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
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- Suicide rates and trends in Sao Paulo, Brazil, according to gender, age and demographic aspects: a joinpoint regression analysis(2012) BANDO, Daniel H.; BRUNONI, Andre R.; FERNANDES, Tiotrefis G.; BENSENOR, Isabela M.; LOTUFO, Paulo A.Objective: To evaluate suicide rates and trends in Sao Paulo by sex, age-strata, and methods. Methods: Data was collected from State registry from 1996 to 2009. Population was estimated using the National Census. We utilized joinpoint regression analysis to explore temporal trends. We also evaluated marital status, ethnicity, birthplace and methods for suicide. Results: In the period analyzed, 6,002 suicides were accrued with a rate of 4.6 per 100,000 (7.5 in men and 2.0 in women); the male-to-female ratio was around 3.7. Trends for men presented a significant decline of 5.3% per year from 1996 to 2002, and a significant increase of 2.5% from 2002 onwards. Women did not present significant changes. For men, the elderly (> 65 years) had a significant reduction of 2.3% per year, while younger men (25-44 years) presented a significant increase of 8.6% from 2004 onwards. Women did not present significant trend changes according to age. Leading suicide methods were hanging and poisoning for men and women, respectively. Other analyses showed an increased suicide risk ratio for singles and foreigners. Conclusions: Specific epidemiological trends for suicide in the city of Sao Paulo that warrant further investigation were identified. High-risk groups - such as immigrants - could benefit from targeted strategies of suicide prevention.
- Are Antidepressants Good for the Soul but Bad for the Matter? Using Noninvasive Brain Stimulation to Detangle Depression/Antidepressants Effects on Heart Rate Variability and Cardiovascular Risk(2012) BRUNONI, Andre Russowsky; LOTUFO, Paulo Andrade; BENSENOR, Isabela M.
- Suicide rates and income in Sao Paulo and Brazil: a temporal and spatial epidemiologic analysis from 1996 to 2008(2012) BANDO, Daniel H.; BRUNONI, Andre R.; BENSENOR, Isabela M.; LOTUFO, Paulo A.Background: In a classical study, Durkheim noted a direct relation between suicide rates and wealth in the XIX century France. Since that time, several studies have verified this relationship. It is known that suicide rates are associated with income, although the direction of this association varies worldwide. Brazil presents a heterogeneous distribution of income and suicide across its territory; however, evaluation for an association between these variables has shown mixed results. We aimed to evaluate the relationship between suicide rates and income in Brazil, State of Sao Paulo (SP), and City of SP, considering geographical area and temporal trends. Methods: Data were extracted from the National and State official statistics departments. Three socioeconomic areas were considered according to income, from the wealthiest (area 1) to the poorest (area 3). We also considered three regions: country-wide (27 Brazilian States and 558 Brazilian micro-regions), state-wide (645 counties of SP State), and city-wide (96 districts of SP city). Relative risks (RR) were calculated among areas 1, 2, and 3 for all regions, in a cross-sectional approach. Then, we used Joinpoint analysis to explore the temporal trends of suicide rates and SaTScan to investigate geographical clusters of high/low suicide rates across the territory. Results: Suicide rates in Brazil, the State of SP, and the city of SP were 6.2, 6.6, and 5.4 per 100,000, respectively. Taking suicide rates of the poorest area (3) as reference, the RR for the wealthiest area was 1.64, 0.88, and 1.65 for Brazil, State of SP, and city of SP, respectively (p for trend <0.05 for all analyses). Spatial cluster of high suicide rates were identified at Brazilian southern (RR = 2.37), state of SP western (RR = 1.32), and city of SP central (RR = 1.65) regions. A direct association between income and suicide were found for Brazil (OR = 2.59) and the city of SP (OR = 1.07), and an inverse association for the state of SP (OR = 0.49). Conclusions: Temporospatial analyses revealed higher suicide rates in wealthier areas in Brazil and the city of SP and in poorer areas in the State of SP. We further discuss the role of socioeconomic characteristics for explaining these discrepancies and the importance of our findings in public health policies. Similar studies in other Brazilian States and developing countries are warranted.
