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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Barbara Sperner-Unterweger
Univ.-Klinik für Psychiatrie Innsbruck · Abteilung für Biologische Psychiatrie
Anichstraße 35
6020 Innsbruck
Österreich
Email: barbara.sperner-unterweger@uibk.ac.at
