Lithium Pharmacogenetics: Where Do We Stand?

ABSTRACT

Bipolar disorder (BPD) is a chronic and disabling psychiatric disorder with a prevalence of 0.8–1.2% in the general population. Although lithium is considered the first‐line treatment, a large percentage of patients do not respond sufficiently. Moreover, lithium can induce severe side effects and has poor tolerance and a narrow therapeutic index. The genetics of lithium response has been largely investigated, but findings have so far failed to identify reliable biomarkers to predict clinical response. This has been largely determined by the highly complex phenotipic and genetic architecture of lithium response. To this regard, collaborative initiatives hold the promise to provide robust and standardized methods to disantenagle this complexity, as well as the capacity to collect large samples of patietnts, a crucial requirement to study the genetics of complex phenotypes. The International Consortium on Lithium Genetics (ConLiGen) has recently published the largest study so far on lithium response reporting significant associations for two long noncoding RNAs (lncRNAs). This result provides relevant insights into the pharmacogenetics of lithium supporting the involvement of the noncoding portion of the genome in modulating clinical response. Although a vast body of research is engaged in dissecting the genetic bases of response to lithium, the several drawbacks of lithium therapy have also stimulated multiple efforts to identify new safer treatments. A drug...

Source: Drug Development Research - September 15, 2016 Category: Drugs & Pharmacology Authors: Claudia Pisanu, Carla Melis, Alessio Squassina Tags: Review Article Source Type: research