Abstract
Lithium has neuroprotective effects that are thought to underpin its clinical effectiveness as a mood stabilizer in the treatment of bipolar disorder. Lithium has a multitude of potentially therapeutic effects on excitotoxic neurotransmission pathways that cause cellular damage and decreased resilience in bipolar disorder. However, isolating the mechanisms that underpin lithium’s therapeutic properties has remained difficult. This chapter reviews the therapeutic effects of lithium on neurotransmission and cellular signal transduction mechanisms underlying neuroprogression in bipolar disorder. In doing so, key glycogen synthase kinase-3β (GSK-3β)-mediated mechanisms are highlighted, as they appear pivotal to therapeutic response. These actions are considered in the context of lithium’s effects on bipolar disorder neurocircuitry, mood dysregulation and neurocognitive dysfunction. Employing the integrative framework developed within this chapter, the underlying mechanisms of lithium treatment can be investigated. This endeavour is imperative for future development of pharmaceutical agents that are more specific and better tolerated than lithium and could be beneficial to untreated and unresponsive patient populations. Future investigation of the specific therapeutic mechanisms of lithium is likely to provide insights into the pathophysiology of bipolar disorder, and given GSK-3β-mediated mechanisms are implicated in neurodegenerative diseases, the identification of lithium’s therapeutic actions and novel treatment targets may be useful for the treatment of other neuroprogressive diseases, such as Alzheimer’s and Parkinson’s disease.
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Malhi, G.S., Outhred, T., Das, P. (2017). Lithium: Neurotransmission and Cellular Mechanism Pathways Underlying Neuroprogression in Bipolar Disorder. In: Malhi, G., Masson, M., Bellivier, F. (eds) The Science and Practice of Lithium Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-45923-3_3
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