Die molekulare Neurobiologie schizophrener Psychosen

Zusammenfassung

Bereits in der griechischen Antike wurde formuliert, dass psychiatrischen Erkrankungen stoffliche Veränderungen zugrunde liegen. Pharmakologisch definierte pathogenetische Konzepte der Schizophrenie ergaben sich aus der Beobachtung, dass dopaminerge und anti-glutamaterge Substanzen psychotomimetisch, Dopaminantagonisten aber antipsychotisch wirken. Mit post-mortem-Studien konnten zelluläre und molekulare Veränderungen im Sinne einer Hirnentwicklungsstörung nachgewiesen werden. Aufbauend auf stabilen Befunden klassischer Genetik gelang es mittels Kopplungsanalysen und Assoziationsstudien, chromosomale Regionen und Kandidatengene wie Dysbindin, Neuregulin und COMT zu definieren. Verschiedene Tiermodelle erlaubten die Überprüfung molekularer Hypothesen. Mithilfe von Befunden der Neuropsychologie, der strukturellen und funktionellen Magnetresonanztomografie (fMRT), kann an neurogenetisch charakterisierten Probanden der Einfluss molekulargenetischer Variationen auf die Hirnfunktion in vivo molekular untersucht werden. Die Kombination der neurobiologischen Methoden verbessert das pathogenetische Verständnis schizophrener Psychosen und kann helfen, neue Therapieformen zu etablieren.

Summary

Neurobiological theories about the molecular pathogenesis of psychotic disorders were first developed in the Hippocratic opus “The sacred disease”. Pharmacological concepts of schizophrenia were guided by observations of psychotomimetic effects of dopaminergic or anti-glutamatergic substances, whereas antidopaminergic agents were antipsychotic. In parallel, neuropathological investigations accumulated evidence in favour of a neurodevelopmental theory of schizophrenia. A set of chromosomal regions linked to increased disease risk were defined by neurogenetic studies and many candidate genes such as dysbindin, neuregulin und COMT were reported. As a tool to test molecular hypotheses, several animal models were established. Neuropsychology, structural and functional magnetic resonance tomography (fMRT) do not reacha molecular resolution. However, the impact of genetic variation on neural function can be studied using translational imaging genetics. In conclusion, the combination of several neurobiological methods improves our knowledge of the pathogenesis of schizophrenia and can facilitate the development of innovative treatment approaches.

Schlüsselwörter

Magnetresonanztomografie - Neurobiologie - Neurogenetik - Pathogenese - Schizophrenie

Keywords

Magnetic resonance tomography - neurobiology - neurogenetics - pathogenesis - schizophrenia

• Literatur

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