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Korrelation zwischen Risikogenvarianten für Schizophrenie und Hirnstrukturanomalien

Correlations between risk gene variants for schizophrenia and brain structure anomalies

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Zusammenfassung

Die genauen Ätiologien der Schizophrenie sind noch weitgehend unklar. Genetische Faktoren stellen wichtige – wenngleich nicht alleinige – Risikofaktoren für die Entwicklung einer Schizophrenie dar. In den letzten Jahren konnten erstmals zahlreiche replizierbare Kandidatengene identifiziert werden. Magnetresonanztomographische Studien konnten strukturelle Gehirnveränderungen charakterisieren, so etwa Ventrikelerweiterungen oder Volumenminderungen der medialen temporalen Strukturen und des Gyrus temporalis superior. Mehrere Studien haben Korrelationen zwischen Genvarianten und hirnstrukturellen Veränderungen bei Gesunden und Schizophrenen nachgewiesen. In dieser Übersicht werden die bisher publizierten Arbeiten zur Korrelation von Varianten in Schizophreniesuszeptibilitätsgenen und Hirnstrukturanomalien bei Patienten und Gesunden referiert. Ziel ist es, eine Übersicht über den momentanen Stand dieser Forschungsrichtung zu geben und diese kritisch zu reflektieren. Durch die Ergebnisse der genomweiten Untersuchungen wird in Bälde eine Vielzahl weiterer Suszeptibilitätsgene für Schizophrenie bekannt werden. Ob und in welchem Ausmaß diese Gene einen Einfluss auf die Hirnstruktur bei Gesunden und Erkrankten haben, kann durch die Untersuchung von Gen-Struktur-Korrelationen geklärt werden. In Anbetracht der vielfältigen möglichen Gen-Gen- und Gen-Umwelt-Interaktionen ist allerdings bei den meisten Varianten davon auszugehen, dass keine einfachen Korrelationen mit großen Effekten gefunden werden können.

Summary

The specific etiologies of schizophrenia are largely unknown. Genetic predisposition constitutes an important, however, not exclusive risk factor for the development of schizophrenia. In recent years, a number of candidate genes were identified and have been consistently replicated. Magnetic resonance imaging studies have characterized structural changes in brain morphology, such as ventricular enlargement or volume reduction of the medial temporal structures and the superior temporal gyrus. Several studies have found correlations between gene variants and changes of brain morphology in schizophrenia patients and healthy controls. In this review, publications examining correlations of schizophrenia susceptibility gene polymorphisms and structural brain anomalies in patients and healthy controls are described. An overview and a critical reflection of the current research are outlined. The results of genome-wide studies will soon provide a multitude of additional schizophrenia susceptibility genes. If and to what extent these genes exert an influence on the brain structure in the healthy and the diseased, can be clarified by gene structure correlations. Given the many possible gene-gene and gene-environment interactions, most variants will probably not show simple interactions with sizable effects.

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Nickl-Jockschat, T., Rietschel, M. & Kircher, T. Korrelation zwischen Risikogenvarianten für Schizophrenie und Hirnstrukturanomalien. Nervenarzt 80, 40–53 (2009). https://doi.org/10.1007/s00115-008-2576-1

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