Moreira Jeverson, Noé Gaëlle, Rangarajan Savithri, Courtin Cindie, Etain Bruno, Geoffroy Pierre A, Laplanche Jean-Louis, Vidal Michel, Bellivier Frank, Marie-Claire Cynthia
Variabilité de réponse aux psychotropes, INSERM U1144/Faculté de Pharmacie de Paris, Université Paris Descartes, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
AP-HP, Hôpital Cochin, Biologie du medicament-Toxicologie, Université Paris Descartes, Paris, France.
World J Biol Psychiatry. 2020 Apr;21(4):317-324. doi: 10.1080/15622975.2018.1487078. Epub 2018 Jul 23.
Lithium is the leading mood stabiliser for maintenance treatment in bipolar disorder (BD). However, response to lithium is heterogeneous with more than 60% of patients experiencing partial or no response. and molecular studies have reported the implication of kinases in the pathophysiology of BD. Since kinases are putative targets for lithium therapeutic action, we conducted the first pilot study using kinase array technology to evaluate the global serine/threonine kinases (STK) profiles in cell lines from BD I subtype patients classified as lithium excellent-responders (ER) and non-responder (NR) to lithium treatment. We found significant differences in the basal STK profiles between ER and NR to lithium. We also tested lithium influence on the global STK profile and found no significant difference between ER vs NR cell lines. The results obtained in this exploratory study suggest that multiplex kinase activity profiling could provide a complementary approach in the study of biomarkers of therapeutic response in BD.
锂是双相情感障碍（BD）维持治疗中主要的心境稳定剂。然而，对锂的反应存在异质性，超过60%的患者出现部分反应或无反应。分子研究报道激酶参与了双相情感障碍的病理生理学过程。由于激酶是锂治疗作用的假定靶点，我们开展了第一项试点研究，使用激酶阵列技术评估来自双相I型亚型患者的细胞系中全球丝氨酸/苏氨酸激酶（STK）谱，这些患者被分类为对锂治疗的优秀反应者（ER）和无反应者（NR）。我们发现锂反应者和无反应者之间的基础STK谱存在显著差异。我们还测试了锂对全球STK谱的影响，发现反应者与无反应者细胞系之间没有显著差异。在这项探索性研究中获得的结果表明，多重激酶活性分析可为双相情感障碍治疗反应生物标志物的研究提供一种补充方法。
