Die Glutamathypothese der Schizophrenie

J. Gallinat; Y. Gudlowski

doi:10.1055/s-0038-1627256

Nervenheilkunde, Table of Contents

Nervenheilkunde 2008; 27(04): 317-325
DOI: 10.1055/s-0038-1627256

Original- und Übersichtsarbeiten - Original and Review Articles

Schattauer GmbH

Die Glutamathypothese der Schizophrenie

The glutamate hypothesis of schizophrenia

J. Gallinat

¹Charité Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Mitte (Klinikdirektor: Prof. Dr. A. Heinz)

,

Y. Gudlowski

¹Charité Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Mitte (Klinikdirektor: Prof. Dr. A. Heinz)

› Author Affiliations

Abstract

Zusammenfassung

Die Dopaminhypothese hat die Erforschung der Schizophrenie über Jahrzehnte geprägt und ist das Haupterklärungsmodell der aktuellen Pharmakotherapie. Darüber hinaus gibt es eine Vielzahl von Hinweisen, dass eine Störung des Glutamatsystems eine bedeutende Rolle in der Pathobiologie der Schizophrenie spielt. Pharmakologische Expositionsversuche mit NMDA-Rezeptorantagonisten induzieren Schizophrenie-ähnliche Bilder mit Positivsymptomen, Negativsymptomen, kognitiven Störungen sowie Veränderungen der Hirnperfusion. In Tierexperimenten zeigt sich neuronale Degeneration nach Applikation von NMDA-Rezeptorantagonisten, die den histopathologischen Veränderungen bei Schizophrenie ähneln. Neue Entwicklungen in der in-vivo-Messung von Glutamat erbringen zudem experimentelle Hinweise für einen veränderten Glutamatgehalt zerebraler Strukturen bei Schizophrenie. Neue Therapieansätze in der Pharmakotherapie zeigen eine Wirksamkeit von Glutamat-aktiven Substanzen auf Positiv- und Negativsymptome bei Schizophrenie und konstituieren möglicherweise eine neue Ära der Schizophreniebehandlung jenseits der Therapie durch Dopamin-Rezeptorantagonisten.

Summary

The dopamine hypothesis has guided schizophrenia research for decades and represents the prime explanation model for the current pharmacotherapy. However, several lines of evidence indicate that a dysfunction of the glutamate system plays a major role in the pathobiology of schizophrenia. Pharmacological challenges with NMDA receptor antagonists mimic schizophrenic psychopathology including negative symptoms and cognitive dysfunction as well as alterations in cerebral perfusion. Animal experiments indicate delayed neuronal degeneration after exposition to NMDA receptor antagonists showing similarities with histological abnormalities in schizophrenia. New techniques for in vivo measurement of cerebral glutamate have provided experimental evidence for abnormal glutamate levels in schizophrenia. Evidence for glutamate dysfunctions in schizophrenia is complementary to the dopamine hypothesis, because both systems are closely connected and interact in a complex way. Recently, novel therapeutic agents acting via glutamatergic mechanisms have been found to improve positive and negative symptoms in schizophrenia in a clinically relevant dimension which may constitute a new era of pharmacotherapy beyond dopamine receptor antagonism.

Schlüsselwörter

Schizophrenie - Glutamat - Dopamin - präfrontal - Genetik - Magnetresonanzspektroskopie

Keywords

Schizophrenia - glutamate - dopamine - prefrontal - genetic - magnetic resonance spectroscopy

Full Text

References

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