ANDREA SCHMITT
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
26 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 26
- Reduction of gyrification index in the cerebellar vermis in schizophrenia: A post-mortem study(2011) SCHMITT, Andrea; SCHULENBERG, Wiebke; BERNSTEIN, Hans-Gert; STEINER, Johann; SCHNEIDER-AXMANN, Thomas; YEGANEH-DOOST, Peyman; MALCHOW, Berend; HASAN, Alkomiet; GRUBER, Oliver; BOGERTS, Bernhard; FALKAI, PeterObjectives. In schizophrenia, alterations of the gyrification index (GI) have been measured in cortical brain regions and are related to neurodevelopmental disturbances. Cerebellar regions have been implicated in the pathophysiolopgy of schizophrenia; however, the GI has not been investigated here so far. Methods. Hence, in a post-mortem study we investigated the GI separately from the vermis, left and right hemisphere of the medial posterior cerebellum in nine schizophrenia patients and 10 healthy controls. GI was defined as length of the inner contour inclusively depth of the sulci divided by length of the outer contour of the cerebellar surface and measured by tracing contours on images obtained by a stereological workstation. Results. In the vermis, GI was reduced in schizophrenia patients according to the methods of Zilles (P = 0.020) and Vogeley (P = 0.015). In the hemispheres, no differences have been observed. GI obtained by the two methods showed a high correlation (P < 0.001). Correlation analysis showed no influence of gender, postmortem interval and age. Conclusions. Decreased GI in the vermis of schizophrenia patients may result from neurodevelopmental disturbances, since folding of the brain occurs mainly during the perinatal period. MRI studies using automated GI processing in larger samples are needed to confirm our results.
- Association between altered hippocampal oligodendrocyte number and neuronal circuit structures in schizophrenia: a postmortem analysis(2020) FALKAI, Peter; RAABE, Florian; BOGERTS, Bernhard; SCHNEIDER-AXMANN, Thomas; MALCHOW, Berend; TATSCH, Laura; HUBER, Verena; SLAPAKOVA, Lenka; DOBROWOLNY, Henrik; SCHMITZ, Christoph; CANTUTI-CASTELVETRI, Ludovico; SIMONS, Mikael; STEINER, Johann; SCHMITT, AndreaIn schizophrenia, decreased hippocampal volume, reduced oligodendrocyte numbers in hippocampal cornu ammonis (CA) subregions and reduced neuron number in the dentate gyrus have been reported; reduced oligodendrocyte numbers were significantly related to cognitive deficits. The hippocampus is involved in cognitive functions and connected to the hypothalamus, anterior thalamus, and cingulate cortex, forming the Papez circuit, and to the mediodorsal thalamus. The relationship between the volume of these interconnected regions and oligodendrocyte and neuron numbers in schizophrenia is unknown. Therefore, we used stepwise logistic regression with subsequent multivariate stepwise linear regression and bivariate correlation to analyze oligodendrocyte and neuron numbers in the posterior hippocampal subregions CA1, CA2/3, CA4, dentate gyrus, and subiculum and volumes of the hippocampal CA region, cingulum, anterior and mediodorsal thalamus and hypothalamus in postmortem brains of 10 schizophrenia patients and 11 age- and gender-matched healthy controls. Stepwise logistic regression identified the following predictors for diagnosis, in order of inclusion: (1) oligodendrocyte number in CA4, (2) hypothalamus volume, (3) oligodendrocyte number in CA2/3, and (4) mediodorsal thalamus volume. Subsequent stepwise linear regression analyses identified the following predictors: (1) for oligodendrocyte number in CA4: (a) oligodendrocyte number in CA2/3, (b) diagnostic group, (c) hypothalamus volume, and (d) neurons in posterior subiculum; (2) for hypothalamus volume: (a) mediodorsal thalamus volume; (3) for oligodendrocyte number in CA2/3: oligodendrocyte number (a) in posterior CA4 and (b) in posterior subiculum; (4) for mediodorsal thalamus volume: volumes of (a) anterior thalamus and (b) hippocampal CA. In conclusion, we found a positive relationship between hippocampal oligodendrocyte number and the volume of the hypothalamus, a brain region connected to the hippocampus, which is important for cognition.
