ANDREA SCHMITT
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
16 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 16
- HDAC1 links early life stress to schizophrenia-like phenotypes(2017) BAHARI-JAVAN, Sanaz; VARBANOV, Hristo; HALDER, Rashi; BENITO, Eva; KAURANI, Lalit; BURKHARDT, Susanne; ANDERSON-SCHMIDT, Heike; ANGHELESCU, Ion; BUDDE, Monika; STILLING, Roman M.; COSTA, Joan; MEDINA, Juan; DIETRICH, Detlef E.; FIGGE, Christian; FOLKERTS, Here; GADE, Katrin; HEILBRONNER, Urs; KOLLER, Manfred; KONRAD, Carsten; NUSSBECK, Sara Y.; SCHERK, Harald; SPITZER, Carsten; STIERL, Sebastian; STOECKEL, Judith; THIEL, Andreas; HAGEN, Martin von; ZIMMERMANN, Joerg; ZITZELSBERGER, Antje; SCHULZ, Sybille; SCHMITT, Andrea; DELALLE, Ivana; FALKAI, Peter; SCHULZE, Thomas G.; DITYATEV, Alexander; SANANBENESI, Farahnaz; FISCHER, AndreSchizophrenia is a devastating disease that arises on the background of genetic predisposition and environmental risk factors, such as early life stress (ELS). In this study, we show that ELS-induced schizophrenia-like phenotypes in mice correlate with a widespread increase of histone-deacetylase 1 (Hdac1) expression that is linked to altered DNA methylation. Hdac1 overexpression in neurons of the medial prefrontal cortex, but not in the dorsal or ventral hippocampus, mimics schizophrenia-like phenotypes induced by ELS. Systemic administration of an HDAC inhibitor rescues the detrimental effects of ELS when applied after the manifestation of disease phenotypes. In addition to the hippocampus and prefrontal cortex, mice subjected to ELS exhibit increased Hdac1 expression in blood. Moreover, Hdac1 levels are increased in blood samples from patients with schizophrenia who had encountered ELS, compared with patients without ELS experience. Our data suggest that HDAC1 inhibition should be considered as a therapeutic approach to treat schizophrenia.
- Comparative serum proteomic analysis of a selected protein panel in individuals with schizophrenia and bipolar disorder and the impact of genetic risk burden on serum proteomic profiles(2022) KOHSHOUR, Mojtaba Oraki; KANNAIYAN, Nirmal R.; FALK, August Jernbom; PAPIOL, Sergi; HEILBRONNER, Urs; BUDDE, Monika; KALMAN, Janos L.; SCHULTE, Eva C.; RIETSCHEL, Marcella; WITT, Stephanie; FORSTNER, Andreas J.; HEILMANN-HEIMBACH, Stefanie; NOETHEN, Markus M.; SPITZER, Carsten; MALCHOW, Berend; MUELLER, Thorsten; WILTFANG, Jens; FALKAI, Peter; SCHMITT, Andrea; ROSSNER, Moritz J.; NILSSON, Peter; SCHULZE, Thomas G.The diagnostic criteria for schizophrenia (SCZ) and bipolar disorder (BD) are based on clinical assessments of symptoms. In this pilot study, we applied high-throughput antibody-based protein profiling to serum samples of healthy controls and individuals with SCZ and BD with the aim of identifying differentially expressed proteins in these disorders. Moreover, we explored the influence of polygenic burden for SCZ and BD on the serum levels of these proteins. Serum samples from 113 individuals with SCZ and 125 with BD from the PsyCourse Study and from 44 healthy controls were analyzed by using a set of 155 antibodies in an antibody-based assay targeting a selected panel of 95 proteins. For the cases, genotyping and imputation were conducted for DNA samples and SCZ and BD polygenic risk scores (PRS) were calculated. Univariate linear and logistic models were used for association analyses. The comparison between SCZ and BD revealed two serum proteins that were significantly elevated in BD after multiple testing adjustment: ""complement C9"" and ""Interleukin 1 Receptor Accessory Protein"". Moreover, the first principal component of variance in the proteomics dataset differed significantly between SCZ and BD. After multiple testing correction, SCZ-PRS, BD-PRS, and SCZ-vs-BD-PRS were not significantly associated with the levels of the individual proteins or the values of the proteome principal components indicating no detectable genetic effects. Overall, our findings contribute to the evidence suggesting that the analysis of circulating proteins could lead to the identification of distinctive biomarkers for SCZ and BD. Our investigation warrants replication in large-scale studies to confirm these findings.
- Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia(2017) AGIS-BALBOA, Roberto Carlos; PINHEIRO, Paulo S.; REBOLA, Nelson; KERIMOGLU, Cemil; BENITO, Eva; GERTIG, Michael; BAHARI-JAVAN, Sanaz; JAIN, Gaurav; BURKHARDT, Susanne; DELALLE, Ivana; JATZKO, Alexander; DETTENHOFER, Markus; ZUNSZAIN, Patricia A.; SCHMITT, Andrea; FALKAI, Peter; PAPE, Julius C.; BINDER, Elisabeth B.; MULLE, Christophe; FISCHER, Andre; SANANBENESI, FarahnazAge-associated memory decline is due to variable combinations of genetic and environmental risk factors. How these risk factors interact to drive disease onset is currently unknown. Here we begin to elucidate the mechanisms by which post-traumatic stress disorder (PTSD) at a young age contributes to an increased risk to develop dementia at old age. We show that the actin nucleator Formin 2 (Fmn2) is deregulated in PTSD and in Alzheimer's disease (AD) patients. Young mice lacking the Fmn2 gene exhibit PTSD-like phenotypes and corresponding impairments of synaptic plasticity, while the consolidation of new memories is unaffected. However, Fmn2 mutant mice develop accelerated age-associated memory decline that is further increased in the presence of additional risk factors and is mechanistically linked to a loss of transcriptional homeostasis. In conclusion, our data present a new approach to explore the connection between AD risk factors across life span and provide mechanistic insight to the processes by which neuropsychiatric diseases at a young age affect the risk for developing dementia.
- Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia part I: Neurophysiology(2015) THIBAUT, Florence; BOUTROS, Nash N.; JAREMA, Marek; ORANJE, Bob; HASAN, Alkomiet; DASKALAKIS, Zafiris Jeffrey; WICHNIAK, Adam; SCHMITT, Andrea; RIEDERER, Peter; FALKAI, PeterThe neurophysiological components that have been proposed as biomarkers or as endophenotypes for schizophrenia can be measured through electroencephalography (EEG) and magnetoencephalography (MEG), transcranial magnetic stimulation (TMS), polysomnography (PSG), registration of event-related potentials (ERPs), assessment of smooth pursuit eye movements (SPEM) and antisaccade paradigms. Most of them demonstrate deficits in schizophrenia, show at least moderate stability over time and do not depend on clinical status, which means that they fulfil the criteria as valid endophenotypes for genetic studies. Deficits in cortical inhibition and plasticity measured using non-invasive brain stimulation techniques seem promising markers of outcome and prognosis. However the utility of these markers as biomarkers for predicting conversion to psychosis, response to treatments, or for tracking disease progression needs to be further studied.
- 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, AndreaBackground 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.
- Reduced cortical neuron number and neuron density in schizophrenia with focus on area 24: a post-mortem case-control study(2023) GAUS, Richard; POPAL, Melanie; HEINSEN, Helmut; SCHMITT, Andrea; FALKAI, Peter; HOF, Patrick R.; SCHMITZ, Christoph; VOLLHARDT, AlisaStructural and functional abnormalities of the anterior cingulate cortex (ACC) have frequently been identified in schizophrenia. Alterations of von Economo neurons (VENs), a class of specialized projection neurons, have been found in different neuropsychiatric disorders and are also suspected in schizophrenia. To date, however, no definitive conclusions can be drawn about quantitative histologic changes in the ACC in schizophrenia because of a lack of rigorous, design-based stereologic studies. In the present study, the volume, total neuron number and total number of VENs in layer V of area 24 were determined in both hemispheres of postmortem brains from 12 male patients with schizophrenia and 11 age-matched male controls. To distinguish global from local effects, volume and total neuron number were also determined in the whole area 24 and whole cortical gray matter (CGM). Measurements were adjusted for hemisphere, age, postmortem interval and fixation time using an ANCOVA model. Compared to controls, patients with schizophrenia showed alterations, with lower mean total neuron number in CGM (- 14.9%, P = 0.007) and in layer V of area 24 (- 21.1%, P = 0.002), and lower mean total number of VENs (- 28.3%, P = 0.027). These data provide evidence for ACC involvement in the pathophysiology of schizophrenia, and complement neuroimaging findings of impaired ACC connectivity in schizophrenia. Furthermore, these results support the hypothesis that the clinical presentation of schizophrenia, particularly deficits in social cognition, is associated with pathology of VENs.
