ANDREA SCHMITT
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
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- Aerobic exercise and its effects on cognition in schizophrenia(2017) FALKAI, Peter; MALCHOW, Berend; SCHMITT, AndreaPurpose of review Schizophrenia is a severe neuropsychiatric disorder with incomplete remission because of negative and cognitive symptoms in a large proportion of patients. Antipsychotic medication is successful in modulating positive symptoms, but only to a lower extent negative symptoms including cognitive dysfunction. Therefore, development of innovative add-on treatment is highly needed. In this review, recent evidence from clinical studies reveals effects of aerobic exercise on cognitive deficits in schizophrenia patients. Recent findings First studies and meta-analyses on aerobic exercise in schizophrenia patients have shown effects on positive, negative, and global symptoms and cognitive domains such as global cognition, working memory, and attention. Underlying neurobiological mechanisms such as neuroplasticity-related synaptogenesis and neurogenesis have been identified in animal studies and possibly mediate effects of aerobic exercise on brain structure and function. Summary Different aspects of methods (e.g., endurance training versus yoga and Tai Chi), length and dose of the intervention, supervision of patients by sports therapists as well as maintenance of cognitive improvement after cessation of training have been raised by previous studies. However, minimal and most effective dosage of the intervention and mechanisms underlying changes in neuroplasticity need to be answered in future basic and large-scale randomized clinical trials.
- 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.
- Concept of the Munich/Augsburg Consortium Precision in Mental Health for the German Center of Mental Health(2022) FALKAI, Peter; KOUTSOULERIS, Nikolaos; BERTSCH, Katja; BIALAS, Mirko; BINDER, Elisabeth; BUEHNER, Markus; BUYX, Alena; CAI, Na; CAPPELLO, Silvia; EHRING, Thomas; GENSICHEN, Jochen; HAMANN, Johannes; HASAN, Alkomiet; HENNINGSEN, Peter; LEUCHT, Stefan; MOEHRMANN, Karl Heinz; NAGELSTUTZ, Elisabeth; PADBERG, Frank; PETERS, Annette; PFAEFFEL, Lea; REICH-ERKELENZ, Daniela; RIEDL, Valentin; RUECKERT, Daniel; SCHMITT, Andrea; SCHULTE-KOERNE, Gerd; SCHEURING, Elfriede; SCHULZE, Thomas G.; STARZENGRUBER, Rudolf; STIER, Susanne; THEIS, Fabian J.; WINKELMANN, Juliane; WURST, Wolfgang; PRILLER, JosefThe Federal Ministry of Education and Research (BMBF) issued a call for a new nationwide research network on mental disorders, the German Center of Mental Health (DZPG). The Munich/Augsburg consortium was selected to participate as one of six partner sites with its concept ""Precision in Mental Health (PriMe): Understanding, predicting, and preventing chronicity."" PriMe bundles interdisciplinary research from the Ludwig-Maximilians-University (LMU), Technical University of Munich (TUM), University of Augsburg (UniA), Helmholtz Center Munich (HMGU), and Max Planck Institute of Psychiatry (MPIP) and has a focus on schizophrenia (SZ), bipolar disorder (BPD), and major depressive disorder (MDD). PriMe takes a longitudinal perspective on these three disorders from the at-risk stage to the first-episode, relapsing, and chronic stages. These disorders pose a major health burden because in up to 50% of patients they cause untreatable residual symptoms, which lead to early social and vocational disability, comorbidities, and excess mortality. PriMe aims at reducing mortality on different levels, e.g., reducing death by psychiatric and somatic comorbidities, and will approach this goal by addressing interdisciplinary and cross-sector approaches across the lifespan. PriMe aims to add a precision medicine framework to the DZPG that will propel deeper understanding, more accurate prediction, and personalized prevention to prevent disease chronicity and mortality across mental illnesses. This framework is structured along the translational chain and will be used by PriMe to innovate the preventive and therapeutic management of SZ, BPD, and MDD from rural to urban areas and from patients in early disease stages to patients with long-term disease courses. Research will build on platforms that include one on model systems, one on the identification and validation of predictive markers, one on the development of novel multimodal treatments, one on the regulation and strengthening of the uptake and dissemination of personalized treatments, and finally one on testing of the clinical effectiveness, utility, and scalability of such personalized treatments. In accordance with the translational chain, PriMe's expertise includes the ability to integrate understanding of bio-behavioral processes based on innovative models, to translate this knowledge into clinical practice and to promote user participation in mental health research and care.
