RENERIO FRAGUAS JUNIOR
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Psiquiatria, Faculdade de Medicina - Docente
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Association among depression, cognitive impairment and executive dysfunction after stroke(2012) TERRONI, Luisa; SOBREIRO, Matildes F.M.; CONFORTO, Adriana B.; ADDA, Carla C.; GUAJARDO, Valeri D.; LUCIA, Mara Cristina S. de; FRÁGUAS, RenérioABSTRACT The relationship between depression and cognitive impairment, frequent after stroke, is complex and has not been sufficiently elucidated. Objective: To review the relationship between post-stroke depression and cognitive impairment. Methods: We performed a PubMed database search spanning the last ten years, using the terms post-stroke depression, cognitive dysfunction, cognitive impairment and neuropsychological tests. Our target studies were original quantitative studies that investigated the relationship between post-stroke depression (PSD) and cognitive impairment in stroke patients. Articles published in English, Spanish, Italian and Portuguese were considered. Selection criteria were the use of neuropsychological tests to assess cognitive function, and of either instruments to diagnose major depression, or scales to assess depressive symptoms, within the first three months after stroke. Results: Six original quantitative studies fulfilled the criteria. The prevalence of PSD within the first three months after stroke ranged from 22% to 31%. Incidence ranged from 25% to 27% and was evaluated in only two studies. PSD was associated with increased cognitive impairment. Cognitive impairment was reported in 35.2% to 87% of the patients. Post-stroke cognitive deficits were reported mostly in executive function, memory, language, and speed of processing. Conclusion: Executive dysfunction and depression occur in stroke survivors, are frequently coexistent, and also associated with worse stroke prognosis. Healthcare professionals need to address and provide adequate treatment for depression and executive dysfunctions in stroke patients early in the first three months after stroke. Future studies should evaluate the efficacy of programs evaluating the early detection and treatment of PSD and executive dysfunction in stroke survivors.
- The association of post-stroke anhedonia with salivary cortisol levels and stroke lesion in hippocampal/parahippocampal region(2015) TERRONI, Luisa; AMARO JR., Edson; IOSIFESCU, Dan V.; MATTOS, Patricia; YAMAMOTO, Fabio I.; TINONE, Gisela; CONFORTO, Adriana B.; SOBREIRO, Matildes F. M.; GUAJARDO, Valeri D.; LUCIA, Mara Cristina S. De; MOREIRA, Ayrton C.; SCAFF, Milberto; LEITE, Claudia C.; FRAGUAS, RenerioBackground: Anhedonia constitutes a coherent construct, with neural correlates and negative clinical impact, independent of depression. However, little is known about the neural correlates of anhedonia in stroke patients. In this study, we investigated the association of post-stroke anhedonia with salivary cortisol levels and stroke location and volume. Patients and methods: A psychiatrist administered the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition to identify anhedonia in 36 inpatients, without previous depression, consecutively admitted in a neurology clinic in the first month after a first-ever ischemic stroke. Salivary cortisol levels were assessed in the morning, evening, and after a dexamethasone suppression test. We used magnetic resonance imaging and a semi-automated brain morphometry method to assess stroke location, and the MRIcro program according to the Brodmann Map to calculate the lesion volume. Results: Patients with anhedonia had significantly larger diurnal variation (P-value =0.017) and higher morning levels of salivary cortisol (1,671.9 +/- 604.0 ng/dL versus 1,103.9 +/- 821.9 ng/dL; P-value =0.022), and greater stroke lesions in the parahippocampal gyrus (Brodmann area 36) compared to those without anhedonia (10.14 voxels; standard deviation +/- 17.72 versus 0.86 voxels; standard deviation +/- 4.64; P-value =0.027). The volume of lesion in the parahippocampal gyrus (Brodmann area 36) was associated with diurnal variation of salivary cortisol levels (rho=0.845; P-value =0.034) only in anhedonic patients. Conclusion: Our findings suggest that anhedonia in stroke patients is associated with the volume of stroke lesion in the parahippocampal gyrus and with dysfunction of the hypothalamic-pituitary-adrenal axis.
