Harrison Paul J
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, United Kingdom.
Curr Opin Neurobiol. 2016 Feb;36:1-6. doi: 10.1016/j.conb.2015.07.002. Epub 2015 Jul 25.
Bipolar disorder is a serious psychiatric disorder, with a high heritability and unknown pathogenesis. Recent genome-wide association studies have identified the first loci, implicating genes such as CACNA1C and ANK3. The genes highlight several pathways, notably calcium signalling, as being of importance. Molecular studies suggest that the risk variants impact on gene regulation and expression. Preliminary studies using reprogrammed patient-derived cells report alterations in the transcriptome and in cellular adhesion and differentiation. Mouse models show that genes involved in circadian biology, acting via dopaminergic effects, reproduce aspects of the bipolar phenotype. These findings together represent significant advances in identification of the genetic and molecular basis of bipolar disorder, yet we are still far from an integrated, evidence-based understanding of its aetiopathogenesis.
双相情感障碍是一种严重的精神疾病，具有高度遗传性且发病机制不明。最近的全基因组关联研究已经确定了首批基因座，涉及如CACNA1C和ANK3等基因。这些基因突显了几个重要途径，尤其是钙信号传导途径。分子研究表明，风险变异体影响基因调控和表达。使用重编程的患者来源细胞进行的初步研究报告了转录组以及细胞黏附和分化方面的改变。小鼠模型显示，参与昼夜节律生物学的基因通过多巴胺能效应发挥作用，重现了双相情感障碍表型的某些方面。这些发现共同代表了在双相情感障碍遗传和分子基础识别方面的重大进展，但我们距离对其病因发病机制形成全面的、基于证据的理解仍有很大差距。
