Immunologische Behandlungsoptionen bei schizophrenen Störungen

Zusammenfassung

Der pathophysiologische Mechanismus, der bei Schizophrenie zur dopaminergen Dysfunktion führt, ist nach wie vor unklar. Ein entzündliches Geschehen scheint dabei eine Schlüsselrolle zu spielen. Eine Dysfunktion in der Aktivierung der Typ-1-Immunantwort ist mit verminderter Aktivität des Schlüsselenzyms im Tryptophan-Kynurenin-Metabolismus, Indolamin-2,3-Dioxygenase (IDO), assoziiert, was zu gesteigerter Produktion von Kynureninsäure – eines N-Methyl-D-Aspartat (NMDA)-Antagonisten – im ZNS und verminderter glutamatergen Neurotransmission führt. Die differenzielle Aktivierung von Mikrogliazellen und Astrozyten als funktionellen Trägern des Immunsystems im ZNS, trägt zur Typ-1-/Typ-2-Inbalance bei. Antipsychotika, die vor allem als Dopamin-D2-Rezeptor-Antagonisten wirken, haben verschiedene Nachteile. Die Immuneffekte vieler Antipsychotika rebalancieren teilweise die Dysbalance der Typ-1-/Typ-2-Immunantwort und die Überproduktion von Kynureninsäure. Das entzündliche Geschehen ist verbunden mit höherer Prostaglandin-E2(PGE-2)-Produktion und erhöhter Cyclooxygenase-2(COX-2)-Expression. Zunehmende Evidenz aus klinischen Studien mit COX-2-Inhibitoren weisen auf einen günstigen Effekt antiinflammatorischer Therapie bei Schizophrenie hin, speziell in frühen Stadien der Krankheit. Weitere Optionen von immunmodulatorischer Therapie bei Schizophrenie werden diskutiert.

Abstract

The pathophysiological mechanism leading to dopaminergic dysfunction in schizophrenia is still unclear. Inflammation seems to play a key role. A dysfunction in the activation of the type 1 immune response is associated with decreased activity of the key enzyme of the tryptophan/kynurenine metabolism, indolamine-2.3-dioxygenase (IDO), results in a higher production of kynurenine acid (KYNA) – an N-methyl-D-aspartate antagonist – in the central nervous system (CNS) and decreased glutamatergic neurotransmission. The differential activation of microglial cells and astrocytes, which serve as immune cells in the CNS, contributes to the TH1-TH2 immune imbalance. Antipsychotics, all acting as dopamine D2 receptor antagonists show several shortcomings. The immune effects of antipsychotics rebalance partly the imbalance of the type-1/type-2 immune response and the overproduction of KYNA. The inflammation is associated with higher prostaglandin E2 (PGE2) production and higher cyclo-oxygenase-2 (COX-2) expression. Increasing evidence from clinical studies with COX-2 inhibitors points to an advantageous effect of anti-inflammatory therapy in schizophrenia, especially in the early stages of the disease. Further options of immunomodulatory therapy in schizophrenia are discussed.

Schlüsselwörter

COX-2-Inhibition - Inflammation - Psychoneuro-Immunologie - Schizophrenie - Therapie

Key words

COX-2 inhibition - inflammation - psychoneuroimmunology - schizophrenia - therapy

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