Pathophysiologische Grundlagen der Schizophrenie und deren Relevanz für die Psychopharmakotherapie
Pathophysiology of Schizophrenia and its Impact on PharmacotherapyC. G. Widschwendter1
, W. W. Fleischhacker1
1Abteilung für Biologische Psychiatrie, Universitätsklinik für Psychiatrie, Medizinische Universität Innsbruck/Österreich
Prof. Fleischhacker hat finanzielle Forschungsunterstützung und Honorare von folgenden Firmen erhalten: Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Organon, Otsuka, Pfizer, Sanofi-Synthelabo.
Ungefähr 1 % der Bevölkerung erkrankt an Schizophrenie. Zu den Hauptsymptomen zählen Halluzinationen, Wahn, Denkarmut, emotionaler und sozialer Rückzug sowie kognitive Defizite. Obwohl neuere Antipsychotika mit breiterem Rezeptorprofil umfassendere Therapiemöglichkeiten bieten, wird ein zufriedenstellendes Therapieansprechen bei vielen Patienten nicht erreicht. Trotz intensiver Forschung sind die molekularbiologischen Grundlagen der Schizophrenie nicht genau geklärt. Auch wenn pharmakologische Studien, funktionelle bildgebende Verfahren und Genforschung auf Veränderungen glutamaterger, GABAerger und serotonerger Systeme hinweisen, kommt der Dopaminhypothese in der Therapie nach wie vor eine zentrale Rolle zu. Dieser Artikel gibt einen Überblick über die pathophysiologischen Grundlagen der Schizophrenie, deren Relevanz für die Psychopharmakologie sowie einen Ausblick auf potenziell erfolgversprechende Forschungsansätze.
Abstract
Schizophrenia is a severe psychiatric illness with a lifetime morbidity risk of around 1 %. Symptoms include hallucinations, delusions, poverty of thought and emotion and social withdrawal and cognitive deficits. Although newer antipsychotics affecting multiple neurotransmitter receptors facilitate therapy, many patients still do not achieve full response. Despite intensive study, the molecular etiology of schizophrenia remains enigmatic in many ways. The dopamine hypothesis of schizophrenia still plays an important role, although pharmacological studies, brain imaging analyses and genetic research indicate additional dysfunctions of glutamate, GABA and serotonin transmission. This article reviews the pathophysiological background of the disorder, its implications for pharmacological treatment and possible directions for future research.
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