Lithium effects on serine-threonine kinases activity: High throughput kinomic profiling of lymphoblastoid cell lines from excellent-responders and non-responders bipolar patients.

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.