ANDRE RUSSOWSKY BRUNONI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
367 resultados
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- Efficacy of non-invasive brain stimulation in decreasing depression symptoms during the peripartum period: A systematic review(2021) PACHECO, Francisca; GUIOMAR, Raquel; BRUNONI, Andre R.; BUHAGIAR, Rachel; EVAGOROU, Olympia; ROCA-LECUMBERRI, Alba; POLESZCZYK, Anna; BERG, Mijke Lambregtse-van den; CAPARROS-GONZALEZ, Rafael A.; FONSECA, Ana; OSORIO, Ana; SOLIMAN, Mahmoud; AVILA, Ana Ganho-Background: Non-invasive brain stimulation (NIBS) techniques have been suggested as alternative treatments to decrease depression symptoms during the perinatal period. These include brain stimulation techniques that do not require surgery and that are nonpharmacological and non-psychotherapeutic. NIBS with evidence of antidepressant effects include repetitive transcranial magnetic stimulation (rTMS), transcranial electric stimulation (TES) and electroconvulsive therapy (ECT). Objectives: This systematic review aims to summarize evidence on NIBS efficacy, safety and acceptability in treating peripartum depression (PPD). Methods: We included randomized, non-randomized and case reports, that used NIBS during pregnancy and the postpartum. The reduction of depressive symptoms and neonatal safety were the primary and co-primary outcomes, respectively. Results: rTMS shows promising results for the treatment of PPD, with clinically significant decreases in depressive symptoms between baseline and end of treatment and overall good acceptability. Although the safety profile for rTMS is adequate in the postpartum, caution is warranted during pregnancy. In TES, evidence on efficacy derives mostly from single-arm studies, compromising the encouraging findings. Further investigation is necessary concerning ECT, as clinical practice relies on clinical experience and is only described in low-quality case-reports. Limitations: The reduced number of controlled studies, the lack of complete datasets and the serious/high risk of bias of the reports warrant cautious interpretations. Conclusions and implications: Existing evidence is limited across NIBS techniques; comparative studies are lacking, and standard stimulation parameters are yet to be established. Although rTMS benefits from the most robust research, future multicenter randomized clinical trials are needed to determine the position of each NIBS strategy within the pathways of care.
- Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder(2021) SHEPHARD, Elizabeth; STERN, Emily R.; HEUVEL, Odile A. van den; COSTA, Daniel L. C.; BATISTUZZO, Marcelo C.; GODOY, Priscilla B. G.; LOPES, Antonio C.; BRUNONI, Andre R.; HOEXTER, Marcelo Q.; SHAVITT, Roseli G.; REDDY, Y. C. Janardhan; LOCHNER, Christine; STEIN, Dan J.; SIMPSON, H. Blair; MIGUEL, Euripedes C.An important challenge in mental health research is to translate findings from cognitive neuroscience and neuroimaging research into effective treatments that target the neurobiological alterations involved in psychiatric symptoms. To address this challenge, in this review we propose a heuristic neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder (OCD). We do this by integrating information from several sources. First, we provide case vignettes in which patients with OCD describe their symptoms and discuss different clinical profiles in the phenotypic expression of the condition. Second, we link variations in these clinical profiles to underlying neurocircuit dysfunctions, drawing on findings from neuropsychological and neuroimaging studies in OCD. Third, we consider behavioral, pharmacological, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions. Finally, we suggest methods of testing this neurocircuit-based taxonomy as well as important limitations to this approach that should be considered in future research.