- Differential improvement in depressive symptoms for tDCS alone and combined with pharmacotherapy: an exploratory analysis from The Sertraline Vs. Electrical Current Therapy For Treating Depression Clinical Study(2014) BRUNONI, Andre R.; FRAGUAS JUNIOR, Renerio; KEMP, Andrew H.; LOTUFO, Paulo A.; BENSENOR, Isabela M.; FREGNI, FelipeTranscranial direct current stimulation (tDCS) is a promising therapy for major depression treatment, although little is known of its effects in ameliorating distinct symptoms of depression. Thus, it is important, not only to increase knowledge of its antidepressant mechanisms, but also to guide its potential use in clinical practice. Using data from a recent factorial, double-blinded, placebo-controlled trial applying tDCS-alone and combined with sertraline to treat 120 depressed outpatients over 6wk (Brunoni et al., 2013), we investigated the pattern of improvement in symptoms of depression from the Montgomery-Asberg depression scale (MADRS). First, we performed one multivariate analysis of variance with the score improvement of the 10 MADRS items as dependent variables. Significant (p<0.05) results were further explored with follow-up analyses of variance. TDCS (alone and combined with sertraline) improved concentration difficulties and pessimistic and suicidal thoughts. The combined treatment also improved apparent and reported sadness, lassitude and inability to feel. Indeed, tDCS/sertraline significantly ameliorated all but the vegetative' depression symptoms (inner tension, sleep and appetite items). We further discuss whether bifrontal tDCS over the dorsolateral prefrontal cortex could be associated with improvement in cognitive (concentration) and affective (pessimistic/suicidal thoughts) processing, while the combined treatment might have a more widespread antidepressant effect by simultaneously acting on different depression pathways. We also identified patterns of antidepressant improvement for tDCS that might aid in tailoring specific interventions for different subtypes of depressed patients, e.g. particularly those with suicidal ideation.
- Cognitive changes after tDCS and escitalopram treatment in major depressive disorder: Results from the placebo-controlled ELECT-TDCS trial(2020) MORENO, Marina L.; GOERIGK, Stephan A.; BERTOLA, Laiss; SUEMOTO, Claudia K.; RAZZA, Lais B.; MOFFA, Adriano H.; VERONEZI, Beatriz P.; TORT, Luara; NOGUEIRA, Barbara S.; GATTAZ, Wagner F.; FRAGUAS, Renerio; PADBERG, Frank; LOTUFO, Paulo A.; BENSENOR, Isabela M.; BRUNONI, Andre R.Background: Cognitive deficits in major depressive disorder (MDD) are associated with low quality of life and higher suicide risk. Antidepressant drugs have modest to null effects in improving such deficits. Therefore, we investigated the cognitive effects of transcranial direct current stimulation (tDCS), which is a promising antidepressant non-pharmacological intervention, in MDD. Methods: An exploratory analysis on cognitive performance was conducted in 243 depressed patients from the Escitalopram vs. Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS), a sham-controlled study comparing the efficacy of tDCS vs. escitalopram. A neuropsychological battery was applied at baseline and endpoint (10 weeks of treatment) to create composite cognitive scores (processing speed, working memory, and verbal fluency). Linear mixed regression models were used to evaluate changes according to intervention groups, adjusted for confounding variables (age, years of schooling, gender, and benzodiazepine use) and depression improvement. Results: No cognitive deterioration was observed in any group. Patients receiving tDCS presented reduced practice gains compared to placebo in processing speed. In patients receiving escitalopram vs. placebo and in the subgroup of clinical responders ( > 50% depression improvement from baseline), those receiving tDCS vs. placebo presented increased performance in verbal fluency. No significant differences between tDCS and escitalopram groups were detected. Limitations: Absence of healthy controls. Conclusion: Prefrontal tDCS did not lead to cognitive deficits in depressed patients, although it reduced practice effects in processing speed. tDCS responders presented increased performance in verbal fluency. Further investigation of tDCS cognitive effects in depression is warranted.
