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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- 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.
- 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.
- Efficacy of non-invasive brain stimulation interventions in reducing smoking frequency in patients with nicotine dependence: a systematic review and network meta-analysis of randomized controlled trials(2022) TSENG, Ping-Tao; JENG, Jia-Shyun; ZENG, Bing-Syuan; STUBBS, Brendon; CARVALHO, Andre F.; BRUNONI, Andre R.; SU, Kuan-Pin; TU, Yu-Kang; WU, Yi-Cheng; CHEN, Tien-Yu; LIN, Pao-Yen; LIANG, Chih-Sung; HSU, Chih-Wei; CHEN, Yen-Wen; LI, Cheng-TaBackground and aims Nicotine is a highly addictive substance in tobacco products that dysregulates several neurotransmitters in the brain and impairs executive function. Non-invasive brain stimulation (NIBS) methods such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are promising treatments for nicotine dependence. We investigated the efficacy and acceptability of NIBS in managing smoking cessation through a systematic review and network meta-analysis (NMA). Methods We conducted a systematic review to identify randomized controlled trials (RCTs) that investigated the efficacy of NIBS for smoking cessation. All pairwise meta-analyses and NMA procedures were conducted using random-effects and frequentist models. The co-primary outcomes were (1) the change in number of cigarettes smoked per day (change in frequency of smoking) in patients with nicotine dependence after NIBS and (2) acceptability (the dropout rate). The effect sizes for co-primary outcomes of change in frequency of smoking and acceptability were assessed according to standardized mean difference (SMD) and odds ratio, respectively. Results Twelve RCTs with 710 participants (mean age: 44.2 years, 31.2% female) were included. Compared with the sham control, 10-Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) was associated with the largest changes in smoking frequency [SMD = -1.22, 95% confidence interval (95% CI) = -1.77 to -0.66]. The 2-mA bifrontal tDCS (SMD = -0.97, 95% CI = -1.32 to -0.62) and 10-Hz deep rTMS over the bilateral DLPFC with cue provocation (SMD = -0.77, 95% CI = -1.20 to -0.34) were associated with a significantly larger decrease in smoking frequency versus the sham. None of the investigated NIBSs was associated with dropout rates significantly different from those of the sham control groups. Conclusion Prefrontal non-invasive brain stimulation interventions appear to reduce the number of cigarettes smoked with good acceptability.
- Cognitive effects and acceptability of non-invasive brain stimulation on Alzheimer's disease and mild cognitive impairment: a component network meta-analysis(2021) CHU, Che-Sheng; LI, Cheng-Ta; BRUNONI, Andre R.; YANG, Fu-Chi; TSENG, Ping-Tao; TU, Yu-Kang; STUBBS, Brendon; CARVALHO, Andre F.; THOMPSON, Trevor; RAJJI, Tarek K.; YEH, Ta-Chuan; TSAI, Chia-Kuang; CHEN, Tien-Yu; LI, Dian-Jeng; HSU, Chih-Wei; WU, Yi-Cheng; YU, Chia-Ling; LIANG, Chih-SungObjectives To compare cognitive effects and acceptability of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI), and to determine whether cognitive training (CT) during rTMS or tDCS provides additional benefits. Methods Electronic search of PubMed, Medline, Embase, the Cochrane Library and PsycINFO up to 5 March 2020. We enrolled double-blind, randomised controlled trials (RCTs). The primary outcomes were acceptability and pre-post treatment changes in general cognition measured by Mini-Mental State Examination, and the secondary outcomes were memory function, verbal fluency, working memory and executive function. Durability of cognitive benefits (1, 2 and >= 3 months) after brain stimulation was examined. Results We included 27 RCTs (n=1070), and the treatment components included high-frequency rTMS (HFrTMS) and low-frequency rTMS, anodal tDCS (atDCS) and cathodal tDCS (ctDCS), CT, sham CT and sham brain stimulation. Risk of bias of evidence in each domain was low (range: 0%-11.1%). HFrTMS (1.08, 9, 0.35-1.80) and atDCS (0.56, 0.03-1.09) had short-term positive effects on general cognition. CT might be associated with negative effects on general cognition (-0.79, -2.06 to 0.48) during rTMS or tDCS. At 1-month follow-up, HFrTMS (1.65, 0.77-2.54) and ctDCS (2.57, 0.20-4.95) exhibited larger therapeutic responses. Separate analysis of populations with pure AD and MCI revealed positive effects only in individuals with AD. rTMS and tDCS were well tolerated. Conclusions HFrTMS is more effective than atDCS for improving global cognition, and patients with AD may have better responses to rTMS and tDCS than MCI.