- Imaging genetics paradigms in depression research: Systematic review and meta-analysis(2018) PEREIRA, Licia P.; KOHLER, Cristiano A.; STUBBSB, Brendon; MISKOWIAK, Kamilla W.; MORRIS, Gerwyn; FREITAS, Barbara P. de; THOMPSON, Trevor; FERNANDES, Brisa S.; BRUNONI, Andre R.; MAES, Michael; PIZZAGALLI, Diego A.; CARVALHO, Andre F.Imaging genetics studies involving participants with major depressive disorder (MDD) have expanded. Nevertheless, findings have been inconsistent. Thus, we conducted a systematic review and meta-analysis of imaging genetics studies that enrolled MDD participants across major databases through June 30th, 2017. Sixty-five studies met eligibility criteria (N = 4034 MDD participants and 3293 controls), and there was substantial between-study variability in the methodological quality of included studies. However, few replicated findings emerged from this literature with only 22 studies providing data for meta-analyses (882 participants with MDD and 616 controls). Total hippocampal volumes did not significantly vary in MDD participants or controls carrying either the BDNF Val66Met 'Met' (386 participants with MDD and 376 controls) or the 5-HTTLPR short 'S' (310 participants with MDD and 230 controls) risk alleles compared to non-carriers. Heterogeneity across studies was explored through meta-regression and subgroup analyses. Gender distribution, the use of medications, segmentation methods used to measure the hippocampus, and age emerged as potential sources of heterogeneity across studies that assessed the association of 5-HTTLPR short 'S' alleles and hippocampal volumes. Our data also suggest that the methodological quality of included studies, publication year, and the inclusion of brain volume as a covariate contributed to the heterogeneity of studies that assessed the association of the BDNF Val66Met 'Met' risk allele and hippocampal volumes. In exploratory voxel-wise meta-analyses, MDD participants carrying the 5-HTTLPR short 'S' allele had white matter microstructural abnormalities predominantly in the corpus callosum, while carriers of the BDNF Val66Met 'Met' allele had larger gray matter volumes and hyperactivation of the right middle frontal gyrus compared to non-carriers. In conclusion, few replicated findings emerged from imaging genetics studies that included participants with MDD. Nevertheless, we explored and identified specific sources of heterogeneity across studies, which could provide insights to enhance the reproducibility of this emerging field.
- Is dynapenia associated with the onset and persistence of depressive and anxiety symptoms among older adults? Findings from the Irish longitudinal study on ageing(2021) CARVALHO, Andre F.; MAES, Michael; SOLMI, Marco; BRUNONI, Andre R.; LANGE, Shannon; HUSAIN, M. Ishrat; KURDYAK, Paul; REHM, Jurgen; KOYANAGI, AiObjectives: The aim of the current study was to assess the associations between dynapenia and the onset and persistence of depression and anxiety among older adults. Methods: This prospective cohort study enrolled community-living older adults (N = 5271; 51.1% females) aged >= 50 years (mean age = 63.2, standard deviation = 9.0) from The Irish Longitudinal Study on Aging (TILDA), Ireland. At baseline, participants completed a handgrip assessment. Depression was defined by a score >= 16 in the Center of Epidemiology Studies Depression (CES-D) tool and anxiety was considered when participants scored >= 8 on the anxiety section of the Hospital Anxiety and Depression Scale (HADS). Outcomes were incident and persistent depression and anxiety at two years follow-up. Multivariable logistic regression models were built for each outcome. Results: After controlling for age, sex, education, marital status, employment status, smoking, body mass index, number of chronic conditions, physical activity, and cognitive function, low handgrip strength indicative of dyapenia (< 30 Kg for men and < 20 Kg for women) was associated with a greater likelihood for incident depressive (OR = 1.44; 95%CI: 1.08-1.92) as well as for persistent depressive (OR = 1.61; 95% CI: 1.01-2.58) and anxiety (OR = 1.61; 95% CI: 1.20-2.14) symptoms. Conclusions: Dynapenia was associated with a higher odds of developing depressive symptoms as well as a greater likelihood to persistent depressive and anxiety symptoms among older adults. Our data suggest that interventions targeting muscle strength may prevent the onset of late-life depression and also may hold promise as novel therapeutic opportunities for depression and anxiety in later life.
- Primum non nocere or primum facere meliorem? Hacking the brain in the 21st century(2017) BORRIONE, Lucas; BRUNONI, Andre R.Abstract Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates cortical excitability. It is devoid of serious adverse events and exerts variable effects on cognition, with several research findings suggesting that it can improve memory, verbal and mathematical skills. Because tDCS devices are low-cost, portable and relatively easy to assemble, they have become available outside of the medical setting and used for non-medical (“cosmetic”) purposes by laypersons. In this sense, tDCS has become a popular technique aiming to improve cognition and the achievement of a better performance not only at work, but also in other fields such as sports, leisure activities (video games) and even the military. In spite of these unforeseen developments, there has been a general paralysis of the medical and regulatory agencies to develop guidelines for the use of tDCS for cosmetic purposes. Several challenges are present, most importantly, how to restrict tDCS use outside of the medical setting in face of variable and sometimes conflicting results from scientific research. This article aims to describe the popular use of tDCS, in light of the pillars of neuroethics, a branch of bioethics relative to brain research. Between two possible but extreme solutions – total release or total restriction of tDCS – it is paramount to develop a spectrum of alternatives, which may vary over time and in different cultural backgrounds.
