Biological Targets Underlying the Antisuicidal Effects of Lithium

Purpose of ReviewThis article highlights the potential relationship of lithium's cellular and molecular targets to its antisuicidal effects in bipolar disorder (BD).Recent FindingsLithium is the mood stabilizer that shows the most robust therapeutic evidence in relapse prevention and mood episodes in BD. Compelling evidence also elucidates lithium's unique effects in reversing and preventing suicidal behavior (SB), mostly in individuals with BD.SummaryThe following review is an up-to-date summary of studies related to the anti-suicidal effects of lithium in patients with BD. We focused on studies investigating the similarities in pathogenesis of BD and SB and the related treatment targets for lithium's anti-suicidal actions. Lithium seems to have beneficial effects in reversing pathophysiological changes in SB and BD associated with its ability to reduce suicidal risk. Several neurobiological targets have been associated with the antisuicidal effects of lithium such as brain atrophy and demyelination, alterations in glutamatergic neurotransmission, and increased central and peripheral inflammation as well as HPA axis hyperactivation, cell signaling pathways, and neurotrophic system dysfunctions. Further studies are required to elucidate the presence of a specific neurobiological signature of SB as an independent clinical dimension and not solely in the context of mood episodes.