ORESTES VICENTE FORLENZA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Psiquiatria, 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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- Bipolar symptoms, somatic burden and functioning in older-age bipolar disorder: A replication study from the global aging & geriatric experiments in bipolar disorder database (GAGE-BD) project(2024) SAJATOVIC, Martha; REJ, Soham; ALMEIDA, Osvaldo P.; ALTINBAS, Kursat; BALANZA-MARTINEZ, Vicent; BARBOSA, Izabela G.; BEUNDERS, Alexandra J. M.; BLUMBERG, Hilary P.; BRIGGS, Farren B. S.; DOLS, Annemiek; FORESTER, Brent P.; FORLENZA, Orestes V.; GILDENGERS, Ariel G.; JIMENEZ, Esther; KLAUS, Federica; LAFER, Beny; MULSANT, Benoit; MWANGI, Benson; NUNES, Paula Villela; OLAGUNJU, Andrew T.; OLUWANIYI, Stephen; ORHAN, Melis; PATRICK, Regan E.; RADUA, Joaquim; RAJJI, Tarek; SARNA, Kaylee; SCHOUWS, Sigfried; SIMHANDL, Christian; SEKHON, Harmehr; SOARES, Jair C.; SUTHERLAND, Ashley N.; TEIXEIRA, Antonio L.; TSAI, Shangying; VIDAL-RUBIO, Sonia; VIETA, Eduard; YALA, Joy; EYLER, Lisa T.Objectives: The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232, mean +/- standard deviation age 47.2 +/- 13.5, 65% women, 49% aged over 50) dataset. Design/Methods: Using mixed models with random effects for cohort, we examined associations between BD symptoms, somatic burden and age and the contribution of these to functioning in W2 and the combined W1 + W2 sample (n = 2601). Results: Compared to W1, the W2 sample was younger (p < 0.001), less educated (p < 0.001), more symptomatic (p < 0.001), lower functioning (p < 0.001) and had fewer somatic conditions (p < 0.001). In the full W2, older individuals had reduced manic symptom severity, but age was not associated with depression severity. Age was not associated with functioning in W2. More severe BD symptoms (mania p <= 0.001, depression p <= 0.001) were associated with worse functioning. Older age was significantly associated with higher somatic burden in the W2 and the W1 + W2 samples, but this burden was not associated with poorer functioning. Conclusions: In a large, independent sample, older age was associated with less severe mania and more somatic burden (consistent with previous findings), but there was no association of depression with age (different from previous findings). Similar to previous findings, worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning.
- Sociodemographic and clinical characteristics of people with oldest older age bipolar disorder in a global sample: Results from the global aging and geriatric experiments in bipolar disorder project(2024) CHEN, Peijun; SAJATOVIC, Martha; BRIGGS, Farren B. S.; MULSANT, Benoit; DOLS, Annemiek A.; GILDENGERS, Ariel; YALA, Joy; BEUNDERS, Alexandra J. M.; BLUMBERG, Hilary P.; REJ, Soham; FORLENZA, Orestes V.; JIMENEZ, Esther; SCHOUWS, Sigfried; ORHAN, Melis; SUTHERLAND, Ashley N.; VIETA, Eduard; TSAI, Shangying; SARNA, Kaylee; EYLER, Lisa T.Objects: Studies of older age bipolar disorder (OABD) have mostly focused on ""younger old"" individuals. Little is known about the oldest OABD (OOABD) individuals aged >= 70 years old. The Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) project provides an opportunity to evaluate the OOABD group to understand their characteristics compared to younger groups. Methods: We conducted