Kriegebaum C, Gutknecht L, Schmitt A, Lesch K-P, Reif A
Klinik für Psychiatrie, Psychosomatik und Psychotherapie, Universität Würzburg.
Fortschr Neurol Psychiatr. 2010 Jun;78(6):332-42. doi: 10.1055/s-0029-1245250. Epub 2010 Mar 9.
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.
多条证据表明血清素(5-羟色胺,5-HT)系统功能失调与情绪行为及应激有关,并指出其与多种神经精神疾病的病因和发病机制相关。行为药理学及遗传学研究均证实了这一点,然而,5-HT系统内的基因变异对人类疾病的影响仍存在争议。缺乏5-HT系统相关基因的组织特异性及诱导性敲除小鼠的产生,进一步证实了5-HT系统对神经元发育及情绪调节的重要性。本综述的这一部分对遗传学、神经生物学和药理学研究以及近期的临床研究进行了总结和批判性讨论。这些数据共同强调了5-HT对人类行为和精神疾病的复杂影响。表观遗传机制增加了5-HT系统的复杂性,未来几年将对其进行更多研究。因此,血清素能系统仍然是目前关于具有情绪调节失调这一共同特征的疾病发病机制假说的核心。