Response to Lithium in Bipolar Disorder: Clinicaland Genetic Findings

摘要

The use of lithium is a cornerstone for preventing recurrences in bipolar disorder (BD). The response of patients with bipolar disorder to lithium has different levels of magnitude. About one-third of lithium-treated patients are excellent lithium responders (ELR), showing total prevention of the episodes. A number of clinical characteristics were delineated in patients with favorable response to lithium as regards to clinical course, family history of mood disorders, and psychiatric comorbidity. We have also demonstrated that temperamental features of hypomania (a hyperthymic temperament) and a lack of cognitive disorganization predict the best results of lithium prophylaxis. A degree of prevention against manic and depressive episodes has been regarded as an endophenotype for pharmacogenetic studies. The majority of data have been gathered from so-called “candidate” gene studies. The candidates were selected on the basis of neurobiology of bipolar disorder and mechanisms of lithium action including, among others, neurotransmission, intracellular signaling, neuroprotection or circadian rhythms. Wedemonstrated that response to lithium has been connected with thegenotype of BDNF gene and serum BDNF levels and haveshown that ELR have normal cognitive functions and serum BDNF levels,even after long-term duration of the illness. A number of genome-wideassociation studies (GWAS) of BD have been also performed in recentyears, some of which also focused on lithium response. The Consortiumon Lithium Genetics (ConLiGen) has established the large sample forperforming the genome-wide association study (GWAS) of lithium responsein BD, and the first results have already been published.