- Mindfulness-based stress reduction for fibromyalgia: A step closer to precision psychiatry?(2019) CARVALHO, Andre F.; FERNANDES, Brisa S.; BRUNONI, Andre R.
- Regulation of leukocyte tricarboxylic acid cycle in drug-naive Bipolar Disorder(2015) SOUSA, Rafael T. de; STRECK, Emilio L.; FORLENZA, Orestes V.; BRUNONI, Andre R.; ZANETTI, Marcus V.; FERREIRA, Gabriela K.; DINIZ, Breno S.; PORTELA, Luis V.; CARVALHO, Andre F.; ZARATE JR., Carlos A.; GATTAZ, Wagner F.; MACHADO-VIEIRA, RodrigoSeveral lines of evidence suggest a role for mitochondrial dysfunction in the pathophysiology of bipolar disorder (BD). The tricarboxylic acid cycle (TCA cycle) is fundamental for mitochondrial energy production and produces substrates used in oxidative phosphorylation by the mitochondrial electron transport chain. The activity of the key TCA cycle enzymes citrate synthase, malate dehydrogenase, and succinate dehydrogenase has never been evaluated in BD. In the present study, these enzymes were assayed from leukocytes of drug-naive BD patients in a major depressive episode (n = 18) and compared to 24 age-matched healthy controls. Drug-naive BD patients did not show differences in activities of citrate synthase (p = 0.79), malate dehydrogenase (p = 0.17), and succinate dehydrogenase (p = 0.35) compared with healthy controls. No correlation between any TCA cycle enzyme activity and severity of depressive symptoms was observed. Overall, these data suggest that the activities of the TCA cycle enzymes are not altered in major depressive episodes of recent-onset BD, which may support the concept of illness staging and neuroprogression in BD.
- Repetitive Transcranial Magnetic Stimulation for the Acute Treatment of Major Depressive Episodes A Systematic Review With Network Meta-analysis(2017) BRUNONI, Andre R.; CHAIMANI, Anna; MOFFA, Adriano H.; RAZZA, Lais B.; GATTAZ, Wagner F.; DASKALAKIS, Zafiris J.; CARVALHO, Andre F.IMPORTANCE Although several strategies of repetitive transcranial magnetic stimulation (rTMS) have been investigated as treatment of major depressive disorder (MDD), their comparative efficacy and acceptability is unknown. OBJECTIVE To establish the relative efficacy and acceptability of the different modalities of rTMS used for MDD by performing a network meta-analysis, obtaining a clinically meaningful treatment hierarchy. DATA SOURCES PubMed/MEDLINE, EMBASE, PsycInfo, and Web of Science were searched up until October 1, 2016. STUDY SELECTION Randomized clinical trials that compared any rTMS intervention with sham or another rTMS intervention. Trials performing less than 10 sessions were excluded. DATA EXTRACTION AND SYNTHESIS Two independent reviewers used standard forms for data extraction and quality assessment. Random-effects, standard pairwise, and network meta-analyses were performed to synthesize data. MAIN OUTCOMES AND MEASURES Response rates and acceptability (dropout rate). Remission was the secondary outcome. Effect sizes were reported as odds ratios (ORs) with 95% CIs. RESULTS Eighty-one studies (4233 patients, 59.1% women, mean age of 46 years) were included. The interventions more effective than sham were priming low-frequency (OR, 4.66; 95% CI, 1.70-12.77), bilateral (OR, 3.96; 95% CI, 2.37-6.60), high-frequency (OR, 3.07; 95% CI, 2.24-4.21), theta-burst stimulation (OR, 2.54; 95% CI, 1.07-6.05), and low-frequency (OR, 2.37; 95% CI, 1.52-3.68) rTMS. Novel rTMS interventions (accelerated, synchronized, and deep rTMS) were not more effective than sham. Except for.-burst stimulation vs sham, similar results were obtained for remission. All interventions were at least as acceptable as sham. The estimated relative ranking of treatments suggested that priming low-frequency and bilateral rTMS might be the most efficacious and acceptable interventions among all rTMS strategies. However, results were imprecise and relatively few trials were available for interventions other than low-frequency, high-frequency, and bilateral rTMS. CONCLUSIONS AND RELEVANCE Few differences were found in clinical efficacy and acceptability between the different rTMS modalities, favoring to some extent bilateral rTMS and priming low-frequency rTMS respectively. These findings warrant the design of larger RCTs investigating the potential of these approaches in the short-term treatment of MDD. Current evidence cannot support novel rTMS interventions as a treatment for MDD.
