Lithium is the most effective prophylactic and therapeutic agent for bipolar disorder, yet we have much still to learn about its mechanisms, report Christina Cruceanau and colleagues in “Lithium: a key to the genetics of bipolar disorder”, a Review article recently published in Genome Medicine.
Bipolar disorder is extremely heterogeneous in terms of susceptibility, symptoms and response to treatment. Genome-wide association studies have revealed many potential susceptibility genes, but their significance is clouded by this extreme phenotypic diversity. It has recently been realized that patients who respond well to the age-old remedy of lithium salts form a useful subgroup for large-scale analysis, sharing a similar disease phenotype with higher heritability of the condition than in the bipolar-affected population as a whole.
Studies of lithium-responders are beginning to unravel some of the complexity surrounding bipolar disorder as well as the mechanisms by which lithium acts. Genome-wide association studies have been followed by candidate gene and microarray analyses, leading to a wide range of disease candidates and drug targets for future study. Knowledge of the molecular pathways affected by lithium may also lead to an understanding of the variable side-effects of this drug. It is clear that new studies of an old therapy hold much promise for the future treatment of bipolar disorder.
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