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Übersichtsarbeit

Genetische Befunde zu Schizophrenie

Published Online:January 23, 2008https://doi.org/10.1024/1422-4917.36.1.17

Abstract

Zusammenfassung: Schizophrene Erkrankungen zeichnen sich durch eine sehr heterogene Symptomatik mit übergreifenden Funktionsstörungen verschiedenster kognitiver Bereiche aus. Die vielfältigen Phänotypen werden durch das Zusammenwirken von genetischer Prädisposition und Umwelteinflüssen erklärt. Pathophysiologische Modelle beinhalten die Dopamin-Überschuss- sowie Glutamat-Mangel-Hypothese, die Radikal-Hypothese und die Hypothese entwicklungsbedingter versus degenerativer Genese. Neben den neurobiologischen Erklärungsansätzen geben Kopplungsstudien mit nachfolgenden Feinkartierungen Hinweise auf potentiell an der Pathophysiologie beteiligte Gene. Den wichtigsten Kandidatengenen, wie Dysbindin (DTNBP1), Neuregulin1 (NRG1) oder DISC-1 (disrupted-in schizophrenia-1), werden Einfluss auf die Signalübertragung sowie der Ausbildung und dem Erhalt der Struktur von neuronalen Netzwerken zugeschrieben. Zu ihnen werden zahlreiche weitere Gene gezählt. Insgesamt ist bei der Pathogenese der Schizophrenie von einer multifaktoriellen Entstehung mit der Interaktion von verschiedenen genetischen und neurobiologischen sowie exogenen Komponenten auszugehen.


Genetic findings in schizophrenia

Summary: Schizophrenia is characterized by a great heterogeneity of symptoms and functional deficits, especially of cognition. Different phenotypes are thought to result from the interaction of genetic predisposition and environmental factors. Pathophysiological models range from the dopamine and glutamate hypotheses to the hypothesis of free radicals and the hypotheses of neurodevelopment as opposed to neurodegeneration. In addition to the neurobiological approaches, linkage studies and subsequent finemappings deliver evidence with regard to genes potentially involved in schizophrenia. The most important candidate genes, such as dysbindin (DTNBP1), neuregulin (NRG1) and DISC-1 (disrupted-in schizophrenia-1), are thought to influence neurotransmission, as well as the development and maintenance of the structure of neuronal networks. The list of potential candidates includes numerous other genes as well. In conclusion, multiple genetic, neurobiological, and exogenous factors are assumed to interact in the pathogenesis of schizophrenia.

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