Academic Department of Psychiatry, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, 2065, Australia.
Sydney Medical School Northern, The University of Sydney, Sydney, NSW, 2006, Australia.
CNS Drugs. 2016 Oct;30(10):931-49. doi: 10.1007/s40263-016-0380-1.
Lithium is the most effective and well established treatment for bipolar disorder, and it has a broad array of effects within cellular pathways. However, the specific processes through which therapeutic effects occur and are maintained in bipolar disorder remain unclear. This paper provides a timely update to an authoritative review of pertinent findings that was published in CNS Drugs in 2013. A literature search was conducted using the Scopus database, and was limited by year (from 2012). There has been a resurgence of interest in lithium therapy mechanisms, perhaps driven by technical advancements in recent years that permit the examination of cellular mechanisms underpinning the effects of lithium-along with the reuptake of lithium in clinical practice. Recent research has further cemented glycogen synthase kinase 3β (GSK3β) inhibition as a key mechanism, and the inter-associations between GSK3β-mediated neuroprotective, anti-oxidative and neurotransmission mechanisms have been further elucidated. In addition to highly illustrative cellular research, studies examining higher-order biological systems, such as circadian rhythms, as well as employing innovative animal and human models, have increased our understanding of how lithium-induced changes at the cellular level possibly translate to changes at behavioural and clinical levels. Neural circuitry research is yet to identify clear mechanisms of change in bipolar disorder in response to treatment with lithium, but important structural findings have demonstrated links to the modulation of cellular mechanisms, and peripheral marker and pharmacogenetic studies are showing promising findings that will likely inform the exploration for predictors of lithium treatment response. With a deeper understanding of lithium's therapeutic mechanisms-from the cellular to clinical levels of investigation-comes the opportunity to develop predictive models of lithium treatment response and identify novel drug targets, and recent findings have provided important leads towards these goals.
锂是治疗双相情感障碍最有效和最成熟的治疗方法，它在细胞途径中有广泛的作用。然而，在双相情感障碍中，治疗效果发生和维持的具体过程仍不清楚。本文为 2013 年 CNS 药物发表的一篇权威综述提供了及时的更新。使用 Scopus 数据库进行了文献检索，并且受到年份的限制（2012 年起）。近年来，技术进步使得人们对锂治疗机制的兴趣重新燃起，也许是因为近年来技术进步使得人们能够检查锂作用的细胞机制以及临床实践中锂的再摄取。最近的研究进一步证实了糖原合成酶激酶 3β（GSK3β）抑制是一种关键机制，并且 GSK3β 介导的神经保护、抗氧化和神经递质传递机制之间的相互关联也得到了进一步阐明。除了具有高度说明性的细胞研究外，研究人员还检查了更高阶的生物系统，如昼夜节律，以及采用创新的动物和人类模型，这增加了我们对锂在细胞水平上引起的变化如何可能转化为行为和临床水平变化的理解。神经回路研究尚未确定锂治疗双相情感障碍的明确变化机制，但重要的结构发现表明与细胞机制的调节有关，外周标志物和遗传药理学研究正在显示出有希望的发现，这些发现可能为探索锂治疗反应的预测因子提供信息。随着对锂治疗机制的深入了解——从细胞水平到临床水平的研究——为开发锂治疗反应的预测模型和确定新的药物靶点提供了机会，最近的发现为实现这些目标提供了重要线索。
