Beech R D, Leffert J J, Lin A, Sylvia L G, Umlauf S, Mane S, Zhao H, Bowden C, Calabrese J R, Friedman E S, Ketter T A, Iosifescu D V, Reilly-Harrington N A, Ostacher M, Thase M E, Nierenberg A
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Keck Foundation Biotechnology Biostatistics Resource, Yale University School of Medicine, New Haven, CT, USA.
Pharmacogenomics J. 2014 Apr;14(2):182-91. doi: 10.1038/tpj.2013.16. Epub 2013 May 14.
This study was designed to identify genes whose expression in peripheral blood may serve as early markers for treatment response to lithium (Li) in patients with bipolar disorder. Although changes in peripheral blood gene-expression may not relate directly to mood symptoms, differences in treatment response at the biochemical level may underlie some of the heterogeneity in clinical response to Li. Subjects were randomized to treatment with (n=28) or without (n=32) Li. Peripheral blood gene-expression was measured before and 1 month after treatment initiation, and treatment response was assessed after 6 months. In subjects treated with Li, 62 genes were differentially regulated in treatment responders and non-responders. Of these, BCL2L1 showed the greatest difference between Li responders and non-responders. These changes were specific to Li responders (n=9), and were not seen in Li non-responders or patients treated without Li, suggesting that they may have specific roles in treatment response to Li.
本研究旨在鉴定其在外周血中的表达可作为双相情感障碍患者对锂（Li）治疗反应的早期标志物的基因。尽管外周血基因表达的变化可能与情绪症状无直接关联，但生化水平上治疗反应的差异可能是对Li临床反应异质性的部分原因。受试者被随机分为接受Li治疗组（n = 28）或未接受Li治疗组（n = 32）。在治疗开始前及开始后1个月测量外周血基因表达，并在6个月后评估治疗反应。在接受Li治疗的受试者中，62个基因在治疗反应者和无反应者中存在差异调节。其中，BCL2L1在Li反应者和无反应者之间表现出最大差异。这些变化是Li反应者（n = 9）特有的，在Li无反应者或未接受Li治疗的患者中未观察到，表明它们可能在对Li的治疗反应中具有特定作用。
