Mikroglia und immunologische Mechanismen in der neuropsychiatrischen Forschung

Zusammenfassung

Die Psychoneuroimmunologie beschäftigt sich mit den Wechselwirkungen zwischen der (gesunden) Psyche, psychischen Störungen und dem Immunsystem. Inzwischen hat sich gezeigt, dass zumindest bei Subgruppen psychischer Störungen wie Schizophrenie und Depression ein entzündlicher Prozess bei der Pathogenese eine Rolle spielt. Da für Schizophrenie und Depression auf diesem Gebiet die meisten Befunde vorliegen, konzentriert sich diese Übersicht auf diese beiden Störungsbilder. Die differenzielle Aktivierung von Mikrogliazellen und Astrozyten als funktionelle Träger des Immunsystems im ZNS, trägt zur Typ-1/Typ-2-Inbalance bei. 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. Sowohl bei Depression als auch bei Schizophrenie ist die Vulnerabilitäts- Stress-Hypothese weitgehend akzeptiert. So zeigte sich z. B. dass – bei entsprechender genetischer Disposition – Stress im frühen Lebensalter oder Separationsstress mit einem Anstieg proinflammatorischer Zytokine einhergehen und zu einer Immunaktivierung führen. Die Interaktionen zwischen dem Immunsystem, Neurotransmittern und dem Tryptophan- Kynurenin-System sind entscheidende Komponenten für die Pathogenese von Stress und Depression. Eine antientzündliche Behandlung, z. B. mit dem COX-2-Inhibitor Celecoxib, zeigt antidepressive Effekte.

Summary

The topic of psychoneuroimmunology is the interaction between (healthy) psychic processes, psychiatric disorders and the immune system. It could be shown that at least in subgroups of psychiatric disorders such as schizophrenia or major depression an inflammatory process plays a key role. Since most of the findings were obtained in schizophrenia and major depression, this review focusses on these disorders. The differential activation of microglia and astrocytes as part of the central nervous system (CNS) immunity contributes to the type-1/type-2 immune inbalance. 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 early stages of the disease. The vulnerability-stress hypothesis is widely accepted both, in schizophrenia and in major depression. It has been shown that – often based on genetic disposition – early live stress or separation stress are associated with an increase of pro-inflammatory cytokines leading to an activation of the immune system and pro-inflammatory prostaglandins. In the CNS, the activation of microglia is crucial. The interactions between the immune system and neuro - transmitters, the tryptophan-kynurenine system, and the glutatmatergic neurotransmission are further links between stress, depression and the immune system. Accordingly, anti-inflammatory therapy, e. g. with the COX 2 inhibitor celecoxib is effective in depression.

Schlüsselwörter

Depression - Schizophrenie - Stress - Immunsystem - Psychoneuroimmunologie - Neurotransmitter - COX-2-Inhibition

Keywords

Depression - schizophrenia - stress - immune system - psychoneuroimmunology - neurotransmitter - cox 2 inhibitor

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