- Development of the Ketamine Side Effect Tool (KSET)(2020) SHORT, Brooke; DONG, Vanessa; GALVEZ, Veronica; VULOVIC, Vedran; MARTIN, Donel; BAYES, Adam J.; ZARATE, Carlos A.; MURROUGH, James W.; MCLOUGHLIN, Declan M.; RIVA-POSSE, Patricio; SCHOEVERS, Robert; FRAGUAS, Renerio; GLUE, Paul; FAM, Johnson; MCSHANE, Rupert; LOO, Colleen K.Background: Currently, no specific, systematic assessment tool for the monitoring and reporting of ketamine-related side effects exists. Our aim was to develop a comprehensive Ketamine Side Effect Tool (KSET) to capture acute and longer-term side effects associated with repeated ketamine treatments. Methods: Informed by systematic review data and clinical research, we drafted a list of the most commonly reported side effects. Face and content validation were obtained via feedback from collaborators with expertise in psychiatry and anaesthetics, clinical trial piloting and a modified Delphi Technique involving ten international experts. Results: The final version consisted of four forms that collect information at time points: screening, baseline, immediately after a single treatment, and longer-term follow-up. Instructions were developed to guide users and promote consistent utilisation. Limitations: Further evaluation of feasibility, construct validity and reliability is required, and is planned across multiple international sites. Conclusions: The structured Ketamine Side Effect Tool (KSET) was developed, with confirmation of content and face validity via a Delphi consensus process. This tool is timely, given the paucity of data regarding ketamine's safety, tolerability and abuse potential over the longer term, and its recent adoption internationally as a clinical treatment for depression. Although based on data from depression studies, the KSET has potential applicability for ketamine (or derivatives) used in other medical disorders, including chronic pain. We recommend its utilisation for both research and clinical scenarios, including data registries.
- Executive function and depressive symptoms of retardation in nonelderly stroke patients(2014) SOBREIRO, Matildes F. M.; MIOTTO, Eliane Correa; TERRONI, Luisa; TINONE, Gisela; IOSIFESCU, Dan V.; LUCIA, Mara C. S. de; SCAFF, Milberto; LEITE, Claudia da Costa; AMARO JR., Edson; FRAGUAS, RenerioThe depression-executive dysfunction syndrome, a late-onset depression of vascular origin with executive dysfunction and psychomotor retardation, has also been described after stroke. We verified whether this syndrome also occurs in nonelderly stroke patients by investigating the association between domains of depressive symptoms with executive functions in 87 first-ever ischemic stroke patients. The retardation domain of the 31-item Hamilton Rating Scale for Depression was associated with decreased performance on verbal fluency (assessed with FAS). The association was maintained for younger patients (aged <60 years) after adjusting for confounders. This result supports the clinical presentation of depression-executive dysfunction syndrome in younger stroke patients. Confirmation of this finding, its neural correlates, and clinical implication deserve further investigation.
- Recommendations for the pharmacological treatment of treatment-resistant depression: A systematic review protocol(2022) GABRIEL, Franciele Cordeiro; STEIN, Airton Tetelbom; MELO, Daniela Oliveira de; FONTES-MOTA, Gessica Caroline Henrique; SANTOS, Itamires Benicio dos; RODRIGUES, Camila da Silva; RODRIGUES, Monica Cristiane; FRAGUAS, Renerio; FLOREZ, Ivan D.; CORREIA, Diogo Telles; RIBEIRO, ElianeIntroductionDepression is a serious and widespread mental health disorder. Although effective treatment does exist, a significant proportion of patients with depression fail to respond to antidepressant treatment trials, a condition named treatment-resistant depression. Efficient approach should be given this condition in order to revert the burden caused by depression. Clinical practice guidelines (CPGs) are evidence-based health promotion instruments to improve diagnosis and treatment. CPGs recommendations for treatment-resistant depression must be trustworthy. The objective of the proposed study is to systematically identify, appraise the quality of CPGs for the treatment of depression and elaborate a synthesis of recommendations for treatment-resistant depression of CPGs considered to be of high quality and with high quality recommendations. Methods and analysisWe will search the databases of organizations, such as PubMed, Embase, Cochrane Library, PsycInfo, and the Virtual Health Library, and organizations that develop CPGs. Three independent researchers will assess the quality of the CPGs and their recommendations using the AGREE II and AGREE-REX instruments, respectively. Given the identification of divergences and convergences as well as weak and strong points among high quality CPGs, our work may help developers, clinicians and eventually patients. Ethics and disseminationNo ethical approval is required for a systematic review, as no patient data will be used. The research results will be disseminated in conferences and submitted to a peer reviewed journal.