conferenceObject Sertraline vs. Electrical Current Therapy for Treating Depression Clinical Trial (SELECT TDCS): Results from a Factorial, Randomized, Controlled Trial(2012) BRUNONI, Andre; VALIENGO, Leandro; BACCARO, Alessandra; ZANAO, Tamires; OLIVEIRA, Janaina Farias de; GOULART, Alessandra; LOTUFO, Paulo; BOGGLE, Paulo; BENSENOR, Isabela; FREGNI, FelipeBackground: Non-invasive brain stimulation has been increasingly used as an intervention for major depressive disorder (MDD). Methods: Randomized, factorial, double-blinded, controlled trial. Participants were randomized to sertraline/placebo and active/sham tDCS. They presented moderate to severe medication-free, nonpsychotic, unipolar, major depressivedisorder. They received 6-week treatment of 2mA anodal left dorsolateral prefrontal tDCS (twelve 30-min sessions: 10 consecutive sessions plus two extra sessions every other week) and sertraline (50mg/day). The primary outcome was the Montgomery-Asberg depression scale (MADRS) score changes at the end of treatment (6-week). A difference of at least 3 points in scores was consideredclinically relevant. Secondary outcomes were remission and response rates, and other depression scales. Results : At six weeks (primary outcome), the combined treatment was superior to sham tDCS - placebo (mean difference= 11.5 points; 95% CI=6.03 to 17.1; p<0.01) to sham tDCS -sertraline (mean 8.5; 95% CI=2.96 to 14.03; p<0.01) and to active tDCS - placebo (mean 5.9; 95%=CI 0.36 to 11.43). TDCS and sertraline alone were not different between each other (mean 2.6; 95% CI=8.13 to -2.9; p=0.35). Secondary efficacy analyses mainly confirmed these findings. Adverse effects were not significantly different when comparing groups, althoughfive of seven episodes of treatment-emergent (hypo)mania were observed in the combined treatment. Conclusions: In MDD, combination of tDCS and sertraline increases the efficacy of each treatment alone. Efficacy/safety did not differ between them.- Analgesic Effects of Noninvasive Brain Stimulation in Rodent Animal Models: A Systematic Review of Translational Findings(2012) VOLZ, Magdalena Sarah; VOLZ, Theresa Sophie; BRUNONI, Andre Russowsky; OLIVEIRA, Joao Paulo Vaz Tostes Ribeiro de; FREGNI, FelipeObjectives: Noninvasive brain stimulation (NIBS) interventions have demonstrated promising results in the clinical treatment of pain, according to several preliminary trials, although the results have been mixed. The limitations of clinical research on NIBS are the insufficient understanding of its mechanisms of action, a lack of adequate safety data, and several disparities with regard to stimulation parameters, which have hindered the generalizability of such studies. Thus, experimental animal research that allows the use of more invasive interventions and creates additional control of independent variables and confounders is desirable. To this end, we systematically reviewed animal studies investigating the analgesic effects of NIBS. In addition, we also explored the investigation of NIBS in animal models of stroke as to compare these findings with NIBS animal pain research. Methods: Of 1916 articles that were found initially, we identified 15 studies (stroke and pain studies) per our eligibility criteria that used NIBS methods, such as transcranial direct current stimulation, paired associative stimulation, transcranial magnetic stimulation, and transcranial electrostimulation. We extracted the main outcomes on stroke and pain, as well as the methods and electrical parameters of each technique. Results: NIBS techniques are effective in alleviating pain. Similar beneficial clinical effects are observed in stroke. The main insights from these animal studies are the following: 1) combination of NIBS with analgesic drugs has a synergistic effect; 2) effects are dependent on the parameters of stimulation, and in fact, not necessarily the strongest stimulation parameter (i.e., the largest intensity of stimulation) is associated with the largest benefit; 3) pain studies show an overall good quality as indexed by Animals in Research: Reporting In Vivo Experiments guidelines of the reporting of animal experiments, but insufficient with regard to the reporting of safety data for brain stimulation; 4) these studies suggest that NIBS techniques have a primary effect on synaptic plasticity, but they also suggest other mechanisms of action such as via neurovascular modulation. Conclusions: We found a limited number of animal studies for both pain and stroke NIBS experimental research. There is a lack of safety data in animal studies in these two topics and results from these studies have not been yet fully tested and translated to human research. We discuss the challenges and limitations of translating experimental animal research on NIBS into clinical studies.
