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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  • article 4 Citação(ões) na Scopus
    Efficacy of Transcranial Direct Current Stimulation to Improve Insight in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Randomized Controlled Trials
    (2022) ADAM, Ondine; BLAY, Martin; BRUNONI, Andre R.; CHANG, Hsin-An; GOMES, July S.; JAVITT, Daniel C.; JUNG, Do-Un; KANTROWITZ, Joshua T.; KOOPS, Sanne; LINDENMAYER, Jean-Pierre; PALM, Ulrich; SMITH, Robert C.; SOMMER, Iris E.; VALIENGO, Leandro do Costa Lane; WEICKERT, Thomas W.; BRUNELIN, Jerome; MONDINO, Marine
    Background and Hypothesis Impaired insight into the illness and its consequences is associated with poor outcomes in schizophrenia. While transcranial direct current stimulation (tDCS) may represent a potentially effective treatment strategy to relieve various symptoms of schizophrenia, its impact on insight remains unclear. To investigate whether tDCS would modulate insight in patients with schizophrenia, we undertook a meta-analysis based on results from previous RCTs that investigated the clinical efficacy of tDCS. We hypothesize that repeated sessions of tDCS will be associated with insight improvement among patients. Study Design PubMed and ScienceDirect databases were systematically searched to identify RCTs that delivered at least 10 tDCS sessions in patients with schizophrenia. The primary outcome was the change in insight score, assessed by the Positive and Negative Syndrome Scale (PANSS) item G12 following active tDCS sessions as opposed to sham stimulation. Effect sizes were calculated for all studies and pooled using a random-effects model. Meta-regression and subgroup analyses were conducted. Study Results Thirteen studies (587 patients with schizophrenia) were included. A significant pooled effect size (g) of -0.46 (95% CI [-0.78; -0.14]) in favor of active tDCS was observed. Age and G12 score at baseline were identified as significant moderators, while change in total PANSS score was not significant. Conclusions Ten sessions of active tDCS with either frontotemporoparietal or bifrontal montage may improve insight into the illness in patients with schizophrenia. The effect of this treatment could contribute to the beneficial outcomes observed in patients following stimulation.
  • 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
  • article 4 Citação(ões) na Scopus
    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.
  • article 64 Citação(ões) na Scopus
    Impact of 5-HTTLPR and BDNF polymorphisms on response to sertraline versus transcranial direct current stimulation: Implications for the serotonergic system
    (2013) BRUNONI, A. R.; KEMP, A. H.; SHIOZAWA, P.; CORDEIRO, Q.; VALIENGO, L. C. L.; GOULART, A. C.; COPRERSKI, B.; LOTUFO, P. A.; BRUNONI, D.; PEREZ, A. B. A.; FREGNI, F.; BENSENOR, I. M.
    Transcranial direct current stimulation (tDCS) has been intensively investigated as a non-pharmacological treatment for major depressive disorder (MDD). While many studies have examined the genetic predictors of antidepressant medications, this issue remains to be investigated for tDCS. In the current study, we evaluated whether the BDNF Val66Met and the 5-HTT (5-HTTLPR) polymorphisms were associated with tDCS antidepressant response. We used data from a factorial trial that evaluated the efficacy of tDCS and sertraline and enrolled 120 moderate-to-severe, antidepressant-free participants. In the present study, we used analyses of variance to evaluate whether the BDNF (Val/Val vs. Met-carries) and 5-HTTLPR alleles (long/long vs short-carriers) were predictors of tDCS (active/sham) and sertraline (sertraline/placebo) response. Analyses were conducted on the polymorphisms separately and also on their interaction. Genotype frequencies were in Hardy-Weinberg equilibrium. BDNF polymorphism was not associated with treatment response. We found that 5-HTTLPR predicted tDCS effects as long/long homozygotes displayed a larger improvement comparing active vs. sham tDCS, while short-allele carriers did not. A dose-response relationship between active-sham differences with the long allele was also suggested. These results strengthen the role of the serotonergic system in the tDCS antidepressant effects and expand previous findings that reported that tDCS mechanisms of action partially involve serotonergic receptors. Therefore, we hypothesize that tDCS is a neuromodulation technique that acts over depression through the modulation of serotonergic system and that tDCS ""top-down"" antidepressant effects might not be optimal in brain networks with a hyperactive amygdala inducing bottom-up effects, such as occurs in short-carriers.
  • article 66 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.
  • article 21 Citação(ões) na Scopus
    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.
  • article 31 Citação(ões) na Scopus
    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, Rodrigo
    Background: 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.