- Improvement in daily functioning after aerobic exercise training in schizophrenia is sustained after exercise cessation(2021) FALKAI, Peter; MAURUS, Isabel; SCHMITT, Andrea; MALCHOW, Berend; SCHNEIDER-AXMANN, Thomas; ROELL, Lukas; PAPIOL, Sergi; WOBROCK, Thomas; HASAN, Alkomiet; KEESER, Daniel
- Polygenic burden associated to oligodendrocyte precursor cells and radial glia influences the hippocampal volume changes induced by aerobic exercise in schizophrenia patients(2019) PAPIOL, Sergi; KEESER, Daniel; HASAN, Alkomiet; SCHNEIDER-AXMANN, Thomas; RAABE, Florian; DEGENHARDT, Franziska; ROSSNER, Moritz J.; BICKEBOELLER, Heike; CANTUTI-CASTELVETRI, Ludovico; SIMONS, Mikael; WOBROCK, Thomas; SCHMITT, Andrea; MALCHOW, Berend; FALKAI, PeterHippocampal volume decrease is a structural hallmark of schizophrenia (SCZ), and convergent evidence from postmortem and imaging studies suggests that it may be explained by changes in the cytoarchitecture of the cornu ammonis 4 (CA4) and dentate gyrus (DG) subfields. Increasing evidence indicates that aerobic exercise increases hippocampal volume in CA subfields and improves cognition in SCZ patients. Previous studies showed that the effects of exercise on the hippocampus might be connected to the polygenic burden of SCZ risk variants. However, little is known about cell type-specific genetic contributions to these structural changes. In this secondary analysis, we evaluated the modulatory role of cell type-specific SCZ polygenic risk scores (PRS) on volume changes in the CA1, CA2/3, and CA4/DG subfields over time. We studied 20 multi-episode SCZ patients and 23 healthy controls who performed aerobic exercise, and 21 multi-episode SCZ patients allocated to a control intervention (table soccer) for 3 months. Magnetic resonance imaging-based assessments were performed with FreeSurfer at baseline and after 3 months. The analyses showed that the polygenic burden associated with oligodendrocyte precursor cells (OPC) and radial glia (RG) significantly influenced the volume changes between baseline and 3 months in the CA4/DG subfield in SCZ patients performing aerobic exercise. A higher OPC- or RG-associated genetic risk burden was associated with a less pronounced volume increase or even a decrease in CA4/DG during the exercise intervention. We hypothesize that SCZ cell type-specific polygenic risk modulates the aerobic exercise-induced neuroplastic processes in the hippocampus.
- Effects of endurance training on brain structures in chronic schizophrenia patients and healthy controls(2016) MALCHOW, Berend; KEESER, Daniel; KELLER, Katriona; HASAN, Alkomiet; RAUCHMANN, Boris-Stephan; KIMURA, Hiroshi; SCHNEIDER-AXMANN, Thomas; DECHENT, Peter; GRUBER, Oliver; ERTL-WAGNER, Birgit; HONER, William G.; HILLMER-VOGEL, Ursula; SCHMITT, Andrea; WOBROCK, Thomas; NIKLAS, Andree; FALKAI, PeterThe objective of this longitudinal magnetic resonance (MR) imaging study was to examine the effects of endurance training on hippocampal and grey matter volumes in schizophrenia patients and healthy controls. 20 chronic schizophrenia patients and 21 age- and gender-matched healthy controls underwent 3months of endurance training (30 min, 3 times per week). 19 additionally recruited schizophrenia patients played table soccer (""foosball"" in the USA) over the same period. MR imaging with 3D-volumetric T1-weighted sequences was performed on a 3 T MR scanner at baseline, after 6 weeks and after the 3-month intervention and 3 additional training-free months. In addition to voxel-based morphometry (VBM), we performed manual and automatic delineation of the hippocampus and its substructures. Endurance capacity and psychopathological symptoms were measured as secondary endpoints. No significant increases in the volumes of the hippocampus or hippocampal substructures were observed in schizophrenia patients or healthy controls. However, VBM analyses displayed an increased volume of the left superior, middle and inferior anterior temporal gyri compared to baseline in schizophrenia patients after the endurance training, whereas patients playing table soccer showed increased volumes in the motor and anterior cingulate cortices. After the additional training-free period, the differences were no longer present. While endurance capacity improved in exercising patients and healthy controls, psychopathological symptoms did not significantly change. The subtle changes in the left temporal cortex indicate an impact of exercise on brain volumes in schizophrenia. Subsequent studies in larger cohorts are warranted to address the question of response variability of endurance training.
