LEANDRO DA COSTA LANE VALIENGO
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
15 resultados
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- Emotional reactivity to valence-loaded stimuli are related to treatment response of neurocognitive therapy(2016) VANDERHASSELT, Marie-Anne; RAEDT, Rudi De; NAMUR, Victoria; VALIENGO, Leandro C. L.; LOTUFO, Paulo A.; BENSENOR, Isabela M.; BAEKEN, Chris; BOGGIO, Paulo S.; BRUNONI, Andre R.Emotional Context Insensitivity (ECI) is a psychological feature observed in depressed patients characterized by a decreased emotional reactivity when presented to positive- and negative valence-loaded stimuli. Given that fronto-cingulate-limbic circuits are implicated in abnormal reactivity to valence-loaded stimuli, neurocognitive treatments engaging the prefrontal cortex may be able to modulate this emotional blunting observed in MDD. Therefore, our goal was to evaluate emotional reactivity in depressed patients before and after a combination of neurocognitive interventions that engage the prefrontal cortex (cognitive control training and/or transcranial direct current stimulation). In line with the premises of the ECI framework, before the start of the antidepressant intervention, patients showed blunted emotional reactivity after exposure to negative valence-loaded stimuli. This emotional reactivity pattern changed after 9 sessions of the intervention: positive affect decreased and negative affect increased after watching a series of negative valence-loaded stimuli (i.e. images). Interestingly, higher emotional reactivity (as indexed by a larger increase in negative affect after watching the valence-loaded stimuli) at baseline predicted reductions in depression symptoms after the intervention. On the other hand, higher emotional reactivity (as indexed by a decrease in positive affect) after the intervention was marginally associated with reductions in depression symptoms. To conclude, emotional reactivity increased after the neurocognitive antidepressant intervention and it was directly associated to the degree of depression improvement.
- A study protocol for an ongoing multi-arm, randomized, double-blind, sham-controlled clinical trial with digital features, using portable transcranial electrical stimulation and internet-based behavioral therapy for major depression disorders: The PSYLECT study(2022) BORRIONE, Lucas; CIRILLO, Patricia C.; APARICIO, Luana V. M.; CAVENDISH, Beatriz A.; VALIENGO, Leandro; MOURA, Darin O.; SOUZA, Juliana P. de; LUETHI, Matthias S.; KLEIN, Izio; BARIANI, Bruna; GALLUCCI-NETO, Jose; SUEN, Paulo; PADBERG, Frank; GOERIGK, Stephan; VANDERHASSELT, Marie-Anne; DENG, Zhi De; O'SHEA, Jacinta; LOTUFO, Paulo A.; BENSENOR, Isabela M.; BRUNONI, Andre R.Background Transcranial electrical stimulation (tES) is considered effective and safe for depression, albeit modestly, and prone to logistical burdens when performed in external facilities. Investigation of portable tES (ptES), and potentiation of ptES with remote psychological interventions have shown positive, but preliminary, results. Research design We report the rationale and design of an ongoing multi-arm, randomized, double-blind, sham-controlled clinical trial with digital features, using ptES and internet-based behavioral therapy (iBT) for major depressive disorder (MDD) (NCT04889976). Methods We will evaluate the efficacy, safety, tolerability and usability of (1) active ptES + active iBT ('double-active'), (2) active ptES + sham iBT ('ptES-only'), and (3) sham ptES + sham iBT ('double-sham'), in adults with MDD, with a Hamilton Depression Rating Scale - 17 item version (HDRS-17) score >= 17 at baseline, during 6 weeks. Antidepressants are allowed in stable doses during the trial. Results We primarily co-hypothesize changes in HDRS-17 will be greater in (1) 'double-active' compared to 'ptES-only,' (2) 'double-active' compared to 'double-sham,' and (3) 'ptES-only' compared to 'double-sham.' We aim to enroll 210 patients (70 per arm). Conclusions Our results should offer new insights regarding the efficacy and scalability of combined ptES and iBT for MDD, in digital mental health.