- A systematic review and meta-analysis of heart rate variability in epilepsy and antiepileptic drugs(2012) LOTUFO, Paulo A.; VALIENGO, Leandro; BENSENOR, Isabela M.; BRUNONI, Andre R.Purpose: Epilepsy is associated with near-fatal and fatal arrhythmias, and sudden unexpected death in epilepsy (SUDEP) is partly related to cardiac events. Dysfunction of the autonomous nervous system causes arrhythmias and, although previous studies have investigated the effects of epilepsy on the autonomic control of the heart, the results are still mixed regarding whether imbalance of sympathetic, vagal, or both systems is present in epilepsy, and also the importance of anticonvulsant treatment on the autonomic system. Therefore, we aimed to investigate epilepsy and its treatment impact on heart rate variability (HRV), assessed by sympathetic and parasympathetic activity expressed as low-frequency (LF) and high-frequency (HF) power spectrum, respectively. Method: We performed a systematic review from the first date available to July 2011 in Medline and other databases; key search terms were ""epilepsy''; ""anticonvulsants''; ""heart rate variability''; ""vagal''; and ""autonomous nervous system.'' Original studies that reported data and/or statistics of at least one HRV value were included, with data being extracted by two independent authors. We used a random-effects model with Hedges's g as the measurement of effect size to perform two main meta-analyses comparing LF and HF HRV values in (1) epilepsy patients versus controls; (2) patients receiving versus not receiving treatment; and (3) well-controlled versus refractory patients. Secondary analyses assessed other time-and frequency-domain measurements (nonlinear methods were not analyzed due to lack of sufficient data sets). Quality assessment of each study was verified and also meta-analytic techniques to identify and control bias. Meta-regression for age and gender was performed. Key Findings: Initially, 366 references were identified. According to our eligibility criteria, 30 references (39 studies) were included in our analysis. Regarding HF, epilepsy patients presented lower values (g -0.69) than controls, with the 95% confidence interval (CI) ranging from -1.05 to -0.33. No significant differences were observed for LF (g -0.18; 95% CI -0.71 to 0.35). Patients receiving treatment presented HF values to those not receiving treatment (g -0.05; 95% CI -0.37 to 0.27), with a trend for having higher LF values (g 0.1; 95% CI -0.13 to 0.33), which was more pronounced in those receiving antiepileptic drugs (vs. vagus nerve stimulation). No differences were observed for well-controlled versus refractory patients, possibly due to the low number of studies. Regression for age and gender did not influence the results. Finally, secondary time-domain analyses also showed lower HRV and lower vagal activity in patients with epilepsy, as shown by the standard deviation of normal-to-normal interval (SDNN) and the root mean square of successive differences (RMSSD) indexes, respectively. Significance: We confirmed and extended the hypothesis of sympathovagal imbalance in epilepsy, as showed by lower HF, SDNN, and RMSSD values when compared to controls. In addition, there was a trend for higher LF values in patients receiving pharmacotherapy. As lower vagal (HF) and higher sympathetic (LF) tone are predictors of morbidity and mortality in cardiovascular samples, our findings highlight the importance of investigating autonomic function in patients with epilepsy in clinical practice. Assessing HRV might also be useful when planning therapeutic interventions, as some antiepileptic drugs can show hazardous effects in cardiac excitability, potentially leading to cardiac arrhythmia.