- Gene expression of glutamate transporters SLC1A1, SLC1A3 and SLC1A6 in the cerebellar subregions of elderly schizophrenia patients and effects of antipsychotic treatment(2013) WILMSDORFF, Martina Von; BLAICH, Carolin; ZINK, Mathias; TREUTLEIN, Jens; BAUER, Manfred; SCHULZE, Thomas; SCHNEIDER-AXMANN, Thomas; GRUBER, Oliver; RIETSCHEL, Marcella; SCHMITT, Andrea; FALKAI, PeterObjectives. The glutamatergic hypothesis of schizophrenia proposes alterations of excitatory amino acid transporters (solute carrier family, SLCs) expression and cerebellar dysfunctions. The influence of the neuregulin-1 (NRG1) risk genotype or effects of antipsychotics on expression of EAATs are unknown. Methods. We compared post-mortem samples from the cerebellar hemispheres and vermis of 10 schizophrenia patients with nine normal subjects by investigating gene expression of SLC1A3, SLC1A1 and SLC1A6 by in-situ hybridization. We further assessed the allelic composition regarding the polymorphism rs35753505 (SNP8NRG221533) near the NRG1 gene. To control for effects due to antipsychotic treatment, we chronically treated rats with the antipsychotics haloperidol or clozapine and assessed gene expression of SLCs. Results. Schizophrenia patients showed increased expression of SLC1A3 in the molecular layer of the vermis. Individuals carrying at least one C allele of rs35753505 (SNP8NRG221533) showed decreased expression of SLC1A6 in the molecular layer of both hemispheres, compared to individuals homozygous for the T allele. The animal model revealed suppression of SLC1A6 by clozapine. Conclusions. Increased SLC1A3 expression indicates facilitated transport and may result in reduced glutamate neurotransmission. Decreased SLC1A6 expression in NRG1 risk variant may be an adaptive effect to restore glutamate signalling, but treatment effects cannot be excluded.
- Effects of Three Months of Aerobic Endurance Training on Motor Cortical Excitability in Schizophrenia Patients and Healthy Subjects(2020) ROEH, Astrid; MALCHOW, Berend; LEVOLD, Katrin; LABUSGA, Marcin; KELLER-VARADY, Katriona; SCHNEIDER-AXMANN, Thomas; WOBROCK, Thomas; SCHMITT, Andrea; FALKAI, Peter; HASAN, AlkomietBackground: Aerobic endurance training has been discussed to induce brain plasticity and improve cognitive functions in healthy subjects and patients with neuropsychiatric disorders. For schizophrenia, a motor cortical inhibitory deficit has been established as one aspect of impaired plasticity, especially involving impairments in GABAergic interneuron networks, but the possibility to restore these deficits via exercise-induced plasticity has not been evaluated yet. Methods: 17 schizophrenia patients and 16 matched healthy controls underwent 3 months of aerobic endurance training (30 min, 3 times a week) on bicycle ergometers. After 6 weeks, computer-assisted cognitive remediation training (30 min, 2 times a week) was added. Transcranial magnetic stimulation of the left and right hemispheres was performed at baseline and at the end of the intervention. We evaluated the intensity to induce a motor-evoked potential of 1 mV (S1mV), the resting motor threshold (RMT), the cortical silent period (CSP) at an intensity of 120 and 150% of the individual RMT, short-latency interval intracortical inhibition (3 ms), and intracortical facilitation (7 and 15 ms). Depending on the variable and hemisphere, follow-up data was available for 7-15 schizophrenia patients and for 10-12 healthy controls. Results: Repeated measures ANOVA revealed no significant time x group interactions for any of the analyzed variables. A significant increase in S1mV and CSP duration at 150% RMT of the left hemisphere could be observed in both groups over time. Conclusion: Regular ergometer training over 3 months increases motor cortical inhibition as displayed by an increase in CSP. The increase in S1mV may also indicate a higher degree of inhibition after the intervention. We could not establish a difference between schizophrenia patients and healthy controls. Due to the limited sample size, our results have to be considered as preliminary and need to be replicated in future trials.
