PAULO JENG CHIAN SUEN
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
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- 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.
- Trajectories of common mental disorders symptoms before and during the COVID-19 pandemic: findings from the ELSA-Brasil COVID-19 Mental Health Cohort(2022) FATORI, Daniel; SUEN, Paulo; BACCHI, Pedro; AFONSO, Leonardo; KLEIN, Izio; CAVENDISH, Beatriz A.; LEE, Younga H.; LIU, Zhaowen; BAUERMEISTER, Joshua; MORENO, Marina L.; VIANA, Maria Carmen; GOULART, Alessandra C.; SANTOS, Itamar S.; BAUERMEISTER, Sarah; SMOLLER, Jordan; LOTUFO, Paulo; BENSENOR, Isabela M.; BRUNONI, Andre R.Aim Evidence indicates most people were resilient to the impact of the COVID-19 pandemic on mental health. However, evidence also suggests the pandemic effect on mental health may be heterogeneous. Therefore, we aimed to identify groups of trajectories of common mental disorders' (CMD) symptoms assessed before (2017-19) and during the COVID-19 pandemic (2020-2021), and to investigate predictors of trajectories. Methods We assessed 2,705 participants of the ELSA-Brasil COVID-19 Mental Health Cohort study who reported Clinical Interview Scheduled-Revised (CIS-R) data in 2017-19 and Depression Anxiety Stress Scale-21 (DASS-21) data in May-July 2020, July-September 2020, October-December 2020, and April-June 2021. We used an equi-percentile approach to link the CIS-R total score in 2017-19 with the DASS-21 total score. Group-based trajectory modeling was used to identify CMD trajectories and adjusted multinomial logistic regression was used to investigate predictors of trajectories. Results Six groups of CMD symptoms trajectories were identified: low symptoms (17.6%), low-decreasing symptoms (13.7%), low-increasing symptoms (23.9%), moderate-decreasing symptoms (16.8%), low-increasing symptoms (23.3%), severe-decreasing symptoms (4.7%). The severe-decreasing trajectory was characterized by age < 60 years, female sex, low family income, sedentary behavior, previous mental disorders, and the experience of adverse events in life. Limitations Pre-pandemic characteristics were associated with lack of response to assessments. Our occupational cohort sample is not representative. Conclusion More than half of the sample presented low levels of CMD symptoms. Predictors of trajectories could be used to detect individuals at-risk for presenting CMD symptoms in the context of global adverse events.
- Association between tDCS computational modeling and clinical outcomes in depression: data from the ELECT-TDCS trial(2021) SUEN, Paulo J. C.; DOLL, Sarah; BATISTUZZO, Marcelo C.; BUSATTO, Geraldo; RAZZA, Lais B.; PADBERG, Frank; MEZGER, Eva; BULUBAS, Lucia; KEESER, Daniel; DENG, Zhi-De; BRUNONI, Andre R.Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention investigated for the treatment of depression. Clinical results have been heterogeneous, partly due to the variability of electric field (EF) strength in the brain owing to interindividual differences in head anatomy. Therefore, we investigated whether EF strength was correlated with behavioral changes in 16 depressed patients using simulated electric fields in real patient data from a controlled clinical trial. We hypothesized that EF strength in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), brain regions implicated in depression pathophysiology, would be associated with changes in depression, mood and anxiety scores. SimNIBS were used to simulate individual electric fields based on the MRI structural T1-weighted brain scans of depressed subjects. Linear regression models showed, at the end of the acute treatment phase, that simulated EF strength was inversely associated with negative affect in the bilateral ACC (left: beta = - 160.463, CI [- 291.541, - 29.385], p = 0.021; right: beta = - 189.194, CI [- 289.479, - 88.910], p = 0.001) and DLPFC (left: beta = - 93.210, CI [- 154.960, - 31.461], p = 0.006; right: beta = - 82.564, CI [- 142.867, - 22.262], p = 0.011) and with depression scores in the left ACC (beta = - 156.91, CI [- 298.51, - 15.30], p = 0.033). No association between positive affect or anxiety scores, and simulated EF strength in the investigated brain regions was found. To conclude, our findings show preliminary evidence that EF strength simulations might be associated with further behavioral changes in depressed patients, unveiling a potential mechanism of action for tDCS. Further studies should investigate whether individualization of EF strength in key brain regions impact clinical response.
