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Der Nervenarzt

, Volume 78, Issue 11, pp 1261–1273 | Cite as

Immunologische Aspekte bei depressiven Störungen

  • N. MüllerEmail author
  • M.J. Schwarz
Übersichten

Zusammenfassung

Neben dem Monoaminmangelkonzept als pathophysiologischem Korrelat der depressiven Störung wird zunehmend die Rolle der gesteigerten glutamatergen Neurotransmission diskutiert. Ursachen und Wechselwirkungen dieser Neurotransmitterveränderungen sind bisher allerdings nicht verstanden. In der vorliegenden Übersicht präsentieren wir ein Konzept, das aktuelle Befunde der Neurotransmitterfehlregulierung sowie immunologische und morphologische Befunde bei depressiven Störungen integriert. Mehrere ineinandergreifende Mechanismen scheinen von Bedeutung zu sein: Ursache des Serotoninmangels und gesteigerter glutamaterger Neurotransmission ist möglicherweise der Anstieg proinflammatorischer Zytokine. Eine Immunaktivierung mit gesteigerter Produktion proinflammatorischer Zytokine aktiviert das tryptophan- und serotoninabbauende Enzym Indolamin-2,3-Dioxygenase (IDO). Der gesteigerte Verbrauch von Serotonin und seinem Vorläufer Tryptophan aufgrund der IDO-Aktivierung kann die verringerte Verfügbarkeit von Serotonin bei Depression erklären. Auch bei entzündlichen somatischen Erkrankungen ist die depressive Stimmungslage mit einem Anstieg proinflammatorischer Zytokine und gesteigertem Verbrauch von Tryptophan assoziiert. Die Aktivierung von IDO durch proinflammatorische Zytokine führt darüber hinaus zur Produktion von glutamatergen Agonisten. Im zentralen Nervensystem (ZNS) wird IDO während entzündlicher Prozesse vor allem in Mikrogliazellen aktiviert. Deshalb ist das Astrozyten-Mikroglia-Gleichgewicht bei Depression von Bedeutung. Die beschriebene Verringerung von Astrozyten im ZNS depressiver Patienten kann sowohl die Gegenregulierung zur IDO-Aktivität in Mikrogliazellen hemmen, als auch eine Veränderung der glutamatergen Neurotransmission bewirken. Auf diesem Wege kann das Ungleichgewicht der Immunantwort, zusammen mit dem Astrozyten-Mikroglia-Ungleichgewicht zu einerseits Serotoninmangel und andererseits glutamaterger Überaktivität bei Depression führen. Die weitere Suche nach neuen antidepressiven Therapieverfahren sollte antientzündliche Substanzen berücksichtigen, zum Beispiel COX-2-Inhibitoren.

Schlüsselwörter

Depression Glutamat Indolamin-2,3-Dioxygenase Mikroglia Psychoneuroimmunologie Serotonin 

Immunological aspects of depressive disorders

Summary

Beside the monoaminergic deficiency concept as a pathophysiological correlate of depressive disorder, the role of increased glutamatergic neurotransmission is increasingly being discussed. Causes and interactions of these neurotransmitter disturbances are not fully understood to date. This review presents a concept integrating actual findings of the neurotransmitter dysregulations with immunological and morphological findings in depressive disorder. Several intertwined mechanisms seem to be important: The common cause of serotonin deficiency and increased glutamatergic neurotransmission seems to be the increase of proinflammatory cytokines. Immune activation with increased production of proinflammatory cytokines activate the tryptophan- and serotonin-degradating enzyme indolamine-2,3-dioxygenase (IDO). The increased consumption of serotonin and its precursor tryptophan due to IDO activation may explain the reduced availability of serotonin in depression. In inflammatory somatic disorders, depressive mood is associated with an increase of proinflammatory cytokines and increased consumption of tryptophan. This activation of IDO by proinflammatory cytokines leads to the production of glutamatergic agonists. In the CNS, IDO is activated during inflammatory processes primarily in microglial cells. Therefore the astrocyte:microglial balance in depression is important. The observed decrease of astrocytes in the CNS of depressive patients may contribute to a regulatory fault in the activity of IDO in microglial cells but also can cause an alteration of the glutamatergic neurotransmission. By this mechanism, the dysbalance of the immune response and the astrocyte:microglia dysbalance may contribute to serotonergic deficiency and glutamatergic overproduction in depression. The further search for new antidepressant therapeutic mechanisms should take into regard anti-inflammatory substances, e.g. cyclo-oxygenase-2 (COX-2)-inhibitors.

Keywords

Depression Glutamate Indolamine-2,3-dioxygenase Microglia Psychoneuroimmunology Serotonin 

Notes

Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehung hin: Die Autoren haben die therapeutische Anwendung der COX-2-Inhibition bei psychiatrischen Indikationen zum Patentschutz eingereicht.

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© Springer Medizin Verlag 2007

Authors and Affiliations

  1. 1.Klinik für Psychiatrie und PsychotherapieLudwig-Maximilians-UniversitätMünchenDeutschland

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