Long-term responsiveness to lithium as a pharmacogenetic outcome variable: treatment and etiologic implications

Abstract

The importance of genes in the etiology of bipolar disorder has been substantiated through family, twin, and adoption studies. Bipolar disorder is treated at the prophylactic and episodic levels; lithium is one of the most common forms of prophylactic treatment. Recently, pharmacogenetics has come to play an active role in the elucidation of genetic factors that may play a role in modulating lithium response. This strategy has provided hope for advancements in understanding the genetics of lithium-responsive bipolar disorder. This review encompasses studies that have used populations of lithium responders and non-responders to carry out family, linkage, or association studies, as well as some insight into possible mechanisms by which lithium produces its prophylactic effect. Although data examining the pharmacogenetics of bipolar disorder remain scarce, this is a promising avenue of investigation to help genetically define more homogeneous populations or to search for genetic predictors of drug response.