LIM/27 - Laboratório de Neurociências
URI Permanente desta comunidade
O Laboratório de Neurociências é ligado ao Departamento de Neurologia da Faculdade de Medicina da Universidade de São Paulo (FMUSP).
Linhas de pesquisa: expressão gênica em amostras cerebrais e outros tecidos derivados de pacientes com doenças neuropsiquiátricas; farmacogenética; biologia celular e culturas primárias de neurônios; ressonância magnética e espectroscopia; metabolismo de fosfolípedes na membrana neuronal; estudos clínico-epidemiológicos e ensaios farmacêuticos; biomarcadores moleculares em doenças neuropsiquiátricas; lítio e neuroproteção na doença de Alzheimer, modelos animais em doenças neuropsiquiátricas.
Site oficial: http://limhc.fm.usp.br/portal/lim27-laboratorio-de-neurociencias/
Linhas de pesquisa: expressão gênica em amostras cerebrais e outros tecidos derivados de pacientes com doenças neuropsiquiátricas; farmacogenética; biologia celular e culturas primárias de neurônios; ressonância magnética e espectroscopia; metabolismo de fosfolípedes na membrana neuronal; estudos clínico-epidemiológicos e ensaios farmacêuticos; biomarcadores moleculares em doenças neuropsiquiátricas; lítio e neuroproteção na doença de Alzheimer, modelos animais em doenças neuropsiquiátricas.
Site oficial: http://limhc.fm.usp.br/portal/lim27-laboratorio-de-neurociencias/
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- LIM/27 - Laboratório de Neurociências
- LIM/27 - Laboratório de Neurociências
- LIM/27 - Laboratório de Neurociências
Submissões Recentes
New treatment strategies for mental health
(2023) HASHIMOTO, Kenji; SCHMITT, Andrea
Disturbed Oligodendroglial Maturation Causes Cognitive Dysfunction in Schizophrenia: A New Hypothesis
(2023) FALKAI, Peter; ROSSNER, Moritz J.; RAABE, Florian J.; WAGNER, Elias; KEESER, Daniel; MAURUS, Isabel; ROELL, Lukas; CHANG, Emily; SEITZ-HOLLAND, Johanna; SCHULZE, Thomas G.; SCHMITT, Andrea
Background and Hypothesis Cognitive impairment is a hallmark of schizophrenia, but no effective treatment is available to date. The underlying pathophysiology includes disconnectivity between hippocampal and prefrontal brain regions. Supporting evidence comes from diffusion-weighted imaging studies that suggest abnormal organization of frontotemporal white matter pathways in schizophrenia. Study Design Here, we hypothesize that in schizophrenia, deficient maturation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes substantially contributes to abnormal frontotemporal macro- and micro-connectivity and subsequent cognitive deficits. Study Results Our postmortem studies indicate a reduced oligodendrocyte number in the cornu ammonis 4 (CA4) subregion of the hippocampus, and others have reported the same histopathological finding in the dorsolateral prefrontal cortex. Our series of studies on aerobic exercise training showed a volume increase in the hippocampus, specifically in the CA4 region, and improved cognition in individuals with schizophrenia. The cognitive effects were subsequently confirmed by meta-analyses. Cell-specific schizophrenia polygenic risk scores showed that exercise-induced CA4 volume increase significantly correlates with OPCs. From animal models, it is evident that early life stress and oligodendrocyte-related gene variants lead to schizophrenia-related behavior, cognitive deficits, impaired oligodendrocyte maturation, and reduced myelin thickness. Conclusions Based on these findings, we propose that pro-myelinating drugs (e.g., the histamine blocker clemastine) combined with aerobic exercise training may foster the regeneration of myelin plasticity as a basis for restoring frontotemporal connectivity and cognition in schizophrenia.
Cellular pathology in the limbic system in schizophrenia
(2023) SCHMITT, Andrea; FALKAI, Peter
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, Geraldo
Introduction 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.
Employment, education, and clinical characteristics in older-age bipolar disorder: Analysis from the GAGE-BD database project
(2023) MALLU, Amulya; CHAN, Carol; EYLER, Lisa; DOLS, Annemiek; REJ, Soham; BLUMBERG, Hilary; SARNA, Kaylee; BRIGGS, Farren; FORESTER, Brent; PATRICK, Regan; FORLENZA, Orestes; JIMENEZ, Esther; VIETA, Eduard; SCHOUWS, Sigfried; PAANS, Nadine; SUTHERLAND, Ashley; YALA, Joy; SAJATOVIC, Martha
Effects of Exercise on Structural and Functional Brain Patterns in Schizophrenia-Data From a Multicenter Randomized-Controlled Study
(2024) ROELL, Lukas; KEESER, Daniel; PAPAZOV, Boris; LEMBECK, Moritz; PAPAZOVA, Irina; GRESKA, David; MUENZ, Susanne; SCHNEIDER-AXMANN, Thomas; SYKOROVA, Eliska B.; THIEME, Christina E.; VOGEL, Bob O.; MOHNKE, Sebastian; HUPPERTZ, Charlotte; ROEH, Astrid; KELLER-VARADY, Katriona; MALCHOW, Berend; STOECKLEIN, Sophia; ERTL-WAGNER, Birgit; HENKEL, Karsten; WOLFARTH, Bernd; TANTCHIK, Wladimir; WALTER, Henrik; HIRJAK, Dusan; SCHMITT, Andrea; HASAN, Alkomiet; MEYER-LINDENBERG, Andreas; FALKAI, Peter; MAURUS, Isabel
Background and Hypothesis: Aerobic exercise interventions in people with schizophrenia have been demonstrated to improve clinical outcomes, but findings regarding the underlying neural mechanisms are limited and mainly focus on the hippocampal formation. Therefore, we conducted a global exploratory analysis of structural and functional neural adaptations after exercise and explored their clinical implications.Study Design: In this randomized controlled trial, structural and functional MRI data were available for 91 patients with schizophrenia who performed either aerobic exercise on a bicycle ergometer or underwent a flexibility, strengthening, and balance training as control group. We analyzed clinical and neuroimaging data before and after 6 months of regular exercise. Bayesian linear mixed models and Bayesian logistic regressions were calculated to evaluate effects of exercise on multiple neural outcomes and their potential clinical relevance.Study Results: Our results indicated that aerobic exercise in people with schizophrenia led to structural and functional adaptations mainly within the default-mode network, the cortico-striato-pallido-thalamo-cortical loop, and the cerebello-thalamo-cortical pathway. We further observed that volume increases in the right posterior cingulate gyrus as a central node of the default-mode network were linked to improvements in disorder severity.Conclusions: These exploratory findings suggest a positive impact of aerobic exercise on 3 cerebral networks that are involved in the pathophysiology of schizophrenia.