cross-sectional analyses of the GAGE-BD database, an integrated, harmonized dataset from 19 international studies. We compared the sociodemographic and clinical characteristics of those aged <50 (YABD, n = 184), 50-69 (OABD, n = 881), and >= 70 (OOABD, n = 304). To standardize the comparisons between age categories and all characteristics, we used multinomial logistic regression models with age category as the dependent variable, with each characteristic as the independent variable, and clustering of standard errors to account for the correlation between observations from each of the studies. Results: OOABD and OABD had lower severity of manic symptoms (Mean YMRS = 3.3, 3.8 respectively) than YABD (YMRS = 7.6), and lower depressive symptoms (% of absent = 65.4%, and 59.5% respectively) than YABD (18.3%). OOABD and OABD had higher physical burden than YABD, especially in the cardiovascular domain (prevalence = 65% in OOABD, 41% in OABD and 17% in YABD); OOABD had the highest prevalence (56%) in the musculoskeletal domain (significantly differed from 39% in OABD and 31% in YABD which didn't differ from each other). Overall, OOABD had significant cumulative physical burden in numbers of domains (mean = 4) compared to both OABD (mean = 2) and YABD (mean = 1). OOABD had the lowest rates of suicidal thoughts (10%), which significantly differed from YABD (26%) though didn't differ from OABD (21%). Functional status was higher in both OOABD (GAF = 63) and OABD (GAF = 64), though only OABD had significantly higher function than YABD (GAF = 59). Conclusions: OOABD have unique features, suggesting that (1) OOABD individuals may be easier to manage psychiatrically, but require more attention to comorbid physical conditions; (2) OOABD is a survivor cohort associated with resilience despite high medical burden, warranting both qualitative and quantitative methods to better understand how to advance clinical care and ways to age successfully with BD.
- Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic(2024) RITTO, Ana Paula; ARAUJO, Adriana Ladeira de; CARVALHO, Carlos Roberto Ribeiro de; SOUZA, Heraldo Possolo De; FAVARETTO, Patricia Manga e Silva; SABOYA, Vivian Renata Boldrim; GARCIA, Michelle Louvaes; KULIKOWSKI, Leslie Domenici; KALLAS, Esper Georges; PEREIRA, Antonio Jose Rodrigues; COBELLO JUNIOR, Vilson; SILVA, Katia Regina; ABDALLA, Eidi Raquel Franco; SEGURADO, Aluisio Augusto Cotrim; SABINO, Ester Cerdeira; RIBEIRO JUNIOR, Ulysses; FRANCISCO, Rossana Pulcineli Vieira; MIETHKE-MORAIS, Anna; LEVIN, Anna Sara Shafferman; SAWAMURA, Marcio Valente Yamada; FERREIRA, Juliana Carvalho; SILVA, Clovis Artur; MAUAD, Thais; GOUVEIA, Nelson da Cruz; LETAIF, Leila Suemi Harima; BEGO, Marco Antonio; BATTISTELLA, Linamara Rizzo; DUARTE, Alberto Jose da Silva; SEELAENDER, Marilia Cerqueira Leite; MARCHINI, Julio; FORLENZA, Orestes Vicente; ROCHA, Vanderson Geraldo; MENDES-CORREA, Maria Cassia; COSTA, Silvia Figueiredo; CERRI, Giovanni Guido; BONFA, Eloisa Silva Dutra de Oliveira; CHAMMAS, Roger; BARROS FILHO, Tarcisio Eloy Pessoa de; BUSATTO FILHO, GeraldoIntroduction The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency.Methods At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output.Results Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19.Discussion Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.
