Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv , Israel.
Genetics Unit, IRCCS, San Giovanni di Dio, Fatebenefratelli , Brescia , Italy.
World J Biol Psychiatry. 2019 Jul;20(6):449-461. doi: 10.1080/15622975.2017.1372629. Epub 2017 Sep 22.
Lithium remains the oldest and most effective treatment for mood stabilisation in bipolar disorder (BD), even though at least half of patients are only partially responsive or do not respond. This study aimed to identify biomarkers associated with lithium response in BD, based on comparing RNA sequencing information derived from lymphoblastoid cell lines (LCLs) of lithium-responsive (LR) versus lithium non-responsive (LNR) BD patients, to assess gene expression variations that might bear on treatment outcome. RNA sequencing was carried out on 24 LCLs from female BD patients (12 LR and 12 LNR) followed by qPCR validation in two additional independent cohorts (41 and 17 BD patients, respectively). Fifty-six genes showed nominal differential expression comparing LR and LNR (FC ≥ |1.3|, ≤ 0.01). The differential expression of and was validated by qPCR in the independent cohorts. We observed higher expression levels of and in BD patients who favourably respond to lithium. Both of these genes are involved in neurogenesis, and has been suggested to be a neurotrophic factor. Additional studies in larger BD cohorts are needed to confirm the potential of and expression levels in blood cells as tentative favourable lithium response biomarkers.
锂仍然是双相情感障碍（BD）情绪稳定的最古老和最有效的治疗方法，尽管至少有一半的患者只有部分反应或没有反应。本研究旨在根据比较锂反应（LR）与锂非反应（LNR）BD 患者的淋巴母细胞系（LCL）的 RNA 测序信息，确定与锂反应相关的生物标志物，以评估可能影响治疗结果的基因表达变化。对 24 名来自女性 BD 患者（12 名 LR 和 12 名 LNR）的 LCL 进行了 RNA 测序，随后在另外两个独立队列（分别为 41 和 17 名 BD 患者）中进行了 qPCR 验证。56 个基因在 LR 和 LNR 之间表现出名义上的差异表达（FC ≥ |1.3|，≤0.01）。qPCR 在独立队列中验证了 和 的差异表达。我们观察到对锂反应良好的 BD 患者中 和 的表达水平较高。这两个基因都参与神经发生，并且 被认为是一种神经营养因子。需要在更大的 BD 队列中进行进一步的研究，以确认血细胞中 和 表达水平作为有希望的锂反应生物标志物的潜力。
