LEANDRO DA COSTA LANE VALIENGO

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Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina

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Autor e Coautores FMUSP-HC Normalizados: WAGNER FARID GATTAZ ×

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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
  • article 11 Citação(ões) na Scopus
    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.
  • article 6 Citação(ões) na Scopus
    Cognitive outcomes after tDCS in schizophrenia patients with prominent negative symptoms: Results from the placebo-controlled STARTS trial
    (2021) BULUBAS, Lucia; GOERIGK, Stephan; GOMES, July S.; BREM, Anna-Katharine; CARVALHO, Juliana B.; PINTO, Bianca S.; ELKIS, Helio; GATTAZ, Wagner F.; PADBERG, Frank; BRUNONI, Andre R.; VALIENGO, Leandro
    Cognitive deficits and negative symptoms in schizophrenia are associated with poor functional outcomes and limited in terms of treatment. The Schizophrenia Treatment With Electric Transcranial Stimulation (STARTS) trial has shown efficacy of transcranial direct current stimulation (tDCS) for improving negative symptoms. In this secondary analysis, we investigate its effects on cognitive performance. In STARTS, a double-blinded, sham controlled, randomized clinical trial, patients were treated with twice-daily, 20-min, 2-mA fronto-temporal tDCS over 5 days or sham-tDCS. In 90 patients, we evaluated the cognitive performance up to 12 weeks post-treatment. We found that active-tDCS showed no beneficial effects over sham-tDCS in any of the tests. Based on a 5-factor cognitive model, improvements of executive functions and delayed memory were observed in favor of shamtDCS. Overall, the applied active-tDCS protocol, primarily designed to improve negative symptoms, did not promote cognitive improvement. We discuss possible protocol modification potentially required to increase tDCS effects on cognition. ClinicalTrials.gov identifier: NCT02535676
  • conferenceObject
    Treatment of Negative Symptoms of Schizophrenia With tDCS (Transcranial Direct Current Stimulation): A Randomized, Sham-Controlled, Double-Blinded Clinical Trial
    (2018) VALIENGO, Leandro; BILT, Martinus Theodorus van de; SERPA, Mauricio; GORDON, Pedro; HELKIS, Helio; GATTAZ, Wagner Farid; LACERDA, Acioly; BRUNONI, Andre
  • conferenceObject
    TREATMENT OF NEGATIVE SYMPTOMS OF SCHIZOPHRENIA WITH TRANSCRANIAL CURRENT STIMULATION (TDCS): RESULTS OF RANDOMIZED, DOUBLE-BLINDED, SHAMCONTROLLED TRIAL
    (2018) VALIENGO, Leandro; GORDON, Pedro; SERPA, Mauricio; LACERDA, Acioly; GATTAZ, Wagner; BILT, Martinus Van de; HELKIS, Helio; BRUNONI, Andre
  • article 49 Citação(ões) na Scopus
    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.
  • conferenceObject
    Plasma Cortisol in First Episode Drug-Naive Mania: Differential Levels in Euphoric Versus Irritable Mood
    (2012) VALIENGO, Leandro L.; SOEIRO-DE-SOUZA, Marcui G.; MARQUES, Andrea H.; JURUENA, Mario F.; ANDREAZZA, Ana C.; GATTAZ, Wagner F.; MACHADO-VIERA, Rodrigo
    Background: Dysregulation of HPA axis have 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-naïve BD subjects during the first manic episode, as well as investigate the relationship between plasma cortisol levels and manic symptomatology. Methods: Twenty-six drug-naïve 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. Conclusions: 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 dd a dimensional approach to the traditional categorical diagnosis for future neurobiological studies in BD.
  • article 75 Citação(ões) na Scopus
    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.
  • article 68 Citação(ões) na Scopus