- 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.
- White matter microstructure associated with anhedonia among individuals with bipolar disorders and high-risk for bipolar disorders(2022) DIAZ, Alexandre Paim; FERNANDES, Brisa S.; TEIXEIRA, Antonio Lucio; MWANGI, Benson; HASAN, Khader M.; WU, Mon-Ju; SELVARAJ, Sudhakar; SUEN, Paulo; ZANAO, Tamires Araujo; BRUNONI, Andre R.; SANCHES, Marsal; SOARES, Jair C.Background: Anhedonia - a key symptom of depression - is highly associated with poorer outcomes and suicidal behavior. Alterations in the circuitry of reward-related brain regions have been robustly associated with anhedonia in unipolar depression, but not bipolar disorder (BD). We investigated white matter microstructures associated with anhedonia in participants with BD types I and II and first-degree relatives of patients with BD (BD-siblings). Methods: Eighty participants (BD types I and II: 56 [70%], and BD-siblings: 24 [30%]) underwent diffusion tensor imaging (DTI); Fractional anisotropy (FA) of different tracts were computed. Anhedonia was assessed using item 8, (""inability to feel"") of the MADRS scale. General linear models were used to compare the FA of different tracts in participants with and without anhedonia controlling for several clinical and demographic variables. Results: The mean age of the sample was 37 (+/- 11) years old, and 68.8% were female. Participants with anhedonia (32.5%) presented lower mean FA in the left uncinate fasciculus (UF) (p = 0.005), right temporal endings of the superior longitudinal fasciculus (SLFT) (p = 0.04), and in the left and right parietal endings of the superior longitudinal fasciculus (SLFP) (p = 0.003, and p = 0.04, respectively). Similar comparisons between participants with or without current depressive episodes and between participants with or without inner tension according to the MADRS did not show significant differences, specificity of the findings for anhedonia. Conclusions: Lower FA in the left UF and SLF are potential neuroimaging markers of anhedonia in individuals with BD and high-risk for BD.
- Prevalence and risk factors of psychiatric symptoms and diagnoses before and during the COVID-19 pandemic: findings from the ELSA-Brasil COVID-19 mental health cohort(2023) BRUNONI, Andre Russowsky; SUEN, Paulo Jeng Chian; BACCHI, Pedro Starzynski; RAZZA, Lais Boralli; KLEIN, Izio; SANTOS, Leonardo Afonso dos; SANTOS, Itamar de Souza; VALIENGO, Leandro da Costa Lane; GALLUCCI-NETO, Jose; MORENO, Marina Lopes; PINTO, Bianca Silva; FELIX, Larissa de Cassia Silva; SOUSA, Juliana Pereira de; VIANA, Maria Carmen; FORTE, Pamela Marques; CARDOSO, Marcia Cristina de Altisent Oliveira; BITTENCOURT, Marcio Sommer; PELOSOF, Rebeca; SIQUEIRA, Luciana Lima de; FATORI, Daniel; BELLINI, Helena; BUENO, Priscila Vilela Silveira; PASSOS, Ives Cavalcante; NUNES, Maria Angelica; SALUM, Giovanni Abrahao; BAUERMEISTER, Sarah; SMOLLER, Jordan W.; LOTUFO, Paulo Andrade; BENSENOR, Isabela MartinsBackground There is mixed evidence on increasing rates of psychiatric disorders and symptoms during the coronavirus disease 2019 (COVID-19) pandemic in 2020. We evaluated pandemic-related psychopathology and psychiatry diagnoses and their determinants in the Brazilian Longitudinal Study of Health (ELSA-Brasil) Sao Paulo Research Center. Methods Between pre-pandemic ELSA-Brasil assessments in 2008-2010 (wave-1), 2012-2014 (wave-2), 2016-2018 (wave-3) and three pandemic assessments in 2020 (COVID-19 waves in May-July, July-September, and October-December), rates