- Transcranial direct current stimulation for the treatment of post-stroke depression: results from a randomised, sham-controlled, double-blinded trial(2017) VALIENGO, Leandro C. L.; GOULART, Alessandra C.; OLIVEIRA, Janaina F. de; BENSENOR, Isabela M.; LOTUFO, Paulo A.; BRUNONI, Andre R.Background Post-stroke depression is a disabling condition occurring in about one-third of patients with stroke. Pharmacological treatments have limited efficacy and important side effects. Recently, transcranial direct current stimulation (tDCS) has shown efficacy in treating depression. This study aimed to assess the efficacy and safety of tDCS for post-stroke depression. Methods 48 antidepressant-free patients with post-stroke depression were randomised into two groups (active and sham tDCS). 12 30 min sessions of 2 mA anodal left/cathodal right dorsolateral prefrontal tDCS were administered over 6 weeks (once daily on weekdays for 2 weeks, then 1 session every other week). The primary outcome was the change in the Hamilton Depression Rating Scale (17-items) at 6 weeks. We employed a repeated-measures analysis of variance; the depression score was the dependent variable, and time and group were independent variables. In this intention-to-treat analysis, missing data were addressed according to the last observation carried forward and the mixed-model repeated-measures analysis methods. Results 5 patients dropped out (two in the active group). Active tDCS was significantly superior to sham at end point (mean difference, 4.7 points; SD=9.21; p<0.001). Response and remission rates were significantly higher in the active (37.5% and 20.8%, respectively) versus the sham (4.1% and 0%, respectively) group, with a number-needed-to-treat of 3 and 5, respectively. Conclusions This was the first controlled study to demonstrate that tDCS was safe and effective for post-stroke depression. Therefore, tDCS might be a favourable option for treating these patients.
- Transcranial direct current stimulation (tDCS) for preventing major depressive disorder relapse: Results of a 6-month follow-up(2019) APARICIO, Luana V. M.; ROSA, Vivianne; RAZZA, Lais M.; SAMPAIO-JUNIOR, Bernardo; BORRIONE, Lucas; VALIENGO, Leandro; LOTUFO, Paulo A.; BENSENOR, Isabela M.; FRAGUAS, Renerio; MOFFA, Adriano H.; GATTAZ, Wagner F.; BRUNONI, Andre RussowskyBackgroundThe efficacy of transcranial direct current stimulation (tDCS) as a continuation therapy for the maintenance phase of the depressive episode is low and insufficiently investigated in literature. We investigated whether it could be enhanced by using a more intensive treatment regimen compared to previous reports. MethodsTwenty-four patients (16 with unipolar depression and eight with bipolar depression) who presented acute tDCS response (50% depression improvement in the Hamilton Depression Rating Scale [HDRS]) after receiving 15 tDCS sessions were followed for up to 6 months or until relapse, defined as clinical worsening and/or HDRS>15. Sessions were performed twice a week (maximum of 48 sessions) over 24weeks. The anode and the cathode were positioned over the left and right dorsolateral prefrontal cortex (2mA current, 30 min sessions were delivered). We performed Kaplan-Meier survival analysis and Cox proportional hazards ratios to evaluate predictors of relapse. ResultsOut of 24 patients, 18 completed the follow-up period. tDCS treatment was well tolerated. The mean survival duration was 17.5weeks (122 days). The survival rate at the end of follow-up was 73.5% (95% confidence interval, 50-87). A trend (P=0.09) was observed for lower relapse rates in nontreatment- vs. antidepressant treatment-resistant patients (7.7%vs. 45.5%, respectively). No differences in efficacy between unipolar and bipolar depression were observed. ConclusionAn intensive tDCS treatment regimen consisting of sessions twice a week achieved relatively low relapse rates after a 6-month follow up of tDCS responders, particularly for nontreatment-resistant patients.