- Transcranial direct current stimulation for the treatment of major depressive disorder: A summary of preclinical, clinical and translational findings(2012) BRUNONI, Andre Russowsky; FERRUCCI, Roberta; FREGNI, Felipe; BOGGIO, Paulo Sergio; PRIORI, AlbertoMajor depressive disorder (MDD) is a common psychiatric illness, with 6-12% lifetime prevalence. It is also among the five most disabling diseases worldwide. Current pharmacological treatments, although relatively effective, present important side effects that lead to treatment discontinuation. Therefore, novel treatment options for MDD are needed. Here, we discuss the recent advancements of one new neuromodulatory technique - transcranial direct current stimulation (tDCS) - that has undergone intensive research over the past decade with promising results. tDCS is based on the application of weak, direct electric current over the scalp, leading to cortical hypo- or hyper-polarization according to the specified parameters. Recent studies have shown that tDCS is able to induce potent changes in cortical excitability as well as to elicit long-lasting changes in brain activity. Moreover, tDCS is a technique with a low rate of reported side effects, relatively easy to apply and less expensive than other neuromodulatory techniques - appealing characteristics for clinical use. In the past years, 4 of 6 phase II clinical trials and one recent meta-analysis have shown positive results in ameliorating depression symptoms. tDCS has some interesting, unique aspects such as noninvasiveness and low rate of adverse effects, being a putative substitutive/augmentative agent for antidepressant drugs, and low-cost and portability, making it suitable for use in clinical practice. Still, further phase II and phase III trials are needed as to better clarify tDCS role in the therapeutic arsenal of MOD.
- Clinical research with transcranial direct current stimulation (tDCS): Challenges and future directions(2012) BRUNONI, Andre Russowsky; NITSCHE, Michael A.; BOLOGNINI, Nadia; BIKSON, Marom; WAGNER, Tim; MERABET, Lotfi; EDWARDS, Dylan J.; VALERO-CABRE, Antoni; ROTENBERG, Alexander; PASCUAL-LEONE, Alvaro; FERRUCCI, Roberta; PRIORI, Alberto; BOGGIO, Paulo Sergio; FREGNI, FelipeBackground Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past 10 years, tDCS physiologic mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodologic, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them. Methods We convened a workgroup of researchers in the field to review, discuss, and provide updates and key challenges of tDCS use in clinical research. Main Findings/Discussion We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (1) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (2) methodologic aspects related to the clinical research of tDCS as divided according to study phase (ie, preclinical, phase I, phase H, and phase HI studies); (3) ethical and regulatory concerns; and (4) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS.
- Cardiovascular risk factors in patients with first-episode psychosis in Sao Paulo, Brazil(2012) BENSENOR, Isabela M.; BRUNONI, Andre R.; PILAN, Luis Augusto; GOULART, Alessandra C.; BUSATTO, Geraldo F.; LOTUFO, Paulo A.; SCAZUFCA, Marcia; MENEZES, Paulo R.Objective: The objective was to evaluate the cardiovascular profile of first-episode psychosis patients in Sao Paulo, Brazil, an issue that has not been sufficiently explored in low-/middle-income countries. Method: A cross-sectional study was performed 1 to 3 years after an initial, larger survey that assessed first-episode psychosis in sao Paulo. We evaluated cardiovascular risk factors and lifestyle habits using standard clinical examination and laboratory evaluation. Results: Of 151 contacted patients, 82 agreed to participate (mean age=35 years; 54% female). The following diagnoses were found: 20.7% were obese, 29.3% had hypertension, 39.0% had dyslipidemia, 19.5% had metabolic syndrome, and 1.2% had a >20% 10-year risk of coronary heart disease based on Framingham score. Also, 72% were sedentary, 25.6% were current smokers, and 7.3% reported a heavy alcohol intake. Conclusion: Compared to other samples, ours presented a distinct profile of higher rates of hypertension and diabetes (possibly due to dietary habits) and lower rates of smoking and alcohol intake (possibly due to higher dependence on social support). Indirect comparison vs. healthy, age-matched Brazilians revealed that our sample had higher frequencies of hypertension, diabetes and metabolic syndrome. Therefore, we confirmed a high cardiovascular risk in first-episode psychosis in Brazil. Transcultural studies are needed to investigate to which extent lifestyle contributes to such increased risk.