Since its approval in 1970 for the treatment of bipolar illness, lithium has become a commonly prescribed mood stabilizer,
with use in depression and psychotic disorders and potential use in neurodegenerative disorders such as Alzheimer disease.
The predominant explanation for lithium’s actions (e.g., in FDA labeling) was for many years limited to alterations in sodium
transport in excitable cells and a “shift” in catecholamine metabolism. Remarkably, specific enzyme activities were subsequently
identified as targets of the simple cation, and the roles of these and other proteins in psychiatric disease were corroborated
as genomic data and animal models of mood became available. New insights into catecholamine signaling, concerning the specificities
of receptor subtypes and novel modalities of receptor signaling, continue to broaden our understanding of lithium’s actions.
In some instances, lithium may affect mood-regulating enzymes that normally utilize magnesium as a cofactor; protein–protein
interactions that control neuronal receptor pathways also appear to be subject to disruption by lithium. These insights have
implications not only for the development of new psychotropic medicines, but also for our understanding of mood and behavior
as functions of discrete molecular interactions.