- Assessment of non-BDNF neurotrophins and GDNF levels after depression treatment with sertraline and transcranial direct current stimulation in a factorial, randomized, sham-controlled trial (SELECT-TDCS): An exploratory analysis(2015) BRUNONI, Andre R.; MACHADO-VIEIRA, Rodrigo; ZARATE JR., Carlos A.; VIEIRA, Erica L. M.; VALIENGO, Leandro; BENSENOR, Isabela M.; LOTUFO, Paulo A.; GATTAZ, Wagner F.; TEIXEIRA, Antonio L.The neurotrophic hypothesis of depression states that the major depressive episode is associated with lower neurotrophic factors levels, which increase with amelioration of depressive symptoms. However, this hypothesis has not been extended to investigate neurotrophic factors other than the brain-derived neurotrophic factor (BDNF). We therefore explored whether plasma levels of neurotrophins 3 (NT-3) and 4 (NT-4), nerve growth factor (NGF) and glial cell line derived neurotrophic factor (GDNF) changed after antidepressant treatment and correlated with treatment response. Seventy-three patients with moderate-to-severe, antidepressant-free unipolar depression were assigned to a pharmacological (sertraline) and a non-pharmacological (transcranial direct current stimulation, tDCS) intervention in a randomized, 2 x 2, placebo-controlled design. The plasma levels of NT-3, NT-4, NGF and GDNF were determined by enzyme-linked immunosorbent assay before and after a 6-week treatment course and analyzed according to clinical response and allocation group. We found that tDCS and sertraline (separately and combined) produced significant improvement in depressive symptoms. Plasma levels of all neurotrophic factors were similar across groups at baseline and remained significantly unchanged regardless of the intervention and of clinical response. Also, baseline plasma levels were not associated with clinical response. To conclude, in this 6-week placebo-controlled trial, NT-3, NT-4, NGF and GDNF plasma levels did not significantly change with sertraline or tDCS. These data suggest that these neurotrophic factors are not surrogate biomarkers of treatment response or involved in the antidepressant mechanisms of tDCS.
- Cytokines plasma levels during antidepressant treatment with sertraline and transcranial direct current stimulation (tDCS): results from a factorial, randomized, controlled trial(2014) BRUNONI, Andre R.; MACHADO-VIEIRA, Rodrigo; ZARATE, Carlos A.; VALIENGO, Leandro; VIEIRA, Erica L. M.; BENSENOR, Isabela M.; LOTUFO, Paulo A.; GATTAZ, Wagner F.; TEIXEIRA, Antonio L.The inflammatory hypothesis of depression states that increased levels of pro-inflammatory cytokines triggered by external and internal stressors are correlated to the acute depressive state. This hypothesis also suggests that pharmacotherapy partly acts in depression through anti-inflammatory effects. Transcranial direct current stimulation (tDCS) is a novel, promising, non-invasive somatic treatment for depression, although its antidepressant mechanisms are only partly understood. We explored the effects of tDCS and sertraline over the immune system during an antidepressant treatment trial. In a 6-week, double-blind, placebo-controlled trial, 73 antidepressant-free patients with unipolar depression were randomized to active/sham tDCS and sertraline/placebo (2 x 2 design). Plasma levels of several cytokines (IL-2, IL-4, IL-6, IL-10, IL-17a, IFN-gamma, and TNF-alpha) were determined to investigate the effects of the interventions and of clinical response on them. All cytokines, except TNF-alpha, decreased over time, these effects being similar across the different intervention-groups and in responders vs. non-responders. tDCS and sertraline (separately and combined) acute antidepressant effects might not specifically involve normalization of the immune system. In addition, being one of the first placebo-controlled trials measuring cytokines over an antidepressant treatment course, our study showed that the decrease in cytokine levels during the acute depressive episode could involve a placebo effect, highlighting the need of further placebo-controlled trials and observational studies examining cytokine changes during depression treatment and also after remission of the acute depressive episode.