  • article 5 Citação(ões) na Scopus
    Adjunctive Therapy to Manage Neuropsychiatric Symptoms in Moderate and Severe Dementia: Randomized Clinical Trial Using an Outpatient Version of Tailored Activity Program
    (2021) OLIVEIRA, Alexandra Martini; RADANOVIC, Marcia; MELLO, Patricia Cotting Homem de; BUCHAIN, Patricia Cardoso; VIZZOTTO, Adriana Dias Barbosa; HARDER, Janaina; STELLA, Florindo; GITLIN, Laura N.; PIERSOL, Catherine Verrier; VALIENGO, Leandro L. C.; FORLENZA, Orestes Vicente
    Background: Neuropsychiatric symptoms (NPS) such as aggression, apathy, agitation, and wandering may occur in up to 90%of dementia cases. International guidelines have suggested that non-pharmacological interventions are as effective as pharmacological treatments, however without the side effects and risks of medications. An occupational therapy method, called Tailored Activity Program (TAP), was developed with the objective to treat NPS in the elderly with dementia and has been shown to be effective. Objective: Evaluate the efficacy of the TAP method (outpatient version) in the treatment of NPS in individuals with dementia and in the burden reduction of their caregivers. Methods: This is a randomized, double-blind, controlled clinical trial for the treatment of NPS in dementia. Outcome measures consisted of assessing the NPS of individuals with dementia, through the Neuropsychiatric Inventory-Clinician rating scale (NPI-C), and assessing the burden on their caregivers, using the Zarit Scale. All the participants were evaluated pre-and post-intervention. Results: 54 individuals with dementia and caregivers were allocated to the experimental (n = 28) and control (n = 26) groups. There was improvement of the following NPS in the experimental group: delusions, agitation, aggressiveness, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor disturbance, and aberrant vocalization. No improvement was observed in hallucinations, sleep disturbances, and appetite disorders. The TAP method for outpatient settings was also clinically effective in reducing burden between caregivers of the experimental group. Conclusion: The use of personalized prescribed activities, coupled with the caregiver training, may be a clinically effective approach to reduce NPS and caregiver burden of individuals with dementia.
  • article 70 Citação(ões) na Scopus
    THE SERTRALINE VERSUS ELECTRICAL CURRENT THERAPY FOR TREATING DEPRESSION CLINICAL STUDY (SELECT-TDCS): RESULTS OF THE CROSSOVER AND FOLLOW-UP PHASES
    (2013) VALIENGO, Leandro; BENSENOR, Isabela Martins; GOULART, Alessandra C.; OLIVEIRA, Janaina Farias de; ZANAO, Tamires Araujo; BOGGIO, Paulo Sergio; LOTUFO, Paulo Andrade; FREGNI, Felipe; BRUNONI, Andre Russowsky
    BackgroundTranscranial direct current stimulation (tDCS) is a promising nonpharmacological therapy for major depression. In the Sertraline versus Electrical Current Therapy for Treating Depression Clinical Trial (SELECT-TDCS) trial, phase-I (Brunoni et al., JAMA Psychiatry, 2013) we found that tDCS is effective for the acute episode. Here, we describe tDCS effects during phases II (crossover) and III (follow-up) of this trial (NCTs: 01149889 and 01149213). MethodsPhase II (n = 25) was the open-label, crossover phase in which phase-I nonresponders who had received sham-tDCS received a 10-day course of active-tDCS. In phase-III (n = 42), all active-tDCS responders (>50% Montgomery-Asberg Depression Rating Scale (MADRS) improvement or MADRS 12) were enrolled to a 24-week, follow-up phase in which a maximum of nine tDCS sessions were performedevery other week for 3 months and, thereafter, once a month for the subsequent 3 monthssessions would be interrupted earlier whether the subject relapsed. TDCS was applied at 2 mA/30 min, with the anode over the left and the cathode over the right dorsolateral prefrontal cortex. Relapse was the outcome measure. ResultsIn phase-II, 52% of completers responded to tDCS. In phase-III, the mean response duration was 11.7 weeks. The survival rate per Kaplan-Meier analysis was 47%. Patients with treatment-resistant depression presented a much lower 24-week survival rate as compared to nonrefractory patients (10% vs. 77%, OR = 5.52; P < .01). Antidepressant use (sertraline 50 mg/day, eight patients) was not a predictor of relapse. TDCS was well tolerated and with few side effects. ConclusionContinuation tDCS protocols should be optimized as to prevent relapse among tDCS responders, particularly for patients with baseline treatment-resistant depression. Depression and Anxiety 30: 646-653, 2013. (C) 2013 Wiley Periodicals, Inc.
  • article 37 Citação(ões) na Scopus
    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.