Peripheral Transcriptomic Signatures Reveal Convergent Neuroinflammatory, Metabolic, and miRNA Dysregulation in Major...

Area of Science:

• Genomics
• Neuroscience
• Immunology

Background:

• Bipolar disorder (BP), schizophrenia (SZ), major depressive disorder (MDD), and social anxiety disorder (SAD) are clinically distinct but share underlying biological pathways.
• Understanding these transdiagnostic mechanisms is crucial for developing effective treatments.

Purpose of the Study:

• To map the transdiagnostic systemic biological mechanisms common to BP, SZ, MDD, and SAD.
• To identify shared transcriptomic signatures and their potential role in neural vulnerabilities.

Main Methods:

• Weighted Gene Co-Expression Network Analysis (WGCNA) was applied to peripheral blood RNA-Seq datasets.
• Evaluated module preservation, hub gene disruption, and microRNA (miRNA) networks across the disorders.

Main Results:

• Seven gene co-expression modules demonstrated robust cross-disease preservation.
• Altered expression of 22 significant hub genes (e.g., IL1B, TLR2, MMP9) was observed, linked to inflammatory signaling and structural remodeling.
• Downregulated ribosomal hubs indicated systemic metabolic stress, potentially evading miRNA regulation.

Conclusions:

• A shared transcriptomic architecture challenges rigid diagnostic boundaries for these disorders.
• Systemic immune dysregulation and metabolic alterations are core pathogenic denominators.
• These findings provide a rationale for transdiagnostic therapies targeting upstream systemic networks to mitigate neural vulnerabilities.