- Digitalized transcranial electrical stimulation: A consensus statement(2022) BRUNONI, Andre R.; EKHTIARI, Hamed; ANTAL, Andrea; AUVICHAYAPAT, Paradee; BAEKEN, Chris; BENSENOR, Isabela M.; BIKSON, Marom; BOGGIO, Paulo; BORRONI, Barbara; BRIGHINA, Filippo; BRUNELIN, Jerome; CARVALHO, Sandra; CAUMO, Wolnei; CIECHANSKI, Patrick; CHARVET, Leigh; CLARK, Vincent P.; KADOSH, Roi Cohen; COTELLI, Maria; DATTA, Abhishek; DENG, Zhi-De; RAEDT, Rudi De; RIDDER, Dirk De; FITZGERALD, Paul B.; FLOEL, Agnes; FROHLICH, Flavio; GEORGE, Mark S.; GHOBADI-AZBARI, Peyman; GOERIGK, Stephan; HAMILTON, Roy H.; JABERZADEH, Shapour J.; HOY, Kate; KIDGELL, Dawson J.; ZONOOZI, Arash Khojasteh; KIRTON, Adam; LAUREYS, Steven; LAVIDOR, Michal; LEE, Kiwon; LEITE, Jorge; LISANBY, Sarah H.; LOO, Colleen; MARTIN, Donel M.; MINIUSSI, Carlo; MONDINO, Marine; MONTE-SILVA, Katia; MORALES-QUEZADA, Leon; NITSCHE, Michael A.; OKANO, Alexandre H.; OLIVEIRA, Claudia S.; ONARHEIM, Balder; PACHECO-BARRIOS, Kevin; PADBERG, Frank; NAKAMURA-PALACIOS, Ester M.; PALM, Ulrich; PAULUS, Walter; PLEWNIA, Christian; PRIORI, Alberto; RAJJI, Tarek K.; RAZZA, Lais B.; REHN, Erik M.; RUFFINI, Giulio; SCHELLHORN, Klaus; ZARE-BIDOKY, Mehran; SIMIS, Marcel; SKORUPINSKI, Pawel; SUEN, Paulo; THIBAUT, Aurore; VALIENGO, Leandro C. L.; VANDERHASSELT, Marie-Anne; VANNESTE, Sven; VENKATASUBRAMANIAN, Ganesan; VIOLANTE, Ines R.; WEXLER, Anna; WOODS, Adam J.; FREGNI, FelipeObjective: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES. Methods: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. Results: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity. Conclusions: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases. Significance: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.
- Acute working memory improvement after tDCS in antidepressant-free patients with major depressive disorder(2013) OLIVEIRA, Janaina F.; ZANAO, Tamires A.; VALIENGO, Leandro; LOTUFO, Paulo A.; BENSENOR, Isabela M.; FREGNI, Felipe; BRUNONI, Andre R.Based on previous studies showing that transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique that employs weak, direct currents to induce cortical-excitability changes, might be useful for working memory (WM) enhancement in healthy subjects and also in treating depressive symptoms, our aim was to evaluate whether tDCS could acutely enhance WM in depressed patients. Twenty-eight age- and gender-matched, antidepressant-free depressed subjects received a single-session of active/sham tDCS in a randomized, double-blind, parallel design. The anode was positioned over the left and the cathode over the right dorsolateral prefrontal cortex. The n-back task was used for assessing WM and it was performed immediately before and 15 min after tDCS onset. We found that active vs. sham tDCS led to an increase in the rate of correct responses. We also used signal detection theory analyses to show that active tDCS increased both discriminability, i.e., the ability to discriminate signal (correct responses) from noise (false alarms), and response criterion, indicating a lower threshold to yield responses. All effect sizes were large. In other words, one session of tDCS acutely enhanced WM in depressed subjects, suggesting that tDCS can improve ""cold"" (non affective-loaded) working memory processes in MDD. Based on these findings, we discuss the effects of tDCS on WM enhancement in depression. We also suggest that the n-back task could be used as a biomarker in future tDCS studies investigating prefrontal activity in healthy and depressed samples.