article 46 Citação(ões) na Scopus Manic Psychosis After Sertraline and Transcranial Direct-Current Stimulation(2011) BRUNONI, Andre Russowsky; VALIENGO, Leandro; ZANAO, Tamires; OLIVEIRA, Janaina Farias de; BENSENOR, Isabela Martins; FREGNI, Felipe- Changes in motor cortical excitability in schizophrenia following transcranial direct current stimulation(2019) GORDON, Pedro Caldana; VALIENGO, Leandro da Costa Lane; PAULA, Vanessa Jesus Rodrigues de; GALHARDONI, Ricardo; ZIEMANN, Ulf; ANDRADE, Daniel Ciampi de; BRUNONI, Andre RussowskySchizophrenia is a disorder associated with cortical inhibition deficits. Transcranial direct current stimulation (tDCS) induces changes in cortical excitability in healthy subjects and individuals with neuropsychiatric disorders depending on the stimulation parameters. Our aim was to investigate whether a previously published tDCS protocol associated with symptomatic improvement in schizophrenia would induce changes in motor cortical excitability, assessed by transcranial magnetic stimulation paradigms, i.e., short-interval intracortical inhibition (SICI) and intra-cortical facilitation (ICF). We assessed cortical excitability measurements in 48 subjects with schizophrenia before and after a single session of active tDCS (20 min, 2 mA, anode over left dorsolateral prefrontal cortex, cathode over left temporoparietal cortex) or sham. Those who received active tDCS had a significant increase of SICI in the left motor cortex compared to those who received sham stimulation (Cohen's d = 0.54, p = .019). No changes were observed for ICF. In addition, lower SICI was associated with higher age (beta = -0.448, p < .01). Increase in intracortical inhibition may indicate a mechanism of action of tDCS in this population. Future studies should investigate whether this finding is a biomarker of treatment response for schizophrenia.
- A systematic review and meta-analysis on placebo response to repetitive transcranial magnetic stimulation for depression trials(2018) RAZZA, Lais B.; MOFFA, Adriano H.; MORENO, Marina L.; CARVALHO, Andre F.; PADBERG, Frank; FREGNI, Felipe; BRUNONI, Andre R.Background: Although several studies indicate that placebo response is large to antidepressant pharmacotherapy in major depressive disorder (MDD), no updated meta-analysis has quantified the magnitude of the placebo (sham) response to repetitive transcranial magnetic stimulation (rTMS) in MDD yet. Objective: To conduct a systematic review and meta-analysis on this issue in randomized controlled trials (RCTs) involving participants with MDD; and to explore potential moderators. Methodology: PubMed/MEDLINE, Embase, PsycINFO, and Web of Science electronic databases were searched from inception up to March 15, 2017 for RCTs that investigated the efficacy of any rTMS modality compared to sham intervention in participants with acute depressive episodes. Cochrane Risk of Bias Tool was used to estimate risks. We estimated the placebo effect size (Hedges's g, random-effects model) response using placebo groups baseline and endpoint depressive symptom scores. Meta-regressions have been employed to explore potential moderators of response. Results: Sixty-one studies met eligibility criteria (N = 1328; mean age, 47 years; 57% females). Placebo response was large (g = 0.8, 95% CI = 0.65-0.95, p < 0.01) regardless of the modality of intervention. Placebo response was directly associated with publication year and depression improvement of the active group, and inversely associated with higher levels of treatment-resistant depression. Other moderators, including gender, age, and stimulator type, were not associated with the outcome. Overall, 24.6%, 67.2%, and 8.2% of studies had an overall low, unclear, and high bias risk, respectively. Conclusion: Placebo response in rTMS depression trials was large and associated with depression improvement of the active treatment group. Such result suggests that excluding placebo responders with a run-in phase may not confer advantage since response to 'active' rTMS may decrease as well. Moreover, placebo response may be a component of therapeutic response to rTMS in MDD. In addition, placebo response increase over time could indicate improvement in rTMS trial designs, including better sham rTMS methods.
