Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting the patients' responsiveness to lithium.
Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting the patients' responsiveness to lithium.
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来自双相情感障碍患者的神经元分为本质上不同的神经元亚群，预测患者对锂的反应
DOI：
10.1038/mp.2016.260
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发表时间：
2018-06
影响因子：
11
通讯作者：
Gage FH
中科院分区：
文献类型：
--
作者：
Stern S;Santos R;Marchetto MC;Mendes APD;Rouleau GA;Biesmans S;Wang QW;Yao J;Charnay P;Bang AG;Alda M;Gage FH
双相情感障碍（BD）是一种渐进式精神病，在全球范围内，患病率超过3％。动物和细胞模型的发展。 BD患者的干细胞（IPSC）衍生的成纤维细胞是电生理学过度的。 . Lymphocytes are readily available for research with a large number of banked lines with associated patient clinical description. We used whole-cell贴片钳记录超过460个神经元来表征来自对照个体和BD患者的神经元。患者和源自李 - 非反应性（NR）患者的患者，这使我们将BD神经元分为两个细胞的亚群，并建议两种不同的细分。 ，两个神经元的种群共享一个大的，快速的后载体（AHP）。 BD的特征和BD神经元快速，持续的尖峰能力的主要贡献，它证实了我们先前的成纤维细胞衍生的DG神经元的报告，慢性LI治疗可降低淋巴细胞的过度症BD的这种新的人类细胞模型的有效性和实用性。
Bipolar disorder (BD) is a progressive psychiatric disorder with more than 3% prevalence worldwide. Affected individuals experience recurrent episodes of depression and mania, disrupting normal life and increasing the risk of suicide greatly. The complexity and genetic heterogeneity of psychiatric disorders have challenged the development of animal and cellular models. We recently reported that hippocampal dentate gyrus (DG) neurons differentiated from induced pluripotent stem cell (iPSC)-derived fibroblasts of BD patients are electrophysiologically hyperexcitable. Here we used iPSCs derived from Epstein–Barr virus-immortalized B-lymphocytes to verify that the hyperexcitability of DG-like neurons is reproduced in this different cohort of patients and cells. Lymphocytes are readily available for research with a large number of banked lines with associated patient clinical description. We used whole-cell patch-clamp recordings of over 460 neurons to characterize neurons derived from control individuals and BD patients. Extensive functional analysis showed that intrinsic cell parameters are very different between the two groups of BD neurons, those derived from lithium (Li)-responsive (LR) patients and those derived from Li-non-responsive (NR) patients, which led us to partition our BD neurons into two sub-populations of cells and suggested two different subdisorders. Training a Naïve Bayes classifier with the electrophysiological features of patients whose responses to Li are known allows for accurate classification with more than 92% success rate for a new patient whose response to Li is unknown. Despite their very different functional profiles, both populations of neurons share a large, fast after-hyperpolarization (AHP). We therefore suggest that the large, fast AHP is a key feature of BD and a main contributor to the fast, sustained spiking abilities of BD neurons. Confirming our previous report with fibroblast-derived DG neurons, chronic Li treatment reduced the hyperexcitability in the lymphoblast-derived LR group but not in the NR group, strengthening the validity and utility of this new human cellular model of BD.
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影响因子：
30.8
作者：
Ferreira, Manuel A. R.;O'Donovan, Michael C.;Meng, Yan A.;Jones, Ian R.;Ruderfer, Douglas M.;Jones, Lisa;Fan, Jinbo;Kirov, George;Perlis, Roy H.;Green, Elaine K.;Smoller, Jordan W.;Grozeva, Detelina;Stone, Jennifer;Nikolov, Ivan;Chambert, Kimberly;Hamshere, Marian L.;Nimgaonkar, Vishwajit L.;Moskvina, Valentina;Thase, Michael E.;Caesar, Sian;Sachs, Gary S.;Franklin, Jennifer;Gordon-Smith, Katherine;Ardlie, Kristin G.;Gabriel, Stacey B.;Fraser, Christine;Blumenstiel, Brendan;Defelice, Matthew;Breen, Gerome;Gill, Michael;Morris, Derek W.;Elkin, Amanda;Muir, Walter J.;McGhee, Kevin A.;Williamson, Richard;MacIntyre, Donald J.;MacLean, Alan W.;Clair, David St;Robinson, Michelle;Van Beck, Margaret;Pereira, Ana C. P.;Kandaswamy, Radhika;McQuillin, Andrew;Collier, David A.;Bass, Nicholas J.;Young, Allan H.;Lawrence, Jacob;Ferrier, I. Nicol;Anjorin, Adebayo;Farmer, Anne;Curtis, David;Scolnick, Edward M.;McGuffin, Peter;Daly, Mark J.;Corvin, Aiden P.;Holmans, Peter A.;Blackwood, Douglas H.;Gurling, Hugh M.;Owen, Michael J.;Purcell, Shaun M.;Sklar, Pamela;Craddock, Nick
通讯作者：
Craddock, Nick
影响因子：
20.3
作者：
Choi, Su Mi;Liu, Hua;Jang, Yoon-Young
通讯作者：
Jang, Yoon-Young
影响因子：
168.9
作者：
Craddock, Nick;Sklar, Pamela
通讯作者：
Sklar, Pamela
影响因子：
5.3
作者：
Hirschfeld, RMA;Calabrese, JR;Wagner, KD
通讯作者：
Wagner, KD
影响因子：
--
作者：
Cotter, D;Mackay, D;Everall, I
通讯作者：
Everall, I