long-term outcome of those who received lithium vs. those who received placebo.Results: Of the original sample (n=61), we were able to reach 36 participants (59% of retention), of whom 22 had previously received lithium (61% of the recall sample) and 14 (39%) had received placebo. Since 30.5% of the recalled sample was deceased, psychometric data were collected only for 69.5% of the participants. We found statistically significant differences in current mean Mini Mental State Examination score according to previous treatment group (25.5 [SD, 5.3] vs. 18.3 [SD, 10.9], p = 0.04). The lithium group also had better performance in the phonemic Verbal Fluency Test than the control group (34.4 [SD, 14.4] vs. 11.6 [SD, 10.10], p o 0.001). Differences in these measures also had large effect sizes, as shown by Cohen's d values of 0.92 and 1.78, respectively.Conclusion: This data set suggests that older adults with amnestic MCI who had been treated with lithium during a previous randomized controlled trial had a better long-term global cognitive outcome than those from a matched sample who did not receive the intervention.
- 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.
- Cognitive impairment in long-COVID and its association with persistent dysregulation in inflammatory markers(2023) DAMIANO, Rodolfo Furlan; ROCCA, Cristiana Castanho de Almeida; SERAFIM, Antonio de Padua M.; LOFTIS, Jennifer; TALIB, Leda Leme; PAN, Pedro Mario; CUNHA-NETO, Edecio; KALIL, Jorge; CASTRO, Gabriela Salim de; SEELAENDER, Marilia F.; GUEDES, Bruno K.; MARIE, Suely K. Nagahashi; SOUZA, Heraldo Possolo de; NITRINI, Ricardo; MIGUEL, Euripedes Constantino; BUSATTO, Geraldo; V, Orestes ForlenzaObjectiveTo analyze the potential impact of sociodemographic, clinical and biological factors on the long-term cognitive outcome of patients who survived moderate and severe forms of COVID-19. MethodsWe assessed 710 adult participants (Mean age = 55 +/- 14; 48.3% were female) 6 to 11 months after hospital discharge with a complete cognitive battery, as well as a psychiatric, clinical and laboratory evaluation. A large set of inferential statistical methods was used to predict potential variables associated with any long-term cognitive impairment, with a focus on a panel of 28 cytokines and other blood inflammatory and disease severity markers. ResultsConcerning the subjective assessment of cognitive performance, 36.1% reported a slightly poorer overall cognitive performance, and 14.6% reported being severely impacted, compared to their pre-COVID-19 status. Multivariate analysis found sex, age, ethnicity, education, comorbidity, frailty and physical activity associated with general cognition. A bivariate analysis found that G-CSF, IFN-alfa2, IL13, IL15, IL1.RA, EL1.alfa, IL45, IL5, IL6, IL7, TNF-Beta, VEGF, Follow-up C-Reactive Protein, and Follow-up D-Dimer were significantly (p<.05) associated with general cognition. However, a LASSO regression that included all follow-up variables, inflammatory markers and cytokines did not support these findings. ConclusionThough we identified several sociodemographic characteristics that might protect against cognitive impairment following SARS-CoV-2 infection, our data do not support a prominent role for clinical status (both during acute and long-stage of COVID-19) or inflammatory background (also during acute and long-stage of COVID-19) to explain the cognitive deficits that can follow COVID-19 infection.