Genes contributing to the adverse effects of lithium therapy in bipolar disorder

Backgrounds: Bipolar disorder is a mental illness involving periods of depression andabnormally-elevated mood that can last several weeks. Pediatric bipolar disorder affects childrenlike in adults. Lithium ion is the first-line treatment acting as a mood-stabilizing agent in thedisorder. Neuroimaging studies indicate that lithium accumulates in the hippocampus and thatchronic lithium medication causes the hippocampal volume to become larger than normal.Materials and Methods: RNA-seq data related to human hippocampal progenitor cells treatedwith low (۰.۷۵ mM) and high (۲.۲۵ mM) doses of lithium was obtained from GEO repository(GSE۱۸۴۹۳۰). Cell parameters implicated in neurogenesis were used as the dependent factor.Data analysis was performed using DESeq۲, and functional genetic enrichment implemented byCytoscape tools.Results: Quality control of the sequencing and gene count data was carried out by checking thegroup boxplots, and indicated cross-comparable groups. Differential gene expression analyses asdone for low-lithium and high-lithium treatments compared to control, revealed two genesessential in lithium-induced progenitor cell growth. ZMPSTE۲۴ encodes the CAAX prenylprotease ۱ homolog, and DHX۳۵ encodes the RNA helicase DHX۳۵. Functional enrichmentsshowed that these genes are involved in regulating the volume of the molecular layer of thedentate gyrus.Conclusion: Results of this study suggest that the effects of lithium on human hippocampalvolume may be mediated by provoking the adult hippocampal neurogenesis in the bipolardisorder brain.

کلیدواژه ها:

Bipolar disorder ، Lithium therapy ، Network pharmacology ، Systems biology ، Differential expression