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
12 resultados
Resultados de Busca
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- A Longitudinal MRI-study of the Effects of Lithium on Cortical Thickness and Brain Volume and its association with Clinical Response in Bipolar Disorder(2019) COSTA, Sabrina C. da; ZANETTI, Marcus V.; SUCHTING, Robert; SOUZA, Rafael T. de; OTADUY, Maria C.; LEITE, Claudia C.; BUSATTO, Geraldo F.; GATTAZ, Wagner F.; SOARES, Jair C.; MACHADO-VIEIRA, Rodrigo
- Does BDNF genotype influence creative output in bipolar I manic patients?(2012) SOEIRO-DE-SOUZA, Marcio Gerhardt; POST, Robert M.; SOUSA, Mario Lucio de; MISSIO, Giovani; PRADO, Carolina Martins do; GATTAZ, Wagner F.; MORENO, Ricardo A.; MACHADO-VIEIRA, RodrigoIntroduction: Creativity is a complex human ability influenced by affective and cognitive components but little is known about its underlying neurobiology. Bipolar Disorder (BD) is highly prevalent among creative individuals. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophic factor, and has been implicated in the pathophysiology of BD. In contrast to the better functioning of the BDNF polymorphism (Val(66)Met) Val allele, the Met allele decreases BDNF transport and has been associated with worsened performance on several cognitive domains in euthymic BD subjects and controls. We hypothesized that the Val allele is associated with increased creativity in bipolar disorder. Materials and methods: Sixty-six subjects with BD (41 in manic and 25 in depressive episodes) and 78 healthy volunteers were genotyped for BDNF Val(66)Met and tested for creativity using the Barrow Welsh Art Scale (BWAS) and neuropsychological tests. Results: Manic patients with the Val allele (Met-) had higher BWAS scores than Met+ carriers. This relationship was not observed among patients in depressive episodes or among control subjects. BDNF Met allele status showed no association with cognitive function in any of the groups. Conclusion: As postulated, these findings suggest that the better functioning allele of BDNF may selectively facilitate creative thinking in subjects with manic episodes, but not in controls or depressives. Further studies exploring the role of BDNF in the neurobiology of creativity in BD and in euthymic phases are warranted.
- Cognitive outcomes of TMS treatment in bipolar depression: Safety data from a randomized controlled trial(2018) MYCZKOWSKI, Martin L.; FERNANDES, Adriano; MORENO, Marina; VALIENGO, Leandro; LAFER, Beny; MORENO, Ricardo A.; PADBERG, Frank; GATTAZ, Wagner; BRUNONI, Andre R.Background: Bipolar depression (BD) is a highly prevalent condition associated with marked cognitive deficits that persist even in the euthymic phase of the illness. Pharmacological treatments for BD might further aggravate cognitive impairment, highlighting the need of developing interventions that present cognitive safety. In this study, we evaluated the cognitive effects of H1-coil (deep) transcranial magnetic stimulation (TMS) in patients with treatment-resistant bipolar depression. Methods: Fourty-three patients were randomized to receive 20 sessions of active (55 trains, 18 Hz, 120% resting motor threshold intensity) or sham rTMS within a double-blind, sham-controlled trial. A battery of 20 neuropsychological assessments, grouped in 6 domains (attention and processing speed, working memory and executive function, inhibitory control, language, immediate verbal memory, and long-term verbal memory) was performed at baseline and after 4 and 8 weeks of trial onset. Depressive symptoms were assessed with the 17 item Hamilton Rating Scale for Depression. Results: Cognitive improvement was shown for all cognitive domains. It occurred regardless of intervention group and depression improvement. For the language domain, greater improvement was observed in the sham group over time. No correlations between depression (at baseline or during treatment) and cognitive improvement were found. Limitations: Absence of healthy control group. Conclusion: The results of this exploratory study provide evidence on the cognitive safety of H1-coil TMS for BD patients. Putative pro-cognitive effects of rTMS in BD were not observed and thus should be further investigated.
- The role of lithium treatment on comorbid anxiety symptoms in patients with bipolar depression(2022) JONES, Gregory; RONG, Carola; VECERA, Courtney M.; I, Christopher Gurguis; CHUDAL, Roshan; KHAIROVA, Rushaniya; LEUNG, Edison; RUIZ, Ana C.; SHAHANI, Lokesh; V, Marcus Zanetti; SOUSA, Rafael T. de; BUSATTO, Geraldo; SOARES, Jair; GATTAZ, Wagner F.; MACHADO-VIEIRA, RodrigoBackground: Comorbid anxiety is pervasive and carries an immense psychosocial burden for patients with bipolar disorder. Despite this, trials reporting anxiety-related outcomes in this population are uncommon, particularly with regards to monotherapies.Methods: Patients (n = 31) with both bipolar I or II disorder in current depressive episodes were enrolled in a sixweek, open-label, single-center trial assessing the efficacy of lithium monotherapy in treating symptoms depression and comorbid anxiety. Patients were mostly medication-free and lithium-naive at baseline.Results: Significant improvements in depression (HAM-D) and anxiety (HAM-A) were observed at the six-week endpoint, with remission and response rates greater than 50%. There was a positive correlation between endpoint HAM-A scores and HAM-D scores, r = 0.80, (p < 0.01). Improvements were realized at low serum lithium concentrations (0.49 +/- 0.20 mEq/L). Limitations: Lack of placebo control and small sample size warrants validation in larger randomized studies.Conclusions: Taken in the context of prior evidence, lithium may have an important role in treating comorbid anxiety in bipolar disorder, both as adjunct and monotherapy. Lower doses of lithium may provide equivalent efficacy and enhance tolerability and compliance.
