Metabolomic Profiling of Extracellular Vesicles Reveals Distinct Metabolic Dysregulation and Treatment-Specific Signatures in Depression.
Biomolecules April 2, 2026 Nikola Balic, Gordana Nedic Erjavec, Marcela Konjevod et al.
Treatment-resistant depression (TRD) shows more pronounced metabolic disruptions than responsive depression, especially in lipid, amino acid, and energy pathways. Elevated lysophospholipids and fatty acids in TRD suggest dysregulated lipid metabolism and inflammation. After eight weeks, duloxetine, bright-light therapy, and esketamine each improved symptoms and partially normalized metabolic profiles, but through different mechanisms: duloxetine modulated amino acid and glycerophospholipid metabolism; bright-light therapy reduced lysophospholipids and mannose; esketamine affected lipid turnover, short-chain fatty acids, carbohydrates, and increased thyrotropin-releasing hormone. Extracellular vesicle metabolomics may help distinguish depression subtypes and treatment effects.