Biologische Hypothesen zur Schizophrenie: Mögliche Einflüsse von Immunologie und Endokrinologie

Zusammenfassung

Bei schizophrenen Patienten sind eine Reihe von biologisch auffälligen Befunden vorhanden, allerdings sind diese Daten sehr heterogen und häufig nicht repliziert. Ein einheitliches Krankheitsbild wird heute nicht mehr angenommen, ebenso wenig wie von einer einzigen Ursache ausgegangen wird, sondern ein Zusammenspiel mehrerer ätiopathologischer Faktoren scheint für die Manifestation der Symptomatik verantwortlich zu sein. Ein integratives Krankheitskonzept bei dem Interaktionen zwischen genetischen Faktoren und umweltbedingten Einflüssen zu einer gestörten neuronalen Entwicklung und in weiterer Folge zu Funktionalitätsveränderungen in den verschiedenen Neurotransmittersystemen führen, scheint der Heterogenität schizophrener Erkrankungen eher zu entsprechen. Der Ausgangspunkt immunologischer Forschung war die Infektionshypothese der Schizophrenie, welche durch die Beobachtung „schizophrenie-ähnlicher” Symptome nach Influenza-Epidemien ausgelöst wurde. Zahlreiche Untersuchungen auf verschiedenste Viren, Antikörper und andere Immunphänomene wurden in dieser Patientengruppe durchgeführt. Obwohl die Befunde nicht einheitlich sind, zeigen Subgruppen schizophrener Patienten ein aktiviertes inflammatorisches Response-System mit Erhöhung der proinflammatorischen Zytokine und der Akut-Phase-Proteine bzw. sind auch Aktivitätsveränderungen im zellulären Immunsystem (IS) beschrieben, wobei eine Verschiebung von primär TH-1 dominierten Funktionen zu einer vermehrten TH-2 Aktivierung festgestellt wurden. Endokrinologisch relevante Faktoren für die Ätiopathogenese schizophrener Erkrankungen betreffen einmal den Einfluss der Sexualhormone, andererseits fokusieren Untersuchungen auf die HPA-Achse und die Bedeutung von Stressauswirkungen zu unterschiedlichen Zeitpunkten auf die Stadien der neuronalen Entwicklung. Veränderungen im IS und in den verschiedenen Hormonsystemen können durch Umweltfaktoren wie Infektionen oder exogene Stresseinwirkungen bedingt sein und infolge der intensiven Vernetzung zwischen ZNS, IS und endokrinem System zu pathologischen Entwicklungen führen, die einem integrativen Krankheitskonzept entsprechen. Relevant für die Manifestation, die Ausprägung und den Verlauf der Erkrankung könnten neben einer genetischen Vulnerabilität, der Zeitpunkt des „primären Insults”, dessen Lokalisation und Schweregrad, sowie eventuelle spätere Kompensations- bzw. Dekompensationsmechanismen sein.

Abstract

A great number of studies show biological alterations in patients with schizophrenia, but many of these data are conflicting. Schizophrenia is a vastly heterogeneous disorder, most likely not caused by one etiological factor, but rather due to a complex network of different, interacting pathogenic influences. Variable clinical pictures may reflect different etiological factors. In a comprehensive theory of the origin of schizophrenic disorders, genetic and environmental influences cause changes in neuronal development which result in functional alterations of different neurotransmittersystems. Immunological research in schizophrenia was initially based on the “infection hypothesis” which was triggered by observing schizophrenia-like psychoses after influenza pandemics. Numerous immunological studies focusing on antibodies against specific viruses, unspecific antibodies and different other immune-phenomena were carried out in schizophrenia patients. Although the variability of the results from these studies is strikingly high, subgroups of patients with schizophrenia show an activated inflammatory response system with increased levels of proinflammatory cytokines and acute phase proteins. Furthermore, some investigations find changing activities in the T-cell system with a shift of TH-1 to an increased TH-2 activity. Endocrinological factors which may play a relevant role in the etiopathogenesis of schizophrenia include sex hormones and all changes caused by stress or other influences which are directly related to the HPA-axis. Alterations of the immune and the endocrinological systems might be caused by environmental factors like infections or exogenous stress. Due to the intensive interaction between the central nervous system, the immune system and different hormones the “development of a pathology” like schizophrenia can be seen in an integrative but multifactorial fashion. The clinical manifestation, the severity and the course of the disease might then be modulated by genetic vulnerability, the time of the “primary insult” - which could be an infection, or psychological stress - and its neuronal localisation and intensity. Different compensatory and decompensatory mechanisms in later life very likely play a crucial role for the further course of the disorder.

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