- Quality of clinical practice guidelines for inadequat response to first-line treatment for depression according to AGREE II checklist and comparison of recommendations: a systematic review(2022) GABRIEL, Franciele Cordeiro; STEIN, Airton Tetelbom; MELO, Daniela Oliveira de; FONTES-MOTA, Gessica Caroline Henrique; SANTOS, Itamires Benicio dos; OLIVEIRA, Aliandra Fantinell de; FRAGUAS, Renerio; RIBEIRO, ElianeObjective To assess similarities and differences in the recommended sequence of strategies among the most relevant clinical practice guidelines (CPGs) for the treatment of depression in adults with inadequate response to first-line treatment. Data sources We performed a systematic review of the literature spanning January 2011 to August 2020 in Medline, Embase, Cochrane Library and 12 databases recognised as CPGs repositories. CPGs quality was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II). Study selection The eligibility criteria were CPGs that described pharmacological recommendations for treating depression for individuals aged 18 years or older in outpatient care setting. We included CPGs considered of high-quality (>= 80% in domain 3 of AGREE II) or recognised as clinically relevant. Data extraction Two independent researchers extracted recommendations for patients who did not respond to first-line pharmacological treatment from the selected CPGs. Results We included 46 CPGs and selected 8, of which 5 were considered high quality (>= 80% in domain 3 of AGREE II) and 3 were recognised as clinically relevant. Three CPGs did not define inadequate response to treatment and 3 did not establish a clear sequence of strategies. The duration of treatment needed to determine that a patient had not responded was not explicit in 3 CPGs and was discordant in 5 CPGs. Most CPGs agree in reassessing the diagnosis, assessing the presence of comorbidities, adherence to treatment, and increase dosage as first steps. All CPGs recommend psychotherapy, switching antidepressants, and considering augmentation/combining antidepressants. Conclusion Relevant CPGs present shortcomings in recommendations for non-responders to first-line antidepressant treatment including absence and divergencies in definition of inadequate response and sequence of recommended strategies. Overall, most relevant CPGs recommend reassessing the diagnosis, evaluate comorbidities, adherence to treatment, increase dosage of antidepressants, and psychotherapy as first steps. PROSPERO registration number CRD42016043364.
- Nonverbal behaviors are associated with increased vagal activity in major depressive disorder: Implications for the polyvagal theory(2017) FERNANDES, Raquel A.; FIQUER, Juliana T.; GORENSTEIN, Clarice; RAZZA, Lais Boralli; FRAGUAS JR., Renerio; BORRIONE, Lucas; BENSENOR, Isabela M.; LOTUFO, Paulo A.; DANTAS, Eduardo Miranda; CARVALHO, Andre F.; BRUNONI, Andre R.Background: Major depressive disorder (MDD) is associated with impairments in nonverbal behaviors (NVBs) and vagal activity. The polyvagal theory proposes that vagal activity regulates heart rate and NVBs by modulating a common anatomically and neurophysiologically discrete social engagement system. However, the association between these putative endophenotypes has not yet been explored. We hypothesize that in MDD, NVBs indicating positive affects and social interest and those indicating negative feelings and social disinterest could be associated with different patterns of vagal activity. Methods: For this cross-sectional study we recruited 50 antidepressant-free participants with moderate-to-severe MDD. Vagal activity was indexed by heart rate variability (HRV) measures, and positive and negative nonverbal behaviors (NVBs) by a validated ethogram. Associations between NVBs and HRV were explored by bivariate analyses and multivariable models were adjusted by age, gender, depression severity, and self-reported positive and negative affects. Results: HRV measures indicative of higher vagal activity were positively correlated with positive NVBs exhibited during the clinical interview. Conversely, NVBs related to negative affects, low energy and social disinterest were not associated with HRV. Limitations: Absence of a control group. Conclusions: The findings highlight that the examined depression endophenotypes (nonverbal behaviors and vagal activity) are related, shedding light on MDD pathophysiology in the context of the polyvagal theory.