Dokument

Zusammenfassung:
In der vorliegenden Studie stand die Frage im Mittelpunkt, ob sich neuronale Korrelate im Arbeitsgedächtnisprozess finden lassen, die einen Zusammenhang mit dem Einfluss des Einzelnukleotidpolymorphismus rs1006737 des Gens CACNA1C aufweisen. In der Vergangenheit wurde der Genabschnitt rs1006737 im Gen CACNA1C in genetischen Assoziationsstudien wiederholt mit dem erhöhten Risiko in Verbindung gebracht, an einer Bipolaren Störung oder Schizophrenie zu erkranken. Entsprechend gängiger Annahmen wird vermutet, dass diesen beiden Erkrankungen Veränderungen neuronaler Strukturen und Prozesse zugrunde liegen, die sich insbesondere auf das Arbeitsgedächtnis und den damit eng assoziierten dorsolateralen Präfrontalkortex (DLPFC) auswirken. Anhand einer Stichprobe von 94 gesunden Probanden konnte in dieser Studie mithilfe der funktionellen Magnetresonanztomographie gezeigt werden, dass homozygote Genträger eine signifikante Aktivierungsminderung im Bereich des rechten DLPFC bei Ausführung einer Arbeitsgedächtnisaufgabe im Vergleich zu heterozygoten und Nicht- Risiko-Allelträgern aufweisen. Diese Ergebnisse stehen ganz im Gegensatz zu bisher veröffentlichten Daten, die nämlich darauf hindeuten, dass der Einfluss des Risikogenabschnittes rs1006737 eine verstärkte Aktivierung im Bereich des rechten DLPFC bewirkt. So führten Bigos und Kollegen bereits 2010 eine Aktivierungsanalyse durch, um diesen Einfluss zu überprüfen. Sie berichteten von einer Aktivierungszunahme im Bereich des rechten DLPFC für Träger des Einzelnukleotidpolymorphismus rs1006737 in CACNA1C (Bigos et al., 2010, Genetic variation in CACNA1C affects brain circuitries related to mental illness: Arch Gen Psychiatry, v. 67, p. 939-45). Zusammenfassend lässt sich also festhalten, dass durch die Ergebnisse der vorliegenden Studie die bisherige Datenlage infrage gestellt ist. Als Konsequenz muss eine Neubeurteilung und Neuinterpretation des Einflusses von rs1006737 in CACNA1C auf neuronale Korrelate im Arbeitsgedächtnisprozess erfolgen.

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