Melatonin in bipolar disorder

A major obstacle to the development of effective medications for bipolar disorder (BD) is the incomplete understanding of BD pathophysiology, as therapeutics that target the causal mechanisms underpinning BD are more likely to fully address symptoms and prevent recurrence of the disease. Converging evidence suggests that reduced melatonin secretion and function (hypomelatoninaemia) may play a key role in the pathophysiology of BD; however, this relationship has not yet been fully characterised. Increased sensitivity of light-induced melatonin suppression and alterations in synthesis, receptor activity, and metabolism of melatonin may contribute to hypomelatoninaemia in BD. Hypomelatoninaemia may also functionally amplify hypercortisolaemia and sleep disturbance that are common in the disorder (and vice versa), and contribute to oxidative stress, heightened inflammation, and dopaminergic dysfunction in BD. Furthermore, melatonin shows promise as a potential therapeutic agent for BD. Here, we review the preclinical and clinical data addressing the relationships between hypomelatoninaemia, hypercortisolaemia, sleep disturbance, oxidative stress, inflammation, and hyperdopaminergia in BD.