    Treatment of Bipolar Depression with Deep TMS: Results from a Double-Blind, Randomized, Parallel Group, Sham-Controlled Clinical Trial
    (2017) TAVARES, Diego F.; MYCZKOWSKI, Martin L.; ALBERTO, Rodrigo L.; VALIENGO, Leandro; RIOS, Rosa M.; GORDON, Pedro; SAMPAIO-JUNIOR, Bernardo de; KLEIN, Izio; MANSUR, Carlos G.; MARCOLIN, Marco Antonio; LAFER, Beny; MORENO, Ricardo A.; GATTAZ, Wagner; DASKALAKIS, Zafiris J.; BRUNONI, Andre R.
    Bipolar depression (BD) is a highly prevalent condition with limited therapeutic options. Deep (H1-coil) transcranial magnetic stimulation (dTMS) is a novel TMS modality with established efficacy for unipolar depression. We conducted a randomized sham-controlled trial to evaluate the efficacy and safety of dTMS in treatment-resistant BD patients. Patients received 20 sessions of active or sham dTMS over the left dorsolateral prefrontal cortex (H1-coil, 55 18 Hz 2 s 120% MT trains). The primary outcome was changes in the 17-item Hamilton Depression Rating Scale (HDRS-17) from baseline to endpoint (week 4). Secondary outcomes were changes from baseline to the end of the follow-up phase (week 8), and response and remission rates. Safety was assessed using a dTMS adverse effects questionnaire and the Young Mania Rating Scale to assess treatment-emergent mania switch (TEMS). Out of 50 patients, 43 finished the trial. There were 2 and 5 dropouts in the sham and active groups, respectively. Active dTMS was superior to sham at end point (difference favoring dTMS = 4.88; 95% CI 0.43 to 9.32, p = 0.03) but not at follow-up. There was also a trend for greater response rates in the active (48%) vs sham (24%) groups (OR = 2.92; 95% CI = 0.87 to 9.78, p = 0.08). Remission rates were not statistically different. No TEMS episodes were observed. Deep TMS is a potentially effective and well-tolerated add-on therapy in resistant bipolar depressed patients receiving adequate pharmacotherapy.
  • article 68 Citação(ões) na Scopus
    Decreased AKT1/mTOR pathway mRNA expression in short-term bipolar disorder
    (2015) MACHADO-VIEIRA, Rodrigo; ZANETTI, Marcus V.; TEIXEIRA, Antonio L.; UNO, Miyuki; VALIENGO, Leandro L.; SOEIRO-DE-SOUZA, Marcio G.; OBA-SHINJO, Sueli M.; SOUSA, Rafael T. de; ZARATE JR., Carlos. A.; GATTAZ, Wagner F.; MARIE, Suety K. N.
    Strong evidence implicates intracellular signaling cascades dysfunction in the pathophysiology of Bipolar Disorder (BD). Regulation of AKT/mTOR pathway is a critical signaling pathway in synaptic neurotransmission and plasticity, also modulating cell proliferation and migration. Gene expression of the AKT/mTOR pathway was assessed in 25 BD (DSM-IV-TR criteria) unmedicated depressed individuals at baseline and after 6 weeks of lithium therapy and 31 matched healthy controls. Decreases in blood AKT/ and mTOR mRNA expression, as well as in BAD/BCL-2 expression ratio were observed in short-term BD patients during depressive episodes in comparison to healthy controls. There was no significant change in the expression of AKT1, mTOR, BCL-2, BAD and NDUFA6 after lithium therapy in the total group of BD subjects. However, the changes in AKT1 expression after lithium treatment were positively correlated with depression improvement. An integrated activity within this pathway was observed at both baseline and post-treatment. The present results support an integrated AKT/mTOR signaling pathway activity in a similar fashion to the described in previous human postmortem and rodents brain studies. Overall, the results reinforce a role for AKT1 and mTOR in the pathophysiology of BD and support the relevance of blood mRNA expression as a valid surrogate biological source to study brain intracellular signaling cascades changes and convergent molecular pathways in psychiatric disorders.