WAGNER FARID GATTAZ
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Psiquiatria, Faculdade de Medicina - Docente
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina - Líder
13 resultados
Resultados de Busca
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conferenceObject EFFICACY AND SAFETY OF TRANSCRANIAL DIRECT CURRENT STIMULATION FOR TREATING NEGATIVE SYMPTOMS IN SCHIZOPHRENIA: THE FOLLOW-UP PHASE(2020) VALIENGO, Leandro; SERPA, Mauricio; ELKIS, Helio; BILT, Martinus Van de; LACERDA, Acioly; GATTAZ, Wagner; BRUNONI, Andre- Three plasma metabolites in elderly patients differentiate mild cognitive impairment and Alzheimer's disease: a pilot study(2020) COSTA, Alana C.; JOAQUIM, Helena P. G.; FORLENZA, Orestes V.; GATTAZ, Wagner F.; TALIB, Leda L.The metabolomic profile of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) may suggest potential diagnostic biomarkers and provide information on the pathophysiology of dementia. Our aim was to quantify plasmatic metabolites of AD patients, MCI and controls. We investigated the metabolomic profile-using the AbsoluteIDQ (R) p180 assay-of 79 older adults with primary cognitive impairment (34 AD and 20 MCI) and 25 healthy elders (controls). A cluster analysis revealed that a combination C12-DC, C12 and PCaaC26:0 could differentiate the patients according to diagnostic. Future studies should combine metabolomic profiles with other biomarkers to identify diagnostic groups.
- Cognitive changes after tDCS and escitalopram treatment in major depressive disorder: Results from the placebo-controlled ELECT-TDCS trial(2020) MORENO, Marina L.; GOERIGK, Stephan A.; BERTOLA, Laiss; SUEMOTO, Claudia K.; RAZZA, Lais B.; MOFFA, Adriano H.; VERONEZI, Beatriz P.; TORT, Luara; NOGUEIRA, Barbara S.; GATTAZ, Wagner F.; FRAGUAS, Renerio; PADBERG, Frank; LOTUFO, Paulo A.; BENSENOR, Isabela M.; BRUNONI, Andre R.Background: Cognitive deficits in major depressive disorder (MDD) are associated with low quality of life and higher suicide risk. Antidepressant drugs have modest to null effects in improving such deficits. Therefore, we investigated the cognitive effects of transcranial direct current stimulation (tDCS), which is a promising antidepressant non-pharmacological intervention, in MDD. Methods: An exploratory analysis on cognitive performance was conducted in 243 depressed patients from the Escitalopram vs. Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS), a sham-controlled study comparing the efficacy of tDCS vs. escitalopram. A neuropsychological battery was applied at baseline and endpoint (10 weeks of treatment) to create composite cognitive scores (processing speed, working memory, and verbal fluency). Linear mixed regression models were used to evaluate changes according to intervention groups, adjusted for confounding variables (age, years of schooling, gender, and benzodiazepine use) and depression improvement. Results: No cognitive deterioration was observed in any group. Patients receiving tDCS presented reduced practice gains compared to placebo in processing speed. In patients receiving escitalopram vs. placebo and in the subgroup of clinical responders ( > 50% depression improvement from baseline), those receiving tDCS vs. placebo presented increased performance in verbal fluency. No significant differences between tDCS and escitalopram groups were detected. Limitations: Absence of healthy controls. Conclusion: Prefrontal tDCS did not lead to cognitive deficits in depressed patients, although it reduced practice effects in processing speed. tDCS responders presented increased performance in verbal fluency. Further investigation of tDCS cognitive effects in depression is warranted.
