The mechanisms of lithium action – an update

Objectives.
The paper aims to present the most important research on the mechanisms of lithium action, published in the years 2019–2024.

Literature review.
The analysis of publications from this period concerning the mechanisms of lithium action was conducted in the context of its prophylactic efficacy in bipolar disorder, defined as good (lithium responders) or poor (lithium non-responders). The results of molecular-genetic studies performed by the Consortium of Lithium Genetics and other genetic and epigenetic research, as well as in vitro studies using induced pluripotent stem cells and lymphoblastoid cell lines, were discussed. The outcomes of recent experimental studies on lithium’s effect on neural cells using mouse models were presented. A growing number of studies suggest a possible mechanism of action for lithium through immunomodulatory and anti-inflammatory effects. The paper also discusses the effects of lithium on biological rhythms and telomere function.

Conclusions.
Clinical and experimental studies, including in vitro ones, showed multidirectional effects of lithium on various processes in the organism, particularly those associated with nervous functions. Some of these help identify mechanisms associated with the therapeutic effects of lithium, especially relapse prevention in bipolar disorder. The main two areas of these mechanisms include the effect of lithium on the excitability and proliferation of cells, especially in the nervous system, and its immunomodulatory and anti-inflammatory effects, referring to the postulated involvement of these factors in the pathogenesis of bipolar disorder as a condition of “low-grade inflammation”.