Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA.
Pharmacogenomics. 2010 Oct;11(10):1439-65. doi: 10.2217/pgs.10.127.
Bipolar disorder (BD) is a serious mental illness with well-established, but poorly characterized genetic risk. Lithium is among the best proven mood stabilizer therapies for BD, but treatment responses vary considerably. Based upon these and other findings, it has been suggested that lithium-responsive BD may be a genetically distinct phenotype within the mood disorder spectrum. This assertion has practical implications both for the treatment of BD and for understanding the neurobiological basis of the illness: genetic variation within lithium-sensitive signaling pathways may confer preferential treatment response, and the involved genes may underlie BD in some individuals. Presently, the mechanism of lithium is reviewed with an emphasis on gene-expression changes in response to lithium. Within this context, findings from genetic-association studies designed to identify lithium response genes in BD patients are evaluated. Finally, a framework is proposed by which future pharmacogenetic studies can incorporate advances in genetics, molecular biology and bioinformatics in a pathway-based approach to predicting lithium treatment response.
双相障碍（BD）是一种严重的精神疾病，具有明确但特征不明显的遗传风险。锂是治疗 BD 的最佳心境稳定剂之一，但治疗反应差异很大。基于这些和其他发现，有人提出锂反应性 BD 可能是心境障碍谱内具有遗传差异的表型。这一断言对 BD 的治疗和理解疾病的神经生物学基础都具有实际意义：锂敏感信号通路内的遗传变异可能赋予优先的治疗反应，而相关基因可能在某些个体中导致 BD。目前，本文重点介绍了锂的作用机制，即基因表达变化对锂的反应。在这方面，评估了旨在确定 BD 患者锂反应基因的遗传关联研究的结果。最后，提出了一个框架，通过该框架，未来的药物遗传学研究可以将遗传学、分子生物学和生物信息学的进展纳入基于途径的方法，以预测锂治疗反应。
