This study investigated the role of circadian clock genes in bipolar disorder (BD) cells’ susceptibility to apoptosis and lithium response. It examined fibroblasts from lithium responders (Li-R), non-responders (Li-NR), and controls, identifying co-expression patterns between circadian clock and cell survival genes that distinguished BD from controls and Li-R from Li-NR cells. The study found that lithium preferentially protected BD fibroblasts from apoptosis. Knockdown of circadian genes Per1 and Per3 had opposite effects on apoptosis, linking circadian rhythms and cell survival pathways. Loss of Per1 function reduced apoptosis, while loss of Per3 function increased it, highlighting their role in lithium responsiveness.

The study suggests that lithium response in BD may depend on the interaction between circadian clock and cell survival pathways, particularly involving PER1 and PER3. These findings indicate that variations in circadian clock genes could predict lithium response and identify biomarkers for more targeted BD treatments. The results imply that lithium’s neuroprotective effects may relate to circadian rhythm regulation and apoptosis, and understanding these pathways could enhance BD treatment strategies.

Reference: Mishra HK, Wei H, Rohr KE, et al. Contributions of circadian clock genes to cell survival in fibroblast models of lithium-responsive bipolar disorder. Eur Neuropsychopharmacol. 2023 Sep;74:1-14. doi: 10.1016/j.euroneuro.2023.04.009. Epub 2023 Apr 29. PMID: 37126998; PMCID: PMC11801370.