Treatment resistant depression: A multi-scale, systems biology approach.
Treatment resistant depression: A multi-scale, systems biology approach.
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DOI：
10.1016/j.neubiorev.2017.08.019
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发表时间：
2018-01
影响因子：
8.2
通讯作者：
Nestler EJ
中科院分区：
文献类型：
--
作者：
Akil H;Gordon J;Hen R;Javitch J;Mayberg H;McEwen B;Meaney MJ;Nestler EJ
据估计，50%的抑郁症患者没有得到充分的治疗。即使最终康复，许多患者也需要试错法，因为没有可靠的指导方针将患者与最佳治疗相匹配，而且许多患者随着时间的推移会产生治疗抵抗。这种情况源于抑郁症的异质性和缺乏不同抑郁症亚型分层的生物标志物。因此，迫切需要新的疗法。为了解决这些已知的挑战，我们提出了一个多尺度的框架，用于抑郁症的基础研究，旨在确定在几种抑郁症动物模型中功能失调的脑回路，以及与这些模型相关的基因表达的变化。当与人类遗传和成像研究相结合时，我们的临床前研究开始识别在疾病模型和患者群体中改变的候选电路和分子。针对这些回路和机制可以产生新一代的抗抑郁药，针对具有独特类型的分子和回路功能障碍的特定患者群体。
An estimated 50% of depressed patients are inadequately treated by available interventions. Even with an eventual recovery, many patients require a trial and error approach, as there are no reliable guidelines to match patients to optimal treatments and many patients develop treatment resistance over time. This situation derives from the heterogeneity of depression and the lack of biomarkers for stratification by distinct depression subtypes. There is thus a dire need for novel therapies. To address these known challenges, we propose a multi-scale framework for fundamental research on depression, aimed at identifying the brain circuits that are dysfunctional in several animal models of depression as well the changes in gene expression that are associated with these models. When combined with human genetic and imaging studies, our preclinical studies are starting to identify candidate circuits and molecules that are altered both in models of disease and in patient populations. Targeting these circuits and mechanisms can lead to novel generations of antidepressants tailored to specific patient populations with distinctive types of molecular and circuit dysfunction.
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影响因子：
11
作者：
Bessa, J. M.;Ferreira, D.;Sousa, N.
通讯作者：
Sousa, N.
影响因子：
11
作者：
通讯作者：
--
影响因子：
9.2
作者：
Cai, Na;Chang, Simon;Li, Yihan;Li, Qibin;Hu, Jingchu;Liang, Jieqin;Song, Li;Kretzschmar, Warren;Gan, Xiangchao;Nicod, Jerome;Rivera, Margarita;Deng, Hong;Du, Bo;Li, Keqing;Sang, Wenhu;Gao, Jingfang;Gao, Shugui;Ha, Baowei;Ho, Hung-Yao;Hu, Chunmei;Hu, Jian;Hu, Zhenfei;Huang, Guoping;Jiang, Guoqing;Jiang, Tao;Jin, Wei;Li, Gongying;Li, Kan;Li, Yi;Li, Yingrui;Li, Youhui;Lin, Yu-Ting;Liu, Lanfen;Liu, Tiebang;Liu, Ying;Liu, Yuan;Lu, Yao;Lv, Luxian;Meng, Huaqing;Qian, Puyi;Sang, Hong;Shen, Jianhua;Shi, Jianguo;Sun, Jing;Tao, Ming;Wang, Gang;Wang, Guangbiao;Wang, Jian;Wang, Linmao;Wang, Xueyi;Wang, Xumei;Yang, Huanming;Yang, Lijun;Yin, Ye;Zhang, Jinbei;Zhang, Kerang;Sun, Ning;Zhang, Wei;Zhang, Xiuqing;Zhang, Zhen;Zhong, Hui;Breen, Gerome;Wang, Jun;Marchini, Jonathan;Chen, Yiping;Xu, Qi;Xu, Xun;Mott, Richard;Huang, Guo-Jen;Kendler, Kenneth;Flintl, Jonathan
通讯作者：
Flintl, Jonathan
影响因子：
56.9
作者：
Ansorge, MS;Zhou, MM;Gingrich, JA
通讯作者：
Gingrich, JA
腹侧海马传入伏隔核调节抑郁的易感性。
影响因子：
16.6
作者：
Bagot, Rosemary C.;Parise, Eric M.;Pena, Catherine J.;Zhang, Hong-Xing;Maze, Ian;Chaudhury, Dipesh;Persaud, Brianna;Cachope, Roger;Bolanos-Guzman, Carlos A.;Cheer, Joseph;Deisseroth, Karl;Han, Ming-Hu;Nestler, Eric J.
通讯作者：
Nestler, Eric J.