- 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.
- Plasma cortisol in first episode drug-naive mania: Differential levels in euphoric versus irritable mood(2012) VALIENGO, Leandro L.; SOEIRO-DE-SOUZA, Marcio G.; MARQUES, Andrea H.; MORENO, Doris H.; JURUENA, Mario F.; ANDREAZZA, Ana Cristina; GATTAZ, Wagner F.; MACHADO-VIEIRA, RodrigoBackground: Dysregulation of HPA axis has been widely described in subjects with bipolar disorder (BD), including changes in cortisol levels during mood episodes and euthymia. However, most of the studies were done with medicated BD patients with variable length of illness, which was shown to interfere on peripheral cortisol levels. Therefore, the present study aims to evaluate plasma cortisol levels in drug-naive BD subjects during the first manic episode, as well as investigate the relationship between plasma cortisol levels and manic symptomatology. Methods: Twenty-six drug-naive patients were enrolled meeting criteria for a first manic episode in bipolar I disorder. Severity of mania was assessed using the Young Mania Rating Scale (YMRS). The control group included 27 healthy subjects matched by age and gender. Cortisol was quantified using a direct radioimmunoassay. Results: Plasma cortisol levels were decreased during first manic episode compared to healthy controls. Higher cortisol levels were positively associated with the presence of irritability (dysphoria), while elated mania showed lower cortisol levels compared to controls. Limitation: Data including larger samples are lacking. Conclusion: Higher cortisol in dysphoric mania compared to predominantly elated/euphoric mania may indicate a clinical and neurobiological polymorphic phenomenon, potentially involving a higher biological sensitivity to stress in the presence of irritable mood. The present findings highlight the importance to add a dimensional approach to the traditional categorical diagnosis for future neurobiological studies in BD.
- 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.
- COMT Met (158) modulates facial emotion recognition in bipolar I disorder mood episodes(2012) SOEIRO-DE-SOUZA, Marcio Gerhardt; BIO, Danielle Soares; DAVID, Denise Petresco; SANTOS JR., Domingos Rodrigues dos; KERR, Daniel Shikanai; GATTAZ, Wagner Farid; MACHADO-VIEIRA, Rodrigo; MORENO, Ricardo AlbetoBackground: One of the many cognitive deficits reported in bipolar disorder (BD) patients is facial emotion recognition (FER), which has recently been associated with dopaminergic catabolism. Catechol-O-methyltransferase (COMT) is one of the main enzymes involved in the metabolic degradation of dopamine (DA) in the prefrontal cortex (PFC). The COMT gene polymorphism rs4680 (Val(158)Met) Met allele is associated with decreased activity of this enzyme in healthy controls. The objective of this study was to evaluate the influence of Val(158)Met on FER during manic and depressive episodes in BD patients and in healthy controls. Materials and methods: 64 BD type I patients (39 in manic and 25 in depressive episodes) and 75 healthy controls were genotyped for COMT rs4680 and assessed for FER using the Ekman 60 Faces (EK60) and Emotion Hexagon (Hx) tests. Results: Bipolar manic patients carrying the Met allele recognized fewer surprised faces, while depressed patients with the Met allele recognized fewer ""angry"" and ""happy"" faces. Healthy homozygous subjects with the Met allele had higher FER scores on the Hx total score, as well as on ""disgust"" and ""angry"" faces than other genotypes. Conclusion: This is the first study suggesting that COMT rs4680 modulates FER differently during BD episodes and in healthy controls. This provides evidence that PFC DA is part of the neurobiological mechanisms of social cognition. Further studies on other COMT polymorphisms that include euthymic BD patients are warranted. ClinicalTrials.gov Identifier: NCT00969.
- Early improvement with lithium in classic mania and its association with later response(2013) MACHADO-VIEIRA, Rodrigo; LUCKENBAUGH, David A.; SOEIRO-DE-SOUZA, Marcio G.; MARCA, Getulio; HENTER, Ioline D.; BUSNELLO, Joao V.; GATTAZ, Wagner F.; ZARATE JR., Carlos A.Objectives: Despite lithium's clinical efficacy in treating mania in bipolar disorder (BD), studies evaluating early improvement and subsequent treatment response are sparse. This study investigated whether early improvement (within one week) to lithium monotherapy predicted later response and remission in individuals with BD mania. Methods: BD-I patients (n=46) experiencing a manic episode received lithium monotherapy for four weeks (initial dose: 600 mg/d, adjusted to therapeutic levels); individuals experiencing a mixed episode, rapid cyclers, previous non-responders to lithium, and those with current drug abuse/dependence were excluded. Symptoms were rated using the Young Mania Rating Scale (YMRS) at baseline and at Days 7, 14, 21, and 28. Results: Thirty-three percent of the total sample responded to lithium within the first week of treatment, defined as a >= 50% decrease from baseline YMRS scores; 63% responded by study endpoint. In addition, 39% of the total sample showed early improvement (at least 20% decrease in YMRS scores) after one week of treatment. In this group, 79% responded to lithium by study endpoint. Among those showing less than 20% improvement at Week 1, only 23% responded to lithium by study endpoint. Limitations: History of episodes sequence was not assessed. Conclusions: Early improvement in response to lithium monotherapy in subjects with BD mania predicted later response and remission. Most patients who did not show early improvement in response to lithium during the first week of treatment showed no response after one month. The findings provide a valuable clinical tool for early identification of those patients most likely to benefit from lithium in clinical practice.
- 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.