The Emerging Neurobiology of Bipolar Disorder.
The Emerging Neurobiology of Bipolar Disorder.
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DOI：
10.1016/j.tins.2017.10.006
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发表时间：
2018-01
影响因子：
15.9
通讯作者：
Tunbridge EM
中科院分区：
文献类型：
--
作者：
Harrison PJ;Geddes JR;Tunbridge EM
双相情感障碍(BD)是导致全球残疾的主要原因。其生物学基础尚不清楚，治疗效果也不理想。在这里，我们回顾了最近取得进展的两个领域。首先，风险基因的发现及其意义，重点放在电压门控钙通道作为疾病过程的一部分和作为药物靶点。其次，在新技术的推动下，越来越明显的是，双相情感表型比简单的反复发作的躁狂和抑郁症状更复杂、更细微。其中一个特征是持续的情绪不稳定，目前正在努力了解其机制和治疗潜力。BD展示了当代神经科学、基因组学和数字方法如何改变精神病学。BD是高度可遗传的，主要归因于影响较小的常见变异。已经确定了几个风险基因和基因网络。钙信号在遗传风险途径中是突出的，目前似乎具有最大的治疗牵引力。正在使用数字技术和复杂的数学和计算分析来量化和理解BD。这些新方法反映并正在推动将BD重新定义为情绪和神经回路的慢性不稳定。干细胞正在成为了解BD及其药物治疗方法不可或缺的一部分。新的实验医学模型正在被应用于识别和快速测试潜在的稳定情绪的治疗方法。
Bipolar disorder (BD) is a leading cause of global disability. Its biological basis is unknown, and its treatment unsatisfactory. Here, we review two recent areas of progress. First, the discovery of risk genes and their implications, with a focus on voltage-gated calcium channels as part of the disease process and as a drug target. Second, facilitated by new technologies, it is increasingly apparent that the bipolar phenotype is more complex and nuanced than simply one of recurring manic and depressive episodes. One such feature is persistent mood instability, and efforts are underway to understand its mechanisms and its therapeutic potential. BD illustrates how psychiatry is being transformed by contemporary neuroscience, genomics, and digital approaches. BD is highly heritable and mostly attributable to common variants of small effect. Several risk genes and gene networks have been identified. Calcium signalling is prominent among the genetic risk pathways, and currently appears to have the greatest therapeutic traction. Digital technologies and sophisticated mathematical and computational analyses are being used to quantify and understand BD. These new methods reflect, and are promoting, reconceptualisation of BD as a chronic instability of mood and neural circuitry. Stem cells are becoming an integral part of the approaches to understanding BD and its pharmacotherapy. New experimental medicine models are being applied to identify and rapidly test potential mood-stabilising treatments.
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影响因子：
25
作者：
Breen G;Li Q;Roth BL;O'Donnell P;Didriksen M;Dolmetsch R;O'Reilly PF;Gaspar HA;Manji H;Huebel C;Kelsoe JR;Malhotra D;Bertolino A;Posthuma D;Sklar P;Kapur S;Sullivan PF;Collier DA;Edenberg HJ
通讯作者：
Edenberg HJ
DOI：
10.1113/jp272262
发表时间：
2016-10-01
期刊：
The Journal of physiology
影响因子：
--
作者：
Dolphin AC
通讯作者：
Dolphin AC
影响因子：
11
作者：
Cipriani, A.;Saunders, K.;Attenburrow, M-J;Stefaniak, J.;Panchal, P.;Stockton, S.;Lane, T. A.;Tunbridge, E. M.;Geddes, J. R.;Harrison, P. J.
通讯作者：
Harrison, P. J.
DOI：
10.1073/pnas.1424958112
发表时间：
2015-03-17
影响因子：
11.1
作者：
Ament, Seth A.;Szelinger, Szabolcs;Roach, Jared C.
通讯作者：
Roach, Jared C.
DOI：
10.1073/pnas.1404082111
发表时间：
2014-07-01
影响因子：
11.1
作者：
Dixson, Luanna;Walter, Henrik;Meyer-Lindenberg, Andreas
通讯作者：
Meyer-Lindenberg, Andreas