- Post-COVID-19 condition: systemic inflammation and low functional exercise capacity(2024) CASTRO, Gabriela Salim de; GAMA, Leonardo R.; RAMOS, Alexandre Ferreira; SILVA, Guilherme Gatti da; TEIXEIRA, Alexandre Abilio de Souza; CUNHA-NETO, Edecio; SOUZA, Heraldo Possolo de; MARIE, Suely K.; TALIB, Leda L.; COELHO, Veronica; KALIL, Jorge; ARAUJO, Adriana Ladeira de; RITTO, Ana Paula; BELON, Alessandro Rodrigo; SANTOS, Amanda Soares; BARRERE, Ana Paula Noronha; SAWAMURA, Marcio V. Y.; LAMAS, Celina Almeida; BALDI, Bruno Guedes; CARVALHO, Carlos R. R.; KULIKOWSKI, Leslie Domenici; DAMIANO, Rodolfo Furlan; IMAMURA, Marta; ROSA NETO, Jose Cesar; LIRA, Fabio S.; OTOCH, Jose Pinhata; MIGUEL, Euripedes Constantino; BATTISTELLA, Linamara; FORLENZA, Orestes V.; BUSATTO, Geraldo; SEELAENDER, MariliaIntroduction Post-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported.Methods In this cross-sectional study, we recruited 227 participants who were hospitalised with acute COVID-19 in 2020 and came back for a follow-up assessment 6-12 months after hospital discharge. The participants were enrolled in two symptomatic groups: Self-Reported Symptoms group (SR, n = 96), who did not present major organ lesions, yet reported several debilitating symptoms such as fatigue, muscle weakness, and persistent loss of sense of smell and taste; and the Self-Reported Symptoms and decreased Pulmonary Function group (SRPF, n = 54), composed by individuals with the same symptoms described by SR, plus diagnosed pulmonary lesions. A Control group (n = 77), with participants with minor complaints following acute COVID-19, was also included in the study. Serum cytokine levels, symptom questionnaires, physical performance tests and general clinical data were obtained in the follow-up assessment.Results SRPF presented lower IL-4 concentration compared with Control (q = 0.0018) and with SR (q = 0.030), and lower IFN-alpha 2 serum content compared with Control (q = 0.007). In addition, SRPF presented higher MIP-1 beta serum concentration compared with SR (q = 0.029). SR presented lower CCL11 (q = 0.012 and q = 0.001, respectively) and MCP-1 levels (q = 0.052 for both) compared with Control and SRPF. SRPF presented lower G-CSF compared to Control (q = 0.014). Female participants in SR showed lower handgrip strength in relation to SRPF (q = 0.0082). Male participants in SR and SRPF needed more time to complete the timed up-and-go test, as compared with men in the Control group (q = 0.0302 and q = 0.0078, respectively). Our results indicate that different PCC symptom profiles are accompanied by distinct inflammatory markers in the circulation. Of particular concern are the lower muscle function findings, with likely long-lasting consequences for health and quality of life, found for both PCC phenotypes.
- Cognition in older age bipolar disorder: An analysis of archival data across the globe(2024) KLAUS, Federica; NG, Hui Xin; BARBOSA, Izabela G.; BEUNDERS, Alexandra; BRIGGS, Farren; BURDICK, Katherine E.; DOLS, Annemieke; FORLENZA, Orestes; GILDENGERS, Ariel; MILLETT, Caitlin; MULSANT, Benoit H.; ORHAN, Melis; RAJJI, Tarek K.; REJ, Soham; SAJATOVIC, Martha; SARNA, Kaylee; SCHOUWS, Sigfried; SUTHERLAND, Ashley; TEIXEIRA, Antonio L.; YALA, Joy A.; EYLER, Lisa T.Background: Cognitive deficits in bipolar disorder (BD) impact functioning and are main contributors to disability in older age BD (OABD). We investigated the difference between OABD and age -comparable healthy comparison (HC) participants and, among those with BD, the associations between age, global cognitive performance, symptom severity and functioning using a large, cross-sectional, archival dataset harmonized from 7 international OABD studies. Methods: Data from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE -BD) database, spanning various standardized measures of cognition, functioning and clinical characteristics, were analyzed. The sample included 662 euthymic to mildly symptomatic participants aged minimum 50 years (509 BD, 153 HC), able to undergo extensive cognitive testing. Linear mixed models estimated associations between diagnosis and global cognitive performance (g -score, harmonized across studies), and within OABD between g -score and severity of mania and depressive symptoms, duration of illness and lithium use and of global functioning. Results: After adjustment for study cohort, age, gender and employment status, there was no significant difference in g -score between OABD and HC, while a significant interaction emerged between employment status and diagnostic group (better global cognition associated with working) in BD. Within OABD, better g -scores were associated with fewer manic symptoms, higher education and better functioning. Limitations: Cross-sectional design and loss of granularity due to harmonization.
