Metabolomics Profile in Depression: A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 ControlsBBMRI-NL Metabolomics Consortium, Bot, M., Milaneschi, Y., Al-Shehri, T., Amin, N., Garmaeva, S., Onderwater, G. L. J., Pool, R., Thesing, C. S., Vijfhuizen, L. S., Vogelzangs, N., Arts, I. C. W., Demirkan, A., van Duijn, C., van Greevenbroek, M., van der Kallen, C. J. H., Köhler, S., Ligthart, L., van den Maagdenberg, A. M. J. M., Mook-Kanamori, D. O., de Mutsert, R., Tiemeier, H., Schram, M. T., Stehouwer, C. D. A., Terwindt, G. M., Willems van Dijk, K., Fu, J., Zhernakova, A., Beekman, M., Slagboom, P. E., Boomsma, D. I. & Penninx, B. W. J. H., 2020, In : Biological Psychiatry. 87, 5, p. 409-418 10 p.
Research output: Contribution to journal › Article › Academic › peer-review
BACKGROUND: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons.
METHODS: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses.
RESULTS: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q < .05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein A1 were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms.
CONCLUSIONS: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity.
|Number of pages||10|
|Publication status||Published - 2020|