The metabolome-wide signature of major depressive disorder

Dr. Rick Jansen. dr. Yuri Milaneschi and prof. dr. Brenda Penninx have co-authored this paper on the metabolome-wide signature of major depressive disorder. This month the article was published in Molecular Psychiatry.

Single metabolite and targeted metabolomics platforms have revealed several metabolic alterations in depression, including energy metabolism, neurotransmission, and lipid metabolism. More comprehensive coverage of the metabolome was needed to further specify metabolic dysregulations in depression and reveal previously untargeted mechanisms. Here, we measured 820 metabolites using the metabolome-wide Metabolon platform in the NESDA baseline cohort, which were repeated at 6-year follow up. This analysis is the largest untargeted metabolomics study of depression to date, performed in a clinical sample with two measurement waves. We identified 79 metabolites associated with depression status and depression severity, 34 were confirmed in internal replication analyses using 6-year follow-up data. Approximately half of the identified metabolites were lipids, showing specific patterns of downregulation in long-chain monounsaturated and saturated fatty acids and upregulation of lysophospholipids in depression. The other half of the metabolites were non-lipid components of a wide range of pathways. Using genetic data, a potential causal effect of lysophospholipid 1-linoleoyl-GPE on depression was confirmed. This metabolomics signature offers a window on depression pathophysiology and a potential access point for the development of novel therapeutic approaches.