- The impact of environmental factors in severe psychiatric disorders(2014) SCHMITT, Andrea; MALCHOW, Berend; HASAN, Alkomiet; FALKAI, PeterDuring the last decades, schizophrenia has been regarded as a developmental disorder. The neurodevelopmental hypothesis proposes schizophrenia to be related to genetic and environmental factors leading to abnormal brain development during the pre- or postnatal period. First disease symptoms appear in early adulthood during the synaptic pruning and myelination process. Meta-analyses of structural MRI studies revealing hippocampal volume deficits in first-episode patients and in the longitudinal disease course confirm this hypothesis. Apart from the influence of risk genes in severe psychiatric disorders, environmental factors may also impact brain development during the perinatal period. Several environmental factors such as antenatal maternal virus infections, obstetric complications entailing hypoxia as common factor or stress during neurodevelopment have been identified to play a role in schizophrenia and bipolar disorder, possibly contributing to smaller hippocampal volumes. In major depression, psychosocial stress during the perinatal period or in adulthood is an important trigger. In animal studies, chronic stress or repeated administration of glucocorticoids have been shown to induce degeneration of glucocorticoid-sensitive hippocampal neurons and may contribute to the pathophysiology of affective disorders. Epigenetic mechanisms altering the chromatin structure such as histone acetylation and DNA methylation may mediate effects of environmental factors to transcriptional regulation of specific genes and be a prominent factor in gene-environmental interaction. In animal models, gene-environmental interaction should be investigated more intensely to unravel pathophysiological mechanisms. These findings may lead to new therapeutic strategies influencing epigenetic targets in severe psychiatric disorders.
- Oligodendrocytes as A New Therapeutic Target in Schizophrenia: From Histopathological Findings to Neuron-Oligodendrocyte Interaction(2019) RAABE, Florian J.; SLAPAKOVA, Lenka; ROSSNER, Moritz J.; CANTUTI-CASTELVETRI, Ludovico; SIMONS, Mikael; FALKAI, Peter G.; SCHMITT, AndreaImaging and postmortem studies have revealed disturbed oligodendroglia-related processes in patients with schizophrenia and provided much evidence for disturbed myelination, irregular gene expression, and altered numbers of oligodendrocytes in the brains of schizophrenia patients. Oligodendrocyte deficits in schizophrenia might be a result of failed maturation and disturbed regeneration and may underlie the cognitive deficits of the disease, which are strongly associated with impaired long-term outcome. Cognition depends on the coordinated activity of neurons and interneurons and intact connectivity. Oligodendrocyte precursors form a synaptic network with parvalbuminergic interneurons, and disturbed crosstalk between these cells may be a cellular basis of pathology in schizophrenia. However, very little is known about the exact axon-glial cellular and molecular processes that may be disturbed in schizophrenia. Until now, investigations were restricted to peripheral tissues, such as blood, correlative imaging studies, genetics, and molecular and histological analyses of postmortem brain samples. The advent of human-induced pluripotent stem cells (hiPSCs) will enable functional analysis in patient-derived living cells and holds great potential for understanding the molecular mechanisms of disturbed oligodendroglial function in schizophrenia. Targeting such mechanisms may contribute to new treatment strategies for previously treatment-resistant cognitive symptoms.
