Insulin signaling as a therapeutic mechanism of lithium in bipolar disorder.
Level 5 - mechanism / opinion, no new human data
Narrative review presenting theoretical mechanism-based reasoning without primary human data.
PubMed 36038539 · doi:10.1038/s41398-022-02122-6
What was done
This narrative review synthesized literature to propose a theoretical model wherein lithium exerts mood-stabilizing effects in bipolar disorder by modulating insulin signaling pathways. The authors specifically evaluated the phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/Akt) pathway, glycogen synthase kinase-3 (GSK3), the phosphatidylinositol cycle, Protein kinase C (PKC), and sodium myo-inositol transporters.
What was found
The abstract reports no empirical data or quantitative findings. Conceptually, the authors propose that lithium's actions on GSK3 and the phosphatidylinositol cycle mediate mood stabilization via PI3K/Akt insulin signaling, align with models of energy dysregulation in bipolar disorder, and account for metabolic comorbidities like type 2 diabetes. They propose future testing using extracellular vesicles to assess neuronal insulin signaling in patients.
Why it matters
It provides a unifying mechanistic hypothesis linking the therapeutic actions of lithium to central insulin signaling and metabolic dysregulation in bipolar disorder.
Limits
The paper is a theoretical review without primary clinical, experimental, or quantitative data. No sample sizes, effect estimates, or systematic review methods are provided.
Cited by
- supports Many major molecular targets of lithium, such as the PI cycle, GSK-3, Akt, and mTOR, are components of the insulin signaling network.