Understanding suicide: Focusing on its mechanisms through a lithium lens

Abstract

Background: Current intervention strategies have been slow in reducing suicide rates, particularly in mood disorders. Thus, for intervention and prevention, a new approach is necessary. Investigating the effects of a medication known for its anti-suicidal properties on neurobiological and neurocognitive substrates of suicidal thinking may provide a deeper and more meaningful understanding of suicide.

Method: A literature search of recognised databases was conducted to examine the intersection of suicide, mood disorders, and the mechanisms of lithium.

Results: This review synthesises the extant evidence of putative suicide biomarkers and endophenotypes and melds these with known actions of lithium to provide a comprehensive picture of processes underlying suicide. Specifically, the central importance of glycogen synthase kinase-3β (GSK3β) is discussed in detail because it modulates multiple systems that have been repeatedly implicated in suicide, and which lithium also exerts effects on.

Limitations: Suicide also occurs outside of mood disorders but we limited our discussion to mood because of our focus on lithium and extending our existing model of suicidal thinking and behaviour that is contextualised within mood disorders.

Conclusions: Focusing on the neurobiological mechanisms underpinning suicidal thinking and behaviours through a lithium lens identifies important targets for assessment and intervention. The use of objective measures is critical and using these within a framework that integrates findings from different perspectives and domains of research is likely to yield replicable and validated markers that can be employed both clinically and for further investigation of this complex phenomenon.

Keywords: Biomarkers; Endophenotypes; GSK3β; Lithium; Pharmacological treatment; Suicide prevention.