Alda M
1] Department of Psychiatry, Dalhousie University, Halifax, NS, Canada [2] Department of Psychiatry and Medical Psychology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Mol Psychiatry. 2015 Jun;20(6):661-70. doi: 10.1038/mp.2015.4. Epub 2015 Feb 17.
After decades of research, the mechanism of action of lithium in preventing recurrences of bipolar disorder remains only partially understood. Lithium research is complicated by the absence of suitable animal models of bipolar disorder and by having to rely on in vitro studies of peripheral tissues. A number of distinct hypotheses emerged over the years, but none has been conclusively supported or rejected. The common theme emerging from pharmacological and genetic studies is that lithium affects multiple steps in cellular signaling, usually enhancing basal and inhibiting stimulated activities. Some of the key nodes of these regulatory networks include GSK3 (glycogen synthase kinase 3), CREB (cAMP response element-binding protein) and Na(+)-K(+) ATPase. Genetic and pharmacogenetic studies are starting to generate promising findings, but remain limited by small sample sizes. As full responders to lithium seem to represent a unique clinical population, there is inherent value and need for studies of lithium responders. Such studies will be an opportunity to uncover specific effects of lithium in those individuals who clearly benefit from the treatment.
经过数十年的研究，锂盐预防双相情感障碍复发的作用机制仍仅得到部分理解。双相情感障碍缺乏合适的动物模型，且不得不依赖外周组织的体外研究，这使得锂盐研究变得复杂。多年来出现了一些不同的假说，但没有一个得到确凿的支持或否定。药理学和遗传学研究中出现的共同主题是，锂盐影响细胞信号传导的多个步骤，通常增强基础活性并抑制刺激后的活性。这些调节网络的一些关键节点包括糖原合酶激酶3（GSK3）、环磷酸腺苷反应元件结合蛋白（CREB）和钠钾ATP酶。遗传学和药物遗传学研究开始产生有前景的发现，但仍受样本量小的限制。由于对锂盐完全反应者似乎代表一个独特的临床群体，对锂盐反应者进行研究具有内在价值和必要性。这类研究将为揭示锂盐对那些明显从治疗中获益的个体的特定作用提供契机。
