Die Glutamathypothese der Schizophrenie

Zusammenfassung

Über viele Jahre war die Dopaminhypothese das alleinige Erklärungsmodell für die Ätiologie der Schizophrenie. Seit der Beobachtung, dass Antagonisten am NMDA-Rezeptor (z. B. PCP) bei gesunden Probanden Symptome der Schizophrenie auslösen können, hat sich die Glutamathypothese der Schizophrenie etabliert. Neben den PCP-induzierten Modellpsychosen gibt es mittlerweile Befunde aus allen Bereichen der modernen Neurowissenschaft, die die Glutamathypothese der Schizophrenie belegen und erweitern. In dieser Übersichtsarbeit werden die aktuell verfügbaren Evidenzen für die Glutamathypothese diskutiert und in Bezug zueinander gesetzt. Basierend hierauf werden die Möglichkeiten der gezielten pharmakologischen Beeinflussung des glutamatergen Systems beschrieben und aktuelle Therapiestudien vorgestellt. Insgesamt lässt sich feststellen, dass die Glutamathypothese mittlerweile gut als ätiologisches Modell der Schizophrenie etabliert ist. Auch wenn die Entwicklung glutamaterger Antipsychotika noch an ihrem Beginn steht, besteht die Hoffnung auf neue Therapiealternativen in der Behandlung der Schizophrenie. Allerdings konnten jüngste Ergebnisse aus Zulassungsstudien das Potential kürzlich entwickelter glutamaterger Medikamente nicht aufzeigen.

Abstract

For many years, the dopamine hypothesis of schizophrenia has been the leading theory explaining the aetiology of schizophrenia. However, since the first observation showed that NMDA-receptor antagonists (e. g., PCP) can induce all kinds of schizophrenia symptoms in humans, the glutamate hypothesis of schizophrenia has been established as an additional explanation model. Apart from the PCP-induced psychoses, many other findings from all areas of modern neuroscience have confirmed and extended the glutamate hypothesis. This review discusses the available evidence for the glutamate hypothesis and puts the different findings into relation. Consecutively, the possibilities for a pharmacological modulation of the glutamate system and recent clinical trials are discussed. To sum up, one could note that the glutamate hypothesis of schizophrenia is now well-established. The development of glutamatergic antipsychotics is still in the early stages, but there is hope for a new generation of antipsychotics based on the glutamate hypothesis of schizophrenia. However, recent findings from registration trials could not provide positive findings for the recently developed glutamatergic drugs.

Schlüsselwörter

Schizophrenie - Neurobiologie - Glutamat

Key words

schizophrenia - neurobiology - glutamate

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