ANDREA SCHMITT
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
13 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 13
- 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, 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.
- Publishing Negative Results of Neurobiological Studies in Mental Disorders Will Advance Knowledge in Pathophysiology(2023) STEINER, Johann; SCHMITT, Andrea; FALKAI, Peter
- The multimodal Munich Clinical Deep Phenotyping study to bridge the translational gap in severe mental illness treatment research(2023) KRCMAR, Lenka; JAEGER, Iris; BOUDRIOT, Emanuel; HANKEN, Katharina; GABRIEL, Vanessa; MELCHER, Julian; KLIMAS, Nicole; DENGL, Fanny; SCHMOELZ, Susanne; PINGEN, Pauline; CAMPANA, Mattia; MOUSSIOPOULOU, Joanna; YAKIMOV, Vladislav; IOANNOU, Georgios; WICHERT, Sven; DEJONGE, Silvia; ZILL, Peter; PAPAZOV, Boris; ALMEIDA, Valeria de; GALINSKI, Sabrina; GABELLINI, Nadja; HASANAJ, Genc; MORTAZAVI, Matin; KARALI, Temmuz; HISCH, Alexandra; KALLWEIT, Marcel S.; MEISINGER, Verena J.; LOEHRS, Lisa; NEUMEIER, Karin; BEHRENS, Stephanie; KARCH, Susanne; SCHWORM, Benedikt; KERN, Christoph; PRIGLINGER, Siegfried; MALCHOW, Berend; STEINER, Johann; HASAN, Alkomiet; PADBERG, Frank; POGARELL, Oliver; FALKAI, Peter; SCHMITT, Andrea; WAGNER, Elias; KEESER, Daniel; RAABE, Florian J.IntroductionTreatment of severe mental illness (SMI) symptoms, especially negative symptoms and cognitive dysfunction in schizophrenia, remains a major unmet need. There is good evidence that SMIs have a strong genetic background and are characterized by multiple biological alterations, including disturbed brain circuits and connectivity, dysregulated neuronal excitation-inhibition, disturbed dopaminergic and glutamatergic pathways, and partially dysregulated inflammatory processes. The ways in which the dysregulated signaling pathways are interconnected remains largely unknown, in part because well-characterized clinical studies on comprehensive biomaterial are lacking. Furthermore, the development of drugs to treat SMIs such as schizophrenia is limited by the use of operationalized symptom-based clusters for diagnosis. MethodsIn line with the Research Domain Criteria initiative, the Clinical Deep Phenotyping (CDP) study is using a multimodal approach to reveal the neurobiological underpinnings of clinically relevant schizophrenia subgroups by performing broad transdiagnostic clinical characterization with standardized neurocognitive assessments, multimodal neuroimaging, electrophysiological assessments, retinal investigations, and omics-based analyzes of blood and cerebrospinal fluid. Moreover, to bridge the translational gap in biological psychiatry the study includes in vitro investigations on human-induced pluripotent stem cells, which are available from a subset of participants. ResultsHere, we report on the feasibility of this multimodal approach, which has been successfully initiated in the first participants in the CDP cohort; to date, the cohort comprises over 194 individuals with SMI and 187 age and gender matched healthy controls. In addition, we describe the applied research modalities and study objectives. DiscussionThe identification of cross-diagnostic and diagnosis-specific biotype-informed subgroups of patients and the translational dissection of those subgroups may help to pave the way toward precision medicine with artificial intelligence-supported tailored interventions and treatment. This aim is particularly important in psychiatry, a field where innovation is urgently needed because specific symptom domains, such as negative symptoms and cognitive dysfunction, and treatment-resistant symptoms in general are still difficult to treat.