- Childhood Trauma in Schizophrenia: Current Findings and Research Perspectives(2019) POPOVIC, David; SCHMITT, Andrea; KAURANI, Lalit; SENNER, Fanny; PAPIOL, Sergi; MALCHOW, Berend; FISCHER, Andre; SCHULZE, Thomas G.; KOUTSOULERIS, Nikolaos; FALKAI, PeterSchizophrenia is a severe neuropsychiatric disorder with persistence of symptoms throughout adult life in most of the affected patients. This unfavorable course is associated with multiple episodes and residual symptoms, mainly negative symptoms and cognitive deficits. The neural diathesis-stress model proposes that psychosocial stress acts on a pre-existing vulnerability and thus triggers the symptoms of schizophrenia. Childhood trauma is a severe form of stress that renders individuals more vulnerable to developing schizophrenia; neurobiological effects of such trauma on the endocrine system and epigenetic mechanisms are discussed. Childhood trauma is associated with impaired working memory, executive function, verbal learning, and attention in schizophrenia patients, including those at ultra-high risk to develop psychosis. In these patients, higher levels of childhood trauma were correlated with higher levels of attenuated positive symptoms, general symptoms, and depressive symptoms; lower levels of global functioning; and poorer cognitive performance in visual episodic memory end executive functions. In this review, we discuss effects of specific gene variants that interact with childhood trauma in patients with schizophrenia and describe new findings on the brain structural and functional level. Additive effects between childhood trauma and brain-derived neurotrophic factor methionine carriers on volume loss of the hippocampal subregions cornu ammonis (CA)4/dentate gyrus and CA2/3 have been reported in schizophrenia patients. A functional magnetic resonance imaging study showed that childhood trauma exposure resulted in aberrant function of parietal areas involved in working memory and of visual cortical areas involved in attention. In a theory of mind task reflecting social cognition, childhood trauma was associated with activation of the posterior cingulate gyrus, precuneus, and dorsomedial prefrontal cortex in patients with schizophrenia. In addition, decreased connectivity was shown between the posterior cingulate/precuneus region and the amygdala in patients with high levels of physical neglect and sexual abuse during childhood, suggesting that disturbances in specific brain networks underlie cognitive abilities. Finally, we discuss some of the questionnaires that are commonly used to assess childhood trauma and outline possibilities to use recent biostatistical methods, such as machine learning, to analyze the resulting datasets.
- Effects of Aerobic Exercise on Metabolic Syndrome, Cardiorespiratory Fitness, and Symptoms in Schizophrenia Include Decreased Mortality(2018) SCHMITT, Andrea; MAURUS, Isabel; ROSSNER, Moritz J.; ROH, Astrid; LEMBECK, Moritz; WILMSDORFF, Martina von; TAKAHASHI, Shun; RAUCHMANN, Boris; KEESER, Daniel; HASAN, Alkomiet; MALCHOW, Berend; FALKAI, PeterSchizophrenia is a severe psychiatric disorder with a lifetime prevalence of about 1%. People with schizophrenia have a 4-fold higher prevalence of metabolic syndrome than the general population, mainly because of antipsychotic treatment but perhaps also because of decreased physical activity. Metabolic syndrome is a risk factor for cardiovascular diseases, and the risk of these diseases is 2- to 3-fold higher in schizophrenia patients than in the general population. The suicide risk is also higher in schizophrenia, partly as a result of depression, positive, and cognitive symptoms of the disease. The higher suicide rate and higher rate of cardiac mortality, a consequence of the increased prevalance of cardiovascular diseases, contribute to the reduced life expectancy, which is up to 20 years lower than in the general population. Regular physical activity, especially in combination with psychosocial and dietary interventions, can improve parameters of the metabolic syndrome and cardiorespiratory fitness. Furthermore, aerobic exercise has been shown to improve cognitive deficits; total symptom severity, including positive and negative symptoms; depression; quality of life; and global functioning. High-intensity interval endurance training is a feasible and effective way to improve cardiorespiratory fitness and metabolic parameters and has been established as such in somatic disorders. It may have more beneficial effects on the metabolic state than more moderate and continuous endurance training methods, but to date it has not been investigated in schizophrenia patients in controlled, randomized trials. This review discusses physical training methods to improve cardiorespiratory fitness and reduce metabolic syndrome risk factors and symptoms in schizophrenia patients. The results of studies and future high-quality clinical trials are expected to lead to the development of an evidence-based physical training program for patients that includes practical recommendations, such as the optimal length and type of aerobic exercise programs and the ideal combination of exercise, psychoeducation, and individual weight management sessions.