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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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
Volume87
Issue number5
Early online date1 Jan 2019
DOIs
Publication statusPublished - 1 Mar 2020

Cite this

Bot, M., Milaneschi, Y., Al-Shehri, T., Amin, N., Garmaeva, S., Onderwater, G. L. J., ... BBMRI-NL Metabolomics Consortium (2020). Metabolomics Profile in Depression: A Pooled Analysis of 230 Metabolic Markers in 5283 Cases With Depression and 10,145 Controls. Biological Psychiatry, 87(5), 409-418. https://doi.org/10.1016/j.biopsych.2019.08.016