Pickard Benjamin S
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK.
Neurotherapeutics. 2017 Jul;14(3):582-587. doi: 10.1007/s13311-017-0554-7.
Lithium is the most successful mood stabilizer treatment for bipolar disorder. However, unlike conventional drugs that are designed to interact with a specific molecular target, the actions of lithium are distributed across many biological processes and pathways. Treatment response is subject to genetic variation between individuals and similar genetic variation may dictate susceptibility to side effects. Transcriptomic, genomic, and cell-model research strategies have all been deployed in the search for the genetic factors and biological systems that mediate the interaction between genetics and the therapeutic actions of lithium. In this review, recent findings from genome-wide studies and patient cell lines will be summarized and discussed from a standpoint that genuine progress is being made to define clinically useful mechanisms of this treatment, to place it in the context of bipolar disorder pathology, and to move towards a time when the prescription of lithium is targeted to those individuals who will derive the greatest benefit.
锂是治疗双相情感障碍最成功的心境稳定剂。然而,与旨在与特定分子靶点相互作用的传统药物不同,锂的作用分布于许多生物过程和途径。治疗反应因个体之间的基因变异而异,类似的基因变异可能决定对副作用的易感性。转录组学、基因组学和细胞模型研究策略均已用于寻找介导基因与锂治疗作用之间相互作用的遗传因素和生物系统。在本综述中,将从正在取得实质性进展以确定该治疗的临床有用机制、将其置于双相情感障碍病理学背景下以及朝着锂的处方针对将获得最大益处的个体这一方向发展的角度,总结和讨论全基因组研究及患者细胞系的最新发现。