- Lithium and disease modification: A systematic review and meta-analysis in Alzheimer's and Parkinson's disease(2024) SINGULANI, Monique Patricio; FERREIRA, Ana Flavia Fernandes; FIGUEROA, Paulina Sepulveda; CUYUL-VASQUEZ, Ivan; TALIB, Leda Leme; BRITTO, Luiz Roberto; FORLENZA, Orestes VicenteThe role of lithium as a possible therapeutic strategy for neurodegenerative diseases has generated scientific interest. We systematically reviewed and meta-analyzed pre-clinical and clinical studies that evidenced the neuroprotective effects of lithium in Alzheimer's (AD) and Parkinson's disease (PD). We followed the PRISMA guidelines and performed the systematic literature search using PubMed, EMBASE, Web of Science, and Cochrane Library. A total of 32 articles were identified. Twenty-nine studies were performed in animal models and 3 studies were performed on human samples of AD. A total of 17 preclinical studies were included in the meta-analysis. Our analysis showed that lithium treatment has neuroprotective effects in diseases. Lithium treatment reduced amyloid-beta and tau levels and significantly improved cognitive behavior in animal models of AD. Lithium increased the tyrosine hydroxylase levels and improved motor behavior in the PD model. Despite fewer clinical studies on these aspects, we evidenced the positive effects of lithium in AD patients. This study lends further support to the idea of lithium's therapeutic potential in neurodegenerative diseases.
- Sex Differences Among Older Adults With Bipolar Disorder: Results From the Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) Project(2024) BLANKEN, Machteld A. J. T.; OUDEGA, Mardien L.; ALMEIDA, Osvaldo P.; SCHOUWS, Sigfried N. T. M.; ORHAN, Melis; BEUNDERS, AlexandraJ. M.; KLUMPERS, Ursula M. H.; SONNENBERG, Caroline; BLUMBERG, Hilary P.; EYLER, Lisa T.; FORESTER, Brent P.; FORLENZA, Orestes V.; GILDENGERS, Ariel; MULSANT, Benoit H.; RAJJI, Tarek; REJ, Soham; SARNA, Kaylee; SUTHERLAND, Ashley; YALA, Joy; VIETA, Eduard; TSAI, Shangying; BRIGGS, Farren B. S.; SAJATOVIC, Martha; DOLS, AnnemiekObjective: Sex -specific research in adult bipolar disorder (BD) is sparse and even more so among those with older age bipolar disorder (OABD). Knowledge about sex differences across the bipolar lifespan is urgently needed to target and improve treatment. To address this gap, the current study examined sex differences in the domains of clinical presentation, general functioning, and mood symptoms among individuals with OABD. Methods: This Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE -BD) study used data from 19 international studies including BD patients aged >= 50 years (N =1,185: 645 women, 540 men).A comparison of mood symptoms between women and men was conducted initially using two -tailed t tests and then accounting for systematic differences between the contributing cohorts by performing generalized linear mixed models (GLMMs). Associations between sex and other clinical characteristics were examined using GLMM including: age, BD subtype, rapid cycling, psychiatric hospitalization, lifetime psychiatric comorbidity, and physical health comorbidity, with study cohort as a random intercept. Results: Regarding depressive mood symptoms, women had higher scores on anxiety and hypochondriasis items. Female sex was associated with more psychiatric hospitalizations and male sex with lifetime substance abuse disorders. Conclusion: Our findings show important clinical sex differences and provide support that older age women experience a more severe course of BD, with higher rates of psychiatric hospitalization. The reasons for this may be biological, psychological, or social. These differences as well as underlying mechanisms should be a focus for healthcare professionals and need to be studied further. (Am J Geriatr Psychiatry 2024; 32:326-338)
