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

BBMRI-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 journalArticleAcademicpeer-review

Copy link to clipboard


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

    Final publisher's version, 420 KB, PDF document

    Request copy


  • BBMRI-NL Metabolomics Consortium
  • 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 Köhler
  • Lannie Ligthart
  • Arn M J M van den Maagdenberg
  • Dennis O Mook-Kanamori
  • Renée de Mutsert
  • Henning 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 I Boomsma
  • Brenda W J H Penninx

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.

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

ID: 120581161