- Affective temperaments and emotional traits are associated with a positive screening for premenstrual dysphoric disorder(2016) CAMARA, Rachel A.; KOEHLER, Cristiano A.; MAES, Michael; NUNES-NETO, Paulo R.; BRUNONI, Andre R.; QUEVEDO, Joao; FERNANDES, Brisa S.; PERUGI, Giulio; HYPHANTIS, Thomas N.; CARVALHO, Andre F.Objectives: Preliminary evidence indicates that premenstrual dysphoric disorder (PMDD) may be frequently co-morbid with bipolar spectrum disorders. In addition, the manifestations of PMDD seem similar to a subthreshold depressive mixed state. Nevertheless, the associations between PMDD and affective temperaments and emotional traits have not been previously investigated. Methods: A consecutive sample of 514 drug-free Brazilian women (mean age: 22.8; SD = 5.4 years) took part in this cross-sectional study. Screening for PMDD was obtained with the validated Brazilian Portuguese version of the Premenstrual Symptoms Screening Tool (PSST). Affective temperaments and emotional dimensions were evaluated with the Affective and Emotional Composite Temperament Scale (AFECTS). In addition, socio-demographic and data on menstrual cycle were collected. Results: According to the PSST, 83 (16.1%) women screened positive for PMDD, while 216 (42.0%) women had no/mild premenstrual symptoms. The cyclothymic temperament was independently associated with PMDD (OR = 4.57; 95% CI: 2.11-9.90), while the euthymic temperament had an independent association with a lower likelihood of a positive screening for PMDD (OR = 0.28; 95% CI: 0.12-0.64). In addition, anger and sensitivity emerged as emotional dimensions significantly associated with PMDD. Conclusions: A positive screening for PMDD was associated with a predominant cyclothymic temperament, while an euthymic temperament was associated with a lower likelihood for a positive screening for PMDD. These data deserve replication in prospective studies. (C) 2016 Published by Elsevier Inc.
- Genetic Studies on the Tripartite Glutamate Synapse in the Pathophysiology and Therapeutics of Mood Disorders(2017) SOUSA, Rafael T. de; LOCH, Alexandre A.; CARVALHO, Andre F.; BRUNONI, Andre R.; HADDAD, Marie Reine; HENTER, Ioline D.; ZARATE JR., Carlos A.; MACHADO-VIEIRA, RodrigoBoth bipolar disorder (BD) and major depressive disorder (MDD) have high morbidity and share a genetic background. Treatment options for these mood disorders are currently suboptimal for many patients; however, specific genetic variables may be involved in both pathophysiology and response to treatment. Agents such as the glutamatergic modulator ketamine are effective in treatment-resistant mood disorders, underscoring the potential importance of the glutamatergic system as a target for improved therapeutics. Here we review genetic studies linking the glutamatergic system to the pathophysiology and therapeutics of mood disorders. We screened 763 original genetic studies of BD or MDD that investigated genes encoding targets of the pathway/mediators related to the so-called tripartite glutamate synapse, including pre- and post-synaptic neurons and glial cells; 60 papers were included in this review. The findings suggest the involvement of glutamate-related genes in risk for mood disorders, treatment response, and phenotypic characteristics, although there was no consistent evidence for a specific gene. Target genes of high interest included GRIA3 and GRIK2 (which likely play a role in emergent suicidal ideation after antidepressant treatment), GRIK4 (which may influence treatment response), and GRM7 (which potentially affects risk for mood disorders). There was stronger evidence that glutamate-related genes influence risk for BD compared with MDD. Taken together, the studies show a preliminary relationship between glutamate-related genes and risk for mood disorders, suicide, and treatment response, particularly with regard to targets on metabotropic and ionotropic receptors.