- The Sertraline vs Electrical Current Therapy for Treating Depression Clinical Study Results From a Factorial, Randomized, Controlled Trial(2013) BRUNONI, Andre R.; VALIENGO, Leandro; BACCARO, Alessandra; ZANAO, Tamires A.; OLIVEIRA, Janaina F. de; GOULART, Alessandra; BOGGIO, Paulo S.; LOTUFO, Paulo A.; BENSENOR, Isabela M.; FREGNI, FelipeImportance: Transcranial direct current stimulation (tDCS) trials for major depressive disorder (MDD) have shown positive but mixed results. Objective: To assess the combined safety and efficacy of tDCS vs a common pharmacological treatment (sertraline hydrochloride, 50 mg/d). Design: Double-blind, controlled trial. Participants were randomized using a 2 x 2 factorial design to sertraline/placebo and active/sham tDCS. Setting: Outpatient, single-center academic setting in Sao Paulo, Brazil. Participants: One hundred twenty antidepressant free patients with moderate to severe, nonpsychotic, unipolar MDD. Interventions: Six-week treatment of 2-mA anodal left/cathodal right prefrontal tDCS (twelve 30-minute sessions: 10 consecutive sessions once daily from Monday to Friday plus 2 extra sessions every other week) and sertraline hydrochloride (50 mg/d). Main Outcome Measures: In this intention-to-treat analysis, the primary outcome measure was the change in Montgomery-Asberg Depression Rating Scale score at 6 weeks (end point). We considered a difference of at least 3 points to be clinically relevant. The analysis plan was previously published. Safety was measured with an adverse effects questionnaire, the Young Mania Rating Scale, and cognitive assessment. Secondary measures were rates of clinical response and remission and scores on other scales. Results: At the main end point, there was a significant difference in Montgomery-Asberg Depression Rating Scale scores when comparing the combined treatment group (sertraline/active tDCS) vs sertraline only (mean difference, 8.5 points; 95% CI, 2.96 to 14.03; P = .002), tDCS only (mean difference, 5.9 points; 95% CI, 0.36 to 11.43; P = .03), and placebo/sham tDCS (mean difference, 11.5 points; 95% CI, 6.03 to 17.10; P < .001). Analysis of tDCS only vs sertraline only presented comparable efficacies (mean difference, 2.6 points; 95% CI, -2.90 to 8.13; P = .35). Use of tDCS only (but not sertraline only) was superior to placebo/sham tDCS. Common adverse effects did not differ between interventions, except for skin redness on the scalp in active tDCS (P = .03). There were 7 episodes of treatment-emergent mania or hypomania, 5 occurring in the combined treatment group. Conclusions and Relevance: In MDD, the combination of tDCS and sertraline increases the efficacy of each treatment. The efficacy and safety of tDCS and sertraline did not differ.
- BDNF plasma levels after antidepressant treatment with sertraline and transcranial direct current stimulation: Results from a factorial, randomized, sham-controlled trial(2014) BRUNONI, Andre R.; MACHADO-VIEIRA, Rodrigo; ZARATE JR., Carlos A.; VIEIRA, Erica L. M.; VANDERHASSELT, Marie-Anne; NITSCHE, Michael A.; VALIENGO, Leandro; BENSENOR, Isabela M.; LOTUFO, Paulo A.; GATTAZ, Wagner F.; TEIXEIRA, Antonio L.Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention that modifies cortical excitability according to the stimulation parameters. Preclinical and clinical studies in healthy volunteers suggest that tDCS induces neuroplastic alterations of cortical excitability, which might explain its clinical effects in major depressive disorder (MDD). We therefore examined whether tDCS, as compared to the antidepressant sertraline, increases plasma brain-derived neurotrophic factor (BDNF) levels, a neurotrophin associated with neuroplasticity. Patients (n=73) with major depressive disorder were randomized to active/ sham tDCS and sertraline/placebo (four groups) in this 6-week, double-blind, placebocontrolled trial. We measured BDNF plasma levels at baseline and endpoint, observing no significant changes of BDNF levels after treatment. In addition, no significant changes were observed in responders and non-responders as well as no relationships between BDNF levels and clinical and psychopathological variables related to depression. Thus, in one of the few placebo-controlled trials evaluating BDNF changes over an antidepressant treatment course, we did not observe BDNF increase regardless of clinical improvement in depressed patients. Regarding tDCS, BDNF plasma levels might not be a good candidate biomarker to evaluate depression improvement or be a predictor of response in patients treated with tDCS, as our results showed that BDNF increase was not necessary to induce clinical response. Finally, our findings do not support a relationship between BDNF and improvement of depression.