Die Gehirnentwicklung vor der psychotischen Erstmanifestation und im weiteren Verlauf der Schizophrenie

Zusammenfassung

Eine umschriebene Assoziation zwischen Copy Number Variations mit der Diagnose Schizophrenie und Autismus, aber nicht bipolarer Störung, unterstützt die Vorstellung, dass die Schizophrenie sowie der Autismus im Kern Hirnentwicklungsstörungen darstellen. Daten an multipel affizierten Familien mit Schizophrenie zeigen, dass hirnstrukturelle Veränderungen wie die des Hippokampus auch bei erstgradigen Angehörigen erkrankter Patienten vorhanden sind, ohne dass diese psychopathologisch auffällig sind. Es ist davon auszugehen, dass es bei der Schizophrenie in fronto-temporalen Regionen Veränderungen gibt, die genetisch bedingt im Sinne einer primären Vulnerabilität früh angelegt werden. Der Übergang dieser Vulnerabilität in ein Prodrom bis zum Vollbild der Erkrankung wird durch relevante Umweltfaktoren getriggert. Den hirnstrukturellen Veränderungen des Hippokampus liegen keine neuronalen Verluste zugrunde. Am ehesten ist von einer Reduzierung des Neuropils und somit einer Störung synaptischer oder, weiter gefasst, regenerativer Mechanismen auszugehen. Hieraus resultiert die Hypothese, dass die Störung dieser regenerativen Mechanismen an den Verlauf der schizophrenen Psychose gekoppelt ist: Je ausgeprägter die Negativsymptomatik, desto deutlicher ist die synaptische oder neuronale Plastizität beeinträchtigt. Abschließend lässt sich anhand erster Daten die Hypothese erheben, dass diese Störung synaptischer/plastischer Prozesse auf eine Beeinträchtigung der epigenetischen Regulation zurückzuführen ist. Dies würde erklären, wie relevante Umweltfaktoren (Schwangerschafts- und Geburtskomplikationen, frühkindlicher Missbrauch oder Cannabismissbrauch) über die Risikogene zu einer Destabilisierung des neuronalen Netzwerks führen, welches auf der Verhaltensebene letztlich die Symptome einer Schizophrenie auslösen kann.

Abstract

A circumscribed association between copy number variations and the diagnosis of schizophrenia or autism but not bipolar disorder supports the notion of schizophrenia and autism principally representing a disturbed brain development. Data of multiply affected families show certain brain structural (e. g. hippocampal) changes to also be present in their first-grade relatives without leading to psychopathological abnormalities. It thus can be concluded that there exist regional fronto-temporal changes in schizophrenia due to genetically early determined primary vulnerability. The transition of this vulnerability into a prodrome to the point of the fully developed disease is triggered by relevant environmental factors. Hippocampal brain structural changes do not base on neuronal loss, for which reason the underlying mechanism might be a reduction of neuropil and thus a disturbance of synaptic processes or even regenerative mechanisms. Thus, disturbed regenerative mechanisms might be linked to the course of schizophrenic psychosis: the more pronounced the negative symptoms, the more evident the impaired synaptic or neuronal plasticity. Based on initial data we speculate the disturbed synaptic/plastic processes to result from an impaired epigenetic regulation. This could explain how relevant environmental factors (pregnancy and birth complications, early childhood abuse or cannabis abuse) via risk genes might lead to a destabilized neuronal network which in the end could trigger schizophrenia symptoms on the behavioral level.

Schlüsselwörter

Gehirnentwicklung - Erstmanifestation - schizophrene Störung

Key words

brain development - first-episode schizophrenia - schizoprenic disorder

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