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. We demonstrated that response to
lithium has been connected with the genotype of
BDNF gene and serum
BDNF levels and have shown that ELR have normal cognitive functions and serum
BDNF levels, even after long-term duration of the illness. A number of genome-wide association studies (GWAS) of BD have been also performed in recent years, some of which also focused on
lithium response. The Consortium on
Lithium Genetics (ConLiGen) has established the large sample for performing the genome-wide association study (GWAS) of
lithium response in BD, and the first results have already been published.