Publishing Negative Results of Neurobiological Studies in Mental Disorders Will Advance Knowledge in Pathophysiology
(2023) STEINER, Johann; SCHMITT, Andrea; FALKAI, Peter
Exercise as an add-on treatment in individuals with schizophrenia: Results from a large multicenter randomized controlled trial
(2023) MAURUS, Isabel; ROELL, Lukas; LEMBECK, Moritz; PAPAZOVA, Irina; GRESKA, David; MUENZ, Susanne; WAGNER, Elias; CAMPANA, Mattia; SCHWAIGER, Rebecca; SCHNEIDER-AXMANN, Thomas; ROSENBERGER, Kerstin; HELLMICH, Martin; SYKOROVA, Eliska; THIEME, Cristina E.; VOGEL, Bob O.; HARDER, Carolin; MOHNKE, Sebastian; HUPPERTZ, Charlotte; ROEH, Astrid; KELLER-VARADY, Katriona; MALCHOW, Berend; WALTER, Henrik; WOLFARTH, Bernd; WOLWER, Wolfgang; HENKEL, Karsten; HIRJAK, Dusan; SCHMITT, Andrea; HASAN, Alkomiet; MEYER-LINDENBERG, Andreas; FALKAI, Peter
Current treatment methods do not achieve recovery for most individuals with schizophrenia, and symptoms such as negative symptoms and cognitive deficits often persist. Aerobic endurance training has been suggested as a potential add-on treatment targeting both physical and mental health. We performed a large-scale multicenter, rater-blind, parallel-group randomized controlled clinical trial in individuals with stable schizophrenia. Participants underwent a professionally supervised six-month training comprising either aerobic endurance training (AET) or flexibility, strengthening, and balance training (FSBT, control group), follow-up was another six months. The primary endpoint was all-cause discontinuation (ACD); secondary endpoints included effects on psychopathology, cognition, functioning, and cardiovascular risk. In total, 180 participants were randomized. AET was not superior to FSBT in ACD and most secondary outcomes, with dropout rates of 59.55% and 57.14% in the six-month active phase, respectively. However, both groups showed significant improvements in positive, general, and total symptoms, levels of functioning and in cognitive performance. A higher training frequency additionally promoted further memory domains. Participants with higher baseline cognitive abilities were more likely to respond to the interventions. Our results support integrating exercise into schizophrenia treatment, while future studies should aim to develop personalized training recommendations to maximize exercise-induced benefits.
Treatment of negative symptoms in schizophrenia: a challenge for clinical research
(2023) SCHMITT, Andrea; MAURUS, Isabel; FALKAI, Peter
The relationship between internet gaming disorder and psychotic experiences: cyberbullying and insomnia severity as mediators
(2023) FEKIH-ROMDHANE, Feten; LAMLOUM, Eya; LOCH, Alexandre Andrade; CHERIF, Wissal; CHEOUR, Majda; HALLIT, Souheil
BackgroundThe nature of the relationship between Internet Gaming Disorder (IGD) and psychosis is unclear so far. There is evidence that greater time spent in playing video games may expose players to both insomnia and a toxic online environment with widespread cyberbullying. These two possible consequences of IGD may, in turn, be associated with greater psychotic experiences (PE). Based on this theoretical framework, the present study proposed to contribute the body of the knowledge in this area, by testing the possible indirect effects of insomnia severity, cyber-victimization and cyberbullying in the cross-sectional association between IGD and PE in a sample of Tunisian university students.MethodWe conducted a cross-sectional study over 4 months (February-May 2022). The Arabic versions of the Brief Symptom Inventory, the Internet Gaming disorder-20 Test, the Insomnia Severity Index, and the Revised Cyber Bullying Inventory-II were administered to a total of 851 students (mean age = 21.26 +/- 1.68 years, 53.7% females).ResultsWe found that 25% of students were at risk of IGD, and 1.8% had an IGD. The results of the mediation analysis showed that insomnia severity fully mediated the association between IGD and paranoid ideation. Higher IGD was significantly associated with more insomnia severity, which was, in turn, significantly associated with more paranoid ideation. Cyberbullying partly mediated the association between IGD and psychoticism. Higher IGD scores were significantly associated with more cyberbullying, which was, in turn, significantly associated with more psychoticism. Finally, greater IGD was significantly and directly associated with higher psychoticism.ConclusionOur findings suggest that insomnia and cyberbullying may be regarded as potential targets for youth mental health promotion, as well as community-focused prevention and early intervention in psychosis. More particular attention should be devoted to the huge potential for engaging in cyberbullying among online gamers. Sleep deprivation should be prevented, assessed and treated in heavy gamers.