Institute of Psychiatry, University of Bologna, Bologna, Italy.
Neuropsychobiology. 2010;62(1):61-71. doi: 10.1159/000314311. Epub 2010 May 7.
Bipolar disorder is a common disease with a high impact in terms of personal suffering and socioeconomic burden. The disentanglement of the molecular deregulations that cause this disorder is pivotal to the understanding of its etiology. This will hopefully cast the engineering of new and more favorable treatments. New insights in the molecular aspects of bipolar disorder may be brought by the understanding of the pharmacodynamics of lithium, the first-line treatment for this disease. The mechanisms by which lithium exerts its activity in the central nervous system are not fully clarified: it is hypothesized that lithium may drive acute molecular events whose activation over time triggers long-lasting modifications in critical neuronal nets. These events are associated with long-lasting changes in the expression profile of genes in neurons that are embedded in these crucial nets. The molecular events that are acutely and chronically triggered by lithium will be reviewed here and matched with the evidence that arises from the pharmacogenetics investigations. Moreover, the pharmacogenetics reports that are not strictly associated with the mechanisms that are thought to be acutely and chronically elicited by lithium will be included in the final part of the paper.
双相情感障碍是一种常见疾病，其对个人痛苦和社会经济负担都有很大影响。解开导致这种疾病的分子失调的谜团对于理解其病因至关重要。这有望为新的、更有利的治疗方法的开发奠定基础。通过了解锂的药效动力学，即这种疾病的一线治疗方法，可能会带来对双相情感障碍分子方面的新认识。锂在中枢神经系统中发挥作用的机制尚未完全阐明：据推测，锂可能会引发急性分子事件，这些事件随着时间的推移激活，从而触发关键神经元网络的持久改变。这些事件与嵌入这些关键网络中的神经元中基因表达谱的持久变化有关。本文将回顾锂急性和慢性触发的分子事件，并将其与来自药物遗传学研究的证据相匹配。此外，本文还将包括与锂被认为急性和慢性引发的机制没有严格关联的药物遗传学报告。
