Introduction: Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination of the central nervous system. Bipolar Disorder (BD) is a complex psychiatric condition. Patients with MS have a significantly elevated risk of developing BD. The present study aimed to investigate the shared genetic mechanisms between MS-BD using systems biology approaches.
Methods: We constructed a protein-protein interaction (PPI) network of the overlapping MS-BD genes using the STRING database and identified functional modules and hub genes with Cytoscape. Gene ontology and pathway enrichment analyses of the modules and hub genes were performed using g:Profiler. Potential drug targets among these genes were further explored using DGIdb.

Results: A total of 206 genes associated with MS and 201 genes associated with BD were retrieved from the NCBI, of which 55 genes were common to both diseases. PPI network analysis revealed ten functional modules. Ten hub genes -TNF, IL6, IL1B, TLR4, AKT1, BCL2, IFNG, APP, NFKB1, and MTOR- were identified as central players in both conditions. TNF and IL6 showed upregulated expression in MS-BD and emerged as promising drug targets. The enriched KEGG pathways included tuberculosis, HIF-1 signaling, AGE-RAGE signaling in diabetic complications, and the Toll-like receptor signaling pathway.
Conclusion: Our findings highlight the shared biological processes and gene expression patterns between MS-BD. These results suggest that MS-BD may involve common underlying mechanisms, which could open new avenues for repurposing existing drugs and developing combined therapeutic strategies. Such insights may ultimately improve prevention and treatment approaches for MS-BD, as well as related comorbidities.