- Efficacy and Safety of Transcranial Direct Current Stimulation for Treating Negative Symptoms in Schizophrenia A Randomized Clinical Trial(2020) VALIENGO, Leandro da Costa Lane; GOERIGK, Stephan; GORDON, Pedro Caldana; PADBERG, Frank; SERPA, Mauricio Henriques; KOEBE, Stephanie; SANTOS, Leonardo Afonso dos; LOVERA, Roger Alberto Marcos; CARVALHO, Juliana Barbosa de; BILT, Martinus van de; LACERDA, Acioly L. T.; ELKIS, Helio; GATTAZ, Wagner Farid; BRUNONI, Andre R.This randomized clinical trial studies the efficacy and safety of transcranial direct current stimulation compared with sham as an add-on treatment for patients with schizophrenia with predominant negative symptoms. Importance Negative symptoms represent a substantial burden in schizophrenia. Although preliminary studies have suggested that transcranial direct current stimulation (tDCS) is effective for some clusters of symptoms, the clinical benefits for negative symptoms are unclear. Objective To determine the efficacy and safety of tDCS vs sham as an add-on treatment for patients with schizophrenia and predominant negative symptoms. Design, Setting, and Participants The double-blind Schizophrenia Treatment With Electric Transcranial Stimulation (STARTS) randomized clinical trial was conducted from September 2014 to March 2018 in 2 outpatient clinics in the state of Sao Paulo, Brazil. Patients with schizophrenia with stable negative and positive symptoms and a minimum score of 20 points in the negative symptoms subscale of the Positive and Negative Syndrome Scale (PANSS) were included. Interventions Ten sessions of tDCS performed twice a day for 5 days or a sham procedure. The anode and the cathode were positioned over the left prefrontal cortex and the left temporoparietal junction, respectively. Main Outcomes and Measures Change in the PANSS negative symptoms subscale score at week 6 was the primary outcome. Patients were followed-up for an additional 6 weeks. Results Of the 100 included patients, 20 (20.0%) were female, and the mean (SD) age was 35.3 (9.3) years. A total of 95 patients (95.0%) finished the trial. In the intention-to-treat analysis, patients receiving active tDCS showed a significantly greater improvement in PANSS score compared with those receiving the sham procedure (difference, 2.65; 95% CI, 1.51-3.79; number needed to treat, 3.18; 95% CI, 2.12-6.99; P < .001). Response rates for negative symptoms (20% improvement or greater) were also higher in the active group (20 of 50 [40%]) vs the sham group (2 of 50 [4%]) (P < .001). These effects persisted at follow-up. Transcranial direct current stimulation was well tolerated, and adverse effects did not differ between groups, except for burning sensation over the scalp in the active group (43.8%) vs the sham group (14.3%) (P = .003). Conclusions and Relevance Transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia. Question Is transcranial direct current stimulation (tDCS) a safe and effective add-on therapy for negative symptoms in schizophrenia? Findings In this randomized clinical trial of 100 patients with schizophrenia with predominant negative symptoms, active tDCS was superior to sham in ameliorating negative symptoms, with superior response rates (20% improvement) for negative symptoms. These effects were sustained at follow-up, and tDCS was not associated with significant adverse effects. Meaning Transcranial direct current stimulation is an affordable, safe, and effective add-on treatment for negative symptoms in schizophrenia.
- Precision non-implantable neuromodulation therapies: a perspective for the depressed brain(2020) BORRIONE, Lucas; BELLINI, Helena; RAZZA, Lais Boralli; AVILA, Ana G.; BAEKEN, Chris; BREM, Anna-Katharine; BUSATTO, Geraldo; CARVALHO, Andre F.; CHEKROUD, Adam; DASKALAKIS, Zafiris J.; DENG, Zhi-De; DOWNAR, Jonathan; GATTAZ, Wagner; LOO, Colleen; LOTUFO, Paulo A.; MARTIN, Maria da Graca M.; MCCLINTOCK, Shawn M.; O'SHEA, Jacinta; PADBERG, Frank; PASSOS, Ives C.; SALUM, Giovanni A.; VANDERHASSELT, Marie-Anne; FRAGUAS, Renerio; BENSENOR, Isabela; VALIENGO, Leandro; BRUNONI, Andre R.Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more ""precision-oriented"" practice.
- Reduced Annexin A3 in schizophrenia(2020) JOAQUIM, Helena P. G.; COSTA, Alana Caroline; SERPA, Mauricio Henriques; TALIB, Leda L.; GATTAZ, Wagner F.The cellular and molecular mechanisms underlying onset and development of schizophrenia have not yet been completely elucidated, but the association of disturbed neuroplasticity and inflammation has gained particular relevance recently. These mechanisms are linked to annexins functions. ANXA3, particularly, is associated to inflammation and membrane metabolism cascades. The aim was to determine the ANXA3 levels in first-onset drug-naive psychotic patients. We investigated by western blot the protein expression of annexin A3 in platelets of first-onset, drug-naive psychotic patients (diagnoses according to DSM-IV: 28 schizophrenia, 27 bipolar disorder) as compared to 30 age- and gender-matched healthy controls. Annexin A3 level was lower in schizophrenia patients as compared to healthy controls (p < 0.001) and to bipolar patients (p < 0.001). Twenty out of 28 schizophrenic patients had undetectable annexin A3 levels, as compared to none from the bipolar and none from the control subjects. ANXA3 was reduced in drug-naive patients with schizophrenia. ANXA3 affects neuroplasticity, inflammation and apoptosis, as well as it modulates membrane phospholipid metabolism. All these processes have been discussed in regard to the biology of schizophrenia. In face of these data, we feel that further studies with larger samples are warranted to investigate the possible role of reduced ANXA3 as a possible risk marker for schizophrenia.
