Signs danger of dating a schizophrenic neurodegeneration are commonly found in schizophrenic patients, albeit still unclear, why they occur and whether they are a cause or rather an effect of schizophrenia. Although there are numerous studies supporting either theory, the working hypothesis of this thesis is that an overactivity of mesolimbic dopaminergic pathways leads to dopamine neurotoxicity in terms of an increased production of reactive oxygen species ROSin time leading to oxidative stress and thereby to so-called atypical neurodegeneration. This in turn negatively influences i. A key player in the body s antioxidant capacity is the peroxisome. This cell organelle is involved in both enzymatic e. Its role in schizophrenia has, however, only been poorly examined, even though peroxisomes additionally are the only known source to-date of major enzymes for the degradation of cofactors of NMDA-receptors including NMDA itself. Changes in peroxisomal metabolism and abundance therefore influence both the brain s capacity to degrade ROS as well as the functionality of its NMDA receptors and vice versa. This thesis therefore examines the reactions of peroxisomes to increased dopamine. Since peroxisomes are involved in a number of other metabolic functions apart from antioxidant defense, their enzyme content is highly heterogeneous. Catalase and ABCD3 are generally used as markers for peroxisomes. Their abundance is, however, highly dependent on metabolic demands and therefore varies extremely between as well as within different organs, tissues and cells. Especially in the brain, both catalase and ABCD3 are barely detectable, thereby leading to a marked underestimation of true peroxisomal abundance and distribution. In the first part of this thesis danger of dating a schizophrenic was therefore attempted to establish a new peroxisomal marker, peroxin 14 Pex14pwhich is part of a docking complex on the peroxisomal membrane relevant for import of all matrix proteins and therefore independent of individual peroxisomal metabolism. Using various morphological methods in a large variety of organs, tissues and cell types from a number of different species it could be shown that Pex14p is indeed present in the membrane of every healthy peroxisome and is expressed in similarly high levels in tissue sections and cell cultures of different organs and species. As Pex14p is also highly suited as a peroxisomal marker in all neuronal tissue, post mortem brain sections of schizophrenic patients and controls were analyzed regarding the abundance and distribution of peroxisomes as well as catalase. The results were, however, inconclusive, wherefore the reactions of peroxisomes to increased dopamine were analyzed under more controllable conditions within the second part of this thesis. The effects of dopamine in vitro were examined using primary murine neuronal and astrocyte cell cultures and the in vivo-effects in a pharmacological mouse model through subchronic systemic administration of the selective, non-competitive NMDAR-antagonist MK Analyses of gene expression patterns from the brains of the animals show i. Morphological experiments show that dopamine changes peroxisomal reactions and neuronal morphology specifically and only in intact neuron-astrocyte interactions, mimicking the atypical neurodegeneration found in schizophrenic patients. Additionally, increased levels danger of dating a schizophrenic selected antioxidant enzymes were found to be increased in the brains of MKtreated animals. It can therefore be concluded that dopamine does indeed lead to increased ROS production in the brain, which is, however, initially still countered by an increase in antioxidant defense mechanisms. This strengthens the initial hypothesis that oxidative stress i. Finally, the dopamine-related increase in the expression of genes encoding for enzymes degrading NMDAR-cofactors, thereby leading to a decrease of NMDAR-mediated neurotransmission, shows that hyperdopaminergia and hypoglutamatergia in schizophrenia are not separate entities, but rather influence, uphold and even exacerbate each other. This led to the proposition of a new integrative model of the etiopathogenesis of schizophrenia, linking both hyperdopaminergia and hypoglutamatergia together. Bezüglich der bei Schizophrenen gefundenen Neurodegeneration ist die Frage nach Ursache und Wirkung unklar. Neben den Mitochondrien und dem Zytoplasma spielt das Peroxisom eine wesentliche Rolle in der enzymatischen z. Die Konzentration des klassischen peroxisomalen Markerenzyms Katalase ist jedoch in Neuronen ausgesprochen niedrig, weshalb im ersten Schritt der Arbeit ein neues Markerprotein für Peroxisomen Peroxin 14, Pex14p an einer Vielzahl verschiedener Gewebe und Zellen mittels Proteinlabelingmethoden für Elektronen- Licht- und Fluoreszenzmiskroskopie etabliert wurde. Über diese neue Methode war es nun möglich, Peroxisomen auch im Nervengewebe unabhängig ihres Katalasegehaltes zu untersuchen. Wir haben daher die Anzahl an Peroxisomen und Katalase an postmortem Hippokampusschnitten von Schizophrenen und Kontrollen verglichen. Aufgrund methodologischer Einschränkungen waren die Befunde jedoch