Lithium pharmacogenetics. Two decades of studies

Abstract

Pharmacogenetic research aims to elucidate associations of genetic variants and individual effects of pharmacotherapy. Personalised expected response to medications might be useful in prognosis for polygenetically determined disorders. In bipolar disorder (BP), that is partly hereditary polygenic disorder, a subgroup of patients excellently responding to lithium prophylaxis was described. During the last 20 years molecular technology allowed to investigate genome of patients treated with lithium and candidate association studies characterised them more precisely than clinical features. The role of several neurotransmitters’ pathways, second messengers, neuroprotection involved genes and clock genes associations were discovered. Further laboratory technics development enables us to perform genome-wide association studies (GWAS) and polygenic risk score (PRS) analyses. We aimed to review research on genes involved in lithium treatment efficacy and safety. PubMed for English papers, articles published in Polish and reference lists from full-text available papers were searched. Pharmacogenetic findings for lithium treatment effects might help develop new personalised strategies and consequently better symptom reduction. So far, chronicity and recurrent course of bipolar disorder impair the functioning of numerous patients and strongly increase the risk of suicide.