Pharmacogenetics of mood stabilizers

Abstract

Mood stabilizers form a cornerstone in the long-term treatment of bipolar disorder (BD). Along with carbamazepine and valproates, lithium belongs to the first generation of mood stabilizers which appeared in psychiatric treatment in the 1960s. Atypical antipsychotics with mood-stabilizing properties and lamotrigine which were introduced in the mid-1990s form the second generation of such drugs. The main phenotype of the response to mood stabilizers is a degree of prevention against recurrences of manic and depressive episodes during long-term treatment. The vast majority of data on genetic influences on the response to mood stabilizers has been gathered in relation to lithium. The studies on the mechanisms of lithium action and on the neurobiology of bipolar disorder have led to the identification of a number of candidate genes connected with neurotransmitters, second messengers, neuroprotection, circadian rhythms, pathogenesis of BD, and those located on chromosome 22q11-13. There are few published pharmacogenomic studies of other mood stabilizers than lithium, mostly on valproate. In recent years, a number of genome-wide association studies (GWAS) in bipolar disorders have been performed, and some of those have also focused on lithium response. Recently, the first data appeared from the Consortium on Lithium Genetics (ConLiGen) establishing the largest sample, to date, for the GWAS of lithium response in bipolar disorder. The study of 2563 patients collected by 22 participating sites demonstrated an association between lithium response and two long noncoding RNAs located on chromosome 21.