- Biobanking in everyday clinical practice in psychiatry-The Munich Mental Health Biobank(2022) KALMAN, Janos L.; BURKHARDT, Gerrit; ADORJAN, Kristina; BARTON, Barbara B.; JONGE, Sylvia De; ESER-VALERI, Daniela; FALTER-WAGNER, Christine M.; HEILBRONNER, Urs; JOBST, Andrea; KEESER, Daniel; KOENIG, Christian; KOLLER, Gabi; KOUTSOULERIS, Nikolaos; KURZ, Carolin; LANDGRAF, Dominic; MERZ, Katharina; MUSIL, Richard; NELSON, Afton M.; PADBERG, Frank; PAPIOL, Sergi; POGARELL, Oliver; PERNECZKY, Robert; RAABE, Florian; REINHARD, Matthias A.; RICHTER, Almut; RUETHER, Tobias; SIMON, Maria Susanne; SCHMITT, Andrea; SLAPAKOVA, Lenka; SCHEEL, Nanja; SCHUELE, Cornelius; WAGNER, Elias; WICHERT, Sven P.; ZILL, Peter; FALKAI, Peter; SCHULZE, Thomas G.; SCHULTE, Eva ChristinaTranslational research on complex, multifactorial mental health disorders, such as bipolar disorder, major depressive disorder, schizophrenia, and substance use disorders requires databases with large-scale, harmonized, and integrated real-world and research data. The Munich Mental Health Biobank (MMHB) is a mental health-specific biobank that was established in 2019 to collect, store, connect, and supply such high-quality phenotypic data and biosamples from patients and study participants, including healthy controls, recruited at the Department of Psychiatry and Psychotherapy (DPP) and the Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany. Participants are asked to complete a questionnaire that assesses sociodemographic and cross-diagnostic clinical information, provide blood samples, and grant access to their existing medical records. The generated data and biosamples are available to both academic and industry researchers. In this manuscript, we outline the workflow and infrastructure of the MMHB, describe the clinical characteristics and representativeness of the sample collected so far, and reveal future plans for expansion and application. As of 31 October 2021, the MMHB contains a continuously growing set of data from 578 patients and 104 healthy controls (46.37% women; median age, 38.31 years). The five most common mental health diagnoses in the MMHB are recurrent depressive disorder (38.78%; ICD-10: F33), alcohol-related disorders (19.88%; ICD-10: F10), schizophrenia (19.69%; ICD-10: F20), depressive episode (15.94%; ICD-10: F32), and personality disorders (13.78%; ICD-10: F60). Compared with the average patient treated at the recruiting hospitals, MMHB participants have significantly more mental health-related contacts, less severe symptoms, and a higher level of functioning. The distribution of diagnoses is also markedly different in MMHB participants compared with individuals who did not participate in the biobank. After establishing the necessary infrastructure and initiating recruitment, the major tasks for the next phase of the MMHB project are to improve the pace of participant enrollment, diversify the sociodemographic and diagnostic characteristics of the sample, and improve the utilization of real-world data generated in routine clinical practice.
- Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia, part III: Molecular mechanisms(2017) SCHMITT, Andrea; MARTINS-DE-SOUZA, Daniel; AKBARIAN, Schahram; CASSOLI, Juliana S.; EHRENREICH, Hannelore; FISCHER, Andre; FONTEH, Alfred; GATTAZ, Wagner F.; GAWLIK, Michael; GERLACH, Manfred; GRUNBLATT, Edna; HALENE, Tobias; HASAN, Alkomiet; HASHIMOTO, Kenij; KIM, Yong-Ku; KIRCHNER, Sophie-Kathrin; KORNHUBER, Johannes; KRAUS, Theo F. J.; MALCHOW, Berend; NASCIMENTO, Juliana M.; ROSSNER, Moritz; SCHWARZ, Markus; STEINER, Johann; TALIB, Leda; THIBAUT, Florence; RIEDERER, Peter; FALKAI, PeterObjectives: Despite progress in identifying molecular pathophysiological processes in schizophrenia, valid biomarkers are lacking for both the disease and treatment response. Methods: This comprehensive review summarises recent efforts to identify molecular mechanisms on the level of protein and gene expression and epigenetics, including DNA methylation, histone modifications and micro RNA expression. Furthermore, it summarises recent findings of alterations in lipid mediators and highlights inflammatory processes. The potential that this research will identify biomarkers of schizophrenia is discussed. Results: Recent studies have not identified clear biomarkers for schizophrenia. Although several molecular pathways have emerged as potential candidates for future research, a complete understanding of these metabolic pathways is required to reveal better treatment modalities for this disabling condition. Conclusions: Large longitudinal cohort studies are essential that pair a thorough phenotypic and clinical evaluation for example with gene expression and proteome analysis in blood at multiple time points. This approach might identify biomarkers that allow patients to be stratified according to treatment response and ideally also allow treatment response to be predicted. Improved knowledge of molecular pathways and epigenetic mechanisms, including their potential association with environmental influences, will facilitate the discovery of biomarkers that could ultimately be effective tools in clinical practice.
- Association Between Physical Activity and Schizophrenia Results of a 2-Sample Mendelian Randomization Analysis(2021) PAPIOL, Sergi; SCHMITT, Andrea; MAURUS, Isabel; ROSSNER, Moritz J.; SCHULZE, Thomas G.; FALKAI, Peter
- Common mechanisms in neurodegeneration and neuroinflammation: a BrainNet Europe gene expression microarray study(2015) DURRENBERGER, Pascal F.; FERNANDO, Francesca S.; KASHEFI, Samira N.; BONNERT, Tim P.; SEILHEAN, Danielle; NAIT-OUMESMAR, Brahim; SCHMITT, Andrea; GEBICKE-HAERTER, Peter J.; FALKAI, Peter; GRUENBLATT, Edna; PALKOVITS, Miklos; ARZBERGER, Thomas; KRETZSCHMAR, Hans; DEXTER, David T.; REYNOLDS, RichardNeurodegenerative diseases of the central nervous system are characterized by pathogenetic cellular and molecular changes in specific areas of the brain that lead to the dysfunction and/or loss of explicit neuronal populations. Despite exhibiting different clinical profiles and selective neuronal loss, common features such as abnormal protein deposition, dysfunctional cellular transport, mitochondrial deficits, glutamate excitotoxicity, iron accumulation and inflammation are observed in many neurodegenerative disorders, suggesting converging pathways of neurodegeneration. We have generated comparative genome-wide gene expression data, using the Illumina HumanRef 8 Beadchip, for Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, Parkinson's disease, and schizophrenia using an extensive cohort (n = 113) of well-characterized post-mortem brain tissues. The analysis of whole-genome expression patterns across these major disorders offers an outstanding opportunity not only to look into exclusive disease-specific changes, but more importantly to look for potential common molecular pathogenic mechanisms. Surprisingly, no dysregulated gene that passed our selection criteria was found in common across all six diseases. However, 61 dysregulated genes were shared when comparing five and four diseases. The few genes highlighted by our direct gene comparison analysis hint toward common neuronal homeostatic, survival and synaptic plasticity pathways. In addition, we report changes to several inflammation-related genes in all diseases. This work is supportive of a general role of the innate immune system in the pathogenesis and/or response to neurodegeneration.