Metabolomics Profile in Depression: A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 Controls

Mariska Bot*, Yuri Milaneschi, Tahani Al-Shehri, Najaf Amin, Sanzhima Garmaeva, Gerrit L. J. Onderwater, Rene Pool, Carisha S. Thesing, Lisanne S. Vijfhuizen, Nicole Vogelzangs, Ilja C. W. Arts, Ayse Demirkan, Cornelia van Duijn, Marleen van Greevenbroek, Carla J. H. van der Kallen, Sebastian Koehler, Lannie Ligthart, M. J. M. van den Maagdenberg, Dennis O. Mook-Kanamori, Renee de MutsertHenning Tiemeier, Miranda T. Schram, Coen D. A. Stehouwer, Gisela M. Terwindt, Ko Willems van Dijk, Jingyuan Fu, Alexandra Zhernakova, Marian Beekman, P. Eline Slagboom, Dorret Boomsma, Brenda W. J. H. Penninx, BBMRI-NL Metabolomics Consortium

*Corresponding author for this work

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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 Al 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.

Original languageEnglish
Pages (from-to)409-418
Number of pages10
JournalBiological Psychiatry
Issue number5
Publication statusPublished - 1 Mar 2020


  • Biomarkers
  • Cardiovascular
  • Depression
  • Metabolites
  • Metabolomics
  • Pooled analysis
  • RISK

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