- Neurodevelopmental disturbances in schizophrenia: evidence from genetic and environmental factors(2023) SCHMITT, Andrea; FALKAI, Peter; PAPIOL, SergiSince more than 3 decades, schizophrenia (SZ) has been regarded as a neurodevelopmental disorder. The neurodevelopmental hypothesis proposes that SZ is associated with genetic and environmental risk factors, which influence connectivity in neuronal circuits during vulnerable developmental periods. We carried out a non-systematic review of genetic/environmental factors that increase SZ risk in light of its neurodevelopmental hypothesis. We also reviewed the potential impact of SZ-related environmental and genetic risk factors on grey and white matter pathology and brain function based on magnetic resonance imaging and post-mortem studies. Finally, we reviewed studies that have used patient-derived neuronal models to gain knowledge of the role of genetic and environmental factors in early developmental stages. Taken together, these studies indicate that a variety of environmental factors may interact with genetic risk factors during the pre- or postnatal period and/or during adolescence to induce symptoms of SZ in early adulthood. These risk factors induce disturbances of macro- and microconnectivity in brain regions involving the prefrontal, temporal and parietal cortices and the hippocampus. On the molecular and cellular level, a disturbed synaptic plasticity, loss of oligodendrocytes and impaired myelination have been shown in brain regions of SZ patients. These cellular/histological phenotypes are related to environmental risk factors such as obstetric complications, maternal infections and childhood trauma and genetic risk factors identified in recent genome-wide association studies. SZ-related genetic risk may contribute to active processes interfering with synaptic plasticity in the adult brain. Advances in stem cell technologies are providing promising mechanistic insights into how SZ risk factors impact the developing brain. Further research is needed to understand the timing of the different complex biological processes taking place as a result of the interplay between genetic and environmental factors.
- Treatment of negative symptoms in schizophrenia: a challenge for clinical research(2023) SCHMITT, Andrea; MAURUS, Isabel; FALKAI, Peter
- Cellular pathology in the limbic system in schizophrenia(2023) SCHMITT, Andrea; FALKAI, Peter
- Sports Therapy for Schizophrenia Psychoses: from the Idea to the Guideline(2023) FALKAI, Peter; SCHWAIGER, Rebecca; SCHMITT, Andrea; ROELL, Lukas; MAURUS, IsabelSchizophrenia psychoses can be treated much better today due to the introduction of antipsychotics about 70 years ago in conjunction with the implementation of specific psychotherapies. However, current treatment options are still limited in the area of negative symptoms and disease-associated cognitive deficits. In the last 15 years, randomised controlled trials (RCTs) have been able to show that physical training and especially endurance training could represent a comprehensive complementary treatment approach and could lead to a significant improvement in positive, but especially also in negative symptoms and cognitive deficits. As a result, sports therapy for schizophrenia psychoses has found its way not only into the national treatment guidelines of the German Society for Psychiatry, Psychotherapy, Psychosomatics and Neurology (DGPPN), but also into European recommendations such as those of the European Psychiatric Association (EPA). With the introduction of the ""Living guideline"" format (here an update takes place at least once a year), a broader implementation in health care will be easier in the future. Based on a narrative review, this paper describes the process of implementing sports therapy for schizophrenia psychoses from its beginnings to its incorporation into guidelines and can be applied analogously to other forms of therapy.
- Association of early life stress and cognitive performance in patients with schizophrenia and healthy controls(2023) SENNER, Fanny; SCHNEIDER-AXMANN, Thomas; KAURANI, Lalit; ZIMMERMANN, Joerg; WILTFANG, Jens; HAGEN, Martin von; VOGL, Thomas; SPITZER, Carsten; SENNER, Simon; SCHULTE, Eva C.; SCHMAUSS, Max; SCHAUPP, Sabrina K.; REIMER, Jens; REICH-ERKELENZ, Daniela; PAPIOL, Sergi; KOHSHOUR, Mojtaba Oraki; LANG, Fabian U.; KONRAD, Carsten; KIRCHNER, Sophie-Kathrin; KALMAN, Janos L.; JUCKEL, Georg; HEILBRONNER, Maria; HEILBRONNER, Urs; FIGGE, Christian; EYL, Ruth E.; DIETRICH, Detlef; BUDDE, Monika; ANGELESCU, Ion-George; ADORJAN, Kristina; SCHMITT, Andrea; FISCHER, Andre; FALKAI, Peter; SCHULZE, Thomas G.As core symptoms of schizophrenia, cognitive deficits contribute substantially to poor outcomes. Early life stress (ELS) can negatively affect cognition in patients with schizophrenia and healthy controls, but the exact nature of the mediating factors is unclear. Therefore, we investigated how ELS, education, and symptom burden are related to cognitive performance.The sample comprised 215 patients with schizophrenia (age, 42.9 +/- 12.0 years; 66.0 % male) and 197 healthy controls (age, 38.5 +/- 16.4 years; 39.3 % male) from the PsyCourse Study. ELS was assessed with the Childhood Trauma Screener (CTS). We used analyses of covariance and correlation analyses to investigate the association of total ELS load and ELS subtypes with cognitive performance.