of common psychiatric symptoms, and depressive, anxiety, and common mental disorders (CMDs) were compared using the Clinical Interview Scheduled-Revised (CIS-R) and the Depression Anxiety Stress Scale-21 (DASS-21). Multivariable generalized linear models, adjusted by age, gender, educational level, and ethnicity identified variables associated with an elevated risk for mental disorders. Results In 2117 participants (mean age 62.3 years, 58.2% females), rates of CMDs and depressive disorders did not significantly change over time, oscillating from 23.5% to 21.1%, and 3.3% to 2.8%, respectively; whereas rate of anxiety disorders significantly decreased (2008-2010: 13.8%; 2016-2018: 9.8%; 2020: 8%). There was a decrease along three wave-COVID assessments for depression [beta = -0.37, 99.5% confidence interval (CI) -0.50 to -0.23], anxiety (beta = -0.37, 99.5% CI -0.48 to -0.26), and stress (beta = -0.48, 99.5% CI -0.64 to -0.33) symptoms (all ps < 0.001). Younger age, female sex, lower educational level, non-white ethnicity, and previous psychiatric disorders were associated with increased odds for psychiatric disorders, whereas self-evaluated good health and good quality of relationships with decreased risk. Conclusion No consistent evidence of pandemic-related worsening psychopathology in our cohort was found. Indeed, psychiatric symptoms slightly decreased along 2020. Risk factors representing socioeconomic disadvantages were associated with increased odds of psychiatric disorders.
- Examining the impact of the COVID-19 pandemic through the lens of the network approach to psychopathology: Analysis of the Brazilian Longitudinal Study of Health (ELSA-Brasil) cohort over a 12-year timespan(2022) SUEN, P. J. C.; BACCHI, P. S.; RAZZA, L.; SANTOS, L. A. dos; FATORI, D.; KLEIN, I.; PASSOS, I. C.; SMOLLER, J. W.; BAUERMEISTER, S.; GOULART, A. C.; SANTOS, I. de Souza; BENSENOR, I. M.; LOTUFO, P. A.; HEEREN, A.; BRUNONI, A. R.Cohort studies have displayed mixed findings on changes in mental symptoms severity in 2020, when the COVID-19 pandemic outbreak started. Network approaches can provide additional insights by analyzing the connectivity of such symptoms. We assessed the network structure of mental symptoms in the Brazilian Longitudinal Study of Health (ELSA-Brasil) in 3 waves: 2008–2010, 2017–2019, and 2020, and hypothesized that the 2020 network would present connectivity changes. We used the Clinical Interview Scheduled-Revised (CIS-R) questionnaire to evaluates the severity of 14 common mental symptoms. Networks were graphed using unregularized Gaussian models and compared using centrality and connectivity measures. The predictive power of centrality measures and individual symptoms were also estimated. Among 2011 participants (mean age: 62.1 years, 58% females), the pandemic symptom 2020 network displayed higher overall connectivity, especially among symptoms that were related to general worries, with increased local connectivity between general worries and worries about health, as well as between anxiety and phobia symptoms. There was no difference between 2008 and 2010 and 2017–2019 networks. According to the network theory of mental disorders, external factors could explain why the network structure became more densely connected in 2020 compared to previous observations. We speculate that the COVID-19 pandemic and its innumerous social, economical, and political consequences were prominent external factors driving such changes; although further assessments are warranted. © 2021 Elsevier Ltd