- Differences in the immune-inflammatory profiles of unipolar and bipolar depression(2020) BRUNONI, Andre R.; SUPASITTHUMRONG, Thitiporn; TEIXEIRA, Antonio Lucio; VIEIRA, Erica L. M.; GATTAZ, Wagner F.; BENSENOR, Isabela M.; LOTUFO, Paulo A.; LAFER, Beny; BERK, Michael; CARVALHO, Andre F.; MAES, MichaelBackground: Major depressive disorder (MDD) and bipolar depression (BD) both share increased immune-inflammatory activation. However, there are unclear patterns of differences in peripheral immune profiles between them. Methods: We examined such differences in 245 MDD and 59 BD patients, recruited in the same center, who were in an acute depressive episode of moderate severity. Hierarchical binary logistic regression analyses and generalized linear models were used to compare levels of plasma biomarkers between groups and to predict dichotomous classification. Results: Interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, soluble TNF receptor (sTNFR)1, IL-12 and IL-10 were significantly higher in MDD than in BD, whereas IL-6, sTNFR2, IL-18, IL-33, ST2 (IL1R Like 1) and KLOTHO were significantly higher in BD than in MDD. Moreover, logistic regression analyses correctly classified BD and MDD patients with 98.1% accuracy, using a combination of IL-6, IL-8, ST2, sTNFR2 (directly associated with BD) and IL-12 and TNF-alpha (directly associated with MDD). Patients with MDD with melancholic features showed higher IL-1 beta levels than those without melancholia. The sTNFR1 / sTNFR2 ratio significantly predicted MDD and state and trait anxiety and negative affect. Results remained significant after covariate adjustment, including drug use. Limitations: Cross-sectional study. Lack of control comparison group. Differences in exposure to medications among participants. Conclusions: Differences in immune profiles between BD and MDD patients exist, especially for the compensatory immune-regulatory system (CIRS): increased IL-10 is the primary immune-regulatory mechanism in MDD, while increased sTNFR2 and KLOTHO are the primary regulatory mechanisms in BD.
- 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.
- Clinical patterns differentially predict response to transcranial direct current stimulation (tDCS) and escitalopram in major depression: A machine learning analysis of the ELECT-TDCS study(2020) KAMBEITZ, Joseph; GOERIGK, Stephan; GATTAZ, Wagner; FALKAI, Peter; BENSENOR, Isabela M.; LOTUFO, Paulo A.; BUEHNER, Markus; KOUTSOULERIS, Nikolaos; PADBERG, Frank; BRUNONI, Andre R.
- Association of BDNF, HTR2A, TPH1, SLC6A4, and COMT polymorphisms with tDCS and escitalopram efficacy: ancillary analysis of a double-blind, placebo-controlled trial(2020) BRUNONI, Andre R.; CARRACEDO, Angel; AMIGO, Olalla M.; PELLICER, Ana L.; TALIB, Leda; CARVALHO, Andre F.; LOTUFO, Paulo A.; BENSENOR, Isabela M.; GATTAZ, Wagner; CAPPI, CarolinaObjective: We investigated whether single nucleotide polymorphisms (SNPs) associated with neuroplasticity and activity of monoamine neurotransmitters, such as the brain-derived neurotrophic factor (BDNF, rs6265), the serotonin transporter (SLC6A4, rs25531), the tryptophan hydroxylase 1 (TPH1, rs1800532), the 5-hydroxytryptamine receptor 2A (HTR2A, rs6311, rs6313, rs7997012), and the catechol-O-methyltransferase (COMT, rs4680) genes, are associated with efficacy of transcranial direct current stimulation (tDCS) in major depression. Methods: Data from the Escitalopram vs. Electrical Current Therapy for Treating Depression Clinical Study (ELECT-TDCS) were used. Participants were antidepressant-free at baseline and presented with an acute, moderate-to-severe unipolar depressive episode. They were randomized to receive escitalopram/tDCS-sham (n=75), tDCS/placebo-pill (n=75), or placebo-pill/sham-tDCS (n=45). General linear models assessed the interaction between treatment group and allele-wise carriers. Additional analyses were performed for each group and each genotype separately. Results: Pairwise group comparisons (tDCS vs. placebo, tDCS vs. escitalopram, and escitalopram vs. placebo) did not identify alleles associated with depression improvement. In addition, exploratory analyses also did not identify any SNP unequivocally associated with improvement of depression in any treatment group. Conclusion: Larger, combined datasets are necessary to identify candidate genes for tDCS response.