Microarray analysis of the leukocyte global gene expression profile following lithium treatment

To further development of our gene expression approach to lithium pharmacodynamics, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish lithium pharmacodynamics across an exposure range relevant for medical decision-making in lithium therapy. 8 healthy male subjects participated in this study. Lithium was prescribed for 2 weeks, enough to reach a therapeutic serum concentration (0.6-1.0mM). Leukocyte counts and serum lithium concentrations were determined at baseline (before medication), after 1 week and 2 weeks medication and post-2-weeks (2 weeks after stopping medication). Gene expression profiling was performed at each time point using Agilent G4112F Whole Human Genome arrays containing approximately 44,000 probe sets. Some of the candidate gene expressions were also determined by real-time PCR. Lithium-induced gene expression in human blood was measured at baseline, after 1 week and 2 weeks of treatment, and after 2 weeks after stopping medication. 4 independent experiments were performed (baseline, 1wk, 2wk, after 2wk) using mixed samples from each donor.