Clinical, genetic, and epigenetic markers associated with lithium response in bipolar disorder

Abstract

Bipolar disorder is a chronic and common psychiatric disease that causes poor quality of life and loss of functionality. Although lithium remains in the first place in the acute mania and maintenance treatment of bipolar disorder, its mechanism of action is still unclear. In addition, the response to lithium varies widely among patients. Up to 30-55% of patients with bipolar disorder do not benefit from lithium treatment or experience side effects that cause them to discontinue the treatment. As a result of the studies carried out to date, some clinical variables that predict the difference in lithium response among individuals have been identified, but consistent results have not been obtained. Difficulties in detecting lithium response over clinical variables, lack of consistent peripheral and neuroimaging markers, and familial clustering of the disease and treatment response led researchers to conduct genetic studies. Researchers have primarily focused on candidate gene studies. However, whole genome association studies have begun to be performed due to the inadequacy of candidate gene studies in detecting the lithium response, which is estimated to be polygenic. Data on lithium response and some single nucleotide polymorphisms, noncoding RNAs, and polygenic risk score associations were acquired from these studies. Recently, researchers have been working to elucidate the epigenetic mechanisms involved in gene-environment interaction. In this article, both clinical features and both prominent genetic and epigenetic markers associated with lithium response are reviewed and critical points that should be considered in future research are emphasized.

Keywords

• lithium
• bipolar disorder
• genetic
• epigenetic
• biomarker