Neue Ansätze in der Schizophrenieforschung: Die Bedeutung von neuropsychologischen Endophänotypen und deren möglicher Nutzen

Zusammenfassung

Die Ätiologie und die einzelnen genetischen Determinanten der Schizophrenie sind trotz eindeutigen Nachweises einer hohen Heritabilität nach wie vor ungeklärt. Wahrscheinliche Erklärung hierfür ist zum einen die Komplexität des genetischen Hintergrundes und zum anderen die deutliche Heterogenität des klinischen Erscheinungsbildes dieser Erkrankung. Eine neue Forschungsstrategie im Rahmen der Schizophrenieforschung besteht darin, klinisch enger definierte Merkmale, so genannte Endophänotypen zu identifizieren, um die Kandidatengensuche zu optimieren. Als Endophänotypen bieten sich die deutlich defizitären kognitiven Funktionen schizophrener Patienten an. Diese zeigen eine enge pathogenetische Beziehung zu den neurobiologischen Grundlagen der Erkrankung und klinisch besonders ungünstige Auswirkungen auf die psychosoziale Funktionsfähigkeit Erkrankter. Die Identifizierung dieser kognitiven Defizite erfolgt - auch in Kombination mit neurophysiologischen Messmethoden - durch neuropsychologische Testverfahren. Die Ausprägung bzw. Beeinflussung kognitiver Defizite wird in den nächsten Jahren somit im Fokus sowohl genetischer Untersuchungen als auch psychosozialer und psychopharmakologischer Therapiestrategien stehen, mit dem langfristigen Ziel einer verbesserten psychosozialen Integration der Betroffenen.

Abstract

Despite the compelling evidence for a strong heritability of schizophrenia, the aetiology and genetic underpinnings of this disabling disease still remain unclear. Reasonable explanations for current problems in identifying candidate genes for schizophrenia are the complexity of its genetic background as well as the heterogeneity of the clinical appearance of this disease. For a higher efficiency in genetic investigations, a new approach came up which defines clinically distinct traits much more precisely: the so called endophenotype concept. Schizophrenic patients suffer from marked cognitive deficits. These deficits are closely related to the neurobiological basis of the disease, exhibit a high negative impact on clinical outcome, and may serve as endophenotypes for genetic studies. Identification of neurocognitive endopenotypes is usually performed in terms of a combination of neuropsychological tests and neurophysiological measurements. Thus, future genetic investigations as well as psychosocial and psychopharmacological therapy strategies will focus on the severity and potential therapeutic modification of cognitive deficits in order to improve psychosocial reintegration of schizophrenic patients in the long-term.

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