Lithium Response Variability: New Avenues and Hypotheses

Abstract

Future research directions that may improve the prediction of lithium response are reviewed, likely to open new avenues for identifying predictive biomarkers of the prophylactic response of lithium, thus facilitating the development of personalized therapeutic strategies. Lithium is the leading treatment for relapse prevention in bipolar disorders, but response prediction remains an important challenge for clinicians. Clinical predictors have poor sensitivity and specificity, and biomarkers predicting lithium response are lacking. This chapter reviews future research directions that may improve the prediction of lithium response. One important area for research is investigation of the blood and brain pharmacokinetics of lithium in humans, in particular the identification of the brain regions where lithium exerts its therapeutic action. Consistent data suggest the existence of variations in the lithium concentration between brain regions, but the association between brain lithium distribution and therapeutic response remains to be studied. It is also reasonable to think that active mechanisms at brain barriers underlie the brain distribution of lithium. Finally, a growing body of scientific data is available on the molecular signature of the lithium response, as well as lithium-targeted signalling pathways. All these areas of research are likely to open new avenues for identifying predictive biomarkers of the prophylactic response of lithium, thus facilitating the development of personalized therapeutic strategies.