Department of Neuroscience, Section of Pharmacology, Uppsala University, Uppsala, Sweden.
Ups J Med Sci. 2010 Feb;115(1):2-10. doi: 10.3109/03009730903573246.
Brain monoamines, and serotonin in particular, have repeatedly been shown to be linked to different psychiatric conditions such as depression, anxiety, antisocial behaviour, and dependence. Many studies have implicated genetic variability in the genes encoding monoamine oxidase A (MAOA) and the serotonin transporter (5HTT) in modulating susceptibility to these conditions. Paradoxically, the risk variants of these genes have been shown, in vitro, to increase levels of serotonin, although many of the conditions are associated with decreased levels of serotonin. Furthermore, in adult humans, and monkeys with orthologous genetic polymorphisms, there is no observable correlation between these functional genetic variants and the amount or activity of the corresponding proteins in the brain. These seemingly contradictory data might be explained if the association between serotonin and these behavioural and psychiatric conditions were mainly a consequence of events taking place during foetal and neonatal brain development. In this review we explore, based on recent research, the hypothesis that the dual role of serotonin as a neurotransmitter and a neurotrophic factor has a significant impact on behaviour and risk for neuropsychiatric disorders through altered development of limbic neurocircuitry involved in emotional processing, and development of the serotonergic neurons, during early brain development.
脑单胺类物质，尤其是 5-羟色胺，已被反复证明与不同的精神疾病有关，如抑郁症、焦虑症、反社会行为和依赖。许多研究表明，编码单胺氧化酶 A（MAOA）和 5-羟色胺转运体（5HTT）的基因的遗传变异性在调节这些疾病的易感性方面起着重要作用。矛盾的是，这些基因的风险变异体在体外被证明会增加 5-羟色胺的水平，尽管许多疾病与 5-羟色胺水平降低有关。此外，在成年人类和具有同源遗传多态性的猴子中，这些功能性遗传变异体与大脑中相应蛋白质的数量或活性之间没有观察到相关性。如果 5-羟色胺与这些行为和精神疾病之间的关联主要是胎儿和新生儿大脑发育过程中发生的事件的结果，那么这些看似矛盾的数据可能就可以得到解释。在这篇综述中，我们根据最近的研究探讨了这样一种假设，即 5-羟色胺作为神经递质和神经营养因子的双重作用，通过改变与情绪处理相关的边缘神经回路的发育，以及 5-羟色胺能神经元的发育，对行为和神经精神障碍的风险产生重大影响，而这些变化发生在早期大脑发育过程中。
