Differential gene expression profiles due to lithium and bipolar disorder

Many pharmacological compounds including mood-stabilizers have been shown to regulate gene expression suggesting that use of drugs to modulate transcription may be a worth-while strategy in the future design of novel therapeutic agents. We used the Affymetrix GeneChip probe arrays, which currently targets ∼7000 human genes, to monitor differential gene expression following in vitro clinically-relevant lithium (Li) treatment in lymphocyte-derived human cell lines from three clinically-defined groups: control subjects, bipolar patients who respond to Li treatment (BP Li R) and bipolar patients who are Li non-responders (BP Li NR). Chronic in vitro Li treatment led to significant differences in gene expression profiles between diagnostic groups. The number of genes upregulated, and the magnitude of the messenger RNA change, was greatest in cell lines from BP Li R. Additionally, transcriptional changes were detected for many genes not previously known to be modulated by this ion and pertinent both to known side effects and Li's therapeutic efficacy. This study shows that a genomic view of Li's actions can bring clarity to the molecular basis of this ion's clinical actions and pinpoints many new targets that may prove to be potential targets for mood-stabilizing drugs.