- Neuropsychiatric symptoms and ApoE genotype in older adults without dementia: a cross-sectional study(2024) STELLA, Florindo; PAIS, Marcos Vasconcelos; LOUREIRO, Julia Cunha; CORDEIRO, Augusto Magno Tranquezi; TALIB, Leda Leme; FORLENZA, Orestes VicenteBackground: The ApoE genotype and neuropsychiatric symptoms (NPS) are known risk factors for cognitive decline in older adults. However, the interaction between these variables is still unclear. The aim of this study was to determine the association between the presence of the ApoE epsilon 4 allele and the occurrence of NPS in older adults without dementia. Methods: In this cross-sectional investigation we determined the apolipoprotein E (ApoE) genotype of 74 older adults who were either cognitively normal (20.3% / Clinician Dementia Rating Scale (CDR): 0) or had mild cognitive impairment (MCI: 79.7% / CDR: 0.5). We used a comprehensive cognitive assessment protocol, and NPS were estimated by the Neuropsychiatric Inventory-Clinician Rating Scale (NPI-C), Mild Behavioural Impairment-Checklist (MBI-C), Hamilton Rating Scale for Depression (HAM-D), and Apathy Inventory. Results: ApoE epsilon 4 carriers had higher MBI-C total scores than ApoE epsilon 4 noncarriers. Correlations between NPS and ApoE genotype were observed for two NPI-C domains, although in opposite directions: the ApoE epsilon 4 allele was associated with a 1.8 unit decrease in the estimated aberrant motor disturbance score and with a 1.3 unit increase in the estimated appetite/eating disorders score. All fitted models were significant, except for the one fitted for the domain delusions from the NPI-C. Among individuals with amnestic MCI, epsilon 4 carriers presented higher depression score (HAM-D) than noncarriers; in turn, epsilon 4 noncarriers exhibited higher aggression score (NPI-C) than epsilon 4 carriers. Conclusions: Our analyses showed associations between NPS and the presence of the ApoE epsilon 4 allele in two NPI-C domains, despite the sample size. Furthermore, compared to noncarriers, the presence of the ApoE epsilon 4 correlated positively with appetite/eating disorders and negatively with aberrant motor disturbance domain. Examination of the amnestic MCI group displayed significant, although weak, associations. Therefore, epsilon 4 carriers exhibited higher depression scores according to the HAM-D scale compared to epsilon 4 noncarriers. Conversely, epsilon 4 noncarriers had higher scores in the aggression domain of the NPI-C than epsilon 4 carriers.
- Non-invasive sound wave brain stimulation with Transcranial Pulse Stimulation (TPS) improves neuropsychiatric symptoms in Alzheimer's disease(2024) SHINZATO, Gilson Tanaka; ASSONE, Tatiane; SANDLER, Paulo C.; PACHECO-BARRIOS, Kevin; FREGNI, Felipe; RADANOVIC, Marcia; FORLENZA, Orestes Vicente; BATTISTELLA, Linamara RizzoBackground: This study explores Transcranial Pulse Stimulation (TPS) as a potential non-invasive treatment for Alzheimer's disease (AD), focusing on its impact on cognitive functions and behavioral symptoms. Methods: In a prospective, one-arm open-label trial, ten patients with mild to moderate dementia due to AD were assessed using the Alzheimer's Disease Assessment Scale (ADAS-Cog), Neuropsychiatric Inventory (NPI), Pfeffer Functional Activities Questionnaire, and Zarit Caregiver Burden Interview. Assessments occurred at 30- and 90days post-treatment. The TPS protocol consisted of 10 sessions over five weeks, using the Neurolith (R) device to deliver 6000 focused shockwave pulses at 0.25 mJ/mm2 and a frequency of 4 Hz. Results: TPS significantly reduced neuropsychiatric symptoms, with NPI scores decreasing by 23.9 points (95% CI: -39.19 to -8.61, p = 0.0042) after 30 days, and by 18.9 points (95% CI: -33.49 to -2.91, p = 0.022) after 90 days. These changes had large effect sizes (Cohen's dz = 1.43 and dz = 0.94, respectively). A decreasing trend was observed in the ADAS-Cog score (-3.6, 95% CI: -7.18 to 0.00, p = 0.05) after 90 days, indicating a potential reduction in cognitive impairment, though not statistically significant. Conclusion: The preliminary results indicate that TPS treatment leads to significant improvement in neuropsychiatric symptoms in AD patients, showing promise as a therapeutic approach for AD. Further research is needed to fully establish its effectiveness, especially concerning cognitive functions.