Biomarkers for major depressive and bipolar disorders using metabolomics: A systematic review

Major depressive disorder (MDD) and bipolar disorder (BD) lack robust biomarkers useful for screening purposes in a clinical setting. A systematic review of the literature was conducted on metabolomic studies of patients with MDD or BD through the use of analytical platforms such as in vivo brain imaging, mass spectrometry, and nuclear magnetic resonance. Our search identified a total of 7,590 articles, of which 266 articles remained for full-text revision. Overall, 249 metabolites were found to be dysregulated with 122 of these metabolites being reported in two or more of the studies included. A list of biomarkers for MDD and BD established from metabolites found to be abnormal, along with the number of studies supporting each metabolite and a comparison of which biological fluids they were reported in, is provided. Metabolic pathways that may be important in the pathophysiology of MDD and BD were identified and predominantly center on glutamatergic metabolism, energy metabolism, and neurotransmission. Using online drug registries, we also illustrate how metabolomics can facilitate the discovery of novel candidate drug targets.