- The Pursuit of DLPFC: Non-neuronavigated Methods to Target the Left Dorsolateral Pre-frontal Cortex With Symmetric Bicephalic Transcranial Direct Current Stimulation (tDCS)(2015) SEIBT, Ole; BRUNONI, Andre R.; HUANG, Yu; BIKSON, MaromBackground: The dose of transcranial direct current stimulation (tDCS) is defined by electrode montage and current, while the resulting brain current flow is more complex and varies across individuals. The left dorsolateral pre-frontal cortex (lDLPFC) is a common target in neuropsychology and neuropsychiatry applications, with varied approaches used to experimentally position electrodes on subjects. Objective: To predict brain current flow intensity and distribution using conventional symmetrical bicephalic frontal 1 x 1 electrode montages to nominally target lDLPFC in forward modeling studies. Methods: Six high-resolution Finite Element Method (FEM) models were created from five subjects of varied head size and an MNI standard. Seven electrode positioning methods, nominally targeting lDLPFC, were investigated on each head model: the EEG 10-10 including F3-F4, F5-F6, F7-8, F9-F10, the Beam F3-System, the 5-5 cm-Rule and the developed OLE-System were evaluated as electrode positioning methods for 5 x 5 cm(2) rectangular sponge-pad electrodes. Results: Each positioning approach resulted in distinct electrode positions on the scalp and variations in brain current flow. Variability was significant, but trends across montages and between subjects were identified. Factors enhancing electric field intensity and relative targeting in lDLPFC include increased inter-electrode distance and proximity to thinner skull structures. Conclusion: Brain current flow can be shaped, but not focused, across frontal cortex by tDCS montages, including intensity at lDLPFC. The OLE-system balances lDLPFC targeting and reduced electric field variability, along with clinical ease-of-use.
- Predicting treatment response using EEG in major depressive disorder: A machine-learning meta-analysis(2022) WATTS, Devon; PULICE, Rafaela Fernandes; REILLY, Jim; BRUNONI, Andre R.; KAPCZINSKI, Flavio; PASSOS, Ives CavalcanteSelecting a course of treatment in psychiatry remains a trial-and-error process, and this long-standing clinical challenge has prompted an increased focus on predictive models of treatment response using machine learning techniques. Electroencephalography (EEG) represents a cost-effective and scalable potential measure to predict treatment response to major depressive disorder. We performed separate meta-analyses to determine the ability of models to distinguish between responders and non-responders using EEG across treatments, as well as a performed subgroup analysis of response to transcranial magnetic stimulation (rTMS), and antidepressants (Registration Number: CRD42021257477) in Major Depressive Disorder by searching PubMed, Scopus, and Web of Science for articles published between January 1960 and February 2022. We included 15 studies that predicted treatment responses among patients with major depressive disorder using machine-learning techniques. Within a random-effects model with a restricted maximum likelihood estimator comprising 758 patients, the pooled accuracy across studies was 83.93% (95% CI: 78.90-89.29), with an Area-Under-the-Curve (AUC) of 0.850 (95% CI: 0.747-0.890), and partial AUC of 0.779. The average sensitivity and specificity across models were 77.96% (95% CI: 60.05-88.70), and 84.60% (95% CI: 67.89-92.39), respectively. In a subgroup analysis, greater performance was observed in predicting response to rTMS (Pooled accuracy: 85.70% (95% CI: 77.45-94.83), Area-Under-the-Curve (AUC): 0.928, partial AUC: 0.844), relative to antidepressants (Pooled accuracy: 81.41% (95% CI: 77.45-94.83, AUC: 0.895, pAUC: 0.821). Furthermore, across all meta-analyses, the specificity (true negatives) of EEG models was greater than the sensitivity (true positives), suggesting that EEG models thus far better identify non-responders than responders to treatment in MDD. Studies varied widely in important features across models, although relevant features included absolute and relative power in frontal and temporal electrodes, measures of connectivity, and asymmetry across hemispheres. Predictive models of treatment response using EEG hold promise in major depressive disorder, although there is a need for prospective model validation in independent datasets, and a greater emphasis on replicating physiological markers. Crucially, standardization in cut-off values and clinical scales for defining clinical response and non-response will aid in the reproducibility of findings and the clinical utility of predictive models. Furthermore, several models thus far have used data from open-label trials with small sample sizes and evaluated performance in the absence of training and testing sets, which increases the risk of statistical overfitting. Large consortium studies are required to establish predictive signatures of treatment response using EEG, and better elucidate the replicability of specific markers. Additionally, it is speculated that greater performance was observed in rTMS models, since EEG is assessing neural networks more likely to be directly targeted by rTMS, comprising electrical activity primarily near the surface of the cortex. Prospectively, there is a need for models that examine the comparative effectiveness of multiple treatments across the same patients. However, this will require a thoughtful consideration towards cumulative treatment effects, and whether washout periods between treatments should be utilised. Regardless, longitudinal cross-over trials comparing multiple treatments across the same group of patients will be an important prerequisite step to both facilitate precision psychiatry and identify generalizable physiological predictors of response between and across treatment options.