uneindeutig. Im nächsten Schritt wurden Mischkulturen muriner Neurone und Astrozyten mit unterschiedlichen Dopaminkonzentrationen inkubiert, wonach sich eine Erhöhung der Katalasemenge vor allem in Astrozyten, begleitet von einer Umverteilung der Peroxisomen aus den Dendriten in die Somata ohne signifikante Zelltoderhöhung zeigte. Wir wiederholten diese Experimente daher mit reinen Astrozytenkulturen und fanden selbst bei Erhöhung der Dopaminkonzentration und Inkubationsdauer keine Unterschiede zu Vehikel-behandelten Kulturen. Dies spricht für die antitoxische Wirkung der Astrozyten und die Spezifität der Reaktionen aus den ersten Zellkulturen für intakte neuroastrozytäre Verbände. In darauf aufbauenden Tierversuchen untersuchten wir die Erhöhung des mesolimbischen Dopamins in männlichen Wildtypmäusen durch Gabe des NMDAR-Antagonisten MK Im Anschluss an Behandlungsdauern von 1hh wurden die Gehirne entnommen und für morphologische Analysen oder Extraktion der RNAs für Expressionsanalysen verwandt. Unsere Befunde stärken die Annahme, dass Dopamin neurodegenerative Veränderungen hervorruft und diese erst im späteren Krankheitsverlauf auftreten und daher vermutlich nicht an der Äthiopathogenese der Schizophrenie beteiligt, sondern eher als Folgeerscheinung der Dopamin-Neurotoxizität anzusehen sind. Dopamine neurotoxicity, oxidative stress and schizophrenia : in vitro and in vivo studies of peroxisomal reactions to increased dopamine. Datum
PubMed CrossRef. Analysis of medication compliance among community-dwelling schizophrenia patients with aggressive behaviour Among community-dwelling patients with schizophrenia and a history of psychiatric drug use, all survey subjects experienced noncompliance with medication 5. Investigating whether controlling and aggressive relationship behaviors are discriminant. Clin Psychol Rev. The improvement from PEPS in the reduction of the capacity to experience syndrome already has been shown in previous studies 22 , The release of dopamine is related to hallucinations in patients, leading to aggressive behaviour in schizophrenia patients [ 52 , 53 ].
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Positive and Negative Syndromes in schizophrenia Relationship between obsessive–compulsive symptoms and smoking habits amongst schizophrenic. In relation to our interest to study the beginning of schizophrenia, systematically, paying special attention to the age and gender distribution of true onset. The Scale for Assessment of Negative Symptoms (SANS) (31) measures schizophrenia's deficit symptoms within the framework of schizophrenic. Though partnerships with schizophrenia patients are at risk of breakdown and separation in many respects, they are often maintained for years. Despite the.The survey included questions about general demographic data and disease-related questionnaires: the Pittsburgh Sleep Quality Index PSQI , the revised Chinese version of the Modified Over Aggression Scale MOAS , the Self-Rating Depression Scale SDS , and the Family Adaptability and Cohesion Scale, Second Edition. Family intimacy refers to the emotional connections between family members, whereas family adaptability refers to the degree to which a family system can flexibly handle problems in different stages of family environment development [ 32 ]. Alexandra Nguyen 1 La Source, School of Nursing Sciences, HES-SO University of Applied Sciences and Arts of Western Switzerland, Lausanne, Switzerland. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY. Participants are younger than those in previous studies, which may explain this unexpected result. Perspect Psychiatr Care. Psychiatr Prax. Some physicians rated more than one patient, and all physicians rated only a few of the patients they treated in total because of the case mix of the patients they were in charge of. PERMALINK Copy. Open Access This article is licensed under a Creative Commons Attribution 4. Zurück zum Zitat Drake CL, Roehrs TA, Burduvali E, Bonahoom A, Rosekind M, Roth T. Prevalence of depression and its relationship with other clinical characteristics in a sample of patients with stable schizophrenia. In applied disciplines such as clinical psychiatry, the external validity must be emphasized to know about the efficacy of an intervention not only in experimental conditions but also in less controlled and more real-life situations. Verlag BioMed Central. CrossRef Majadas S, Olivares J, Galan J, Diez T. PubMedCrossRef Zung WW. Fachgebiete Chevron down icon Chevron up icon Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin. The rating system is ordinal, from 0 absent to 5 severe. Masked depression in children and adolescents. Zurück zum Zitat Messent P. The total score of this scale ranges from 0 to 21 points, and the higher the score is, the poorer the sleep quality of the study subjects. SANS, Scale for Assessment of Negative Symptoms; TEPS, Temporal Experience of Pleasure Scale; SBI, Savoring Beliefs Inventory—French version. Both the total anticipatory and consummatory scores of TEPS were used. See Table 3. PMCID: PMC PMID: Results Basic information and correlation analysis of the research subjects The study population consisted of males
