Jeverson Moreira1, Gaëlle Noé2,3, Savithri Rangarajan4, Cindie Courtin1, Bruno Etain1,5,6, Pierre A Geoffroy1,5,6, Jean-Louis Laplanche1,7, Michel Vidal2,3, Frank Bellivier1,5,6, Cynthia Marie-Claire1. 1. Variabilité de réponse aux psychotropes, INSERM U1144/Faculté de Pharmacie de Paris, Université Paris Descartes, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. 2. AP-HP, Hôpital Cochin, Biologie du medicament-Toxicologie, Université Paris Descartes, Paris, France. 3. UMR8638 CNRS, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 4. PamGene International BV, 's-Hertogenbosch, The Netherlands. 5. AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, Paris, France. 6. Fondation FondaMental, Créteil, France. 7. Département de Biochimie and Biologie moléculaire, AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Paris, France.
Abstract
Objectives: 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. In vitro and in vivo molecular studies have reported the implication of kinases in the pathophysiology of BD. Methods: 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. Results: 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.Conclusions: 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.
Objectives: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. In vitro and in vivo molecular studies have reported the implication of kinases in the pathophysiology of BD. Methods: 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. Results: 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.Conclusions: 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.