A Preliminary Metabolomic Analysis of Older Adults with and Without Depression

Background: Metabolomics, the global science of biochemistry, is an emerging field that enables detection and quantification of small molecules involved in metabolic and signaling pathways. Metabolic signatures for disease and its treatment could provide valuable biomarkers and insights about disease mechanisms. In this pilot study, we evaluate the potential of metabolomics in the study of older depressed patients.

Methods: We performed a metabolomic analysis of blood plasma from nine depressed, 11 remitted, and ten never-depressed older adults. Approximately 800 metabolites were analyzed, with comparisons made among the three groups.

Results: Metabolites that were altered in currently depressed patients when compared with controls included several fatty acids, glycerol and gamma-aminobutyric acid (GABA). Analyses comparing concentrations in remitted and currently depressed patients revealed a pattern of metabolite alterations similar to the control vs currently depressed analyses. One difference observed in the remitted patients relative to the depressed patients was elevation of the concentration of the ketone 3-hydroxybutanoic acid.

Conclusion: These observations suggest that the depressed state may be associated with alterations in the metabolism of lipids and neurotransmitters, and that treatment with antidepressants adjusts some of the aberrant pathways in disease so that the patients in remission have a metabolic profile more similar to controls than to the depressed population. These results will need to be examined and validated in larger longitudinal cohorts.