Metabolomics in stress-related disorders: a systematic review and bioinformatics analysis

Stress-related disorders, including major depressive disorder (MDD), bipolar disorder (BD), and post-traumatic stress disorder (PTSD), share complex biological mechanisms and overlapping symptoms, posing challenges for diagnosis and treatment. This in silico study aimed to identify metabolomic patterns and explore dysfunctional metabolic pathways that are common and specific within a transdiagnostic psychiatric sample. A systematic review was conducted to identify metabolomic studies using mass spectrometry on blood samples from patients with MDD, BD, and PTSD. Study screening was performed using Rayyan, and metabolite codes were retrieved from the HMDB and ChEBI databases. Identified metabolites were classified using the R software, and metabolic pathway enrichment analysis was conducted in MetaboAnalyst. Thirteen eligible studies were identified, reporting 583 metabolites. Among these, four metabolites-arginine, inosine, 5-oxoproline (5-OP), and pyruvic acid-were consistently altered across disorders. Bioinformatics analysis revealed key metabolic pathways primarily related to amino acid, energy, carbohydrate, and lipid metabolism, suggesting shared biological mechanisms. These findings reinforce the transdiagnostic nature of metabolic dysfunction in psychiatric disorders and may contribute to the development of personalized therapeutic strategies and biomarker panels for improved diagnosis and treatment.