Abstract Lithium is the most commonly used medicine to treat bipolar disorder (BD). It is considered a mood regulator, and the mechanisms underlying this effect still need to be elucidated. Some modulations are involved in neuroprotection, including neuronal communication, neuron differentiation and survival, synaptic modulation and plasticity, modulation of cognition, contribution to antioxidant defense, and reduction of inflammation, glial dysfunction, and apoptosis. In general, about 50% of the concentrations in serum are in the brain. However, it is essential to note that many gene expression differences influence the concentrations and actions of individuals. This review discusses the various mechanisms of lithium in BD I and II, its effects on neurotransmitters and receptors, the hypothalamic–pituitary–adrenal (HPA) axis, inflammation and neuroinflammation, immune functions, oxidative and nitrosative stress, mitochondrial respiratory chain function, intracellular signaling, and brain plasticity, as well as toxicity and side effects.
Bertollo et al. (2026) studied this question.