- Regulation of immune-modulatory genes in left superior temporal cortex of schizophrenia patients: a genome-wide microarray study(2011) SCHMITT, Andrea; LEONARDI-ESSMANN, Fernando; DURRENBERGER, Pascal F.; PARLAPANI, Eleni; SCHNEIDER-AXMANN, Thomas; SPANAGEL, Rainer; ARZBERGER, Thomas; KRETZSCHMAR, Hans; HERRERA-MARSCHITZ, Mario; GRUBER, Oliver; REYNOLDS, Richard; FALKAI, Peter; GEBICKE-HAERTER, Peter J.Objectives. The role of neuroinflammation in schizophrenia has been an issue for long time. There are reports supporting the hypothesis of ongoing inflammation and others denying it. This may be partly ascribed to the origin of the materials (CSF, blood, brain tissue) or to the genes selected for the respective studies. Moreover, in some locations, inflammatory genes may be up-regulated, others may be down-regulated. Methods. Genome-wide microarrays have been used for expression profiling in post-mortem brains of schizophrenia patients. Array data have been analyzed by gene set enrichment analysis (GSEA) and further confirmed with selected genes by real-time PCR. Results. In Brodman Area 22 of left superior temporal cortex, at least 70 genes (19%) out of 369 down-regulated genes (P < 0.05) belonged to the immune system. 23 from those 70 genes were randomly selected for real-time PCR. Six reached significance level at P < 0.05. Conclusions. The present data support a brain-specific view of the role immune-modulatory genes may play in the left superior temporal cortex in schizophrenia, because immune functions in the patients are not disturbed. In keeping with comparable, previous studies supporting the notion that schizophrenia is a disease of the synapse, we hypothesize that dysregulation of immune-related genes modifies synaptic functions and stability in this region.
- Effects of Endurance Training Combined With Cognitive Remediation on Everyday Functioning, Symptoms, and Cognition in Multiepisode Schizophrenia Patients(2015) MALCHOW, Berend; KELLER, Katriona; HASAN, Alkomiet; DOERFLER, Sebastian; SCHNEIDER-AXMANN, Thomas; HILLMER-VOGEL, Ursula; HONER, William G.; SCHULZE, Thomas G.; NIKLAS, Andree; WOBROCK, Thomas; SCHMITT, Andrea; FALKAI, PeterAerobic exercise has been shown to improve symptoms in multiepisode schizophrenia, including cognitive impairments, but results are inconsistent. Therefore, we evaluated the effects of an enriched environment paradigm consisting of bicycle ergometer training and add-on computer-assisted cognitive remediation (CACR) training. To our knowledge, this is the first study to evaluate such an enriched environment paradigm in multiepisode schizophrenia. Twenty-two multiepisode schizophrenia patients and 22 age-and gender-matched healthy controls underwent 3 months of endurance training (30 min, 3 times/wk); CACR training (30 min, 2 times/wk) was added from week 6. Twenty-one additionally recruited schizophrenia patients played table soccer (known as ""foosball"" in the United States) over the same period and also received the same CACR training. At baseline and after 6 weeks and 3 months, we measured the Global Assessment of Functioning (GAF), Social Adjustment Scale-II (SAS-II), schizophrenia symptoms (Positive and Negative Syndrome Scale), and cognitive domains (Verbal Learning Memory Test [VLMT], Wisconsin Card Sorting Test [WCST], and Trail Making Test). After 3 months, we observed a significant improvement in GAF and in SAS-II social/leisure activities and household functioning adaptation in the endurance training augmented with cognitive remediation, but not in the table soccer augmented with cognitive remediation group. The severity of negative symptoms and performance in the VLMT and WCST improved significantly in the schizophrenia endurance training augmented with cognitive remediation group from week 6 to the end of the 3-month training period. Future studies should investigate longer intervention periods to show whether endurance training induces stable improvements in everyday functioning.
- Post-mortem gene expression of calcium channels Cav1.2 and Cav1.3 in schizophrenia(2022) SCHMITT, Andrea; UHRIG, Stefanie; SPANAGEL, Rainer; WILMSDORFF, Martina von; KALMAN, Janos L.; SCHNEIDER-AXMANN, Thomas; FALKAI, Peter; HANSSON, Anita C.
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