Serotonin Kompakt – Teil 2[*]

Zusammenfassung

Ein dysfunktionales Serotonin-(5-HT-)System ist sowohl an einer veränderten emotionalen Reaktion als auch einer veränderten Stress-Antwort und damit an der Ätiologie und Pathogenese verschiedener neuropsychiatrischer Erkrankungen beteiligt. Dies wird sowohl durch verhaltenspharmakologische Experimente als auch genetische Studien belegt, wobei jedoch die Einflüsse unterschiedlicher Varianten in Genen, die dem serotonergen System zuzurechnen sind, kontrovers diskutiert werden. Die Untersuchung von Knockout-Mäusen, bei denen ganz gezielt gewebs- und entwicklungsspezifisch Gene des serotonergen Systems ausgeschaltet werden, unterstreicht die wichtige Bedeutung von 5-HT während der Entwicklung und insbesondere hinsichtlich der Entstehung emotionaler Verhaltensweisen. In diesem zweiten Teil des Übersichtsartikels werden neben den tierexperimentellen Studien genetische und pharmakologische Untersuchungen, gepaart mit klinischen Studien, zusammengefasst und kritisch diskutiert. Die Datenlage belegt die komplexen Funktionen von 5-HT, das im Zentrum zahlreicher neurobiologischer Vorgänge steht und weitreichende Implikationen für menschliches Verhalten aufweist. Epigenetische Regulationsmechanismen werden in den kommenden Jahren zunehmend erforscht werden und tragen zur Komplexität des serotonergen Systems bei. Nach wie vor steht daher das 5-HT-System im Mittelpunkt aktueller Hypothesen zur Pathogenese von Erkrankungen mit dem Kernsymptom emotionaler Dysregulation.

Abstract

Several lines of evidence implicate a dysregulation of the serotonin (5-HT) system in emotional behavior and stress, and point to its relevance for the etiology and pathogenesis of various neuropsychiatric disorders. This is evidenced by behavioral pharmacology as well as genetic studies, yet the impact of genetic variation within the 5-HT system on human disorders remains controversial. The generation of tissue-specific and inducible knockout mice lacking genes belonging to the 5-HT system further established the importance of the 5-HT system for neuronal development and the regulation of emotions. This part of the review provides a summary and critical discussion of genetic, neurobiological and pharmacological studies along with recent clinical research. Together, these data underscore the complex effects of 5-HT on human behavior and psychiatric disorders. Epigenetic mechanisms add to the complexity of the 5-HT system and will be increasingly studied in the coming years. Thus, the serotonergic system still remains in the centre of current hypotheses regarding the pathogenesis of disorders with the shared feature of emotional dysregulation.

Schlüsselwörter

Verhalten - Genetik - psychiatrische Erkrankungen - Depression - Tiermodelle

Keywords

behavior - genetic - psychiatric disorders - depression - animal models

1 Die dieser Arbeit zugrundeliegenden Untersuchungen wurden durch die DFG (GK-1156, an CK und KPL, RE1632/1-5 an AR, KFO 125 an AR und KPL; SFB 581 an AS und KPL, SFB TRR 58 an AR und KPL), das BMBF (IZKF Würzburg, 01KS9603, an KPL; IZKF N-27-N, an AR) und die EU (NEWMOOD LSHM-CT-2003-503474, an KPL) gefördert.

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1 Die dieser Arbeit zugrundeliegenden Untersuchungen wurden durch die DFG (GK-1156, an CK und KPL, RE1632/1-5 an AR, KFO 125 an AR und KPL; SFB 581 an AS und KPL, SFB TRR 58 an AR und KPL), das BMBF (IZKF Würzburg, 01KS9603, an KPL; IZKF N-27-N, an AR) und die EU (NEWMOOD LSHM-CT-2003-503474, an KPL) gefördert.